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Keratometric Change After XEN, Trabeculectomy and Tube Shunts Study Overview ================= Brief Summary ----------------- The main goal of this study is to assess the severity of postoperative corneal astigmatism induced by implantation of the XEN Gel Stent compared to that induced by traditional filtering surgery (trabeculectomy and GDDs). Corneal astigmatism can be assessed using corneal topography, a non-invasive tool which provides an accurate estimate of corneal curvature in all meridians. To the best of our knowledge, no study has yet attempted to quantify the amount of astigmatism induced by the XEN Gel Stent. Detailed Description ----------------- Following glaucoma surgery, patients often experience decreased visual acuity (VA) which can partly be explained by induced changes to the optical properties of the cornea. Corneal astigmatism can be assessed using corneal topography, a non-invasive tool which provides an accurate estimate of corneal curvature in all meridians. Obtained keratometric measures (termed K values) can allow clinicians to quantify the amount of astigmatism before and after surgical intervention. Multiple studies have been previously published to evaluate induced postoperative astigmatism after trabeculectomy. However, only two studies have characterized the impact of GDDs on keratometric values. To the best of our knowledge, no study has yet attempted to quantify the amount of astigmatism induced by the XEN Gel Stent. Assessing the impact of the XEN implant on corneal astigmatism is important to better characterize the expected course of postoperative visual rehabilitation, the impact of novel glaucoma devices on corneal properties and the predictability of refractive outcomes after XEN implantation. Compared to traditional filtering surgery, the XEN Gel Stent is inserted without opening the conjunctiva and is implanted further from the corneal limbus (5 mm). These factors may allow for a reduced amount of surgically induced corneal astigmatism. We hypothesize that the XEN Gel Stent implantation induces less corneal astigmatism compared to traditional filtering surgery, such as the trabeculectomy and GDDs (BGI or AGV). The main goal of this prospective interventional comparative study is to assess the severity of postoperative corneal astigmatism induced by implantation of the XEN Gel Stent compared to that induced by traditional filtering surgery (trabeculectomy and GDDs). Secondary objectives are evaluation of visual acuity recovery as well as IOP reduction and other parameters between groups. Glaucoma surgery (XEN Gel Stent, trabeculectomy or GDD implantation) will be performed by the ophthalmologists in charge of the study according to standard procedures. For each patient, the most appropriate type of glaucoma surgery will be recommended by the ophthalmologist regardless of patients' participation in the study, as dictated by the specific nature of their glaucoma and following current standards of care. Official Title ----------------- Comparison of Keratometric Change After Xen Gel Stent Implantation, Trabeculectomy, and Tube Shunts Conditions ----------------- Glaucoma, Open-Angle, Glaucoma, Angle-Closure, Glaucoma Secondary, Glaucoma Eye Intervention / Treatment ----------------- * Diagnostic Test: Corneal topography: OPD-Scan * Diagnostic Test: Corneal topography: Pentacam Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Eyes with an IOP above target and/or progressing on maximally tolerated medical therapy; Patients aged 18 years or older; Ability to provide informed consent; Ability to be followed for the entire duration of the study. Exclusion Criteria: Patients less than 18 years old; Inability to provide informed consent; Inability to be followed for the entire duration of the study; Patients undergoing surgery combined with cataract extraction; Presence of severe dry eye disease; Presence of ocular comorbidities other than glaucoma, such as corneal or retinal disease. Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Non-Randomized Intervention Model: Factorial Assignment Interventional Model Description: 3 groups will be compared: Group 1: 30 participants suffering from glaucoma who are candidates for XEN Gel Stent implantation Group 2: 30 participants suffering from glaucoma who are candidates for trabeculectomy Group 3: 30 participants suffering from glaucoma who are candidates for GDD implantation (BGI or AGV) Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: XEN Gel Stent implantation<br>Participants suffering from glaucoma who are candidates for XEN Gel Stent implantation | Diagnostic Test: Corneal topography: OPD-Scan<br>* Corneal topography photography, taken by specular reflection (OPD-Scan) by measuring corneal curvature, thickness and topography.<br>Diagnostic Test: Corneal topography: Pentacam<br>* Corneal topography photography, taken by Scheimpflug imaging (Pentacam) by measuring corneal curvature, thickness and topography.<br>| | Experimental: Trabeculectomy<br>Participants suffering from glaucoma who are candidates for trabeculectomy | Diagnostic Test: Corneal topography: OPD-Scan<br>* Corneal topography photography, taken by specular reflection (OPD-Scan) by measuring corneal curvature, thickness and topography.<br>Diagnostic Test: Corneal topography: Pentacam<br>* Corneal topography photography, taken by Scheimpflug imaging (Pentacam) by measuring corneal curvature, thickness and topography.<br>| | Experimental: GDD implantation<br>Participants suffering from glaucoma who are candidates for GDD implantation (BGI or AGV) | Diagnostic Test: Corneal topography: OPD-Scan<br>* Corneal topography photography, taken by specular reflection (OPD-Scan) by measuring corneal curvature, thickness and topography.<br>Diagnostic Test: Corneal topography: Pentacam<br>* Corneal topography photography, taken by Scheimpflug imaging (Pentacam) by measuring corneal curvature, thickness and topography.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Keratometric values (OPD-Scan) | Change in simulated keratometric (K) values obtained by OPD-Scan between the indicated timepoints. | Baseline, 2 months, 6 months, 12 months | | Keratometric values (Pentacam) | Change in simulated keratometric (K) values obtained by Pentacam between the indicated timepoints. | Baseline, 2 months, 6 months, 12 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Best-corrected visual acuity change | Evaluation of visual acuity change, measured using the Snellen chart. | Baseline, 2 months, 6 months, 12 months | | Intraocular pressure change | Evaluation of intraocular pressure control, measured using gold standard Goldmann applanation tonometry. | Baseline, 2 months, 6 months, 12 months | | Visual field change change | Evaluation of visual field change. Visual field change will be calculated using the mean deviation (MD) values and pattern standard deviation (PSD) values measured using automated Humphrey 24-2 perimetry. | Baseline, 6 months, 12 months | | Retinal nerve fiber layer thickness change | Evaluation of retinal nerve fiber layer (RNFL) thickness change (µm), using the average RNFL thickness values measured using Spectral Domain Optical Coherence Tomography (SD-OCT). The change in thickness (µm) will be calculated between the time points described. | Baseline, 6 months, 12 months | | Ganglion cell layer thickness change | Evaluation of ganglion cell layer (GCL+) thickness. This GCL+ thickness is measured using the values for the average ganglion cell layer and inner plexiform layer thickness of the retina (value called Average GCL + IPL thickness) obtained by Spectral Domain Optical Coherence Tomography (SD-OCT). The change in thickness (µm) will be calculated between the time points described. | Baseline, 6 months, 12 months | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Xen Gel Stent, Baerveldt glaucoma implant, Ahmed glaucoma implant, Trabeculectomy, Glaucoma drainage devices

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Flares of Low Back Pain With Activity Research Study Study Overview ================= Brief Summary ----------------- Low back pain (LBP) is the most common cause of disability worldwide. Although general activity is encouraged in the treatment of LBP, there is limited empirical information available on the specific types of activities that are beneficial or harmful for patients seen in primary care for LBP. This study will identify those physical activities with short-term (transient) effects on LBP exacerbations (or flares of LBP), as well as identifying the long-term (cumulative) effects of such activities on functional recovery. Detailed Description ----------------- This research will use a novel approach to distinguish the short-term effects on LBP of physical activities from the long-term effects of such activities, by conducting a longitudinal case-crossover study nested within a cohort study. This design accounts for measured and unmeasured confounds by using each case as his/her own control- an entirely observational study that is analogous to a crossover experiment- capitalizing on modern mobile health and actigraphy technology. The primary exposures of interest are 10 self-reported physical activities commonly performed during work and activities of daily living, and actigraphy-assessed physical activity. Other exposures of interest include psychological factors, social factors, lifestyle-related factors, and work-related factors. The primary outcomes are participant-reported flares of low back pain (Aim 1) and participant-reported back-related functional limitations (mobility and activities of daily living [ADLs]) at 1-year follow-up, as measured by the Roland-Morris Disability Questionnaire. This observational study will include up to 550 Veterans with LBP aged 18 and older recruited from the VA Puget Sound Health Care System (VAPSHCS). The study will not affect participants' medical care in any way. After informed consent, recruitment, and baseline data collection, study participants will complete frequent, serial electronic e-Questionnaires using their own personal electronic devices (personal computer [PC], tablet, or smartphone) over the 1-year period of follow-up. Participants may also wear ActiGraph units for the 1st 4 weeks of follow-up. Long-term outcomes will be assessed by extended e-Questionnaires completed at 1-year follow-up. Aim 1 analyses will examine the short-term effects of 10 specific activity categories on participant-reported flares across all study assessments over 1-year follow-up. Aim 2 analyses will examine associations between the frequency of exposure to 10 specific activity categories over weeks 1-4 of follow-up, and long-term functional recovery at 12 months as defined by the RMDQ. All analyses will use a biopsychosocial framework accounting for potential confounders (sociodemographics, psychological factors, etc.) and effect modifiers, and will include sensitivity analyses to examine the robustness of findings and important study assumptions. This study was registered prior to the start of enrollment. Official Title ----------------- Effects of Physical Activities on Pain and Functional Recovery in Low Back Pain Conditions ----------------- Low Back Pain Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Veterans age 18-65 years seen in VA primary care for LBP Must have regular access (every day, during most hours of the day) to a computer, tablet, or smartphone with internet access at home or at work Basic computer literacy Having a mobile phone capable of receiving alerts using text messages Must be able to understand and read English, sufficient to provide informed consent and validly complete the study assessments. Participants must complete basic requirements during a 2-week run-in period, such as completing e-Questionnaires Exclusion Criteria: Red flag' spine conditions (spinal cord injury, infection, malignancy, fracture) or spondyloarthropathy Pregnancy Prisoners or incarcerated Severe active medical or psychiatric comorbidities likely to be a barrier to study participation including completing frequent, serial assessments (e.g., metastatic cancer). Thoracolumbar spine surgery in the past 1 year Other major orthopedic surgery potentially impeding normal physical activities (such as surgeries involving the hip, knee, ankle, shoulder, elbow, wrist joints) within the past 6 months, or major abdominal or chest surgery within the past 6 months.* Planned major orthopedic, abdominal, or chest surgery in the next 2 months. Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 65 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Observational cohort<br>This is a case-crossover study nested within a cohort study. | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Participant-reported flares of low back pain (Aim 1) | At each study assessment, participants are presented with the flare definition used in this study, which was derived from a previously validated flare definition by Costa et al (2000). The definition is: A 'flare' of low back pain is a worsening of your low back pain that lasts from hours to weeks. Participants are then asked to self-report whether a flare of low back pain is currently ongoing, by responding to the question According to the definition above, are you currently experiencing a flare of your low back pain?, with response options of yes or no. These response options define participant-reported flares. | Flares over 1-year follow-up | | Roland-Morris Disability Questionnaire (Aim 2) | Roland-Morris Disability Questionnaire (Aim 2) | 1-year follow-up |

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Heart Exercise And Resistance Training - Peer Lead ActivitY Study Overview ================= Brief Summary ----------------- Numerous studies show that regular physical activity / exercise significantly improves exercise tolerance as well as clinical outcomes in cardiovascular disease (CVD). Exercise as a reliable adjunctive intervention, however, remains limited due to poor short- as well as long-term adherence. The study examines the effectiveness of the peer-led Heart Exercise And Resistance Training - Peer Lead ActivitY (HEART-PLAY) intervention to significantly sustain exercise adherence among CR patients, as compared a standard CR intervention. In a rigorous cluster randomized controlled trial at the UCSD Step Family Cardiovascular Rehabilitation and Wellness Center, the study assesses the HEART-PLAY intervention program in 264 socioeconomically and ethnically diverse women and men 18+ years old who have been referred to standard CR. Participants in the HEART-PLAY and in the STANDARD CR programs will both participate in 36 sessions of CR across approximately 12 weeks, as prescribed by their physician. Participants in HEART-PLAY will additionally receive peer and staff leadership, self-monitoring tools and feedback, group education and materials, and motivational, goal-setting, and relapse prevention counseling sessions. The study will demonstrate that the peer-led HEART-PLAY program based in the clinic setting will significantly enhance the primary study endpoint of adherence to 150 min/week of moderate physical activity/week. Detailed Description ----------------- This study examines the effectiveness of the Heart Exercise And Resistance Training - Peer Lead ActivitY (HEART-PLAY) intervention to significantly sustain exercise adherence in patients referred for Cardiac Rehabilitation (CR). CR Clinic staff and CR patients who meet study inclusion criteria and are willing to serve as peer leaders, will be taught to lead the intervention activities with trained health educators and research staff. The HEART-PLAY program and behavior change will be sustainable because of the presence of peer and staff leadership and because it employs proven strategies from social cognitive theory and ecological models including self-monitoring, feedback, social support, role modeling, and relapse prevention. HEART-PLAY teaches patients how to accumulate meaningful PA across the day and provides a supportive social infrastructure to maintain motivation. Since the aim is to test an augmented CR program that can be widely adopted, the project employs a design that allows for the concurrent testing of both intervention and implementation strategies and outcomes. Across the five days of the week and the AM and PM clinic sessions, there will be approximately 25 different peer-led groups (clusters) run to obtain complete data on a total of 264 women and men 18+ years old of varied socioeconomic and ethnic backgrounds referred for CR. HEART-PLAY and STANDARD participants will be scheduled to visit the Step Clinic on distinctly different days/times to avoid contamination. Participants in the STANDARD condition will receive the standard of care cardiac rehabilitation, consisting of 36 sessions across 12 weeks of prescribed, supervised exercise sessions, Participants in the HEART-PLAY will receive standard CR and additionally receive pedometers, resistance bands, and the National Institute of Aging (NIA) exercise guide. Patients will further receive counseling from peer health coaches, social support from group education sessions, and supplemental educational materials. After the 12 weeks of prescribed, supervised exercise sessions, HEART-PLAY group participants will continue to receive support from peers and clinic staff with check-in calls, feedback on pedometer goals, and bi-weekly group events including walks and/or resistance band group exercise classes. Pilot data support that the peer-led approach in the clinic setting will be enthusiastically received by patients and significantly increase PA and adherence. Official Title ----------------- Heart Exercise And Resistance Training - Peer Lead ActivitY (HEART-PLAY) Conditions ----------------- Cardiovascular Diseases Intervention / Treatment ----------------- * Behavioral: HEART-PLAY * Behavioral: Standard Cardiac Rehabilitation Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Age 18+ Referred to the UCSD Step Clinic for 36 sessions of cardiac rehabilitation across 12-14 weeks for one of the following medical conditions: myocardial infarction, coronary artery bypass surgery, stable angina, heart valve repair or replacement, coronary angioplasty or stenting, or congestive heart failure. Able to give informed consent in English Able to perform study assessments as described Blood pressure <180/110 mmHg Able to perform light to moderate exercise Have not had a fall during the previous 6 months resulting in an injury Clinical staff's permission to participate, including their assessment that participant is a good candidate for this particular research study Ability to complete written or computer-based surveys Completion of a post-consent comprehension test Exclusion Criteria: Referred to CR following VAD (Ventricular Assist Device) procedure, peripheral arterial disease (PAD), or heart or lung transplant. Angina not adequately managed with nitrates Oxygen-dependent COPD Recent stroke or significant cerebral neurologic impairment that would interfere with participation Major depressive disorder per eMR Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: Cluster randomized controlled trial Masking: Double Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Standard Cardiac Rehabilitation<br>Participants in the STANDARD condition will receive the standard of care cardiac rehabilitation, consisting of 36 sessions across 12 weeks of prescribed, supervised exercise sessions. | Behavioral: Standard Cardiac Rehabilitation<br>* During the 12-week intervention period, the STANDARD intervention participants will receive standard of care by attending the 36 sessions of standard CR as prescribed by his/her physician and administered by the Step Clinic.<br>| | Experimental: HEART-PLAY<br>Participants in the HEART-PLAY will receive standard CR and additionally receive pedometers, resistance bands, and the National Institute of Aging (NIA) exercise guide. They will further receive counseling from peer health coaches, social support from group education sessions, and supplemental educational materials. After the 12 weeks of prescribed, supervised exercise sessions, HEART-PLAY group participants will continue to receive support from peers and clinic staff with check-in calls, feedback on pedometer goals, and twice weekly group events including walks and/or resistance band group exercise classes. | Behavioral: HEART-PLAY<br>* Participants assigned to the HEART-PLAY intervention will receive standard CR. Additionally, they will receive pedometers, group education, and educational materials introduced by peer Health Coaches for 12 months. Before or after their regularly scheduled CR appointments, they will meet at the clinic as a group twice per week to receive Health Tips and participate in discussions. At 8 weeks in to the 12-week CR, they will begin to discuss with their peer Health Coaches the transition from the formal CR setting into community-based exercise. As part of this transition, peer Health Coaches will slowly introduce group community walks and train participants in the proper use of resistance bands. Health Coaches will have talk with their assigned participants about relapse prevention and sustaining exercise following the termination of formal CR.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in Minutes of Moderate Physical Activity (PA) | 7-day actigraphy records will be used to assess amount of moderate PA | 3 months, 6 months, and 12 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in Health-related quality of life (QoL) | Demonstrate improved QoL as determined by the NIH-supported PROMIS-29 | 3 months, 6 months, and 12 months | | Improved Cost-effectiveness | Determine cost-effectiveness using Markov Models | 12 months | | Change in BNP levels | Assess reductions in circulating cardiac health biomarkers using standard biomarkers assays | 3 months, 6 months, and 12 months | | Change in Galectin-3 levels | Assess reductions in circulating cardiac health biomarkers using standard biomarkers assays | 3 months, 6 months, and 12 months | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- cardiac rehabilitation, physical activity

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The DIEP Flap as a Model of Ischemia-Reperfusion: an Intervention Study Study Overview ================= Brief Summary ----------------- The investigators will examine whether administration of certain medications will decrease or prevent ischemia-reperfusion injury. Official Title ----------------- The DIEP Flap as a Model of Ischemia-Reperfusion: an Intervention Study Conditions ----------------- Ischemia-Reperfusion Intervention / Treatment ----------------- * Drug: Antioxidant * Other: Placebo * Drug: Anti-inflammatory drug Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patients undergoing breast reconstruction Exclusion Criteria: Diabetes mellitus Kidney or liver disease Use of immunosuppressants Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- Female Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Prevention Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Placebo Comparator: 1<br>Placebo tablet and iv | Other: Placebo<br>* Placebo tablet and iv<br>| | Experimental: 2<br>Placebo tablet and intervention iv | Drug: Antioxidant<br>* Antioxidant iv bolus<br>| | Experimental: 3<br>Intervention tablet and placebo iv | Drug: Anti-inflammatory drug<br>* Anti-inflammatory tablet<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Antioxidant concentrations | | 0,5-24 hours |

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Internet-based Depression Treatment: Differential Efficacy of Different Therapeutic Components Study Overview ================= Brief Summary ----------------- The objective of the present project is to study the differential effectiveness of three brief self-applied via the Internet interventions for mild to moderate depression: a global protocol composed of several therapeutic components (psychoeducation, cognitive restructuring, behavioral activation, positive psychology, and relapse prevention), a protocol just based on behavioral activation (BA), and a protocol just based on positive psychology (PP). The purpose is to know the specific contribution of each therapeutic components in the treatment of depression. Detailed Description ----------------- Depression is one of the most important health problems worldwide, which generates important costs, both from the economic point of view as from the social and personal one. If not properly treated, it may become chronic and therefore interferes significantly in all areas of operation. Hence, one of the most important challenges within this scope is the design of new ways to apply treatments in a way that maximizes its therapeutic efficiency. Information and Communication Technologies (ICTs) have proven their utility as they are very useful in order to provide help to all those in need. It is a field of study very novel which will become more important in the short term. Several internationally renowned research groups have launched self-applied treatment programs through the Internet in order to address this issue. Results obtained so far are consistent and promising, and show these treatments as effective. However, these treatments have different therapeutic components and it is important to identify the specific contribution of each of them. Therefore, the objective of the present project is to study the differential effectiveness of three brief self-applied via the Internet interventions for mild to moderate depression: a global protocol composed of several therapeutic components (psychoeducation, cognitive restructuring, behavioral activation, positive psychology, and relapse prevention), a protocol just based on behavioral activation (BA), and a protocol just based on positive psychology (PP). A minimum of 192 participants diagnosed with mild to moderate depression symptoms will be randomly assigned to one of the three experimental conditions: an Internet-based global protocol composed of several therapeutic components (n=64); a Internet-based protocol based on BA (n=64), and an Internet-based program based on PP (n=64). Our hypothesis is that it is possible to progress and improve in the treatment of depression through intervention strategies applied through the Internet. Official Title ----------------- Internet-based Depression Treatment. Differential Efficacy of Different Specific Therapeutic Components: Behavioral Activation and Positive Psychology. Conditions ----------------- Depression Intervention / Treatment ----------------- * Behavioral: Internet-based Global Protocol * Behavioral: Internet-based Behavioral Activation Protocol * Behavioral: Internet-based Positive Psychology Protocol Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: 18-65 years old. Having mild to moderate depression symptoms. Providing written, informed consent. Being able to understand and read Spanish. Having daily access to the Internet in their natural environment. Exclusion Criteria: Being diagnosed a severe mental disorder (people with the following mental disorders will be excluded from the study: schizophrenia, bipolar disorder and personality disorders from clusters A and B). Being diagnosed an alcohol and/or substance dependence disorder. The presence of high suicidal risk. A medical disease or condition which prevent the participant from carry out the psychological treatment. Receiving another psychological treatment while the study is still ongoing. The increase and/or changes in the medication of participants receiving pharmacological treatment during the study. Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 65 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Single Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Internet-based Global Protocol<br>Intervention group that carries out the Internet-based Global Protocol and receives therapist support. | Behavioral: Internet-based Global Protocol<br>* Internet-based Global Protocol is an Internet-based treatment which includes therapeutic components of evidence-based treatments for depression: Motivation, Psychoeducation, Cognitive Therapy, and Relapse Prevention. Furthermore, it incorporates a Behavioural Activation component (BA). The whole protocol stresses the importance and benefits of being active and remaining involved in life, values and goals. The program also includes a component of Positive Psychology (PP). It allows the individual to learn and practice adaptive ways to cope with depressive and anxiety symptoms and confront daily problems. It is a multimedia (video, image, etc.) interactive program designed for optimal use on the computer, but it can also be used on a tablet.<br>| | Experimental: Internet-based Behavioral Activation Protocol<br>Intervention group that carries out the Internet-based Behavioral Activation Protocol and receives therapist support. | Behavioral: Internet-based Behavioral Activation Protocol<br>* Internet-based Behavioral Activation Protocol is an Internet-based treatment based on Behavioral Activation. It stresses the importance and benefits of being active and remaining involved in life, values and goals . It is a multimedia (video, image, etc.) interactive program designed for optimal use on the computer, but it can also be used on a tablet.<br>| | Experimental: IInternet-based Positive Psychology Protocol<br>Intervention group that carries out the Internet-based Positive Psychology Protocol and receives therapist support. | Behavioral: Internet-based Positive Psychology Protocol<br>* Internet-based Positive Psychology Protocol is an Internet-based treatment based on Positive Psychology, offering strategies to promote and enhance positive mood. It is an Internet-based treatment based on Positive Psychology. It is a multimedia (video, image, etc.) interactive program designed for optimal use on the computer, but it can also be used on a tablet.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in the Beck Depression Inventory II (BDI-II) (Beck, Steer, & Brown, 1996) at pre, post intervention and at 3 and 12 months follow-ups. | The BDI-II is one of the most widely used questionnaires to evaluate the severity of depression in pharmacological and psychotherapy trials. It consists of 21 items about the different symptoms characterizing the major depression disorder, summed to obtain the total score, which can be a maximum of 63 points. The instrument has good internal consistency (Cronbach's alpha of 0.76 to 0.95) and a test-retest reliability of around 0.8. | Up to 12 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | The Positive and Negative Affect Schedule (PANAS) (Watson, Clark y Tellegen, 1988; Sandín et al., 1999) at pre, post intervention and at 3 and 12 months follow-ups. | The PANAS consists of 20 items that evaluate two independent dimensions: positive affect (PA) and negative affect (NA). The range for each scale (10 items on each) is from 10 to 50. The Spanish version has demonstrated high internal consistency (α = 0.89 and 0.91 for PA and NA in women, respectively, and α = 0.87 and 0.89 for PA and NA in men, respectively) in college students. | Up to 12 months | | Overall Anxiety Severity and Impairment Scale (OASIS) Overall Depression Severity and Impairment Scale (ODSIS) at pre, post intervention and at 3 and 12 months follow-ups. | OASIS consists of 5 items that measure the frequency and severity of anxiety, as well as the level of avoidance, work/ school/home interference, and social interference associated to anxiety. A psychometric analysis of the OASIS scale found good internal consistency (Cronbach's alpha = 0.80), test-retest reliability (k = 5.82) and convergent validity for this scale. | Up to 12 months | | Overall Depression Severity and Impairment Scale (ODSIS) at pre, post intervention and at 3 and 12 months follow-ups. | ODSIS is a self-report measure which consists of 5 items, evaluating experiences related to depression. ODSIS measures the frequency and severity of depression, as well as the level of avoidance, work/school/home interference, and social interference associated to depression. | Up to 12 months | | Multicultural Quality of Life Index (MQLI) at pre, post intervention and at 3 and 12 months follow-ups. | It is a self-administered questionnaire that uses 10 items to assess global perception of quality of life in addition to physical and emotional well-being, self-care, occupational, and interpersonal functioning, community and services support, and personal and spiritual fulfilment. The homogeneity of the questionnaire proved to be good, yielding a Cronbach's alpha coefficient of 0.79 and has applicability, reliability, and validity. | Up to 12 months | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Internet, Behavioral Activation, Positive Psychology

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Nurturing Healthy Teachers Study Overview ================= Brief Summary ----------------- The purpose of this trial is to compare the impact of a fruit and vegetable access plus nutrition education intervention to a nutrition education-only control on the health, well-being, and food security of early care and education (ECE) professionals. The intervention, called Nurturing Healthy Teachers, combines strategies from two evidence-based programs - Create Healthy Futures (CHF) and Brighter Bites (BB). Detailed Description ----------------- The purpose of this trial is to evaluate the impact of the Nurturing Healthy Teachers program on food insecurity, dietary behaviors, mental health, and cardiometabolic health among early care and education (ECE) professionals who teach Pre-Kindergarten or Kindergarten. Nurturing Healthy Teachers is a novel, comprehensive program that combines strategies from two evidence-based programs - Brighter Bites (implemented by Brighter Bites 501c3 non-profit) and Create Healthy Futures (implemented by Penn State Better Kid Care). Brighter Bites (BB) is a 501c3 non-profit organization that implements an evidence-based coordinated school health program that combines access to fresh produce and nutrition education proven to improve dietary intake among preschool and elementary school teachers, low-income children, and their families. For 16 weeks in the school year, Brighter Bites teachers and families receive a weekly distribution of about 20 lbs (50 servings) of primarily donated fresh vegetables, plus weekly healthy recipe tastings, and nutrition education. The program has proven effectiveness at engaging teachers, parents, increasing healthy dietary behaviors and improving the school and home nutrition environment of low-income elementary school children in the short-term. Developed and implemented by Penn State Extension Better Kid Care (BKC), Create Healthy Futures (CHF) is a web-based nutrition education program that targets nutrition knowledge, self-efficacy, mindfulness, and social support to create healthy habits among teachers. CHF also includes facilitated group meetings to reinforce information from the online modules. The trial will be conducted in 30 elementary schools that have pre-Kindergarten and Kindergarten classes that serve predominantly low-income families in Houston. Schools in the intervention arm (n=15) will receive Brighter Bites plus the complete Create Healthy Futures program including online modules and in-person meetings, and they will be drawn from schools that are already scheduled to receive Brighter Bites during the 2022-2023 school year. Schools in the control arm (n=15) will only receive passive access to the online modules of the Create Healthy Futures program, and they will be drawn from remaining schools across the district, as long as they have not participated in Brighter Bites in the previous two years. The intervention and control programs will be implemented over one school year (9months). Brighter Bites non-profit organization and Penn State Better Kid Care will implement the Nurturing Healthy Teachers program, while UTHealth School of Public Health investigators will conduct the evaluation of the program. Official Title ----------------- Nurturing Healthy Teachers: A Cluster-RCT to Improve the Health, Well-being, and Food Security of Early Care and Education (ECE) Professionals Conditions ----------------- Nutrition, Healthy, Mental Health Wellness 1, Diabetes Mellitus Risk, Obesity Intervention / Treatment ----------------- * Behavioral: Brighter Bites (BB) Produce Distribution * Behavioral: Brighter Bites (BB) Nutrition Education * Behavioral: Create Healthy Futures (CHF) Weekly Wellness Groups * Behavioral: Create Healthy Futures (CHF) Web-Based Module Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria for Teachers: Employed as a pre-K or kindergarten teaching staff at the participating study schools in the 2022-2023 school year. Ability to read English at the 4th grade reading level Ability to complete study measures Exclusion Criteria for Teachers: Have recently (in the past 6 months) or are currently participating in an exercise or weight loss program Inclusion Criteria for Schools: Have at least 25 eligible early childhood education (ECE) professionals Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Prevention Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: BB Produce Distribution + BB Nutrition Education + CHF Weekly Wellness Groups + CHF Web-Based Module<br>BB is Brighter Bites. CHF is Create Healthy Futures. | Behavioral: Brighter Bites (BB) Produce Distribution<br>* For 16 weeks in the school year, teachers in participating program schools will receive distributions of 8-10 different types of produce items.<br>Behavioral: Brighter Bites (BB) Nutrition Education<br>* Brighter Bites Nutrition Education will consist of recipes, food preparation and storage ideas, and tips and tools to budget and plan meals. Teachers will be trained in a nutrition education curriculum, which will be implemented in the program schools as part of the BB program.<br>Behavioral: Create Healthy Futures (CHF) Weekly Wellness Groups<br>* Peer-facilitators will lead virtual weekly group discussions. Penn State Better Kid Care will train the wellness facilitators.<br>Behavioral: Create Healthy Futures (CHF) Web-Based Module<br>* Create Healthy Futures Web-Based Module is self-paced and focuses on the following topics: 1) Introduction, 2) Challenges of the food environment, 3) Nutrition and your health, 4) Food culture reform, and 5) Providers' role in creating healthy futures. The Create Healthy Futures module utilizes several educational methods to increase interactivity and engagement, including video footage of content experts, reflection activities, downloadable handouts, and action planning. Each chapter takes approximately 30-40 minutes to complete. The program is delivered on the Better Kid Care On Demand platform, an asynchronous learning management system that provides professional development training for teachers in all 50 states and 69 countries.<br>| | Active Comparator: CHF Web-Based Module<br>CHF is Create Healthy Futures. | Behavioral: Create Healthy Futures (CHF) Web-Based Module<br>* Create Healthy Futures Web-Based Module is self-paced and focuses on the following topics: 1) Introduction, 2) Challenges of the food environment, 3) Nutrition and your health, 4) Food culture reform, and 5) Providers' role in creating healthy futures. The Create Healthy Futures module utilizes several educational methods to increase interactivity and engagement, including video footage of content experts, reflection activities, downloadable handouts, and action planning. Each chapter takes approximately 30-40 minutes to complete. The program is delivered on the Better Kid Care On Demand platform, an asynchronous learning management system that provides professional development training for teachers in all 50 states and 69 countries.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Household Food Insecurity as assessed by the U.S. Department of Agriculture self-report food insecurity survey | Household Food insecurity will be measured on an electronically administered using the 10-item self-report previously validated U.S. Department of Agriculture food insecurity survey. The survey will measure food insecurity over the past 30 days. The total score is the sum of affirmative responses to the 10 questions, with a total score range of 0-10. Scores indicate the following about extent of food insecurity: score of zero-High food security score of 1-2-Marginal food security score of 3-5-Low food security score of 6-10-Very low food security | baseline | | Household Food Insecurity as assessed by the U.S. Department of Agriculture self-report food insecurity measure | Household Food insecurity will be measured on an electronically administered using the 10-item self-report previously validated U.S. Department of Agriculture food insecurity survey. The survey will measure food insecurity over the past 30 days. The total score is the sum of affirmative responses to the 10 questions, with a total score range of 0-10. Scores indicate the following about extent of food insecurity: score of zero-High food security score of 1-2-Marginal food security score of 3-5-Low food security score of 6-10-Very low food security | 4 months | | Household Food Insecurity as assessed by the U.S. Department of Agriculture self-report food insecurity measure | Household Food insecurity will be measured on an electronically administered using the 10-item self-report previously validated U.S. Department of Agriculture food insecurity survey. The survey will measure food insecurity over the past 30 days. The total score is the sum of affirmative responses to the 10 questions, with a total score range of 0-10. Scores indicate the following about extent of food insecurity: score of zero-High food security score of 1-2-Marginal food security score of 3-5-Low food security score of 6-10-Very low food security | 9 months | | Household Food Insecurity as assessed by the U.S. Department of Agriculture self-report food insecurity measure | Household Food insecurity will be measured on an electronically administered using the 10-item self-report previously validated U.S. Department of Agriculture food insecurity survey. The survey will measure food insecurity over the past 30 days. The total score is the sum of affirmative responses to the 10 questions, with a total score range of 0-10. Scores indicate the following about extent of food insecurity: score of zero-High food security score of 1-2-Marginal food security score of 3-5-Low food security score of 6-10-Very low food security | 14 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Dietary intake as assessed by self-report survey | Dietary intake will be self-reported on an electronically administered survey using a food frequency screener. The survey items will measure the frequency of consumption of various foods including fruits, vegetables, whole grains, protein, water, beverages, desserts, processed food, and candy. Data will be reported categorically as the number of times the surveyed foods were consumed. | baseline | | Dietary intake as assessed by self-report survey | Dietary intake will be self-reported on an electronically administered survey using a food frequency screener. The survey items will measure the frequency of consumption of various foods including fruits, vegetables, whole grains, protein, water, beverages, desserts, processed food, and candy. Data will be reported categorically as the number of times the surveyed foods were consumed. | 9 months | | Anxiety as assessed by the Generalized Anxiety Disorder 7-item (GAD-7) survey | The Generalized Anxiety Disorder 7-item (GAD) survey has a total score from 0 to 21, with a higher score indicating greater anxiety. | baseline | | Anxiety as assessed by the Generalized Anxiety Disorder 7-item (GAD-7) survey | The Generalized Anxiety Disorder 7-item (GAD) survey has a total score from 0 to 21, with a higher score indicating greater anxiety. | 9 months | | Anxiety as assessed by the Generalized Anxiety Disorder 7-item (GAD-7) survey | The Generalized Anxiety Disorder 7-item (GAD) survey has a total score from 0 to 21, with a higher score indicating greater anxiety. | 14 months | | Anxiety impact as assessed by the impact item of the GAD-7 survey | For participants who scored 1 or above on the GAD-7, they will be asked how difficult the anxiety-related issues have made it to do work, take care of things at home, or get along with other people. Data will be reported categorically as number of participants who answered: Not difficult at all; Somewhat difficult; Very difficult; Extremely difficult; Prefer not to say. | baseline | | Anxiety impact as assessed by the impact item of the GAD-7 survey | For participants who scored 1 or above on the GAD-7, they will be asked how difficult the anxiety-related issues have made it to do work, take care of things at home, or get along with other people. Data will be reported categorically as number of participants who answered: Not difficult at all; Somewhat difficult; Very difficult; Extremely difficult; Prefer not to say. | 9 months | | Anxiety impact as assessed by the impact item of the GAD-7 survey | For participants who scored 1 or above on the GAD-7, they will be asked how difficult the anxiety-related issues have made it to do work, take care of things at home, or get along with other people. Data will be reported categorically as number of participants who answered: Not difficult at all; Somewhat difficult; Very difficult; Extremely difficult; Prefer not to say. | 14 months | | Depression as assessed by the Patient Health 9-item Questionnaire (PHQ-9) | The Patient Health 9-item Questionnaire (PHQ-9) has a total score of 0 to 27, with a higher score indicating greater depression. | baseline | | Depression as assessed by the Patient Health 9-item Questionnaire (PHQ-9) | The Patient Health 9-item Questionnaire (PHQ-9) has a total score of 0 to 27, with a higher score indicating greater depression. | 9 months | | Depression as assessed by the Patient Health 9-item Questionnaire (PHQ-9) | The Patient Health 9-item Questionnaire (PHQ-9) has a total score of 0 to 27, with a higher score indicating greater depression. | 14 months | | Depression impact as assessed by the impact item of the PHQ-9 | For participants who scored 1 or above on the PHQ-9, they will be asked how difficult the depression-related issues have made it to do work, take care of things at home, or get along with other people. Data will be reported categorically as number of participants who answered: Not difficult at all; Somewhat difficult; Very difficult; Extremely difficult; Prefer not to say. | baseline | | Depression impact as assessed by the impact item of the PHQ-9 | For participants who scored 1 or above on the PHQ-9, they will be asked how difficult the depression-related issues have made it to do work, take care of things at home, or get along with other people. Data will be reported categorically as number of participants who answered: Not difficult at all; Somewhat difficult; Very difficult; Extremely difficult; Prefer not to say. | 9 months | | Depression impact as assessed by the impact item of the PHQ-9 | For participants who scored 1 or above on the PHQ-9, they will be asked how difficult the depression-related issues have made it to do work, take care of things at home, or get along with other people. Data will be reported categorically as number of participants who answered: Not difficult at all; Somewhat difficult; Very difficult; Extremely difficult; Prefer not to say. | 14 months | | Well-being as assessed by the 5-item World Health Organization Well-Being Index (WHO-5) | The 5-item World Health Organization Well-Being Index (WHO-5) has a total score or 0 -25, with a higher score indicating greater well-being. | baseline | | Well-being as assessed by the 5-item World Health Organization Well-Being Index (WHO-5) | The 5-item World Health Organization Well-Being Index (WHO-5) has a total score or 0 -25, with a higher score indicating greater well-being. | 9 months | | Well-being as assessed by the 5-item World Health Organization Well-Being Index (WHO-5) | The 5-item World Health Organization Well-Being Index (WHO-5) has a total score or 0 -25, with a higher score indicating greater well-being. | 14 months | | General health as assessed by the general health item of the Centers for Disease Control and Prevention (CDC) Health-related quality of life (HRQoL) 4-item questionnaire (CDC HRQoL-4) | Only one item on the CDC HRQoL-4 will be asked, and this is the item related to general health. Participants will be asked if they would say that in general that their health is Excellent, Very good, Good, Fair, Poor, or Prefer not to say. Data will be reported categorically as number of participants who answered: Excellent; Very good; Good; Fair; Poor; Prefer not to say. | baseline | | General health as assessed by the general health item of the Centers for Disease Control and Prevention (CDC) Health-related quality of life (HRQoL) 4-item questionnaire (CDC HRQoL-4) | Only one item on the CDC HRQoL-4 will be asked, and this is the item related to general health. Participants will be asked if they would say that in general that their health is Excellent, Very good, Good, Fair, Poor, or Prefer not to say. Data will be reported categorically as number of participants who answered: Excellent; Very good; Good; Fair; Poor; Prefer not to say. | 9 months | | General health as assessed by the general health item of the Centers for Disease Control and Prevention (CDC) Health-related quality of life (HRQoL) 4-item questionnaire (CDC HRQoL-4) | Only one item on the CDC HRQoL-4 will be asked, and this is the item related to general health. Participants will be asked if they would say that in general that their health is Excellent, Very good, Good, Fair, Poor, or Prefer not to say. Data will be reported categorically as number of participants who answered: Excellent; Very good; Good; Fair; Poor; Prefer not to say. | 14 months | | Glycosylated hemoglobin (HbA1c) level as assessed by blood test | Finger stick blood samples will be obtained from teachers in the school, and HbA1c level in the blood sample will be analyzed. | baseline | | Glycosylated hemoglobin (HbA1c) level as assessed by blood test | Finger stick blood samples will be obtained from teachers in the school, and HbA1c level in the blood sample will be analyzed. | 9 months | | Blood pressure (systolic) as assessed by automated oscillometric device | Blood pressure measurements will be taken using an automated oscillometric device. | baseline | | Blood pressure (systolic) as assessed by automated oscillometric device | Blood pressure measurements will be taken using an automated oscillometric device. | 9 months | | Blood pressure (diastolic) as assessed by automated oscillometric device | Blood pressure measurements will be taken using an automated oscillometric device. | baseline | | Blood pressure (diastolic) as assessed by automated oscillometric device | Blood pressure measurements will be taken using an automated oscillometric device. | 9 months | | Skin carotenoid level as assessed by The Veggie Meter | Skin carotenoid level will be assessed by The Veggie Meter, which is a small, portable non-invasive device that can be clipped to the finger briefly to detect skin carotenoid concentrations in ∼15-20 seconds for a single reading. | baseline | | Skin carotenoid level as assessed by The Veggie Meter | Skin carotenoid level will be assessed by The Veggie Meter, which is a small, portable non-invasive device that can be clipped to the finger briefly to detect skin carotenoid concentrations in ∼15-20 seconds for a single reading. | 9 months | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- food insecurity, nutrition, healthy eating, wellness, teachers

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Equistasi and Gait in Hemiparesis Study Overview ================= Brief Summary ----------------- The purpose of the study is to evaluate the effect of Equistasi device on quantitative and qualitative gait characteristics in patients affected by hemiparesis. Official Title ----------------- Efficacy of Equistasi on the Gait of Patients Affected by Hemiparesis Due to Cerebrovascular Accident Conditions ----------------- Hemiparesis Intervention / Treatment ----------------- * Device: equistasi * Device: placebo Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: subacute hemiparesis Functional Ambulation Classification <4 Exclusion Criteria: previous neurological deficits Glasgow Coma Scale <13 Complete sensory deficit in the lower limbs Levels of Cognitive Functioning ≤5 polyneuropathy contraindications to mobilization/verticalization Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 80 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: treatment<br>3 Equistasi devices will be placed during physiotherapy, 5 times per week, for 4 weeks | Device: equistasi<br>* 3 devices will be placed in each patient: 1 at the spinosus process of L5; 1 at the insertion of transverse abdominis; 1 at the insertion of the gluteus medius to the femur. The devices will be kept for 55 minutes, during standard Physiotherapy<br>| | Placebo Comparator: controls<br>3 placebo devices will be placed during physiotherapy, 5 times per week, for 4 weeks | Device: placebo<br>* 3 devices will be placed in each patient: 1 at the spinosus process of L5; 1 at the insertion of transverse abdominis; 1 at the insertion of the gluteus medius to the femur. The devices will be kept for 55 minutes, during standard Physiotherapy<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | disability change assessed using Functional Independence Measure scale | | 0. 30. 60. 120 days | | balance change assessed using Berg Balance Scale | | 0. 30. 60. 120 days | | gait pattern change assessed using Functional Ambulation Classification scale | | 0. 30. 60. 120 days | | gait speed change assessed using Timed Up and Go scale | | 0. 30. 60. 120 days | | gait pattern change using Tinetti scale for gait | | 0. 30. 60. 120 days | | gait speed change assessed using 10 meter walking test scale | | 0. 30. 60. 120 days | | swaying of the center of gravity change assessed with stabilometric platform indexes | | 0. 30. 60. 120 days |

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Peer Genetic Coaches for Enhancing Genetic Testing Awareness, Navigation, and Delivery Among African American Men With Metastatic Prostate Cancer, The EXPAND Network Study Overview ================= Brief Summary ----------------- This trial evaluates whether a network of peer genetic coaches is useful for addressing disparities in genetic testing and screening among African American men with prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic). While genetic testing has become central to prostate cancer care, African American men are less likely seek testing due to lack of awareness, cultural beliefs, financial limitations, fear of discrimination, and mistrust in the healthcare system. A network of peer genetic coaches may help address barriers, beliefs, and needs of African American men in the community and provide navigation to increase engagement in genetic testing. Detailed Description ----------------- PRIMARY OBJECTIVES: I. Identify and train 6 African American (AA) men as peer genetic coaches (PGCs) for the Extending Prostate Genetic Awareness, Navigation, and Delivery (EXPAND) Network. (Train peer genetic coaches) II. Conduct a feasibility study of peer genetic coaching. (Provide individual coaching) SECONDARY OBJECTIVE: I. Patient-related outcomes will include change in decisional conflict for genetic counseling, acceptability/attitude toward genetic counseling and testing, and change of genetics knowledge. OUTLINE: AIM 1: Peer genetic coaches undergo training and education on study. AIM 2: Patients receive an educational booklet and attend a discussion with a peer genetic coach on study. Official Title ----------------- Extending Prostate Genetic Awareness, Navigation, and Delivery: The EXPAND Network Conditions ----------------- Metastatic Prostate Carcinoma, Stage IIIB Prostate Cancer AJCC v8, Stage IIIC Prostate Cancer AJCC v8, Stage IV Prostate Cancer AJCC v8 Intervention / Treatment ----------------- * Behavioral: Training and Education * Other: Educational Intervention * Procedure: Discussion Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: AIM 1: Are 18 years old or older AIM 1: Are able to read and speak English comfortably AIM 1: Men who have experience with both prostate cancer (PCA) and genetic counseling and testing will be a priority for training, as well as men who have considerable peer education or navigation experience AIM 2: Are 18 years old or older AIM 2: Are African American AIM 2: Are able to read and speak English comfortably AIM 2: Men who meet any one of the following criteria: (1) metastatic prostate cancer; (2) prostate cancer with high-risk features (T3 or higher, Gleason 8 or higher, node positive disease); (3) with or without a diagnosis of prostate cancer with strong family history (2 or more first-degree or second-degree relatives) with prostate cancer (particularly metastatic prostate cancer or died from prostate cancer), breast cancer, ovarian cancer, pancreatic cancer, colorectal cancer, uterine cancer, renal cancer, urothelial cancer, or upper bowel cancer Exclusion Criteria: Patients that do not meet the inclusion criteria Children under the age of 18 Anyone who has trouble understanding the consent or with significant anxiety detected during the consent process Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- Male Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Supportive Care Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Supportive care (training, education, discussion)<br>AIM 1: Peer genetic coaches undergo training and education on study. AIM 2: Patients receive an educational booklet and attend a discussion with a peer genetic coach on study. | Behavioral: Training and Education<br>* Undergo training and education<br>Other: Educational Intervention<br>* Receive educational booklet<br>* Other names: Educational;Procedure: Discussion<br>* Attend discussion with peer genetic coach<br>* Other names: Discuss;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Number of inquiries to the central number (feasibility) | | Up to 1 year | | Percent of callers screened and eligible to participate (feasibility) | | Up to 1 year | | Percent of eligible callers who enroll in the study (feasibility) | | Up to 1 year | | Percent who complete the endpoint assessment (feasibility) | | Up to 1 year | | Number and percent of men making genetic counseling appointments | | Up to 1 year | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in decisional conflict for genetic counseling | Reported with mean and standard deviation. | Baseline up to 1 year | | Change in acceptability/attitude toward genetic counseling and testing | Reported with mean and standard deviation. | Baseline up to 1 year | | Change of genetics knowledge | Reported with mean and standard deviation | Baseline up to 1 year |

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AC220 for Children With Relapsed/Refractory ALL or AML Study Overview ================= Brief Summary ----------------- This is a phase I study of the investigational drug AC220 combined with cytarabine and etoposide in pediatric patients with relapsed acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML). Detailed Description ----------------- This is a study for pediatric patients with relapsed acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML). Some people diagnosed with leukemia have changes in a receptor located on the surface of white blood cells called FLT3. This is known as a FLT3 mutation. FLT3 plays an important role in the way cells grow and divide. In normal cells, the FLT3 receptor is switched off most of the time and only switches on when it gets a chemical signal from outside. But cells with the FLT3 mutation have the grow signal permanently switched on. This means leukemia cells with the FLT3 mutation are growing and dividing all the time. Doctors have found that people with leukemia cells that carry FLT3 mutations are less likely to go into remission with chemotherapy and have a higher risk of the leukemia coming back after treatment. This is a study of an investigational drug called AC220. AC220 is considered investigational because it has not been approved in the United States by the Food and Drug Administration (FDA). AC220 is a drug which is able to turn off the FLT3 grow signal. AC220 will be given with cytarabine and etoposide to treat the relapsed leukemia. This is a phase I study, which means that the study is being done to find the highest dose of AC220 that can be given safely with the drugs cytarabine and etoposide to children and young adults. Official Title ----------------- A Phase I Study of AC220 for Children With Relapsed or Refractory ALL or AML Conditions ----------------- Lymphoblastic Leukemia, Acute, Childhood, Myelogenous Leukemia, Acute, Childhood Intervention / Treatment ----------------- * Drug: AC220 * Drug: Cytarabine * Drug: Etoposide * Drug: Methotrexate Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patients must be greater than 1 month and ≤ 21 years of age at study entry. Patients must have a diagnosis of relapsed/refractory AML, ALL or acute leukemia of ambiguous lineage and meet the following criteria: Patients with AML or leukemia with ambiguous lineage must have greater than or equal to 5% blasts in the bone marrow. Patients with ALL must have an M3 marrow (marrow blasts >25%). Patients with ALL must have MLL gene rearrangement or hyperdiploid >50 chromosomes. Patients with treatment related AML (t-AML) are eligible, provided they meet all other eligibility criteria. Karnofsky > 50% for patients >16 years of age and Lansky >50% for patients ≤16 years of age. Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study. Myelosuppressive chemotherapy: Patients with ALL who relapse during standard maintenance therapy are eligible at time of relapse. For patients with ALL and AML who relapse while they are receiving cytotoxic therapy, at least 14 days must have elapsed since the completion of cytotoxic therapy. Cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start of AC220. Patients who have received other FLT3 inhibitors (ex. lestaurtinib, sorafenib) are eligible for this study. Hematopoietic growth factors: At least 7 days since the completion of therapy with a growth factor. Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair. XRT: 2 wks must have elapsed since local palliative XRT for CNS chloromas; No washout period is necessary for other chloromas; at least 3 months must have elapsed if prior TBI, craniospinal XRT. Hematopoetic Stem Cell Transplant: At least 90 days must have elapsed since hematopoietic stem cell transplant (HSCT) and patients must not have active GVHD. Patient must have adequate renal and hepatic functions as indicated by the following laboratory values: Patients must have a calculated creatinine clearance or radioisotope GFR ≥70mL/min/1.73m2 or a normal serum creatinine based on age/gender. Total bilirubin <1.5 x ULN for age or normal conjugated bilirubin. Alanine transaminase (ALT) <5 × ULN (unless related to leukemic involvement). Patient must have a shortening fraction of ≥ 27% by echocardiogram, OR an ejection fraction of ≥ 50% by radionuclide angiogram. Reproductive Function Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed within 2 weeks prior to enrollment. Female patients with infants must agree not to breastfeed their infants while on this study. Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study and for a minimum of 6 months after study treatment. Exclusion Criteria: Patients will be excluded if they have CNS 3 disease. Patients will be excluded if they have uncontrolled or significant cardiovascular disease, including: A myocardial infarction within 12 months. Uncontrolled angina within 6 months. Diagnosed or suspected congenital long QT syndrome or any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes [TdP]); any history of arrhythmia will be discussed with the Sponsor's Medical Monitor prior to patient's entry into the study. Prolonged QTcF interval on pre-entry ECG (≥450 ms). Any history of second or third degree heart block (may be eligible if the patient currently has a pacemaker). Heart rate < 50/minute on pre-entry ECG. Uncontrolled hypertension. Complete left bundle branch block. Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or TdP. Patients will be excluded if they have a systemic fungal, bacterial, viral or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment. The patient needs to be off pressors and have negative blood cultures for 48 hours. Patient is receiving or plans to receive concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol. Any significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results. Patients who are concurrently receiving CYP3A4 and 5 inhibitors and inducers Ages Eligible for Study ----------------- Minimum Age: 1 Month Maximum Age: 21 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Non-Randomized Intervention Model: Sequential Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: ALL AC220 @ 25mg/m2/day (Dose Level 1)<br>The starting dose is Dose Level 1 at 25 mg/m2/day. Dose escalation will proceed from level 1 to 2 to 3, and so on, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age. | Drug: AC220<br>* Dose assigned at study entry. AC220 will be given orally once daily on days 7-28.<br>* Other names: Quizartinib;Drug: Cytarabine<br>* All patients receive 1000 mg/m2/day IV given every 12 hours on days 1 through 5. Additionally, AML patients and patients with ambiguous leukemia receive cytarabine intrathecally on day 1 of course 1 and 2. Dose defined by age: 20 mg for patients age <1 yr 30 mg for patients age 1-1.99 years of age 50 mg for patients age 2-2.99 years of age 70 mg for patients >3 years of age<br>* Other names: Arabinosylcytosine;Drug: Etoposide<br>* 150 mg/m2/day IV on days 1 through 5.<br>* Other names: Etoposide phosphate;Drug: Methotrexate<br>* IT methotrexate given intrathecally to patients with ALL on day 0 of course 1 and 2. Dose defined by age 6 mg for patients age < 1yr 8 mg for patients age 1-1.99 10 mg for patients age 2-2.99 12 mg for patients 3-8.99 years of age 15 mg for patients >9 years of age<br>* Other names: Methotrexate Sodium;| | Experimental: AML AC220 @ 25mg/m2/day (Dose Level 1)<br>The starting dose is Dose Level 1 at 25 mg/m2/day. Dose escalation will proceed from level 1 to 2 to 3, and so on, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT cytarabine will be given to patients with AML on Day 0, dose assigned by age. | Drug: AC220<br>* Dose assigned at study entry. AC220 will be given orally once daily on days 7-28.<br>* Other names: Quizartinib;Drug: Cytarabine<br>* All patients receive 1000 mg/m2/day IV given every 12 hours on days 1 through 5. Additionally, AML patients and patients with ambiguous leukemia receive cytarabine intrathecally on day 1 of course 1 and 2. Dose defined by age: 20 mg for patients age <1 yr 30 mg for patients age 1-1.99 years of age 50 mg for patients age 2-2.99 years of age 70 mg for patients >3 years of age<br>* Other names: Arabinosylcytosine;Drug: Etoposide<br>* 150 mg/m2/day IV on days 1 through 5.<br>* Other names: Etoposide phosphate;| | Experimental: ALL AC220 @ 40mg/m2/day (Dose Level 2)<br>Dose escalation will proceed from level 1 to level 2 for AC220 at 40mg/m2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age. | Drug: AC220<br>* Dose assigned at study entry. AC220 will be given orally once daily on days 7-28.<br>* Other names: Quizartinib;Drug: Cytarabine<br>* All patients receive 1000 mg/m2/day IV given every 12 hours on days 1 through 5. Additionally, AML patients and patients with ambiguous leukemia receive cytarabine intrathecally on day 1 of course 1 and 2. Dose defined by age: 20 mg for patients age <1 yr 30 mg for patients age 1-1.99 years of age 50 mg for patients age 2-2.99 years of age 70 mg for patients >3 years of age<br>* Other names: Arabinosylcytosine;Drug: Etoposide<br>* 150 mg/m2/day IV on days 1 through 5.<br>* Other names: Etoposide phosphate;Drug: Methotrexate<br>* IT methotrexate given intrathecally to patients with ALL on day 0 of course 1 and 2. Dose defined by age 6 mg for patients age < 1yr 8 mg for patients age 1-1.99 10 mg for patients age 2-2.99 12 mg for patients 3-8.99 years of age 15 mg for patients >9 years of age<br>* Other names: Methotrexate Sodium;| | Experimental: ALL AC220 @ 60mg/m2/day (Dose Level 3)<br>Dose escalation will proceed from level 2 to 3 for AC220 at 60mg/m2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age. If toxicity at Dose Level 3 would allow further escalation, but demonstrated sufficient AC220 activity, no further dose escalation will be required. | Drug: AC220<br>* Dose assigned at study entry. AC220 will be given orally once daily on days 7-28.<br>* Other names: Quizartinib;Drug: Cytarabine<br>* All patients receive 1000 mg/m2/day IV given every 12 hours on days 1 through 5. Additionally, AML patients and patients with ambiguous leukemia receive cytarabine intrathecally on day 1 of course 1 and 2. Dose defined by age: 20 mg for patients age <1 yr 30 mg for patients age 1-1.99 years of age 50 mg for patients age 2-2.99 years of age 70 mg for patients >3 years of age<br>* Other names: Arabinosylcytosine;Drug: Etoposide<br>* 150 mg/m2/day IV on days 1 through 5.<br>* Other names: Etoposide phosphate;Drug: Methotrexate<br>* IT methotrexate given intrathecally to patients with ALL on day 0 of course 1 and 2. Dose defined by age 6 mg for patients age < 1yr 8 mg for patients age 1-1.99 10 mg for patients age 2-2.99 12 mg for patients 3-8.99 years of age 15 mg for patients >9 years of age<br>* Other names: Methotrexate Sodium;| | Experimental: ALL AC220 @ 90mg/m2/day (Dose Level 4)<br>If the study dose of 60 mg/m2/day at Dose Level 3 is well tolerated but does not show sufficient AC220 activity, the study may proceed to Dose Level 4 at 90 mg/m2/day. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age. If toxicity at Dose Level 4 would allow further escalation, but demonstrated sufficient AC220 activity, no further dose escalation will be required. | Drug: AC220<br>* Dose assigned at study entry. AC220 will be given orally once daily on days 7-28.<br>* Other names: Quizartinib;Drug: Cytarabine<br>* All patients receive 1000 mg/m2/day IV given every 12 hours on days 1 through 5. Additionally, AML patients and patients with ambiguous leukemia receive cytarabine intrathecally on day 1 of course 1 and 2. Dose defined by age: 20 mg for patients age <1 yr 30 mg for patients age 1-1.99 years of age 50 mg for patients age 2-2.99 years of age 70 mg for patients >3 years of age<br>* Other names: Arabinosylcytosine;Drug: Etoposide<br>* 150 mg/m2/day IV on days 1 through 5.<br>* Other names: Etoposide phosphate;Drug: Methotrexate<br>* IT methotrexate given intrathecally to patients with ALL on day 0 of course 1 and 2. Dose defined by age 6 mg for patients age < 1yr 8 mg for patients age 1-1.99 10 mg for patients age 2-2.99 12 mg for patients 3-8.99 years of age 15 mg for patients >9 years of age<br>* Other names: Methotrexate Sodium;| | Experimental: ALL AC220 @ 130 mg/m2/day (Dose Level 5)<br>If the study dose of 90 mg/m2/day at Dose Level 4 is well tolerated but does not show sufficient AC220 activity, the study may proceed to Dose Level 5 at 130 mg/m2/day. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT Methotrexate will be given to patients with ALL on Day 0, dose assigned by age. Dose Level 5 is the highest dose for this study. | Drug: AC220<br>* Dose assigned at study entry. AC220 will be given orally once daily on days 7-28.<br>* Other names: Quizartinib;Drug: Cytarabine<br>* All patients receive 1000 mg/m2/day IV given every 12 hours on days 1 through 5. Additionally, AML patients and patients with ambiguous leukemia receive cytarabine intrathecally on day 1 of course 1 and 2. Dose defined by age: 20 mg for patients age <1 yr 30 mg for patients age 1-1.99 years of age 50 mg for patients age 2-2.99 years of age 70 mg for patients >3 years of age<br>* Other names: Arabinosylcytosine;Drug: Etoposide<br>* 150 mg/m2/day IV on days 1 through 5.<br>* Other names: Etoposide phosphate;Drug: Methotrexate<br>* IT methotrexate given intrathecally to patients with ALL on day 0 of course 1 and 2. Dose defined by age 6 mg for patients age < 1yr 8 mg for patients age 1-1.99 10 mg for patients age 2-2.99 12 mg for patients 3-8.99 years of age 15 mg for patients >9 years of age<br>* Other names: Methotrexate Sodium;| | Experimental: AML AC220 @ 40mg/m2/day (Dose Level 2)<br>Dose escalation will proceed from level 1 to level 2 for AC220 at 40mg/m2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT cytarabine will be given to patients with AML on Day 0, dose assigned by age. | Drug: AC220<br>* Dose assigned at study entry. AC220 will be given orally once daily on days 7-28.<br>* Other names: Quizartinib;Drug: Cytarabine<br>* All patients receive 1000 mg/m2/day IV given every 12 hours on days 1 through 5. Additionally, AML patients and patients with ambiguous leukemia receive cytarabine intrathecally on day 1 of course 1 and 2. Dose defined by age: 20 mg for patients age <1 yr 30 mg for patients age 1-1.99 years of age 50 mg for patients age 2-2.99 years of age 70 mg for patients >3 years of age<br>* Other names: Arabinosylcytosine;Drug: Etoposide<br>* 150 mg/m2/day IV on days 1 through 5.<br>* Other names: Etoposide phosphate;| | Experimental: AML AC220 @ 60mg/m2/day (Dose Level 3)<br>Dose escalation will proceed from level 2 to 3 for AC220 at 60mg/m2/day, assuming the maximum tolerated dose is not exceeded. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT cytarabine will be given to patients with AML on Day 0, dose assigned by age. If toxicity at Dose Level 3 would allow further escalation, but demonstrated sufficient AC220 activity, no further dose escalation will be required. | Drug: AC220<br>* Dose assigned at study entry. AC220 will be given orally once daily on days 7-28.<br>* Other names: Quizartinib;Drug: Cytarabine<br>* All patients receive 1000 mg/m2/day IV given every 12 hours on days 1 through 5. Additionally, AML patients and patients with ambiguous leukemia receive cytarabine intrathecally on day 1 of course 1 and 2. Dose defined by age: 20 mg for patients age <1 yr 30 mg for patients age 1-1.99 years of age 50 mg for patients age 2-2.99 years of age 70 mg for patients >3 years of age<br>* Other names: Arabinosylcytosine;Drug: Etoposide<br>* 150 mg/m2/day IV on days 1 through 5.<br>* Other names: Etoposide phosphate;| | Experimental: AML AC220 @ 90mg/m2/day (Dose Level 4)<br>If the study dose of 60 mg/m2/day at Dose Level 3 is well tolerated but does not show sufficient AC220 activity, the study may proceed to Dose Level 4 at 90 mg/m2/day. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT cytarabine will be given to patients with AML on Day 0, dose assigned by age. If toxicity at Dose Level 4 would allow further escalation, but demonstrated sufficient AC220 activity, no further dose escalation will be required. | Drug: AC220<br>* Dose assigned at study entry. AC220 will be given orally once daily on days 7-28.<br>* Other names: Quizartinib;Drug: Cytarabine<br>* All patients receive 1000 mg/m2/day IV given every 12 hours on days 1 through 5. Additionally, AML patients and patients with ambiguous leukemia receive cytarabine intrathecally on day 1 of course 1 and 2. Dose defined by age: 20 mg for patients age <1 yr 30 mg for patients age 1-1.99 years of age 50 mg for patients age 2-2.99 years of age 70 mg for patients >3 years of age<br>* Other names: Arabinosylcytosine;Drug: Etoposide<br>* 150 mg/m2/day IV on days 1 through 5.<br>* Other names: Etoposide phosphate;| | Experimental: AML AC220 @ 130mg/m2/day (Dose Level 5)<br>If the study dose of 90 mg/m2/day at Dose Level 4 is well tolerated but does not show sufficient AC220 activity, the study may proceed to Dose Level 5 at 130 mg/m2/day. Patients will received etoposide and cytarabine on Days 1-5, and AC220 on Day 7 through 28. IT cytarabine will be given to patients with AML on Day 0, dose assigned by age. Dose Level 5 is the highest dose for this study. | Drug: AC220<br>* Dose assigned at study entry. AC220 will be given orally once daily on days 7-28.<br>* Other names: Quizartinib;Drug: Cytarabine<br>* All patients receive 1000 mg/m2/day IV given every 12 hours on days 1 through 5. Additionally, AML patients and patients with ambiguous leukemia receive cytarabine intrathecally on day 1 of course 1 and 2. Dose defined by age: 20 mg for patients age <1 yr 30 mg for patients age 1-1.99 years of age 50 mg for patients age 2-2.99 years of age 70 mg for patients >3 years of age<br>* Other names: Arabinosylcytosine;Drug: Etoposide<br>* 150 mg/m2/day IV on days 1 through 5.<br>* Other names: Etoposide phosphate;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | The Dose of AC220 That is Safe and Biologically Active When Given in Sequential Combination With Ara-C/Etoposide | The incidence of dose limiting toxicity (DLT) will be measured. The maximum tolerated dose will be the highest study dose at which 1 or fewer of six patients experience DLT during cycle 1 of therapy. Plasma inhibitor activity (PIA) will be measured Pre-treatment and on Days 7, 14, 21 and 28 of Course 1. For the MTD to be considered biologically active, we will require that 7 of 9 patients achieve PIA of > 90% at 3 of 4 trough time points. | 4 weeks from therapy start | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Disease Response | Possible outcomes are: Complete Remission (CR), Complete Remission without Platelet Recovery (CRp), complete response with incomplete hematologic recovery (CRi), Stable Disease, Progressive Disease, Induction Death, or Relapse | 10 weeks | | Count of Participants According to Inhibition of FLT3 Phosphorylation | PIA samples will be collected pre-treatment and on Days 7, 14, 21 and 28 of Course 1. | 4 weeks from therapy start | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Refractory, Myelogenous, Acute, Childhood, Pediatric, ALL, AML, Relapse, Lymphoblastic, Leukemia, AC220

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Ketogenic Diet and Chemotherapy in Affecting Recurrence in Patients With Stage IV Breast Cancer Study Overview ================= Brief Summary ----------------- This pilot clinical trial studies how well a ketogenic diet and chemotherapy work in affecting the return of cancer in patients with stage IV breast cancer. Ketogenic diet may be more effective than standard nutrition and may affect quality of life, inflammation, and tumor-related changes. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ketogenic diet and chemotherapy may be better in patients with breast cancer. Detailed Description ----------------- PRIMARY OBJECTIVES: I. To evaluate the feasibility of implementing a diet that induces nutritional ketosis in women who are initiating palliative chemotherapy to treat advanced stage breast cancer (BC). II. To determine the effects of a ketogenic diet on tumor progression. III. To determine the effects of nutritional ketosis on biologic and behavioral health markers. OUTLINE: Patients are assigned to 1 of 2 arms. ARM I: Patients receive standard of care therapy with paclitaxel. ARM II: Patients receive standard of care with paclitaxel. Patients undergo a controlled feeding period ketogenic diet comprising of meals prepared in the research kitchen for 3 months. Beginning 2 weeks prior to completion of the controlled feeding period, patients also undergo free living ketogenic diet program for 3 months comprising of group format, individual sessions, and online digital content to educate patients to implement a ketogenic eating pattern into their lifestyle. Official Title ----------------- Ketogenic Diet and Chemotherapy to Affect Recurrence of Breast Cancer (The KETO-CARE Study) Conditions ----------------- Stage IV Breast Cancer AJCC v6 and v7 Intervention / Treatment ----------------- * Dietary Supplement: Dietary Intervention * Other: Laboratory Biomarker Analysis * Drug: Paclitaxel * Other: Quality-of-Life Assessment * Other: Questionnaire Administration Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Body mass index (BMI) >= 22 kg/m^2 Confirmed diagnosis of metastatic or stage IV BC Fludeoxyglucose F-18 (FDG)-positron emission tomography (PET) avid tumors Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (0=participant has either normal activity, 1= participant has some symptoms but is nearly full ambulatory) Life expectancy > 6 months Able and willing to follow prescribed diet intervention Exclusion Criteria: Prior chemotherapy for metastatic breast cancer (MBC) (prior adjuvant chemotherapy permitted as long as > 12 months [mo]) BMI < 25 kg/m^2 Weight change > 5% within 3 months of enrollment Type 1 diabetes History of diabetes with retinopathy requiring treatment Current use of insulin or sulfonylureads for glycemic control, or history of ketoacidosis Intestinal obstruction Bilirubin > 2 Albumin < 3.5 Glomerular filtration rate (GFR) < 55 mL/min Creatinine > 2.0 Urinary albumin > 1 g/day Congestive heart failure Pregnant or nursing women Unable to provide informed consent Uncontrolled concurrent medical conditions that would limit compliance with study requirements Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Supportive Care Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Arm I (standard of care)<br>Patients receive standard of care therapy with paclitaxel. | Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Drug: Paclitaxel<br>* Given standard of care therapy with paclitaxel<br>* Other names: Taxol Konzentrat;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>| | Experimental: Arm II (standard of care, ketogenic diet)<br>Patients receive standard of care with paclitaxel. Patients undergo a controlled feeding period ketogenic diet comprising of meals prepared in the research kitchen for 3 months. Beginning 2 weeks prior to completion of the controlled feeding period, patients also undergo free living ketogenic diet program for 3 months comprising of group format, individual sessions, and online digital content to educate patients to implement a ketogenic eating pattern into their lifestyle. | Dietary Supplement: Dietary Intervention<br>* Undergo ketogenic diet<br>* Other names: Nutritional Interventions;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Drug: Paclitaxel<br>* Given standard of care therapy with paclitaxel<br>* Other names: Taxol Konzentrat;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Adherence and compliance to the ketogenic diet | Summaries from diet assessments and ketone logs will be plotted over time to assess adherence and compliance to the ketogenic diet. | Up to 26 weeks | | Changes in psychosocial measures | Summary measures such as Cohens d will be used. Linear and nonlinear mixed models will be used as appropriate to model changes in tumor markers, comorbidity risk factors, and other measures over time, with emphasis will be on estimating effect sizes (such as slopes of change). Post hoc tests will be used to examine pairwise comparisons when significant main or interaction effects are observed. The alpha level for significance will be set at p =< 0.05. | Baseline up to 26 weeks | | Changes in physiologic outcomes | Summary measures such as Cohens d will be used. Linear and nonlinear mixed models will be used as appropriate to model changes in tumor markers, comorbidity risk factors, and other measures over time, with emphasis will be on estimating effect sizes (such as slopes of change). Post hoc tests will be used to examine pairwise comparisons when significant main or interaction effects are observed. The alpha level for significance will be set at p =< 0.05. | Baseline up to 26 weeks |

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ThinkingFit: Combined Physical, Cognitive and Social Treatment in Mild Cognitive Impairment (MCI) Study Overview ================= Brief Summary ----------------- Dementia is serious problem and around 700 000 people are affected in the UK alone. Currently there is no cure however early diagnosis and effective treatment offers hope for reducing the impact. Dementia sufferers require care due to physical disability, cognitive deficits, social isolation and emotional symptoms (depression). Delaying the onset of dementia will improve quality of life for patients and reduce the cost of residential care (£42 000 per person per year). People with mild cognitive impairment (MCI) are at high risk of developing dementia. They have impaired cognitive abilities, such as memory, but still manage their everyday activities. Studies show that 8 out of 10 people with MCI will have developed dementia 6 years after diagnosis. Regular physical activities and performing a variety of cognitive activities reduce the risk of dementia and improves abilities and quality of life in healthy people. Therefore a combination of these activities may reduce the risk of developing dementia in MCI. The investigators want to see if they can develop a program which combines these activities in a fun and social way that gets people active and keeps them active. The aims are to improve fitness, cognition and quality of life. The investigators plan to use computers and the internet to help with the activities and to make them available to people who are isolated. Physical activity will involve walking from home, cognitive activities will be computer based games and puzzles and socialising will involve regular varied group-based activities. Participants (128) will be recruited from the UCL Derwent Memory Clinic and will complete a 26 week program. They will then be followed up yearly to monitor their progress. The main outcome of the study is engagement in the activities. The investigators will also measure fitness, cognition, quality of life and conversion to dementia. Official Title ----------------- Piloting a Complex Intervention Involving Physical Exercise, Cognitive Training and Socialising to Delay the Onset of Dementia in Mild Cognitive Impairment Conditions ----------------- Mild Cognitive Impairment Intervention / Treatment ----------------- * Procedure: ThinkingFit programme Participation Criteria ================= Eligibility Criteria ----------------- Inclusion criteria for patients with MCI Patients fulfilling criteria for AMCI [Petersen et al. 2001b]: i. Memory impairment for age and education ii. No impairment in other cognitive domains iii. Normal social activities iv. Patient is not demented For the other subtypes of MCI, cognitive impairment in one or more nonmemory domain Sedentary lifestyle with no regular participation in physical exercise defined as two or three times a week for at least 20 minutes duration, or participation in active sport more than once a week, in the previous six months. Willing and able to give informed consent. Availability and access to safe exercise environments, such as paths or roads with sidewalks for walking or cycling. At low risk from serious adverse effects from increased physical activity as indicated by performance on the revised Physical activity readiness questionnaire (PARQ). Exclusion Criteria: Exclusion criteria for patients with MCI Type 1 (insulin dependent) diabetes mellitus. Blood pressure of 160/100 mmHg or more. Body weight more than 140% of ideal body weight. Musculoskeletal or other medical problems preventing safe participation in regular moderate intensity exercise (65-77% of predicted maximum heart rate). This will include a resting tachycardia (heart rate above 100 bpm) and history of myocardial infarction or unstable angina within the last month. Participants with modifiable exclusion criteria will be reconsidered after successful management. Patients will be referred for medical treatment prior to commencing exercise if indicated by the PARQ and the intervention will be guided by the PARmedX. Participants taking medications affecting heart rate will need to be on a stable dosing regime for 3 months prior to commencing in order to control for potential spurious results on fitness measures caused by these treatments. Ages Eligible for Study ----------------- Minimum Age: 40 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: ThinkingFit<br> | Procedure: ThinkingFit programme<br>* Combined physical, cognitive and social stimulation activties.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Activity Compliance | Number of participants to have completed 50% or more of the programmed activity sessions during the intervention period. | Compliance with programmed activities will be assessed at the end of participation which is expected to be at 24 weeks | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Cardiovascular fitness measure | Cardiovascular fitness will be measured with a modified Siconolfi Step Test. | This will be measured at the start, after the control period (12 weeks) and after completion of the activity interventions at around 24 weeks. | | Cognitive measures | Participants will complete the following cognitive measures: Visual and auditory divided attention task Verbal episodic encoding and recognition task Halstead Trail Making test (TMT) Verbal fluency Working memory tests: digit span forwards/ backwards | This will be measured at the start, after the control period (12 weeks) and after completion of the activity interventions at around 24 weeks. | | Measures of quality of life and everyday activities | Quality of life will be measured on the World Health Organization Quality of Life (WHOQOL) - BREF and change in every day activities on the Alzheimer's Disease Cooperative Study MCI Activities of Daily Living Scale (ADCS-MCI-ADL) | This will be measured at the start, after the control period (12 weeks) and after completion of the activity interventions at around 24 weeks. |

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Prevalence of Gastroesophageal Reflux Disease (GERD) in Patients With Upper Gastrointestinal Track (GIT) Symptoms in Thailand Study Overview ================= Brief Summary ----------------- This is a prospective , epidemiological, multi-centre, phase IV study, approximately 5,000 patients who suffer with upper gastrointestinal tract symptoms. Each patient will be assessed for GERD with GerdQ Thai Version. Official Title ----------------- Prevalence of GERD in Patients With upperGITsymptoms in Thailand Conditions ----------------- Upper GIT Symptoms Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Provision of informed consent prior to any study specific procedures Female or male aged at least 18 years Patient must be having symptoms suggestive of upper gastrointestinal tract symptoms such as heart burn/ regurgitation Exclusion Criteria: Involvement in the planning and /or conduct of the study (applies to both AstraZeneca staff and /or staff at study site Participation in a clinical study(excluding non-interventional study or registry) during the last 3 months Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Prevalence of gastroesophageal reflux disease (GERD) in patients presented with upper gastrointestinal tract symptoms | | | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Response to various treatments for patients who have been diagnosed of GERD | | | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- GerdQ

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Efficacy of Early Tracheostomy to Reduce Incidence of Ventilator Acquired Pneumonia (VAP) Study Overview ================= Brief Summary ----------------- The study aims to assess early (one to three days after intubation) tracheostomy effectiveness in terms of reduction in ventilator associated pneumonia (VAP) incidence. Detailed Description ----------------- Tracheostomy is an essential and irreplaceable procedure for critically ill patients requiring mechanical ventilatory support and adequate airway control. The therapeutical choice of performing a tracheostomy is supported by a number of clinical benefits, such as less use of drugs for sedation, fewer days of mechanical ventilation and hence shorter Intensive Care Unit (ICU) length of stay, as well as better resource rationalization. Actually there is no agreement on the best timing for tracheostomy. The aim of this study is to verify if an early tracheostomy (one to three days after intubation) increases ventilator associated pneumonia-free days. Secondary endpoints are: increase of ventilator free-days and mortality reduction. Conditions ----------------- Respiratory Insufficiency Intervention / Treatment ----------------- * Procedure: Tracheostomy on day 3-5 in early group and 10-12 in late group Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Oro/nasotracheal intubation for less than three days Simplified Acute Physiology Score (SAPS II) between 35 and 65 upon admission to Intensive Care Unit (ICU) Exclusion Criteria: Oro/nasotracheal intubation > three days Age < 18 years Previous otolaryngologic or maxillofacial procedures Brain injury patients with intracranial pressure > 20 mmHg without pharmacological treatment (or intracranial pressure > 15 mmHg under specific pharmacological treatment) and with cerebral perfusion pressure < 60 mmHg Pregnancy Ventilator associated pneumonia, hospital acquired pneumonia, community acquired pneumonia diagnosis before randomization Infection in the tracheostomic area Acute worsening of chronic obstructive pulmonary disease (COPD) Pre-existing malignancies in the tracheostomic area Immunosuppressed and/or immunodepressed patients: leukocytes < 1000/microliters neutrophils < 500/microliters AIDS long-term steroid treatment (daily dose > 0.5 mg/kg for more than 30 days) Patients already enrolled in other trials Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Early (A)<br>Patients of the EARLY group (A) will be submitted to tracheostomy on day 3-5 from oro/nasotracheal intubation. | Procedure: Tracheostomy on day 3-5 in early group and 10-12 in late group<br>* Upon admission to ICU, acute respiratory failure patients requiring at least 3 days of mechanical ventilation and defined by a SAPS II score between 35 and 65, will be randomly assigned to either arm A or B of the study.<br>| | Active Comparator: Late (B)<br>Patients of the LATE group (B) will undergo tracheostomy on day 10-12 from oro/nasotracheal intubation. | Procedure: Tracheostomy on day 3-5 in early group and 10-12 in late group<br>* Upon admission to ICU, acute respiratory failure patients requiring at least 3 days of mechanical ventilation and defined by a SAPS II score between 35 and 65, will be randomly assigned to either arm A or B of the study.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Increase of ventilator associated pneumonia-free days | | Follow-up terminates on day 28 from the date of oro/nasotracheal intubation. | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Increase of ventilator-free days | | Follow-up terminates on day 28 from the date of oro/nasotracheal intubation | | Reduction of mortality | | one year | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Tracheostomy, Tracheostomy timing, Ventilator associated pneumonia, Mechanical ventilation

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Study of Levalbuterol, Racemic Albuterol and Placebo in Subjects Twelve Years of Age and Older With Asthma Study Overview ================= Brief Summary ----------------- The primary objective of this study is to investigate the efficacy of levalbuterol 90 ug (2 actuations, 45 ug each) versus placebo (2 actuations) in the treatment and prevention of bronchoconstriction in adolescent and adult subjects with asthma, with all treatments administered 4 times a day (QID). Detailed Description ----------------- A double-blind, randomized, placebo- and active-controlled, multicenter, parallel-group trial of levalbuterol in subjects 12 years of age and older with asthma. Study participation will include one 1-week single-blind placebo run-in and an 8-week, randomized,double-blind, active-treatment period with four treatment groups. This study was previously posted by Sepracor Inc. In October 2009, Sepracor Inc. was acquired by Dainippon Sumitomo Pharma., and in October 2010, Sepracor Inc's name was changed to Sunovion Pharmaceuticals Inc. Official Title ----------------- An Efficacy and Safety Study of Levalbuterol, Racemic Albuterol and Placebo in Subjects Twelve Years of Age and Older With Asthma Conditions ----------------- Asthma Intervention / Treatment ----------------- * Drug: levalbuterol Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria Must give written informed consent (IC) prior to participation in the study. For subjects 12 - 17 years of age, the IC must be signed parent or legal guardian. Females must sign the Women of Childbearing Potential Addendum Be willing and able to comply with the study procedures and visit schedules Male or female, at least 12 years of age Females 12-60 years of age must have a negative serum pregnancy test at Visit 1 (V1) Women of child bearing potential must be using an acceptable method of birth control Must have a documented diagnosis of asthma for a min. of 6 mos. prior to V1 At V1, the subject must demonstrate a baseline FEV1 within >45% and <75% of predicted for their height, age, gender, and race Following abstention from medications used to treat asthma, subject must demonstrate >12% reversibility of airflow obstruction within 15-30 min. following inhalation of 180 µg (2 actuations, 90 µg ea.) of racemic albuterol MDI Must have stable baseline asthma and have been using a B-adrenergic agonist, and/or anti-asthma anti-inflammatory medication, and/or OTC asthma medication for at least 6 mos. prior to V1 Must be in good health with the exception of their reversible airways disease and not suffering from any chronic condition that might affect their respiratory function Must have a chest X-ray that is not diagnostic of pneumonia, atelectasis, pulmonary fibrotic disease, pneumothorax, chronic obstructive pulmonary disease, etc. Must be able to complete the diary cards and medical event calendars reliably on a daily basis and demonstrate how to use the MiniWright PEF meter Exclusion Criteria Subject who is expected to require any disallowed medications Female subject who is pregnant or lactating Subject who has participated in an investigational drug study within 30 days prior to V1, or who is currently participating in another clinical trial Schedule prevents him or her from taking the first daily dose of study medication and/or starting study visits before 9AM Subject who has travel commitments during the study that would interfere with trial measurements or compliance or both Subject who has a history of hospitalization for asthma within 45 days prior to V1, or who is scheduled for in-patient hospitalization during the trial Have a known sensitivity to levalbuterol or racemic albuterol, or any of the excipients contained in any of these formulations Subject using any prescription drug with which albuterol sulfate administration is contraindicated Subject with currently diagnosed life-threatening asthma Subject with clinically significant abnormalities that may interfere with the metabolism or excretion of the study drug Have a history of cancer (exception: basal cell carcinoma in remission) Have hyperthyroidism, diabetes, hypertension, cardiac diseases, or seizure disorders not well controlled by medication or that may interfere with the successful completion of this protocol Have a history of substance or drug abuse within 12 mos. preceding V1 or a positive urine drug screening at V1 Have greater than 10 pack year history of cigarette smoking or use of any tobacco products within 6 mos. of V1 Have a documented history of bronchopulmonary aspergillosis or any form of allergic alveolitis Have suffered from a clinically significant upper or lower respiratory tract infection in the 2 weeks prior to V1 Have any clinically significant abnormal laboratory values Have a clinically significant abnormal 12-lead ECG that may jeopardize the subject's ability to complete study Subject who is a staff member or relative of a staff member Ages Eligible for Study ----------------- Minimum Age: 12 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Triple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: I<br>Levalbuterol 90 ųg QID (manufacturing site A or B) | Drug: levalbuterol<br>* Levalbuterol 90 ųg QID (manufacturing sites A or B); Racemic Albuterol 180 ųg QID; Placebo QID<br>* Other names: Xopenex HFA (levalbuterol tartrate)Inhalation Aerosol;| | Active Comparator: II<br>Racemic Albuterol 180 ųg QID | Drug: levalbuterol<br>* Levalbuterol 90 ųg QID (manufacturing sites A or B); Racemic Albuterol 180 ųg QID; Placebo QID<br>* Other names: Xopenex HFA (levalbuterol tartrate)Inhalation Aerosol;| | Placebo Comparator: III<br>Placebo QID | Drug: levalbuterol<br>* Levalbuterol 90 ųg QID (manufacturing sites A or B); Racemic Albuterol 180 ųg QID; Placebo QID<br>* Other names: Xopenex HFA (levalbuterol tartrate)Inhalation Aerosol;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | FEV1 (peak percent change from pre-dose averaged over the double-blind period). | | 8 weeks | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | --FEV1 [area under the % change from pre-dose FEV1 curve] and FEV1 [area under the % change from study baseline FEV1 curve] | | 9 weeks | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- levalbuterol, asthma, bronchoconstriction, adolescent, adult

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Immune Boost In Non-Small Cell Lung Cancer Study Overview ================= Brief Summary ----------------- Insufficient migration and activation of tumour specific effector T cells seems to be the one important reason for inadequate host anti-tumour immune response. Ionizing radiation can induce a variety of immune responses. The goal of this randomized trial is to assess if a preoperative single fraction low dose radiation is able to improve anti-tumour immune response in operable early stage lung cancer. Official Title ----------------- A Randomized Phase II Study of Radiation Induced Immune Boost in Operable Non-small Cell Lung Cancer Conditions ----------------- Non-small Cell Lung Cancer Intervention / Treatment ----------------- * Radiation: Preoperative radiation Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Histologically proven clinical stage I to IIA pulmonary adenocarcinoma Lung tumor is felt to be curatively resectable by the treating physicians Sufficient pulmonary function for lobectomy according to current guidelines The patient is free of distant metastases as confirmed by contrast-enhanced chest and upper abdomen CT-scan and by contrast-enhanced CT or MRI of the brain Age over 50years at the time of consent due to federal radiation protection law In female patients of childbearing potential there must be a negative pregnancy test Eastern Cooperative Oncology Group performance status of 0,1, 2 or 3 at the time of randomization Patients who the investigator believes can and will comply with the requirements of this protocol Written informed consent according to good clinical practise and national/regional regulations Exclusion Criteria: The patient shows clinical signs of pneumonia The patient receives immunosuppressive drugs (alkylating agents, antimetabolites, methotrexate, azathioprine, mercaptopurine, cytotoxic antibodies, ciclosporin, tacrolimus, sirolimus, interferon, mycophenolate, small biological agents) The patient has been diagnosed with a potential immune mediated disease Elevated blood leukocyte count or erythrocyte sedimentation rate Pregnancy The patient has received any cancer specific treatment, including radiotherapy, immunotherapy, hormonal therapy or chemotherapy The patient is diagnosed with a concomitant malignancy and/or has a history of malignancy within the past five years or has had a malignancy that has been in complete remission for less than 5 years The patient needs chronic long term oxygen therapy The patient has undergone splenectomy The patient is known to be HIV positive The patient has an uncontrolled bleeding disorder Ages Eligible for Study ----------------- Minimum Age: 50 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Basic Science Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | No Intervention: No radiation<br>Lobectomy for lung cancer without preoperative radiation | | | Experimental: Preoperative radiation<br>Lobectomy for lung cancer with preoperative radiation | Radiation: Preoperative radiation<br>* Lobectomy for lung cancer following preoperative radiation<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Cluster of differentiation (CD)8+ T cells in resected NSCLC | Frequencies of CD8+ T cells in resected NSCLC tumors determined by immunohistochemistry | 7 days | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | T cell subtypes in resected NSCLC | Frequencies of CD3+, CD4+, CD45RO and Foxp3+ T cells in resected NSCLC tumors determined by immunohistochemistry and flow cytometry | 7 days |

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An Open-Label Study of N-Acetyl Cysteine in Pathological Gambling Study Overview ================= Brief Summary ----------------- After completing all screening evaluations, subjects will receive unblinded N-Acetyl Cysteine 600 mg/day for 2 weeks. The dose will be raised to 1200 mg/day at visit 4 and to 1800 mg/day at visit 6 unless clinical improvement has been attained at a lower dose (clinical improvement will be assessed by the investigator with respect to gambling thoughts, urges and behavior). If it is clinically necessary to modify this schedule (e.g., because of side effects or an adequate response to a lower dose), the dose will be raised more slowly or the target dose will not be reached. Subjects will start no other psychotropic medications during the study but may continue on previously prescribed psychotropic medications if on a stable dose for 3 months prior to study entry. Psychotherapy of any form (including cognitive-behavioral therapy) will not be initiated during the study but subjects may continue with current psychotherapy if they have been undergoing therapy for at least three months prior to study entry. Subjects will be evaluated with the PG-YBOCS, G-SAS, CGI, HAM-D, HAM-A and the Sheehan Disability Inventory at screening and at each visit for the remainder of the study. Medication side effects will be evaluated at each study visit. A tablet count will be kept for each dose of medication taken. Detailed Description ----------------- Before beginning N-Acetyl Cysteine, all subjects will receive a psychiatric, medical, and family history evaluation as well as the Structured Clinical Interview for DSM-IV (SCID-P) for Axis I disorders. At the screening visit, patients will also receive standard laboratory tests (including ß-HCG), and a physical examination. The following instruments will be completed at the screening visit and periodically throughout the study: 1) Yale-Brown Obsessive Compulsive Scale Modified for Pathological Gambling (PG-YBOCS), a reliable and valid semi-structured clinician-administered scale that assesses current severity of PG; 2) Gambling Symptom Assessment Scale (G-SAS), a reliable and valid self-report measure of gambling symptoms; 3) the 17-item Hamilton Rating Scale for Depression (HAM-D); 4) the 17-item Hamilton Rating Scale for Anxiety (HAM-A); 5) Clinical Global Impression scale; 6) the Sheehan Disability Inventory; and 7) the Quality of Life Inventory. Safety evaluations, including pulse and blood pressure, and assessment of side effects will be done at each visit. After completing all screening evaluations, subjects will receive unblinded N-Acetyl Cysteine 600 mg/day for 2 weeks. The dose will be raised to 1200 mg/day at visit 4 and to 1800 mg/day at visit 6 unless clinical improvement has been attained at a lower dose (clinical improvement will be assessed by the investigator with respect to gambling thoughts, urges and behavior). If it is clinically necessary to modify this schedule (e.g., because of side effects or an adequate response to a lower dose), the dose will be raised more slowly or the target dose will not be reached. Subjects will start no other psychotropic medications during the study but may continue on previously prescribed psychotropic medications if on a stable dose for 3 months prior to study entry. Psychotherapy of any form (including cognitive-behavioral therapy) will not be initiated during the study but subjects may continue with current psychotherapy if they have been undergoing therapy for at least three months prior to study entry. Subjects will be evaluated with the PG-YBOCS, G-SAS, CGI, HAM-D, HAM-A and the Sheehan Disability Inventory at screening and at each visit for the remainder of the study. Medication side effects will be evaluated at each study visit. A tablet count will be kept for each dose of medication taken. Official Title ----------------- An Open-Label Study of N-Acetyl Cysteine in Pathological Gambling Conditions ----------------- Pathological Gambling Intervention / Treatment ----------------- * Drug: N-Acetyl Cysteine Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Men and women age 18-65 Current DSM-IV PG Exclusion Criteria: Unstable medical illness on physical examination History of seizures Myocardial infarction within 6 months Current pregnancy or lactation, or inadequate contraception in women of childbearing potential Clinically significant suicidality Lifetime history of DSM-IV bipolar disorder type I, dementia, or schizophrenia or any other DSM-IV psychotic disorder Current or recent (past 3 months) DSM-IV substance abuse or dependence Illegal substance within 2 weeks of study initiation Initiation of psychotherapy or behavior therapy from a mental health professional within 3 months prior to study baseline Previous treatment with N-Acetyl Cysteine Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 65 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Intervention/Treatment | | --- | |Drug: N-Acetyl Cysteine|nan| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | PG-YBOCS | | | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | G-SAS | | | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Gambling, Gambler, Gamble, Pathological

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Study of Jaktinib In Patients With Myelofibrosis Who Were Relapsed or Refractory of Ruxolitinib Treatment. Study Overview ================= Brief Summary ----------------- This was a phase 2, single-arm, open-label, non-randomised, multicentre, study to evaluate the efficacy and safety of Jaktinib in patients with myelofibrosis who were relapsed or refractory of ruxolitinib treatment. Detailed Description ----------------- All subjects will receive a minimum of 6 treatment cycles or 24 weeks (a 28-day treatment cycle is defined as one treatment cycle). Official Title ----------------- A Phase II Study To Evaluate The Efficacy And Safety of Jaktinib Hydrochloride Tablets In Patients With Myelofibrosis Who Were Relapsed or Refractory of Ruxolitinib Treatment Conditions ----------------- Myelofibrosis Intervention / Treatment ----------------- * Drug: Jaktinib Hydrochloride Tablets Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Subjects voluntarily sign the informed consent form (ICF); Age ≥ 18 years, either male or female; Subjects diagnosed with a PMF according to World Health Organization (WHO) criteria (2016 Edition), or patients diagnosed with a Post-PV-MF or Post-EF-MF according to International Working Group for Myeloproliferative Neoplasms Research and Treatment (2007 IWG-MRT) criteria; Subjects with intermediate-2 or high-risk myelofibrosis, or Intermediate-1 myelofibrosis with symptoms according to the Dynamic International Prognostic System (DIPSS) scoring system; Subjects are relapsed/refractory to Ruxolitinib: Relapsed defined as Ruxolitinib treatment for ≥ 3 months, following an initial response, regrowth to < 10% spleen volume reduction (SVR) by MRI or < 30% decrease in spleen size by palpation from baseline; Refractory defined as Ruxolitinib treatment for ≥ 3 months observed inadequate efficacy response: < 10%volume SVR by MRI or < 30% decrease in spleen size by palpation from baseline. Subject has a measurable splenomegaly: spleen volume of ≥ 450 cm3 by MRI/CT and ≥ 5 cm below left costal margin by palpation spleen measuring; Expected life expectancy is greater than 24 weeks; Eastern Cooperative Oncology Group (ECOG) performance Score 0-2; Laboratory examination within 7 days before the randomization, fulfilling the following criteria: Neutrophil count ≥ 0.75 x 109/L, platelet count ≥ 75 x 109/L; Peripheral blood blasts ≤ 10%; ALT and AST≤ 3 ULN, DBIL ≤ 2.0 ULN; Serum creatinine ≤ 2.0 ULN. Exclusion Criteria: Subjects who have been previously exposed to Janus kinase (JAK) inhibitors other than Ruxolitinib for a total of> 2 weeks; Subjects who have taken Ruxolitinib or other JAK inhibitor within 1 week prior to screening; Subjects with any significant clinical and laboratory abnormalities which may affect the safety evaluation, such as uncontrolled diabetes, uncontrolled hypertension after taking two or more hypotensive drugs or peripheral neuropathy; Subjects with congestive heart failure (NCI-CTCAE V5.0) Class II or above, uncontrolled or unstable angina or myocardial infarction, cerebrovascular accident, or pulmonary embolism within 6 months prior to screening; Subjects who have a history of chronic or recurrent respiratory diseases, such as: chronic obstructive pulmonary disease, recurrent lung infections, etc., or have a history of lung infections within 3 months before screening, or currently have upper respiratory tract infections that have not recovered; Subjects who have not fully recovered from surgical operation within 4 weeks prior to screening; Subjects suffering from arrhythmia and requiring treatment, or QTcB > 480ms at screening; Subjects with clinical symptoms of active bacterial, viral, parasitic or fungal infections requiring treatment at screening; Subjects who had undergone splenectomy, or received radiotherapy to the spleen within 6 months before screening; Subjects with known human immunodeficiency virus (HIV), known active infectious Hepatitis B (HepB), and/or known active infectious Hepatitis C (HepC); Female subjects who are pregnant, currently breastfeeding, planning to become pregnant; Subjects who had experienced malignant tumors (except for adequately treated local basal cell or squamous cell carcinoma of the skin and cervical carcinoma in situ that have been cured) or in combination with other serious diseases within the past 5 years; Subjects who have participated in another clinical trial of a new drug or medical instrument within 1 month before screening. Subjects who have any other conditions that are not specified in the protocol but the investigator believes that they are not suitable for inclusion in this trial. Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Jaktinib 100mg Bid<br>Jaktinib twice daily for 6 consecutive 28-day cycles, orally, empty stomach | Drug: Jaktinib Hydrochloride Tablets<br>* Jaktinib 100mg Bid<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Spleen Volume Response rate (SVRR) at Week 24 | The proportion of subjects with spleen volume reduction from baseline ≥ 35% measured by MRI or CT. | at Week 24 | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Clinical Objective Response Rate (complete remission (CR) + partial remission (PR)) | International Working Group for Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) response criteria. | Baseline, up to Year 2 | | Spleen Response | Best response rate: the proportion of subjects with at least one spleen volume reduction ≥ 35% against the baseline; Time to response: the length of time from the date of first dose to the date on which the first spleen volume reduction ≥ 35% against the baseline; Duration of maintenance of at least 35% Reduction in Spleen Volume (DoMSR): the length of time from the date of the first spleen volume reduction ≥ 35% against the baseline to the date of the spleen volume reduction is less than 35% against the baseline due to spleen volume increase. | up to Year 2 | | Anemia Response | Proportion of transfusion dependent patients（Transfusion dependent patients：received RBC transfusion ≥ 12 U within 12 weeks before receiving the investigational drug） at baseline turned to non-transfusion dependent patients (non-transfusion dependent patients: no transfusion for at least 12 consecutive weeks and Hgb ≥ 85 g/L); Proportion of hemoglobin (Hgb) elevation ≥ 20 g/L in non-transfusion dependent patients (Hgb ≤ 100 g/L) at baseline; Decline in red blood cell (RBC) transfusion dependence: Number of RBC transfusions decreases by 50%. | up to Year 2 | | Response rate of MF-related symptoms | Proportion of patients with Myeloproliferative neoplasm symptom assessment form (MPN-SAF) TSS decreasing from baseline by ≥ 50%; The change in MPN-SAF TSS from baseline. | Baseline, up to Year 2 | | Progression free survival (PFS) | The length of time from the date of first dose to the date of any of the following events: 1) ≥ 25% increase in spleen volume over nadir since the treatment; 2) death from any cause. | From the date of first dose to the earliest date of either increase in spleen volume ≥ 25% from on-study nadir or death, up to Year 2 | | Leukemia free survival (LFS) | The length of time from the date of first dose to the date of any of the following events: 1) the first bone marrow blast count ≥ 20%; 2) the first peripheral blast count ≥ 20% ; 3) death from any cause. | From the date of first dose to the earliest date of either leukemia or death, up to Year 2 | | Overall survival (OS) | The length of time from the date of first dose to death from any cause. | From the date of first dose to the date of death, up to Year 2 |

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Cross-sectoral Collaboration in Multidisciplinary Treatment of Trauma-affected Refugees Study Overview ================= Brief Summary ----------------- INTRODUCTION Trauma-affected refugees are at high risk of developing mental health problems including post-traumatic stress disorder (PTSD) and depression. In addition to traumatic stress, refugees are furthermore subject to a range of post-migration stressors e.g. unemployment, poor finances and language difficulties. These stressors can moderate or exacerbate mental health outcomes in refugees. Cross-sectoral collaboration and coordination of municipal social interventions and regional mental health services are currently limited. The overall aim of this study is to investigate the effect of a psychosocial treatment with a focus on social stressors in an integrated cross-sectoral collaboration with the municipality for trauma-affected refugees MATERIALS AND METHODS The study is being conducted at Competence Centre for Transcultural Psychiatry (CTP) in Denmark. Included in the study are refugees with post-traumatic stress disorder (PTSD), who are unemployed and attending a municipal job centre in one of the five collaborating municipalities. Approximately 200 patients will be included. The randomised controlled trial is comparing treatment as usual (TAU) comprising 10 sessions with a medical doctor (pharmacological treatment and psycho-education) and 16-21 sessions with a psychologist (manual-based cognitive behavioural therapy) with add-on of the social intervention. Overall, the intervention seeks to integrate working with social stressors alongside treatment for trauma-related mental health problems. This is done in two ways; by a cross-sectoral collaboration with municipality through collaborative meetings and by a systematic focus on social stressors during the treatment. The primary outcome is functioning, measured by WHODAS 2.0 12 item version together with a variety of secondary outcomes measuring mental health symptoms, quality of life and degree of social stressors. RESULTS The study is expected to bring forward new perspectives and knowledge on psychosocial treatment of trauma-affected refugees as well as cross-sectoral collaboration. Detailed Description ----------------- INTRODUCTION Treatment-seeking trauma-affected refugees possess a complexity involving past trauma and ongoing social stressors, which challenges treatment of mental health problems. There is therefore a great need for developing holistic cross-sectoral interventions, where dealing with these complex challenges are integrated in treatment for trauma-related mental health problems. This research gap has led to the present research study. The overall aim of this study is to examine a psychosocial intervention with an integrated cross-sectoral collaboration for refugees with post-traumatic stress disorder (PTSD) in a randomised controlled trial (RCT) supplemented by a qualitative study. For the RCT the objectives are: To investigate the treatment effect of a psychosocial, cross-sectoral intervention on outcomes of functioning, quality of life and mental health symptoms compared to treatment as usual (TAU) at Competence Center for Transcultural Psychiatry (CTP). To study social stressors as a predictor of severity of mental health symptoms, quality of life and functioning at baseline. To examine predictors for positive outcomes of treatment including social stressors as a predictor. Course of treatment and data collection will follow the SPIRIT statement PATIENT RECRUITMENT Patients can be referred to the clinic by any MD. A senior psychiatrist at CTP assess all referrals, and based on the referral, patients are invited for an initial assessment by an MD at CTP. If it is clear from the referral that the patient does not belong to the clinic's target group, the patient is not invited for an assessment. Previously randomised trials in the CTP have included about 150 patients per year, and the most recent project included 100 patients per year. In all trials 65-75 % of the patients have completed the project. For the present trial the collaborating municipalities cover about 80 % of the referred patients' municipal affiliation. Counteracting this, the investigators expect more patients to be interested in participating in the present trial compared to previous trials that have included psychopharmacological interventions. Therefore approximately 200 project patients are deemed realistic within the given time frame. INITIAL ASSESSMENT The initial assessment is scheduled for all patients that are assessed to be in the target group of CTP. The content of the assessment is not specific for this trial but applies to all initial assessments at CTP. The initial assessment is planned as 2-4 sessions of approximately 45 minutes with an MD, resulting in a total of about two-three hours assessment and consists of; recording of the trauma history, the migration process, social situation, somatic and psychiatric medical history, as well as a clinical and diagnostic assessment. Standardised diagnostic tools such as part of Schedules for Clinical Assessment in Neuropsychiatry (SCAN), the ICD-10 research criteria and the International Trauma Interview (ITI) for ICD-11 section one (PTSD) will be applied in the interview. Various instruments of symptom severity and functioning are completed as self- and observer ratings. Oral and written information about the treatment and the trial is given. If the patient fulfils eligibility criteria and consents to participate, the patient will be randomised after the initial assessment. RANDOMISATION All patients will be randomised after a total of two to three-hour initial assessment with an MD in accordance with inclusion and exclusion criteria. An equal number of patients are randomised in to the two groups (TAU and intervention). The actual randomisation is carried out in REDCap (Research Electronic Data Capture). Stratification by the five municipalities will be carried out before randomisation. BLINDING Blinding patients and practitioners are not assessed to be appropriate due to the different nature of the treatment interventions. However, an intervention-group blinded Hamilton (depression and anxiety) rating will be carried out at the beginning and at the end of treatment. Hamilton-raters will be trained at the clinic and will take part in regular joint ratings to ensure high quality and interrater reliability. Data assessment and data analysis will be performed blinded. REPRESENTATIVITY Patients have not been selected based on more specific criteria than elsewhere in the treatment system and are therefore representative for the population at other clinics treating trauma-related mental health problems in refugees. The results can thus be generalised to other corresponding patient groups and are directly applicable in the planning of treatment for this patient population in general. TRIAL FIDELITY In order to determine trial fidelity, patient attendance will be registered and after each consultation with an MD, psychologist or social counsellor, the topics addressed will be registered, as well as the methods used during the consultation and whether the patient has completed his/her exercises between sessions as planned. At each consultation with an MD any changes in medication will also be recorded. VARIABILITY IN THE COURSE OF TREATMENT All patients will follow the predefined treatment course as accurate as possible, but due to the pragmatic nature of the study there will possibly be some variation in attendance and timing of meetings and sessions, as the patients may become ill or for some other reason not show up for sessions or meetings. FREQUENCY OF RATINGS Patients will be asked to complete self-ratings several times during treatment: at the diagnostic interview/assessment, transition between phase 1 and phase 2, and at the end of the treatment course. Observer ratings and blinded Hamilton ratings will take place at the beginning and end of treatment. In addition, ratings will also be carried out at follow-up 6 months after end of treatment. DATA COLLECTION Data will only be collected at CTP and the municipalities are not involved in any data collection or processing. After each session the clinicians will fill out the case report form (CRF) in the research database through REDCap (Research Electronic Data Capture). All ratings will be carried out by a CTP practitioner (MD, psychologist or social counsellor). Blinded observer Hamilton ratings will be carried out by medical students not linked to the team of practitioners, but to an independent Hamilton rating team with thorough training in using the Hamilton rating scale. In order to ensure quality and inter-rater reliability, the members in the Hamilton team participate regularly in joint ratings under the guidance of one of the senior psychiatrists at CTP (six joint ratings per year). The investigator is overall responsible for the data collection. DATA SECURITY All data collected for this project will be protected according to the General Data Protection Regulation (EU) 2016/679 (GDPR), Act on Processing of Personal Data as well as the Danish Health Act. Information regarding the patients' health concerning trauma history, the migration process, social situation, somatic and psychiatric medical history, medicine, allergies, abuse of drugs or alcohol and ratings will be passed on from the patient record to investigator. SOURCE DATA All data registered about the patients will be kept as source data in the form of original rating forms completed by the patients or practitioners, as well as structured patient records. Data will be saved for 15 years after the trial has ended, which will be stated in a letter of attorney signed by the patients. Case Report Form is source data, this will be described in the source data document, which will be filed in the Trial Master File. QUALITY ASSURANCE Quality control and quality assurance will follow regular procedures as described in sections 3 and 4 of the Danish Executive Order on Good Clinical Practice (GCP). The previous RCTs at CTP has been under GCP monitoring, but the GCP unit has assessed that GCP monitoring is not necessary for the current trial as CTP is assessed to have high-quality internal monitoring. The internal monitoring during the trial follows a manual and is carried out by a team not directly involved in the data collection. The trial is approved by the Danish Data Protection Agency through the Capital Region of Denmark. Managing and filing data will be in accordance with current guidelines for research. Manuals are used in sessions with all clinicians to establish shared standard procedures. In order to ensure interrater reliability, all MDs will attend a SCAN course and regular joint ratings including clinical assessment and observer-ratings will be carried out. POWER CALCULATION A Minimal Clinically Important Difference score for the WHODAS 2.0 has not yet been established. In the literature it has been difficult to find studies with populations comparable to the present study. Based on clinical experience and the sparse available literature a conservative Minimal Clinically Important Difference was taken to be 5 scale points on WHODAS 2.0 12-item version and within-groups SD was taken to be 10 scale points. With a power level of 80 % and alpha 0.05 the investigators estimate a sample size of each group of 64 and a total of 128. The completion rate in the preceding randomised trials at CTP was two-thirds, and the investigators therefore set expected drop-out rate to 35 % for this study. Therefore, the investigators increased the number of patients included to 128 x (1/(100%-35%)) and consequently estimated a total sample size of 197 patients. Inclusion will be stopped when approximately 197 patients have been included in the trial. It must be noted that in the case that a Minimal Clinically Important Difference for WHODAS 2.0 is established during the time frame of the trial, it will be considered in the analyses. DROP-OUT ANALYSIS Drop-out analysis is based on the patients who show up at the pre-treatment assessment. The participant will be compared to the patients, who were excluded at the initial assessment on several dimensions in order to identify possible systematic selection bias. The participants included in the trial, but who eventually drop out and do not complete the trial, will be analysed in an intention-to-treat analysis. In addition, completer analyses will be carried out. DATA PROCESSING The primary outcome variables are differences during the treatment course calculated as differences between baseline and end of treatment ratings. The differences between the two intervention groups can be measured with adjustment for baseline and stratification variables by ANCOVA/linear regression and with multiple imputations to handle missing data. The role of social stressors as a predictor for baseline mental health symptom severity, functioning and quality of life will be examined by linear regression with mental health indices, respectively, as dependent variable and social factors as independent variables. Potential predictors of outcome can be analysed by linear regression. A number of analyses are planned with changes in outcome measures as dependent variables and independent variables of social stressors including age, gender and other demographic and baseline data in an attempt to isolate predictors of positive outcome. Official Title ----------------- The Effect of Integrating Cross-sectoral Collaboration With the Municipality in Multidisciplinary Treatment of Trauma-affected Refugees; a Randomised Controlled Trial Conditions ----------------- Post Traumatic Stress Disorder, Depression, Psychosocial Problem Intervention / Treatment ----------------- * Behavioral: Cross-sectoral psychosocial intervention * Behavioral: Treatment as usual (TAU) Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Adults (18 years or older). Refugees or persons who have been family reunified with a refugee. PTSD pursuant to the ICD-10 research criteria. Psychological trauma experienced outside Denmark in the anamnesis. Trauma is imprisonment or detention with torture (according to the United Nations' definition of torture) or acts of cruel, inhuman and degrading treatment or punishment. Trauma can also be organised violence, long-term political persecution and harassment, or war and civil war experiences. Home address in one of the five collaborating municipalities. Unemployed and assigned to a jobcentre in a collaborating municipality. Signed informed consent. Exclusion Criteria: Severe psychotic disorder (defined as patients with an ICD-10 diagnosis F2x and F30.1-F31.9). Participants are excluded only if the psychotic experiences are assessed to be part of an independent psychotic disorder and not part of a severe PTSD and/or depression. Dependence syndrome of drugs or alcohol: Active dependence and use (F1x.24-F1x.26). Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Single Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Treatment as usual (TAU)<br>8-12 months of treatment | Behavioral: Treatment as usual (TAU)<br>* Medical doctor, 10 sessions: Pharmacological treatment according to standard algorithm and psychoeducation. Psychologist 16-21 sessions: Manual-based cognitive behavioural therapy.<br>| | Experimental: Cross-sectoral social intervention<br>8-12 months of treatment | Behavioral: Cross-sectoral psychosocial intervention<br>* The intervention seeks to integrate working with social stressors alongside treatment for trauma-related mental health problems. This is done in two ways; by a cross-sectoral collaboration with the patient's case counsellor in the municipality including three collaborative meetings and by a systematic focus on social stressors during the treatment.<br>Behavioral: Treatment as usual (TAU)<br>* Medical doctor, 10 sessions: Pharmacological treatment according to standard algorithm and psychoeducation. Psychologist 16-21 sessions: Manual-based cognitive behavioural therapy.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | The World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0), interviewer administered 12-item version | Measure of health and disability across cultures. Scoring range: 0-48, lower scores reflect better outcome. | Change from baseline to end-of-treatment after approximately 10 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | The Harvard Trauma Questionnaire (HTQ) Part IV | Self-administered rating scale assessing the severity of PTSD symptoms. Scoring range: 0-4, lower scores reflect better outcome. | Change from baseline to end-of-treatment after approximately 10 months | | Hopkins Symptom Check List - 25 (HSCL-25) | Self-administered rating scale assessing the severity of anxiety and depression symptoms. Scoring range: 0-4, lower scores reflect better outcome. | Change from baseline to end-of-treatment after approximately 10 months | | World Health Organisation - 5 Well-being Index (WHO-5) | Self-administered questionnaire evaluating quality of life. Scoring range: 0-100, higher scores reflect better outcome. | Change from baseline to end-of-treatment after approximately 10 months | | European Quality of Life (EQ-5D-5L) | Self-administered questionnaire on health status. Scoring range (index value): -0,624-1, higher scores reflect better outcome. | Change from baseline to end-of-treatment after approximately 10 months | | Sheehan Disability Scale (SDS) | Self-administered questionnaire on functioning. Scoring range: 0-30, lower scores reflect better outcome. | Change from baseline to end-of-treatment after approximately 10 months | | Post-migration Living Difficulties Check List (PMLD) | Self-administered rating scale examining post-migration challenges. Scoring range: 0-68, lower scores reflect better outcome. | Change from baseline to end-of-treatment after approximately 10 months | | Consumer Health Activation Index (CHAI) | Self-rating scale assessing patient activation. Scoring range: 0-100, higher scores reflect better outcome. | Change from baseline to end-of-treatment after approximately 10 months | | Global Assessment of Functioning - Symptoms (GAF-S) | Observer rating scale used to assess the degree of symptoms. Scoring range: 1-100, higher scores reflect better outcome. | Change from baseline to end-of-treatment after approximately 10 months | | Global Assessment of Functioning - Functioning (GAF-F) | Observer rating scale used to assess the degree of social and psychological functioning. Scoring range: 1-100, higher scores reflect better outcome. | Change from baseline to end-of-treatment after approximately 10 months | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Post Traumatic Stress Disorder, Refugees, Cross-sectoral collaboration, Treatment

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Radiation Therapy With Concomitant and Adjuvant Temozolomide Versus Radiation Therapy With Adjuvant PCV Chemotherapy in Patients With Anaplastic Glioma or Low Grade Glioma Study Overview ================= Brief Summary ----------------- Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving radiation with concomitant and adjuvant temozolomide versus radiation with adjuvant PCV is more effective in treating anaplastic glioma or low grade glioma. Detailed Description ----------------- This study will be a randomized phase III for patients with newly diagnosed co-deleted 1p/19q anaplastic glioma or high risk low grade glioma. The trial will only enroll patients with 1p/19q co-deletion. This study includes two arms as described in the Arms section. A dynamic allocation procedure will be used to allocate an equal number of patients to different arms (Arms A:B = 1:1). This procedure will balance the marginal distributions of the stratification factors among arms. The stratification factors that will be used are cooperative groups (EORTC vs. all North American groups), age (≤ 50 vs. > 50), performance score (ECOG 0-1 vs. 2), and tumor grade (anaplastic glioma vs. low grade glioma). The primary goal is to determine whether patients who receive radiotherapy with concomitant temozolomide (TMZ) followed by adjuvant temozolomide (RT + TMZ --> TMZ) (Arm B) have a marginally better progression free survival (PFS) as compared with patients who receive radiotherapy followed by PCV chemotherapy (RT --> PCV)(Arm A). Secondary Goals: Time to Progression - To determine whether patients who receive (RT + TMZ --> TMZ) have a significantly longer time to progression (clinical or radiographic progression) as compared with patients who receive radiotherapy followed by adjuvant PCV chemotherapy (RT --> PCV). Correlation between exploratory biomarkers and survival - To determine whether there is a difference in survival based on t(1;19)(q10, p10) translocation status and MGMT promoter hypermethylation status. Descriptive Comparisons of Additional Secondary Endpoints - To perform descriptive comparisons of additional secondary outcome endpoints, including overall survival, objective tumor response, prognostic factor analysis and quality of life. Toxicity - To determine the toxicity of the treatment in each arm and perform descriptive comparisons. Neurocognitive and Quality of Life (QOL) Effects - To determine the neurocognitive and QOL effects in patients treated on this protocol and correlate these results with outcome endpoints. Banking of Biospecimens and Neuroimaging Studies - To store blood products (i.e., plasma, DNA and buffy coat), tumor tissue and MRI/CT images for future scientific investigations. After completion of study treatment, patients are followed every 12 weeks for 1 year, then every 4 months for 2 years and then every 6 months until progressive disease or until the end of study participation. Official Title ----------------- Phase III Intergroup Study of Radiotherapy With Concomitant and Adjuvant Temozolomide Versus Radiotherapy With Adjuvant PCV Chemotherapy in Patients With 1p/19q Co-deleted Anaplastic Glioma or Low Grade Glioma Conditions ----------------- Brain and Central Nervous System Tumors Intervention / Treatment ----------------- * Drug: concomitant temozolomide (TMZ) * Radiation: radiotherapy * Drug: procarbazine * Drug: adjuvant temozolomide (TMZ) * Drug: CCNU * Drug: vincristine Participation Criteria ================= Eligibility Criteria ----------------- Pre-Registration Inclusion Criteria: United States (US) and Canadian sites: * This review is mandatory prior to registration to confirm eligibility; patients must be willing to submit tissue samples for mandatory central pathology review submission; it should be initiated as soon after surgery as possible Tissue must have been determined to have local 1p/9q co-deletion and IDH mutation prior to submission for central path review Tumor tissue must show co-deletion of chromosomes 1p and 19q; for eligibility, the 1p/19q analysis results will be accepted from the local site, as determined by either a locally available or reference laboratory (for US, must be Clinical Laboratory Improvement Act [CLIA] certified); acceptable methods for determination of 1p/19q loss include fluorescent in-situ hybridization (FISH), by genomic sequencing or methylomic analyses; US and Canadian sites must send a copy of the official report to the pathology coordinator and quality assurance specialist (QAS) Tumor must also show evidence of IDH mutation by immunohistochemistry or genomic analyses; this should be performed at the local site (US: performed in a CLIA certified laboratory); the site must send a copy of the official report to the pathology coordinator and QAS Registration Inclusion Criteria: Newly diagnosed and =< 3 months from surgical diagnosis; patients are also eligible if they have had a prior surgical procedure > 3 months earlier for low grade glioma, as long as the patient has not received prior radiation or prior chemotherapy Histological evidence of World Health Organization (WHO) grade III anaplastic glioma or WHO grade II low grade glioma with locally diagnosed combined 1p/19q loss and the presence of an either IDH1 or IDH2, both as established by a local or referenced laboratory qualified for the study * Note: mixed gliomas are eligible, regardless of the degree of astrocytic or oligodendrocytic predominance, as long as the tumor is also co-deleted for 1p and 19q Patients with codeleted low grade gliomas must also be considered high risk by exhibiting one or more of the following characteristics: Age >= 40 and any surgical therapy Age < 40 with prior and subtotal resection or biopsy (i.e., anything less than gross total resection) Documented growth following prior surgery (NOTE: patients with prior surgery cannot have received prior radiation, chemotherapy or targeted therapy) Intractable seizures Surgery (partial or gross total resection or biopsy) must be performed >= 2 weeks prior to registration; patient must have recovered adequately from the effects of surgery Absolute neutrophil count (ANC) >= 1,500/mm^3 obtained =< 21 days prior to registration Platelet (PLTs) count >= 100,000/mm^3 obtained =< 21 days prior to registration Hemoglobin (Hgb) > 9.0 g/dL obtained =< 21 days prior to registration Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) obtained =< 21 days prior to registration Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 3 x ULN obtained =< 21 days prior to registration Creatinine =< 1.5 x ULN obtained =< 21 days prior to registration Negative serum or urine pregnancy test done =< 7 days prior to registration, for women of childbearing potential only Willingness and ability to personally complete neurocognitive testing (without assistance) and willingness to complete the QOL testing, (either personally or with assistance) Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1 or 2 Written informed consent Willingness to return to enrolling institution for follow-up during the active monitoring phase (that is, the active treatment and observation portion) of the study); patients who have been formally transferred to another active and approved site participating in this study would not need to return to the enrolling institution for this purpose Willingness to allow the provision of tissue samples for correlative research, as long as adequate tissues are available; patients will not be excluded from participation in the study, if they are willing to allow provision of tissues for the correlative research, but there are insufficient quantities of tissue for the correlative analyses (e.g., a patient otherwise eligible and willing who had biopsy only) Willingness to allow the provision of blood samples for correlative research; patients are not excluded from participation in the study, if they are willing to provide the mandatory biospecimens for translational/correlative research, but for logistical reasons the specimens(s) were not obtainable or if the volume collected was insufficient Registration Exclusion Criteria: The following categories are ineligible: Pregnant women Nursing women Men or women of childbearing potential who are unwilling to employ adequate contraception or contraceptive method during this study and 6 months following the completion of chemotherapy treatments History of prior radiation therapy or chemotherapy for glioma; note: patients who have a history of prior low grade glioma (with or without a distant history of prior surgery for that glioma), but who have never received prior chemotherapy or radiation therapy for the glioma are eligible for the study Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens Concomitant serious immunocompromised status (other than that related to concomitant steroids) that would compromise the safety of the patient on the study Patients known to be human immunodeficiency virus (HIV) positive and currently receiving retroviral therapy are not eligible; note: patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for the study Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Receiving any other investigational agent that would be considered as a treatment for the primary neoplasm Other active malignancy within 5 years of registration; exceptions: non-melanotic skin cancer or carcinoma-in-situ of the cervix; note: if there is a history of prior malignancy, the patient is not eligible if they are receiving other specific treatment (with the exclusion of hormonal therapy or Her-2 inhibitors) for their cancer or if they have received prior total body irradiation which included the brain History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias Recent history of hepatitis infection or if the treating physician determined that the patient would be at significant risk of reactivation of hepatitis Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Arm A (RT, procarbazine, lomustine, vincristine)<br>Patients undergo 3D-CRT or IMRT on days 1-5 for 5-7 weeks. Patients also receive procarbazine hydrochloride PO on days 8-21, lomustine PO on day 1 and vincristine sulfate IV on days 8 and 29 of courses 3-8. Treatment repeats every 6-7 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. | Radiation: radiotherapy<br> <br> Drug: procarbazine<br>* Days 8-21: 60 mg/m^2 orally<br>Drug: CCNU<br>* Day 1: 110 mg/m^2 orally<br>Drug: vincristine<br>* Days 8 and 29: 1.4 mg/m^2 IV<br>| | Experimental: Arm B (RT, temozolomide)<br>Patients undergo RT as in arm I and receive temozolomide PO QD on days 1-5 for 5-7 weeks. Beginning 4 weeks after completion of concurrent chemoradiotherapy, patients receive adjuvant temozolomide PO QD days 1-5. Treatment with adjuvant temozolomide repeats every 4 weeks for 6-12 courses in the absence of disease progression and unacceptable toxicity. | Drug: concomitant temozolomide (TMZ)<br>* 75 mg/m^2, orally daily<br>Radiation: radiotherapy<br> <br> Drug: adjuvant temozolomide (TMZ)<br>* 150 or 200 mg/m^2 orally<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Progression-free survival | The distribution of progression free survival for Arms A and B will be estimated using the Kaplan-Meier method. The hazard ratios and median progression free survival (PFS) will be estimated with their confidence intervals. The Cox proportional hazards model will be used to assess whether the distributions of progression survival times differ with respect to treatment regimen having adjusted for all stratification factors (cooperative groups, age, and performance score). Both non-inferiority and superiority will be tested in this trial for the primary goal and no multiple-comparison adjustment will be considered. | Time from study registration to time of tumor progression or death due to any cause, whichever comes first, assessed up to 16 years | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Time to progression | Estimated by Kaplan-Meier method and analyzed by Cox regression model adjusting all stratification factors. Correlations among baseline neurocognitive test scores and progression free survival will be analyzed using Cox proportional hazards model. | Time from study registration to the earliest evidence of clinical progression, radiographic progression or neurocognitive progression, assessed up to 16 years | | Time to neurocognitive progression, assessed using the Hopkins Verbal Learning Test-Revised for Free Recall, Delayed Recall, and Delayed Recognition; the Controlled Oral Word Association test; and the Trail Making Test Part A or B | Estimated by Kaplan-Meier method and analyzed by Cox regression model adjusting all stratification factors. For each test in the battery, a standard error of measurement will be used to derive the Reliable Change Index (RCI) which will be used to represent the 90% confidence interval for the difference in raw scores from baseline to follow-up assessment will be coded as 1 (deterioration), 2 (no change), and 3 (improved) according to the RCI. | Time from study registration to the first cognitive failure, assessed up to 16 years | | Overall survival | The Cox proportional hazards model will be used to assess whether the distributions of overall survival times differ with respect to treatment regimen having adjusted for all stratification factors (cooperative groups, age, and Performance Score). The distribution of overall survival for Arm A and B will be estimated using the Kaplan-Meier method. The hazard ratios and median survivals will be estimated with their 95% confidence intervals. | Time from study registration to time of death due to any cause, assessed up to 16 years | | Objective tumor response defined as a complete response or partial response | Summarized for each arm and compared between the arms using the Chi square test. | Up to 16 years | | Treatment-related adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 | The maximum grade for each type of treatment-related adverse event will be recorded for each patient, and frequency tables for each arm will be reviewed to determine patterns. In addition, will review all adverse event data that is graded as 3, 4, or 5 and classified as either unrelated or unlikely to be related to study treatment in the event of an actual relationship developing. Adverse events and treatment-related adverse events will be evaluated using all patients. Treatment-related adverse events will be tabulated for each arm. | Up to 16 years | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- adult anaplastic astrocytoma, adult anaplastic oligodendroglioma, adult mixed glioma

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Phase 1 TheraSphere + Everolimus With Neuroendocrine Tumors (NETs) + Liver Only or Liver Dominant Disease Study Overview ================= Brief Summary ----------------- The goal of this clinical research study is to find the highest tolerable dose of the combination of everolimus with TheraSphere that can be given to patients with advanced NETs that have spread to the liver. The safety of everolimus and TheraSphere will also be studied. Everolimus is designed to block a protein inside the cancer cells, which is also involved in cancer growth. TheraSphere is a medical device containing a radioactive material called yttrium-90 (Y-90). Tiny glass beads called microspheres are filled with Y-90 and then injected through an artery directly into the liver. This allows a large dose of radiation to be given directly to the tumor, which may lower the risk of side effects from the radiation to other parts of the body and/or to healthy liver tissue. The radiation from TheraSphere stays in the body and begins to lose its effect within 12 days. The glass microspheres will stay in the body from that point on. The radiation will eventually decay (go away). By the time a participant leaves the hospital, the amount of radiation outside of the body will be low enough to not be a threat to others. Detailed Description ----------------- Study Groups: If patient is are found to be eligible to take part in this study, they will be assigned to a dose level of everolimus based on when they joined this study. Up to 3 dose levels of everolimus will be tested. Up to 6 participants will be enrolled at each dose level. The first group of participants will receive the low dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. If intolerable side effects are seen, the dose may be lowered. This will continue until the highest tolerable dose of everolimus is found. After that, 10 additional participants will be enrolled at the highest tolerable dose that was found. All participants will receive the same dose level of TheraSphere. Study Drug Administration: Each study cycle is 28 days. On Day 1 of Cycle 1, 2 weeks before the TheraSphere procedure, patient will start taking everolimus. Patient will take 1-2 tablets of everolimus by mouth 1 time every day. Patient will take the everolimus tablets with a glass of water in the morning at the same time every day. The tablets should be swallowed whole and not chewed or crushed. The tablets may be taken either always with or always without food. If patient vomits after taking their dose, they should not take another tablet that day. It is very important that patients take the tablets given to them just as the study doctor tells them and that they do not miss any tablets. If patient does forget to take it one day, they should not take any extra doses the next day. Instead, patient should contact their doctor and ask for advice. On the days of patient's study visits, they should take their dose of everolimus at the clinic, not at home. TheraSphere Administration: About 2 weeks before the TheraSphere procedure, patient will have an angiogram. An angiogram is an imaging test that uses contrast dye to help the doctor look at the body's blood vessels. Patient will be given drugs by vein in their arm or hand to help them relax, but patient will stay awake during the procedure. An area in patient's groin will be numbed with anesthetic. During the procedure, the doctor will insert a catheter into a blood vessel in patient's groin that leads to their liver. Dye will be injected into the catheter, and a series of x-rays will be taken that will allow the doctor to see the blood vessels in patient's liver. At the end of the procedure, the catheter will be removed from patient's groin area. The x-rays taken will be looked at by patient's doctor to plan for their TheraSphere procedure. The angiogram procedure should take about 1½ to 3 hours. On Day 15 of Cycle 1, patient will receive TheraSphere. Before the procedure, patient will be given drugs by vein in their arm or hand to help them relax, but patient will stay awake during the procedure. An area in patient's groin will be numbed with anesthetic. Patient may ask the study staff for information about how the anesthesia drugs are given and their risks. The doctor will insert a catheter into a blood vessel in patient's groin that leads to their liver. Based on the planning from patient's angiogram procedure, the doctor will guide the catheter to the target blood vessel. Once the catheter is in the proper blood vessel, the TheraSphere microspheres containing Y-90 will be injected into the catheter to reach the tumor in the liver. After the TheraSphere microspheres are injected, the catheter will be removed from patient's groin. The entire procedure will take about 1½ to 3 hours. After receiving the TheraSphere microspheres, patient will stay in the recovery area for several hours so that the staff can check patient for possible side effects. If patient has any serious side effects, they may be admitted to the hospital to be checked on and for treatment, if needed. Study Visits: Before all visits, patient must fast starting at midnight the night before. On Day 1 of Cycle 1, if the tests have not been done in the last 5 days: Patient will have a physical exam, including measurement of their weight and vital signs. Patient will be asked about any symptoms they may have had and any drugs they may be taking. Patient's performance status will be recorded. Blood (about 4 tablespoons) will be drawn for routine tests and tumor marker testing. Urine will be collected for routine tests. If patient's doctor thinks it is needed, blood (about 2 teaspoons) will be drawn to check for hepatitis B and/or C. On Day 14 or 15 of Cycle 1: Patient will have a physical exam, including measurement of their weight and vital signs. Patient will be asked about any side effects they may have had. Patient's performance status will be recorded. Blood (about 3 tablespoons) will be drawn for routine tests. On Day 1 of Cycles 2 and beyond: Patient will have a physical exam, including measurement of their weight and vital signs. Patient will be asked about any side effects they may have had and any drugs they may be taking. Patient's performance status will be recorded. Blood (about 1 tablespoon) will be drawn for routine tests. On Day 1 of Cycles 2 and 3 and every 3-6 weeks after that, blood (about 2 teaspoons) will be drawn to check for hepatitis B and/or C if the doctor thinks it is needed. On Day 1 of Cycles 2, 4, and every 3 cycles after that, blood (about 2 tablespoons) will be drawn for tumor marker testing and additional routine tests. On Day 1 of Cycles 4 and beyond, urine will be collected for routine tests. On Day 1 of Cycle 4 and every 3 cycles after that, patient will have a CT scan, MRI, and/or x-ray to check the status of the disease. Length of Dosing: Patient will receive TheraSphere on Day 15 of Cycle 1 and they may continue taking everolimus for up to 12 cycles, as long as the doctor thinks it is in patient's best interest. Patient will no longer be able to take everolimus if the disease gets worse, if intolerable side effects occur, or if they are unable to follow study directions. Patient's participation on the study will be over once they have completed the follow-up. End-of-Dosing Visit: Within 1 week after patient stops taking the study drug, the following tests and procedures will be performed. Patient must fast starting at midnight the night before this visit. Patient will have a physical exam, including measurement of their weight and vital signs. Patient will be asked about any side effects they may have had. Patient's performance status will be recorded. Blood (about 3 tablespoons) will be drawn for routine tests and tumor marker testing. This blood draw will include a pregnancy test if patient can become pregnant. Urine will be collected for routine tests. Patient will have a CT scan, MRI, and/or x-ray to check the status of the disease. Follow-up: At least 1 time a week by phone or at the clinic for up to 30 days after patient's last everolimus dose, the study staff will follow up with patient. Patient will be asked about any side effects they may have had. The call should last about 10-15 minutes. If patient left the study because of a side effect, they will continue to be contacted by the study staff until the side effect has gone away or become stable. This is an investigational study. Everolimus is commercially available and FDA approved to treat advanced pancreatic NETs and other types of cancer. The combination of everolimus and TheraSphere in this study is investigational. TheraSphere is commercially available and FDA approved as a radiation treatment for liver cancer. The use of TheraSphere in this study is investigational. Up to 22 participants will be enrolled in this study. All will take part at MD Anderson. Official Title ----------------- Phase I Study of TheraSphere and Everolimus Among Patients With Neuroendocrine Tumors and Liver Only or Liver Dominant Disease Conditions ----------------- Liver Cancer Intervention / Treatment ----------------- * Other: TheraSphere * Drug: Everolimus * Other: Phone Call Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: All patients must sign an informed consent indicating that they are aware of the investigational nature of this study. Patients must have histologically or cytologically confirmed low or intermediate grade neuroendocrine tumor, for which standard curative measures do not exist. Patients with neuroendocrine tumors associated with multiple endocrine neoplasia type 1 (MEN1 syndrome) will be eligible. Patients must have liver-only or liver-dominant disease. Patient deemed suitable for TheraSphere therapy after review of anatomic imaging by an Interventional Radiologist. No prior biliary enteric anastomosis. Intact portal vein and hepatic artery. Age >/= 18 years of age. World Health Organization (WHO) performance status of 0 or 1. Patients must have normal organ and marrow function as defined below: a) leukocytes >/= 3,000/mcL; b) absolute neutrophil count >/= 1,500/mcL; c) hemoglobin >/= 9 g/dL*; d) platelets >/= 100,000/mcL; e) total bilirubin </= 1.5 X upper limit of normal (ULN); f) AST (SGOT) and ALT (SGPT) </= 1.5 X institutional ULN (5x if liver function test [LFT] elevations due to liver metastases); g) creatinine </= 1.5 X institutional ULN OR creatinine clearance > 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal. *Eligibility level for hemoglobin may be reached by transfusion. The patient must have fasting serum glucose </= 1.3 X upper limit of normal. Fasting serum cholesterol </= 300 mg/dL OR </= 7.75 mmol/L AND fasting triglycerides </= 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication. The effects of TheraSphere and everolimus on the developing human fetus are unknown. For this reason, women of child-bearing potential must agree to use highly effective contraception from the time of study enrollment continuing for the duration of study therapy and for 8 weeks after the last dose of TheraSphere and/or everolimus. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective contraception during the study and for 8 weeks after stopping treatment. Highly effective contraception is defined as either: 1) Total abstinence: When this is in line with the preferred and usual lifestyle of the subject. [Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.]; Continuation of # 12: 2) Sterilization: have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment; 3) Male partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate). [For female subjects on the study, the vasectomised male partner should be the sole partner for that subject.]; 4) Use of a combination of any two of the following (a+b or a+c or b+c): a. Use of oral, injected, implanted or other hormonal methods of contraception; b. Placement of an intrauterine device (IUD) or intrauterine system (IUS); c. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository. Continuation of # 13: In case of use of oral contraception, women should have been stable on the oral agent before taking study treatment. Sexually active males must use a condom during intercourse while taking the drug and for 8 weeks after stopping treatment and should not father a child in this period. A condom is required to be used also by vasectomised men in order to prevent delivery of the drug via seminal fluid. Female partners of male patients must also be advised to use one of the following contraception methods: Use of (1) oral, injected, implanted or other hormonal methods of contraception, or (2) intrauterine device (IUD) or intrauterine system (IUS), or (3) prior male/female sterilization. Women of childbearing potential must have a serum pregnancy test within 7 days prior starting study treatment. Patients must have at least one measurable site of disease according to RECIST in liver. Patients may have received prior systemic anti-neoplastic therapy. There are no limitations on the number of prior regimens. At least 28 days must have elapsed since last treatment. Prior somatostatin analogs use is allowed. The patients on 3 months of stable dose of concurrent somatostatin analogs will be allowed to continue while on study treatment. Patients must have international normalized ratio (INR) </= 1.5. Exclusion Criteria: Patients may not be receiving any other treatment-related investigational agents. Uncontrolled intercurrent illness including but not limited to: a) ongoing or active infection requiring parenteral therapy at the time of study registration; b) liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class B or C) Note: A detailed assessment of Hepatitis B/C medical history and risk factors must be done at screening for all patients. Testing required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection; c) symptomatic congestive heart failure resulting in a resting O2 saturation of < 92% on room air; d) unstable angina or pectoris myocardial infarction within 6 months of start of study drug; e) serious uncontrolled cardiac arrhythmia; f) known severely impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or oxygen saturation that is 88% or less at rest on room air. Pulmonary function test (PFT) is not required at study entry. Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, etc.). Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study. Patients who previously received liver directed therapy, with either radiofrequency ablation (RFA), transarterial hepatic embolization (TACE) with or without chemotherapy must have >/= 60 days elapsed since last treatment. A known history of human immunodeficiency virus (HIV) seropositivity. Chronic treatment with systemic steroids or another immunosuppressive agent. Female patients who are pregnant or breast feeding, or of reproductive potential who are not using effective birth control methods. Patients with a known history of allergic reactions and/or hypersensitivity attributed compounds of similar chemical or biologic composition to everolimus or other rapamycins (sirolimus, temsirolimus). Known history of brain or leptomeningeal metastases. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study. Patients who have had hormonal therapy (other than replacement) within 4 weeks prior to entering the study. Not recovered from adverse events related to previous treatment (excluding alopecia) to active Common Terminology Criteria for Adverse Events (CTCAE) Ver. 4 </= grade 1. With the exception of tumor common to a single genetic cancer syndrome (ie MEN1, MEN2, von Hippel-Lindau [vHL], tuberous sclerosis complex [TSC] etc), patients with evidence of more than one active malignancy are excluded. Active malignancy is defined as the presence of primary, regional nodal, or distant metastatic neoplasm that has not undergone definitive therapy. The patient has poorly controlled diabetes mellitus. Patients with a history of diabetes mellitus are allowed to participate, provided that their blood glucose is within 1.3 X institutional upper limit of normal and that they are on a stable dietary or therapeutic regimen for this condition. Patients who have received prior treatment with everolimus or an mTOR inhibitor (sirolimus, temsirolimus, everolimus). Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: TheraSphere + Everolimus<br>Each cycle is 28 days. Target dose of TheraSphere is fixed at 120 Gy to entire tumor bearing portion of liver given at a single session on Cycle 1 Day 15. The dose of everolimus will be escalated in 2 sequential cohorts of 6 TheraSphere-treated patients each. Starting dose of everolimus is 5 mg by mouth daily for cycles 1 and 2. Patients will receive standard dose of Everolimus at 10 mg PO daily starting cycle 3 day 1. Once DLT is defined or dose level 2 has been completed, a dose expansion cohort of 10 patients with advanced low to intermediate grade neuroendocrine tumor will be enrolled. At least 1 time a week by phone or at the clinic for up to 30 days after last everolimus dose, study staff will follow up. Patient asked about any side effects they may have had. | Other: TheraSphere<br>* TheraSphere glass microspheres containing Y-90 injected into catheter, and will deliver 120 Gy to entire tumor bearing portion of the liver given at a single session on Cycle 1 Day 15.<br>Drug: Everolimus<br>* Starting dose: is 5 mg by mouth daily for cycles 1 and 2. Patients will receive standard dose of Everolimus at 10 mg by mouth daily starting cycle 3 day 1. Dose Expansion Cohort Starting Dose: Maximum tolerated dose from dose escalation cohort.<br>* Other names: RAD001;Other: Phone Call<br>* At least 1 time a week by phone or at the clinic for up to 30 days after last everolimus dose, study staff will follow up. Patient asked about any side effects they may have had. The call should last about 10-15 minutes.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Dose Limiting Toxicities (DLT) for Combination of TheraSphere and Everolimus | Dose limiting toxicity (DLT) defined as any toxicity occurring during the first 56 days of therapy with definite, possible or probable attribution to TheraSphere and/or Everolimus and meets CTCAE version 4.0 criteria. | 56 days | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Liver dominant disease, Liver cancer, Neuroendocrine tumors, NET, TheraSphere, Yttrium-90, Y-90, Everolimus, Afinitor, Zortress, RAD001, Microspheres

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Trehalose in Subjects With Neuronal Ceroid Lipofuscinoses Study Overview ================= Brief Summary ----------------- Neuronal Ceroid Lipofuscinoses (NCL) or Batten's disease are the most common juvenile neurodegenerative disease, characterized by early blindness, movement disorders, cognitive and behavioral impairment, epilepsy, and retinopathy. This study aims to collect clinical and laboratory data of patients with NCL taking Trehalose. Detailed Description ----------------- This study aims to collect clinical and laboratory data of patients with NCL taking Trehalose. Official Title ----------------- A Study in Subjects With Neuronal Ceroid Lipofuscinoses Taking Trehalose Conditions ----------------- Neuronal Ceroid-Lipofuscinoses Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: NCL genetic diagnosis (mutation in genes CLN3 or CLN6) Signed informed consent Exclusion Criteria: Other concomitant neurodegenerative diseases. Therapeutic and eating changes in the last four months prior to the study Unstable clinical conditions (myoclonus worsening, instability in sleep, parenteral nutrition) Refusal to sign the informed consent Ages Eligible for Study ----------------- Minimum Age: 7 Years Maximum Age: 45 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change from Baseline clinical status assessed using Annex VII of the Unified Batten Disease Rating Scale (UBDRS) (score 0-5 where 5 is the worst outcome) at 12 and 24 months | Blood samples | month 0, month 12, month 24 | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change from Baseline using Annex VII of Unified Batten Disease Rating Scale (UBDRS) (score 0-5 where 5 is the worst outcome) at 12 and 24 months | Blood samples | month 0, month 12, month 24 | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Juvenile Neuronal Ceroid-Lipofuscinoses, Unified Batten Disease Rating Scale

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Genetic Testing to Understand and Address Renal Disease Disparities Across the United States Study Overview ================= Brief Summary ----------------- The primary aim is to determine the effect of participant and provider knowledge of a positive APOL1 status and accompanying guideline based clinical decision support (CDS) on blood pressure management on change in systolic blood pressure (SBP) from baseline to 3 months after randomization among the APOL1 positive participants. Secondary aims are to: Determine the effect of participant and provider knowledge of a positive APOL1 status on the probability of appropriate CKD diagnosis. Determine the effect of participant and provider knowledge of a positive APOL1 status on the probability of receiving a urine microalbumin/creatinine testing and ACE-I/ARB prescription based on results of the urine microalbumin level. Explore cost effectiveness, mediators, moderators, psychobehavioral impact of results disclosure on participants, and effects of participant and provider knowledge of APOL1 status on provider treatment recommendations. PGX Substudy In addition, GUARDD-US will include a substudy to determine the effect of knowledge of genetic test results that predict efficacy of various antihypertensive medications on change in SBP from baseline to 3 months in APOL1 negative individuals. Approximately 6,650 participants of African ancestry age 18-70 with hypertension that either: 1) do not have diabetes and do not have CKD, or 2) have CKD. Participants with diabetes may be included as long as they also have CKD. Population for Main Study: Participants from Randomized Population (above) who test positive for APOL1 Population for PGx Substudy: Participants from Randomized Population (above) randomized to Intervention and who test negative for APOL1 Main Study Analyses: To determine the effect of participant and provider knowledge of a positive APOL1 status on SBP, we will compare the change in SBP from baseline to 3 months of the Intervention - APOL1 positive group to the change in SBP from baseline to 3 months of the Control - APOL1 positive group using a two sided t-test, as appropriate, with a two-sided type I error of 0.05. The effect of knowledge of a positive APOL1 status on all secondary endpoints will be compared between Intervention - APOL1 positives to Control - APOL1 positives with the proportion difference test. Additional analyses will include analysis of time trends in SBP, subset analyses, and exploratory analyses of cost effectiveness, mediators, moderators, psychobehavioral impact of results disclosure on participants, and effects of knowledge of APOL1 status on provider treatment recommendations. Substudy Analyses: All primary and secondary endpoint analyses conducted for the APOL1 main study will be repeated for the PGx substudy focusing on differences in outcomes between APOL1 negative individuals with immediate PGx ROR (PGx Intervention) and APOL1 negative individuals with delayed PGx ROR (PGx Control). Official Title ----------------- Genetic Testing to Understand and Address Renal Disease Disparities Across the United States Conditions ----------------- Renal Disease Intervention / Treatment ----------------- * Diagnostic Test: APOL1 status Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Self reported African ancestry English Speaking Age 18-70 years Have diagnosis of hypertension Diagnosis of hypertension is defined by either: ICD10 diagnosis codes (i.e., I10; I11.x; I12.x; I13.x; I16.x) OR On active antihypertensive therapy for indication of hypertension OR Having systolic blood pressure of 140 mm Hg or greater in at least 2 of the last 3 consecutive recorded values in the EHR OR Having hypertension in the patient's medical record problem list Have been seen at ≥1 time in past year at a participating primary care site Either: 1) do not have diabetes and do not have CKD, or 2) have CKD; Participants with diabetes may be included as long as they also have CKD. CKD is defined by either: 1) ICD10 codes (i.e., N18.x; E08.22; E09.22; E10.22; E11.22;E13.22 (exclude Z94.0; N18.6; Z99.2)) OR 15 ≤ eGFR ≤ 60 ml/min for 2 time periods ≥ 3 months Diabetes is defined by: HbA1c ≥ 6.5 at least one time in the last year OR ICD10 diagnosis codes (see Appendix A) OR Having diabetes in the patient's medical record problem list Exclusion Criteria: Have diabetes, but no CKD. Are currently on dialysis (ICD 10 codes N18.6, Z99.2 and Z94.0) Have ESRD (eGFR<15 ml/min) Have a left ventricular assist device (LVAD) Have a terminal illness Have patient-reported known pregnancy at time of enrollment Have had a liver, kidney, or bone marrow transplant Too cognitively impaired to provide informed consent and/or complete the study protocol Institutionalized or too ill to participate (i.e. incarcerated, psychiatric or nursing home facility) Plan to move out of the area within 6 months of enrollment Not a current patient seeing a provider who cares for their hypertension (i.e., family medicine, internal medicine, nephrology, HIV provider, cardiology, hypertension specialists) at a participating site Previously participated in the GUARDD pilot study OR have previously undergone APOL1 testing Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 70 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: Immediate versus delayed return of Apolipoprotein L1 (APOL1) gene testing results to provider and participant. Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Immediate Return of Results<br>Immediate return of results to inform participant of APOL1 status (either positive or negative). | Diagnostic Test: APOL1 status<br>* Participants will be randomized to immediate versus delayed return of results for positive or negative APOL1 status.<br>| | Active Comparator: Delayed Return of Results<br>Delayed return of results of APOL1 status (either positive or negative) after the completion of the 6 month final study visit. | Diagnostic Test: APOL1 status<br>* Participants will be randomized to immediate versus delayed return of results for positive or negative APOL1 status.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in systolic blood pressure from baseline to 3 months | Change in systolic blood pressure | Baseline to 3 month study visit | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in urine microalbuminuria/proteinuria | Change in urine microalbuminuria/proteinuria | From baseline to 6 months | | Appropriate order of microalbuminuria/proteinuria tests | Appropriate order of microalbuminuria/proteinuria tests | baseline to 6 months | | Change in appropriate diagnosis for stage 3 CKD | Change in appropriate diagnosis for stage 3 CKD | baseline to 6 months | | Appropriate diagnosis of CKD stage 3 and above | Appropriate diagnosis of CKD stage 3 and above | baseline to 6 months | | Change in appropriate diagnosis for any stage CKD | Change in appropriate diagnosis for any stage CKD | Baseline to 6 months | | Appropriate diagnosis of all stage CKD | Appropriate diagnosis of all stage CKD | Baseline to 6 months |

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Study to Compare the Triple ACT AL+AQ With the ACT AL in Cambodia and Vietnam Study Overview ================= Brief Summary ----------------- This study is a multi-centre, open-label randomised trial to assess the efficacy, safety and tolerability of the Triple ACT artemether-lumefantrine+amodiaquine (AL+AQ) compared to the ACT artemether-lumefantrine (AL) in uncomplicated falciparum malaria in Cambodia and Vietnam. The estimated total sample size is 600 patients from 2 sites in Cambodia and 2 sites in Vietnam. There are 2 treatment arms Arm 1: Artemether-lumefantrine for 3 days Arm 2: Artemether-lumefantrine for 3 days plus Amodiaquine for 3 days. According to the World Health Organization guideline, all patients except children under 10 kilograms will also be treated with a single dose of primaquine as a gametocytocidal treatment. Funder :Bill & Melinda Gates Foundation (BMGF) Grant reference number: OPP1132628 Detailed Description ----------------- The study of artemether-lumefantrine or artemether-lumefantrine combined with amodiaquine will be a two-arm randomized open label comparative study. The main activity proposed is a series of detailed in vivo clinical, parasitological and pharmacological assessments in 600 subjects across 2 sites in Cambodian (400 subjects) and 2 sites in Vietnam (200 subjects). The subjects will be randomized between the ACT artemether-lumefantrine and the TACT artemether-lumefantrine+amodiaquine. Parasite clearance rates will be assessed by repeated assessments of the parasite counts after the start of the antimalarial treatments. Efficacy, safety and tolerability of ACTs and TACTs will be assessed through weekly follow up visits where vital signs, symptom questionnaires, physical examinations, blood smears, biochemistry assays and full blood counts will be performed. Ex vivo assessments of parasite susceptibility to artemisinins and partner drugs will be measured and compared to historical data, clinical phenotype and other sites in an effort to identify artemisinin and partner drug resistance. This study will obtain data on the effect of antimalarials on the corrected QT intervals. In addition, the effects of antimalarials on factors such as post-treatment haematocrit and haemoglobin levels will be assessed. Extensive pharmacokinetic analysis will allow for an assessment of drug-drug interactions. Plasma histidine-rich protein 2 (HRP2) levels (a marker of parasite biomass) that could potentially serve for the estimation of parasitaemia dynamics before and after treatment will be measured and subsequently modelled. Official Title ----------------- A Multi-centre, Open-label Randomised Trial to Assess the Efficacy, Safety and Tolerability of the Triple ACT Artemether-lumefantrine+Amodiaquine (AL+AQ) Compared to the ACT Artemether-lumefantrine (AL) in Uncomplicated Falciparum Malaria in Cambodia and Vietnam Conditions ----------------- Malaria, Falciparum Intervention / Treatment ----------------- * Drug: ACT * Drug: TACT Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Male or female, aged from 2 years to 65 years old Acute uncomplicated P. falciparum malaria, confirmed by positive blood smear with asexual forms of P. falciparum (or mixed with non-falciparum species) Asexual P. falciparum parasitaemia: 16 to 200,000/microlitre, determined on a thin or thick blood film Fever defined as > 37.5°C tympanic temperature or a history of fever within the last 24 hours Written informed consent (by parent/guardian in case of children) Willingness and ability of the patients or parents/guardians to comply with the study protocol for the duration of the study Exclusion Criteria: Signs of severe/complicated malaria Haematocrit < 25% or Hb < 8 g/dL at screening Acute illness other than malaria requiring treatment For females: pregnancy, breast feeding Patients who have received artemisinin or a derivative or an artemisinin-containing combination therapy (ACT) within the previous 7 days History of allergy or known contraindication to artemisinins, lumefantrine or amodiaquine Previous splenectomy corrected QT interval > 450 milliseconds at moment of presentation Documented or claimed history of cardiac conduction problems Previous participation in the current study or another study in the previous 3 months Ages Eligible for Study ----------------- Minimum Age: 2 Years Maximum Age: 65 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: open-label randomised trial Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: ACT<br>Artemether-lumefantrine for 3 days plus primaquine at hour 24 | Drug: ACT<br>* Artemether-lumefantrine (20/120 mg) as a fixed dose combination twice daily for 3 days according to weight plus low dose primaquine at hour 24<br>| | Experimental: TACT<br>Artemether-lumefantrine for 3 days plus Amodiaquine for 3 days plus primaquine at hour 24 | Drug: TACT<br>* Artemether-lumefantrine (20/120 mg) as a fixed dose combination twice daily for 3 days according to weight plus Amodiaquine (150mg) twice daily for 3 days according to weight plus low dose primaquine at hour 24<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Polymerase Chain Reaction Corrected Efficacy Defined as Adequate Clinical and Parasitological Response (ACPR) by Study Arm | Efficacy is defined as participants, following initial parasite and fever clearance, not having a recrudescence of the original plasmodium infection and fever, up to 42 days of follow up. | 42 days | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | 42-day Polymerase Chain Reaction Corrected Efficacy According to Site/Geographic Region | 42-day polymerase chain reaction corrected efficacy defined as adequate clinical and parasitological response (ACPR) according to site/geographic region. | 42 day | | Parasite Clearance Half-life | Parasite clearance half-life assessed by microscopy as primary parameter to determine parasite clearance | 42 day | | Fever Clearance Time | The time taken for the tympanic temperature to fall below 37.5˚C and remain there for at least 24 hours | 42 day | | Number of Severe Adverse Events by Study Arm | All numerators in AE tables mean that the AE was reported as present according to the definitions defined in the US government DAIDS 2017 grading tables for reporting of adverse events. The AEs are reported without grading in this table, but are graded in the paper reporting this clinical trial. All Primary analyses are reported (also in the accepted manuscript) along with the secondary outcomes needed to support the primary analysis. Secondary outcomes not involving the randomised comparison will be updated when the analyses are available. Please note that analyses of these Secondary outcomes will take time. | 42 days | | Incidence of Adverse Events Concerning Markers of Hepatic or Renal Toxicity | Total bilirubin, Alanine transaminase, Aspartate transaminase, Alkaline phosphatase and creatinine will be measured | 42 day | | Incidence of Prolongation of the Corrected QT Interval | We record the number of events where the QT interval exceeds 500ms or increases by 60ms or greater. | 28 day | | Prolongation of the Corrected QT Interval | We record the number of events where the QT interval exceeds 500ms or increases by 60ms or greater. There were zero events of this at any time point in either study arm. So no further analyses are possible. | Hour 4, Hour 24, Hour 28, Hour 48, Hour 52, Hour 60, Hour 64, Day 7 and Day 28 and between these time points | | Parasite Reduction Rates | Parasite reduction rates and ratios at 24 and 48 hours assessed by microscopy The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study. | 24 and 48 hours | | Parasite Count to Fall 50% | Time for parasite count to fall 50% of initial parasite density The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study. | 42 days | | Parasite Count to Fall 90% | Time for parasite count to fall 90% of initial parasite density The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study. | 42 days | | Parasite Count to Fall 99% | Time for parasite count to fall 99% of initial parasite density The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study. | 42 days | | Change in Haematocrit | Change in haematocrit at specified time points according to geographical location and study arm, stratified for G6PD status The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study. | Day 1 to 7, 14, 21, 28, 35, 42 | | Correlation Between the Host Genotype and the Pharmacokinetics and Pharmacodynamics of Antimalarials | Correlation between the host genotype and the pharmacokinetics and pharmacodynamics of antimalarials The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study. | 42 day | | Proportion of Patients That Reports Completing a Full Course of Observed TACT or ACT | Proportion of patients that reports completing a full course of observed TACT or ACT without withdrawal of consent or exclusion from study because of drug related serious adverse event The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study. | 42 day | | Prevalence of Kelch13 Mutations of Known Significance | Prevalence of Kelch13 mutations of known significance The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study. | 42 day | | Prevalence/Incidence of Other Genetic Markers of Antimalarial Drug Resistance Such as Multidrug Resistance Gene 1 Copy Number and Multidrug Resistance Gene 1 Mutations | Prevalence/incidence of other genetic markers of antimalarial drug resistance such as multidrug resistance gene 1 copy number and multidrug resistance gene 1 mutations The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study. | 48 hours | | Genome Wide Association With in Vivo/in Vitro Sensitivity Parasite Phenotype | Genome wide association with in vivo/in vitro sensitivity parasite phenotype The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study. | 42 day | | Correlation Between Single Nucleotide Polymorphisms and Whole Genome Sequencing | Correlation between single nucleotide polymorphisms measured in dry blood spots and whole genome sequencing in leukocyte depleted blood samples The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study. | 42 day | | A Comparison of Transcriptomic Patterns Between Sensitive and Resistant Parasites | Transcriptomic patterns measure at baseline and at specified time points after the start of treatment comparing sensitive and resistant parasites. The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study. | baseline and t = 6 hours | | Correlation Between Quantitative Polymerase Chain Reaction Based Versus Microscopy Based Assessments of Parasite Clearance Dynamics | Correlation between qPCR based versus microscopy based assessments of parasite clearance dynamics The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study. | 14 days | | Proportion of Patients With Gametocytaemia Before, During and After Treatment With TACT or ACT | Proportion of patients with gametocytaemia before, during and after treatment with TACT or ACT stratified by the presence of gametocytes at enrolment The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study. | At admission and up to day 14 | | Levels of RNA Transcription Coding for Male or Female Specific Gametocytes | Levels of RNA transcription coding for male or female specific gametocytes at admission up to day 14, stratified by the presence of gametocytes at enrolment The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study. | 14 days | | In Vitro Sensitivity of P. Falciparum to Artemisinins and Partner Drugs | In vitro sensitivity of P. falciparum to artemisinins and partner drugs according to study sites and genotype The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study. | At admission & subjects with recurrent parasitaemia, up to 42 days | | Pharmacokinetic Profiles and Interactions (Cmax) of Artemisinin-derivatives and Partner Drugs | Pharmacokinetic profiles and interactions (Cmax) of artemisinin-derivatives and partner drugs in 20 ACT treated and 20 TACT treated patients of both study arms in Vietnam The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study. | 42 days | | Pharmacokinetic Profiles and Interactions (AUC) of Artemisinin-derivatives and Partner Drugs | Pharmacokinetic profiles and interactions (AUC) of artemisinin-derivatives and partner drugs in 20 ACT treated and 20 TACT treated patients of both study arms in Vietnam The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study. | 42 days | | Day 7 Drug Levels of Partner Drugs in Association With Treatment Efficacy and Treatment Arm | Day 7 drug levels of partner drugs in association with treatment efficacy and treatment arm The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study. | 7 days | | Correlation Between Histidine-rich Protein 2 (HRP2) Based Versus Microscopy Based Assessments of Parasite Clearance Dynamics | Correlation between histidine-rich protein 2 (HRP2) based versus microscopy based assessments of parasite clearance dynamics The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study. | 42 days | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Malaria, Falciparum, Malaria, Protozoan Infections, Lumefantrine, Artemether, Amodiaquine, Piperaquine, Artemether-lumefantrine combination, Artemisinins, Dihydroartemisinin, Mefloquine, Artemisinin, Antimalarials, Antiparasitic Agents, Anti-Infective Agents, ACT, TACT, Triple ACT(s), Resistance, Antimalarial resistance, Cardiotoxicity, Safety, Tolerability, Efficacy

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Gastric Emptying of Water and Sports Drink in Labor Study Overview ================= Brief Summary ----------------- To determine the half time of the emptying of the stomach of women in early labor with and without epidural pain relief when drinking either water or a carbohydrate-based sports drink. Detailed Description ----------------- This is a randomized un-blinded study comparing the gastric emptying halftime of water versus a carbohydrate-based sports drink. Cohorts Women in early labor who have not received pain medication will be enrolled in the study. This will be called the 'unmedicated' group. A second cohort of women who have received an epidural in early labor will be enrolled and studied using identical methods. This will be the 'epidural' group. Study Intervention Subjects in each group will drink one of two drinks: water or sports drink. The changing volume in the stomach will be measured using ultrasound over the next 60 minutes. Subjects will be asked their degree of hunger on a 10-centimeter visual analogue scale prior to drinking, and for the next two hours at regular intervals. Subjects will be free to consume as per obstetric protocols. The study will be finished once the patient consumes food or drink, feels hunger ≥4/10, or two hours after the sports drink. Hypothesis The primary hypothesis is that water will empty faster than the sports drink. A second hypothesis is that women with epidural pain relief will have similar gastric halftimes as women without pain medications. Official Title ----------------- Examining the Gastric Emptying Halftime of Water Versus a Carbohydrate in Early Labor Conditions ----------------- Pregnancy, Gastric Emptying Intervention / Treatment ----------------- * Dietary Supplement: Sports drink * Dietary Supplement: Water Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Gestational age of 36 weeks or greater American Society of Anesthesiology Physical Status 2 or 3 Induction of labor or early labor (cervical dilation < 6cm) Singleton gestation Exclusion Criteria: Recent food ingestion (<3 hours) Preeclampsia Receiving magnesium sulfate Having received narcotics within 12 hours Diabetes mellitus Multiple gestations Active nausea or reflux symptoms Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 50 Years Sexes Eligible for Study ----------------- Female Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Other Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: Subjects in each group will drink one of two drinks: water or sports drink. We will measure the changing volume in the stomach using ultrasound over the next 60 minutes. Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Early labor, no analgesia: Sports drink<br>Subject will ingest 100 ml of a carbohydrate sports drink | Dietary Supplement: Sports drink<br>* Drink that will be ingested<br>| | Placebo Comparator: Early Labor, no analgesia: Water<br>Subject will ingest 100 ml of water | Dietary Supplement: Water<br>* Drink that will be ingested<br>| | Active Comparator: Early labor, analgesia: Sports drink<br>Subject will ingest 100 ml of a carbohydrate sports drink | Dietary Supplement: Sports drink<br>* Drink that will be ingested<br>| | Placebo Comparator: Early labor, analgesia: Water<br>Subject will ingest 100 ml of water | Dietary Supplement: Water<br>* Drink that will be ingested<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Gastric emptying half time | The time in minutes that half of the volume of the stomach has emptied | 60 minutes | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Hunger | The amount of hunger that the subject feels measured on a visual analogue 10-centimeter line, with the left (0 cm) being labeled 'No Hunger' and the right (10 cm) being labeled 'Maximum hunger' | 60 minutes |

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Quality of Life in Patients Undergoing Colorectal Resection for Deep Infiltrating Endometriosis Study Overview ================= Brief Summary ----------------- The aim of this study is to evaluate the quality of life of patients undergoing colorectal resection for deep infiltrating endometriosis of the bowel. Questionnaires about pre operative status have been submitted retrospectively, while post operative questionnaires have been submitted prospectively during last follow up visit Detailed Description ----------------- All patients fit for the study will be asked to complete a visual analogue scales (VAS) for dysmenorrhea, deep dyspaurenia, dysuria, dyschesia and chronic pelvic pain (CPP) Patients will fill in the Endometriosis QoL Questionnaire (EHP30), the gastrointestinal well-being questionnaires Bristol Stool Chart, GSCG (Gastrointestinal Symptom Rating Scale), STAY (1 and 2), the Psychological General Well-Being Index (PGWBI), Generalized Self-Efficacy, CD-RISC - Connor-Davidson scale about their pre operative and actual status. Surgery includes laparoscopic resection of all visible endometriosis, including resection of the affected bowel with primary anastomosis Perioperative and post-operative complications will be collected using the Extended Clavien-Dindo classification of surgical complications divided in early (within 30 days after surgery onset) and late (over 30 days after surgery onset). Official Title ----------------- Evaluation of Quality of Life and Gastrointestinal Well-being in Patients Undergoing Colorectal Resection for Deep Infiltrating Endometriosis. Retrospective Observational Cohort Study Conditions ----------------- Endometriosis Intervention / Treatment ----------------- * Procedure: colorectal resection Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Women aged between 18 and 45 years Clinical diagnosis of deep endometriosis infiltrating the bowel Women undergoing surgical removal with colorectal resection with or without loop ileostomy creation Exclusion Criteria: History of previous or ongoing neoplastic pathology Contraindications to surgical intervention Not complete eradicating surgery Psychiatric disorders Surgical, spontaneous or pharmacological menopause - Intestinal surgery different from segmental bowel resection and colorectal anastomosis Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 45 Years Sexes Eligible for Study ----------------- Female Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | colorectal resection arm<br>Patients affected by symptomatic deep infiltrating endometriosis involving the bowel and submitted to colo-rectal resection | Procedure: colorectal resection<br>* Surgery includes laparoscopic resection of all visible endometriosis, including resection of the affected bowel with primary anastomosis<br>* Other names: ileostomy creation;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Pre-post colorectal resection-and-anastomosis evaluation of gastrointestinal symptoms (stipsi, dyschezia, regurgitation, nausea and vomit, abdominal distension and belching) | Pre-post colorectal-resection-and-anastomosis evaluation (mean difference or percentage variation) of stipsi, dyschezia, regurgitation, nausea and vomit, abdominal distension and belching, through the administration of the GSRS (Gastrointestinal Symptom Rating Scale) to patients. The GSRS is a disease-specific instrument that includes 15 items combined into five-symptom clusters addressing different gastrointestinal symptoms. The five-symptom clusters depict reflux, abdominal pain, indigestion, diarrhoea and constipation. The GSRS has a seven-graded scale where 1 represents absence of bothersome symptoms and 7 represents very bothersome symptoms | from surgery to last follow up visit (which varies from 12 months to a maximum of 157 months) | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Pre-post colorectal resection-and-anastomosis evaluation of anxiety, depression, positivity and well-being, self control, general health and vitality | Pre-post colorectal-resection-and-anastomosis evaluation (mean difference or percentage variation) of anxiety, depression, positivity and well-being, self control, general health and vitality, through the administration of the PGWBI (Psychological General Well-Being Index) to patients. The PGWBI is a brief self-administered questionnaire which contains 20 items rated on a six-point scale, where a higher score indicates a better quality of life and measures six mood states (anxiety, depressed mood, positive well-being, self-control, general health, vitality). The six mood states are scored as follows: 25 for anxiety, 20 for positive well-being and vitality and 15 for remaining | from surgery to last follow up visit (which varies from 12 months to a maximum of 157 months) | | Pre-post colorectal resection-and-anastomosis evaluation of the coping ability of daily living | Pre-post colorectal-resection-and-anastomosis evaluation (mean difference or percentage variation) of the coping ability of daily living, through the administration of the GSE (General Self-Efficacy Scale) to patients. The GSE consists of 10 items, with a 4-point Likert scale ranging from 1 (I Completely Disagree) to 4 (I Completely Agree), aimed at identifying, as expressed in the introduction, self-efficacy beliefs in view of difficult situations | from surgery to last follow up visit (which varies from 12 months to a maximum of 157 months) | | Pre-post colorectal-resection-and-anastomosis evaluation of patients ability to thrive in the face of adversity | Pre-post colorectal-resection-and-anastomosis evaluation (mean difference or percentage variation) of the ability to thrive in the face of adversity, through the administration of the CD-RISC (Connor-Davidson Resilience Scale) to patients. The CD-RISC contains 25 items, all of which carry a 5-point range of responses, as follows: not true at all (0), rarely true (1), sometimes true (2), often true (3), and true nearly all of the time (4). The scale is rated based on how the subject has felt over the past month. The total score ranges from 0-100, with higher scores reflecting greater resilience | from surgery to last follow up visit (which varies from 12 months to a maximum of 157 months) | | Pre-post colorectal resection-and-anastomosis evaluation of the effects that endometriosis can have on women's lives (includes work and family life, sexual life, fertility issues) | Pre-post colorectal resection-and-anastomosis evaluation of the effects that endometriosis can have on women's lives (work and family life, sexual life, fertility issues), through the administration of the EHP-30(Endometriosis Health Profile questionnaire).The EHP-30 consists of a 30-item core questionnaire, covers five subscales (11 items on pain, 6 on control and powerlessness, 6 on emotions, 4 on social support, 3 on self-image), and a second 23-item modular questionnaire contains six subscales (5 items on work life, 2 on relationship with children, 5 on sexual intercourse, 4 on medical profession, 3 on treatment and 4 on infertility). Response categories are rated on a five-point Likert scale (0-4), and items within each subscale are summed to create a raw-score.Each raw scale is translated into a score ranging from 0(best possible health status) to 100 by dividing the total raw scores in each subscale by the maximum possible raw-score within the subscale and multiplying it by 100 | from surgery to last follow up visit (which varies from 12 months to a maximum of 157 months) | | Pre-post colorectal-resection-and-anastomosis evaluation of the menstrual pain | Pre-post colorectal-resection-and-anastomosis evaluation (mean difference or percentage variation) of the menstrual pain, through the administration of the VAS (Visual Analogic Scale) to patients. The VAS using a 10-cm line represented the continuum of the patient's opinion of the degree of pain. One extremity of the line represented unbearable pain, and the other extremity represented no pain at all. The participants were asked to rate the degree of pain by making a mark on the line. The scores received from the scale were classified into mild dysmenorrhea if it was between 1 and 3 points moderate between 4 and 7 points, and severe between 8 and 10 points | from surgery to last follow up visit (which varies from 12 months to a maximum of 157 months) | | Prevalence of post-operative complications (rectovaginal fistulae, bowel leakage, pelvic abscesses, and postoperative bleeding) | Perioperative and post-operative complications were collected using the Extended Clavien-Dindo classification of surgical complications divided in early (within 30 days after surgery onset) and late (over 30 days after surgery onset). Major complications were defined as those requiring surgical, endoscopic, or radiological intervention (grade III or higher according to the Clavien-Dindo classification), and include rectovaginal fistulae, bowel leakage, pelvic abscesses, and postoperative bleeding after surgery. Minor complications were defined as those that could be solved with a conservative approach (Clavien-Dindo grade I and II) | from surgery to last follow up visit (which varies from 12 months to a maximum of 157 months) | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- deep infiltrating endometriosis, colorectal resection, quality of life

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Susceptibility of Human Volunteers With Different Histo-Blood With Different Histo-Blood Group Antigens to Norovirus Study Overview ================= Brief Summary ----------------- Objectives: To evaluate the role of human histo-blood group antigens in susceptibility to Norovirus infections. Description of Study Design: Healthy volunteers with different blood types and low antibody titers to the challenge strain will be challenged orally with a Norovirus in the CCCR inpatient facility. Subjects with resistant (non-secretors) or susceptible (secretors (of either A, B or O blood group)) to the challenge strain will be recruited. The challenge study will be conducted in two groups of twenty, each with approximately ten secretors and ten non-secretors. Three additional subjects per group will serve as alternates in the event that any of the study subjects are unavailable or become ineligible at the time of the inpatient study. Subjects will be monitored daily in the isolation facility for at least five days following this challenge for daily clinical and virological evaluations. Subjects will return to the investigational site for evaluation the day after discharge from the inpatient unit and about 30 days (28-35 days) post challenge. Study Endpoints: Norovirus infection as assessed by viral shedding, seroconversion and clinical illness assessed by the duration and severity of symptoms Detailed Description ----------------- Noroviruses are single-stranded, positive-sense RNA viruses that cause acute gastroenteritis in humans. The prototype Norwalk virus (NV) was identified in a large outbreak of acute gastroenteritis in an elementary school in Norwalk, Ohio, in 1968. Since then, many strains have been described and named by the locations of their first isolation. Genetically, Noroviruses belong to one of four genera within Caliciviridae (CV). Phylogenetic analysis has shown that the Norovirus genus is divided into five genogroups and each genogroup can be further divided into genetic clusters; at least 30 genetic clusters of Noroviruses have been identified. Noroviruses have been recognized as the most important cause of non-bacterial epidemics of acute gastroenteritis, affecting individuals of all ages, in both developing and developed countries. Such outbreaks usually have high attack rates and have occurred in child care centers, schools, restaurants, summer camps, hospitals, nursing homes, ships (both civilian and military) as well as deployed military troops. The viruses are highly contagious and are able to survive in the environment for extended periods of time. They are spread by contact with environmental surfaces and person-to-person transmission. Noroviruses normally cause moderate-to-severe diarrhea and the disease is often incapacitating and can be fatal in the young and elderly. The most important public health concern is that Noroviruses can cause large water- and food-borne outbreaks, resulting in the virus being classified as a Category B agent. Noroviruses have also been implicated in several military outbreaks. The Desert Shield virus (DSV) isolated in US troops in the 1991 Gulf War was subsequently identified as a Norovirus. Similarly the recently reported mysterious attacks of acute gastroenteritis affecting the British troops in Afghanistan were also caused by a Norovirus. Large outbreaks of Norovirus-associated gastroenteritis are common on US Navy ships, similar to those that occurred on board cruise ship lines. Surveillance of acute gastroenteritis on board five US Navy combat ships in 1998-1999 showed that all the ships experienced large outbreaks of Norovirus acute gastroenteritis during their deployment in the Pacific and Indian Oceans, following port visits. Because of the rapid spread of the disease, many departments and units on board the ships were unable to function during the peak of the outbreaks. Noroviruses are difficult to study because: 1) they are genetically and antigenically highly diverse and multiple strains with distinct genetic identities co-circulate in the same communities, making diagnosis and disease control extremely difficult; and 2) the virus cannot be cultivated in cell culture and 3) no small animal model for studying Noroviruses exists. The molecular cloning of the prototype Norwalk Virus (NV) in 1990 by one of the co-investigators of this application has allowed rapid progress in studying Noroviruses and other genera; however, many issues on Norovirus infection, pathogenesis, immunology and host range remain unknown. The discovery of Norovirus receptors provides new opportunities to evaluate the pathogenesis and epidemiology of Noroviruses. A host genetic factor involving Norovirus infection was originally suggested by many researchers before the cloning of Noroviruses in the 1990s because about 20-30% of individuals who did not have antibodies against Noroviruses were never infected following a challenge with NV, and in outbreaks, individuals who remained healthy were clustered in families that had the same exposure to Noroviruses as the ill families. Further, pre-existing antibodies against NV were not protective against NV infection, while individuals who had high levels of antibodies against NV were more susceptible to NV than individuals who did not have the antibodies. These observations indicate that, in addition to immune responses, there must be another factor(s) that controls the host-specificity of Norovirus infection. We recently discovered that Noroviruses recognize human histo-blood group antigens as receptors. Using recombinant capsid proteins from different Noroviruses representing different genetic clusters, we have identified four binding patterns of Noroviruses to human histo-blood group antigens, which are defined by the host Lewis, secretor and ABO blood types. This finding provides a new approach to develop strategies to control the disease. Specifically, if Noroviruses rely on the histo-blood group antigens on the surfaces of the intestinal epithelial cells as receptors, a compound that inhibits the interaction between the virus and receptors could be developed as an antiviral drug for Noroviruses. This finding provides the basis for this protocol which seeks to confirm the relationship between specific Norovirus susceptibility and specific histo-blood group antigen presence as well as establish a model to evaluated future interventions (drugs and vaccines). The specificity of the NV interaction with the sugar moieties of histo-blood group antigens was shown by specific blocking of the binding by human milk from a secretor, by monoclonal antibodies specific for secretor human blood-group antigens (HBGAs), by synthetic oligosaccharide conjugates containing secretor antigens, and by treatment of the tissues with a1,2 fucosidase. NV also binds to differentiated CaCo2 cells and differentiated CaCo2 cells express human histo-blood group antigens. Transfection of Chinese Hamster Ovary (CHO) cells with a a1,2-linked fucosyl-transferase cDNA allowed attachment of NV virus-like particles (VLPs). The bound rNV VLPs were internalized following incubation of the cells at 37oC. To further investigate the association between secretor status and susceptibility to Norwalk virus (NV), we collaborated with Dr. Christine Moe at Emory University's School of Medicine on a volunteer challenge study. This study utilized the prototype NV, the first Norovirus strain to be used for human challenge studies. Saliva samples from 77 NV-challenged volunteers were tested for secretor status and for NV-binding. Fifty-five (71%) of the 77 volunteers were secretors. Among the 55 secretors, 34 (62%) were infected with NV following challenge and saliva from 41 (75%) bound NV recombinant VLPs. None of the saliva samples from the 22 non-secretor volunteers bound NV virus-like particles (VLPs) and none of them became infected following NV challenge; strongly suggesting that the susceptibility to NV is determined at least in part by the ability of the host to bind the norovirus strain. More recently we performed a study to determine whether other strains of Noroviruses have a similar pattern of host-specificity and have extended the binding patterns to 7 based on examination of fourteen Noroviruses. The 7 patterns have been classified into two groups according to their interactions with three major epitopes (A/B, H and Lewis) of HBGAs: the A/B binding group and the Lewis-binding group. Strains in the A/B binding group recognize the A and/or B and H antigens, but not the Lewis antigens, while strains in the Lewis-binding group react only to the Lewis and/or H antigens. This classification also resulted in a model of the Norovirus/HBGA interaction, in which a maximum of two binding sites within a receptor binding interface are involved in NV/HBGA interaction. The A, B and H side chains are responsible for binding by the A/B binding strains while the Lewis epitopes are responsible for the Lewis binding strains. Phylogenetic analyses showed that strains with identical or closely related binding patterns tended to be clustered, but strains in both binding groups can be found in both genogroups I and II. Our results suggest that Noroviruses have a wide spectrum of host range and human HBGAs play an important role in Norovirus evolution. Since human Noroviruses cannot be cultivated in vitro or infect animals, it is necessary to perform human volunteer challenge studies to study the pathobiology of the infection. The study will further the concept that Norovirus has a narrow host range which is fundamental in the pathogenesis and immunology of Noroviruses. Additionally, we recently have identified more than a dozen compounds that specifically block Norovirus attachment to their receptors. The human challenge study should also establish a model that can be used in the evaluation of these new compounds in regards to their capacity to block virus replication (anti-viral drug). Furthermore, our study will re-evaluate whether acquired immunity is an independent factor in Norovirus infections which may provide additional information in host immunity potentially useful in vaccine development. Finally, the study will allow for banking of the Norovirus challenge strain by collecting the diarrheal stools passed by the study subjects. Banking of additional specimen, as mentioned above, is critical for future clinical trials because the virus cannot be cultivated in vitro and must be isolated from humans infected with the virus. A specific challenge study would only use one challenge strain and any challenge strain used in human clinical trials would have a separate IND and FDA approval prior to administration to subjects. Official Title ----------------- Evaluation of the Susceptibility of Human Volunteers With Different Histo-Blood Group Antigens to Norovirus Conditions ----------------- Healthy Adults Intervention / Treatment ----------------- * Biological: Norovirus Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Healthy adults between the ages of 18 and 49 years Willing and able to provide written informed consent Able to comply with all study procedures Have a body mass index of at least 19 Have a serum IgG antibody titer of < 1:1,600 to Norovirus Female subjects of child bearing potential must have negative urine pregnancy tests Female subjects must be of non-childbearing potential, or if of childbearing potential (as determined by investigator) must be practicing abstinence or using an effective licensed method of birth control for one month before receipt of challenge through one month after completing the inpatient isolation facility stay. Have normal screening laboratories Score at least 70% on a test of understanding of this research study. Exclusion Criteria: Expected to be noncompliant with study procedures or planning to move within the anticipated total duration of the study Pregnant or breastfeeding HIV, Hepatitis B or C positive Norovirus antibody screening titer of > 1:1600 Clinically significant findings on history or physical examination Clinically significant history of diseases or treatments that may affect the immune system's function Receipt of systemic corticosteroids for greater than 7 days within the past six months Abnormal screening electrocardiogram (ECG) Clinically significant respiratory disease, endocrine disease, liver disease, renal disease, or neurological disease History of malabsorption or maldigestion disorder, major gastrointestinal (GI) surgery, or any other chronic GI disorders that would interfere with the study Clinically significant abnormalities of the health screening laboratory work Use of antibiotics within 7 days prior to entry into the inpatient isolation facility (Day -1) Any medical illness requiring a new prescription medication or hospitalization during the screening period Temperature ≥38.0°C Diarrhea or vomiting during the 7 days prior to challenge administration Allergy to sodium bicarbonate solution Treatment within the past year for an eating disorder History of alcohol or drug abuse within past 3 years Receipt of any vaccine, licensed or investigational, or any investigational product within 30 days of challenge administration or plan to receive any vaccine or investigational product through the study duration Use of any H2 receptor antagonists or prescription acid suppression medication or over-the-counter (OTC) antacids within 72 hours of investigational product administration (Day 0) Use of prescription and OTC medications containing acetaminophen, aspirin, ibuprofen, and other non-steriodal anti-inflammatory drugs within 48 hours prior to investigational product administration Regular use of laxatives or anti-motility agents Receipt of blood or blood products within the past six months Subjects who are unwilling or unable to cease smoking for the duration of the inpatient stay Any other condition, such as a medical, psychiatric, or social condition or occupational responsibility that, in the judgment of the investigator, would interfere with or serve as a contraindication to the subject's participation in the study or assessment of the investigational product Plan to be living in a confined environment within 3 weeks after receiving the challenge strain Commercial food handlers, day care workers, or health care workers involved in direct patient contact Provide child day care services either in a home or in a nonresidential facility Provide direct care to individuals over 65 years of age, young children (<2 years) at home or with household contacts who are: Immunocompromised Pregnant, or Breast feeding Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 49 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: Quadruple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Norovirus Challenge<br> | Biological: Norovirus<br>* Norovirus challenge pool administered to each subject<br>* Other names: Norovirus challenge pool;| | Experimental: Norovirus challenge<br> | Biological: Norovirus<br>* Norovirus challenge pool administered to each subject<br>* Other names: Norovirus challenge pool;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Measurement of the number of people who develop symptomatic illness after challenge with Norovirus | The number of subjects that become infected, as measured by the number of subjects found to be shedding norovirus in their stool, as well as the number of symptomatic infections (viral shedding in addition to other symptoms such as vomiting, diarrhea, abdominal cramps) will be the primary outcome measure. We will also assess the number of subjects who show at least a 4-fold rise in antibodies against Norovirus (comparing pre-challenge and post-challenge antibody levels). | 1 month after challenge |

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3D Bioprinted Models for Predicting Chemotherapy Response in Colorectal Cancer With/Without Liver Metastases Study Overview ================= Brief Summary ----------------- The therapeutic regimens of adjuvant and neoadjuvant chemotherapy for colorectal cancer (CRC) remain largely relied on clinical experience, and thus preclinical models are needed to guide individualized medicine. The investigators are going to establish 3D bioprinted CRC models and organoids from surgically resected tumor tissues of CRC patients with or without liver metastases. In vitro 3D models and organoids will be treated with the same chemotherapy drugs with the corresponding patients from whom the models are derived. The sensitivity of chemotherapy drugs will be tested in these two types of in vitro models, and the actual response to chemotherapy in patients will be evaluated. The predictive ability of 3D models for chemotherapy sensitivity in CRC patients will be compared with that of the organoids. This observational study will validate the potential value of 3D bioprinted tumor models in predicting the response to chemotherapy in CRC. Official Title ----------------- Validation of the Three-dimensional Bioprinted Tumor Models as a Predictive Method of the Response to Chemotherapy for Colorectal Cancer With or Without Liver Metastases Conditions ----------------- Colorectal Cancer, Colorectal Cancer Liver Metastasis Intervention / Treatment ----------------- * Procedure: surgical resection * Other: adjuvant chemotherapy * Other: neoadjuvant therapy Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: More than 18 years old Diagnosed as colorectal cancer with or without liver metastases before Pathologically proven colorectal cancer after surgery Exclusion Criteria: Medical history with other malignancies or serious diseases Disable to sign the informed consent independently Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Group A<br>colorectal cancer patients at resectable stage II/III who will receive adjuvant chemotherapy after surgery | Procedure: surgical resection<br>* Surgical resection will be performed for locoregional lesions or liver metastases.<br>Other: adjuvant chemotherapy<br>* Regimens of adjuvant chemotherapy are directed by clinical guidance and experience.<br>| | Group B<br>colorectal cancer patients at locally advanced stage who will receive neoadjuvant chemotherapy before surgery and adjuvant chemotherapy after surgery | Procedure: surgical resection<br>* Surgical resection will be performed for locoregional lesions or liver metastases.<br>Other: adjuvant chemotherapy<br>* Regimens of adjuvant chemotherapy are directed by clinical guidance and experience.<br>Other: neoadjuvant therapy<br>* Regimens of neoadjuvant chemotherapy are directed by clinical guidance and experience.<br>| | Group C<br>colorectal cancer patients with liver metastases | Procedure: surgical resection<br>* Surgical resection will be performed for locoregional lesions or liver metastases.<br>Other: adjuvant chemotherapy<br>* Regimens of adjuvant chemotherapy are directed by clinical guidance and experience.<br>Other: neoadjuvant therapy<br>* Regimens of neoadjuvant chemotherapy are directed by clinical guidance and experience.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Response of 3D tumor models/organoids to the same chemotherapy drugs as the corresponding patients. | The investigators will establish and culture 3D colorectal cancer models and organoids. The 3D models and organoids will be treated with the same chemotherapy drugs as the corresponding patients. The viability of the 3D tumor models and organoids will be observed after treatment and the IC50 of each drug will be calculated. The correlation of 3D model/organoid sensitivity and the patient response will be analyzed. | 2021.03-2021.12 | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Response of the colorectal cancer patients to neoadjuvant chemotherapy. | For patients who receive neoadjuvant chemotherapy before surgery, the response to neoadjuvant chemotherapy will be evaluated according to clinical imaging results and the RECIST scores. | 2021.03-2022.03 | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- colorectal cancer, colorectal cancer liver metastasis, three-dimensional bioprinting, chemotherapy

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Study of Irinotecan and Cetuximab Versus Irinotecan as Second-Line Treatment in Patients With Metastatic, EGFR-Positive Colorectal Cancer Study Overview ================= Brief Summary ----------------- The purpose of this study is to determine whether overall survival is prolonged in subjects with metastatic, epidermal growth factor receptor (EGFR)-positive colorectal cancer treated with cetuximab in combination with irinotecan compared with irinotecan alone as second-line therapy following treatment with a fluoropyrimidine and oxaliplatin based, non-irinotecan-containing regimen. Official Title ----------------- Revised Protocol 07 to Protocol CA225006 - A Phase III Randomized, Open-Label, Multicenter Study of Irinotecan and Cetuximab vs. Irinotecan as Second-Line Treatment in Patients With Metastatic, EGFR-Positive Colorectal Carcinoma Conditions ----------------- Colorectal Cancer Intervention / Treatment ----------------- * Drug: cetuximab * Drug: Irinotecan * Drug: Irinotecan Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Histologically documented colorectal cancer which is EGFR-positive by immunohistochemistry [IHC] (may be based on archival samples) and is metastatic. Prior oxaliplatin administered for the first-line treatment of metastatic colorectal cancer. Prior fluoropyrimidine-containing regimen (5-fluorouracil [5-FU], capecitabine, or uracil/tegafur [UFT]), for the first-line treatment of metastatic disease. Exclusion Criteria: A serious uncontrolled medical disorder that, in the opinion of the Investigator, would impair the ability of the subject to receive protocol therapy Unresolved diarrhea, bowel obstruction, or history of inflammatory bowel disease Known or documented brain metastases Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Arm A<br> | Drug: cetuximab<br>* Vial, IV, 400 mg/m² week 1 then 250 mg/m², weekly, until PD/Toxicity/Pt-PI Decision<br>* Other names: Erbitux;Drug: Irinotecan<br>* Vial, IV, 350 mg/m², Q 3 Weeks, Until PD/Toxicity/Pt-PI Decision<br>| | Active Comparator: Arm B<br> | Drug: Irinotecan<br>* Vial, IV, 350 mg/m², Q 3 Weeks, Until PD/Toxicity/Pt-PI Decision<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Overall Survival | | Every 3 months after subject off-treatment | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Progression Free Survival | | Q6 Weeks | | Response | | Q6 Weeks | | Duration of Response | | Q6 Weeks | | Time to Response | | Q6 Weeks | | Disease Control Rate | | Q6 Weeks | | Safety | | Q3 Weeks | | Quality of Life | | Q6 Weeks | | Health Economics | | Q3 Weeks |

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Phase I Study of Lurbinectedin (PM01183) in Combination With Paclitaxel, With or Without Bevacizumab, in Selected Advanced Solid Tumors Study Overview ================= Brief Summary ----------------- Clinical trial of PM01183 in combination with paclitaxel, with or without bevacizumab, in patients with solid tumors Detailed Description ----------------- Clinical trial to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of PM01183 in combination with weekly paclitaxel, with or without bevacizumab. Once a recommended dose is defined for the PM01183 and weekly paclitaxel combination, the feasibility of adding bevacizumab to this combination will be explored in a selected cohort of patients to characterize the safety profile and feasibility of this combination, to obtain preliminary information on antitumor activity, to obtain preliminary information on quality of life (QoL), to characterize the pharmacokinetics (PK) of this combination and to detect major drug-drug PK interactions and PK(pharmacokinetic)/PD(pharmacodynamic) correlation and to conduct an exploratory pharmacogenomic(PGx) analysis in patients with selected advanced solid tumors. Official Title ----------------- Phase I Multicenter, Open-label, Clinical and Pharmacokinetic Study of Lurbinectedin (PM01183) in Combination With Weekly Paclitaxel, With or Without Bevacizumab, in Patients With Selected Advanced Solid Tumors Conditions ----------------- Breast Cancer, Ovarian Cancer, Gynecological Cancer, Head and Neck Carcinoma, Non-small Cell Lung Cancer, Small Cell Lung Cancer, Non-squamous Cell Lung Cancer Intervention / Treatment ----------------- * Drug: PM01183 + paclitaxel +/- bevacizumab Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Voluntarily signed and dated written informed consent Age between 18 and 75 years old (both inclusive) Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤ 1 Life expectancy ≥ 3 months. Patients with a histologically/cytologically confirmed diagnosis of advanced and/or unresectable disease of any of the following tumors: Breast cancer Epithelial ovarian cancer or gynecological cancer Head and neck squamous cell carcinoma Non-small cell lung cancer Small cell lung cancer Platinum-refractory germ-cell tumors. Adenocarcinoma or carcinoma of unknown primary site Adequate bone marrow, renal, hepatic, and metabolic function Recovery to grade ≤ 1 or to baseline from any Adverse Event (AE) derived from previous treatment (excluding alopecia of any grade). Pre-menopausal women must have a negative pregnancy test before study entry and agree to use a medically acceptable method of contraception throughout the treatment period and for at least six weeks after treatment discontinuation Exclusion Criteria: Prior treatment with PM01183 or weekly paclitaxel or nanoalbumin-paclitaxel Patients who have previously discontinued paclitaxel-based regimes due to drug related toxicity. Known hypersensitivity to bevacizumab or any component of its formulation Patients who have previously discontinued bevacizumab-containing regimes due to drug-related toxicity. More than three prior lines of chemotherapy Less than three months since last taxane-containing therapy. Wash-out period: Less than three weeks since the last chemotherapy-containing regimen Less than three weeks since the last radiotherapy dose Less than four weeks since last monoclonal antibody-containing therapy Concomitant diseases/conditions: Unstable angina, myocardial infarction, valvular heart disease, encephalopathy, ischemic attacks, hemorrhagic or ischemic cerebrovascular accident (CVA) or ongoing pulmonary embolism within last year, arrhythmia, hepatopathy, uncontrolled infection, hemoptysis or oxygen requiring dyspnea, known HIV infection, bleeding risk, muscular problems, peripheral neuropathy, Symptomatic or progressive brain metastases or leptomeningeal disease. Men or pre-menopausal women who are not using an effective method of contraception as previously described; actively breast feeding women. Patients who have pelvic irradiation with doses ≥ 45 Grays (Gy). History of previous bone marrow and/or stem cell transplantation. Confirmed bone marrow involvement Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 75 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Treatment<br>PM01183 + paclitaxel +/- bevacizumab | Drug: PM01183 + paclitaxel +/- bevacizumab<br>* PM01183: 1 mg and 4 mg vials. Powder for concentrate for solution for infusion paclitaxel: 6 mg/ml concentrate for solution for infusion bevacizumab: 25 mg/ml concentrate for solution for infusion Once a recommended dose is defined for the PM01183 and weekly paclitaxel combination, the feasibility of adding bevacizumab to this combination will be explored in a prospectively selected cohort of patients<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Maximum Tolerated Dose (MTD) | The MTD will be the lowest level at which one third or more evaluable patients experience a DLT in Cycle 1. DLTs are defined as AEs or laboratory abnormalities related to the study drugs occurred during Cycle 1. | The MTD was followed mainly during Cycle 1 through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (cycle duration: 3 weeks) | | Recommended Dose (RD) | The RD will be the highest DL explored with less than one third of the patients experiencing a DLT during Cycle 1. DLTs are defined as AEs or laboratory abnormalities related to the study drugs occurred during Cycle 1. | The RD was followed mainly during Cycle 1 through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (cycle duration: 3 weeks) | | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | DLTs are defined as AEs or laboratory abnormalities related to the study drugs occurred during Cycle 1. | DLT was followed mainly during Cycle 1 through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (cycle duration: 3 weeks) | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Best Tumor Response | Best overall response:Best response recorded from the start of the study treatment until the end of treatment Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to<10 mm Partial Response (PR):At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression) Stable Disease (SD):Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum diameters while on study Treatment failure (TF):symptomatic deterioration or death due to progression | Through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (1 cycle =3 weeks) | | Progression-free Survival | Progression-free survival (PFS) was defined as the time from the date of first infusion of study treatment to the date of progression or death (due to any cause). If progression or death had not occurred at the time of the analysis, the PFS was censored. | Through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (1 cycle =3 weeks) | | Duration of Response (DR) | Duration of response (DR) was defined as the time from the date when the response criteria (PR or CR, whichever was reached first) were fulfilled, to the first date when PD, recurrence or death was documented | Through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (1 cycle =3 weeks) | | Quality of Life (QoL) | Change from baseline to last cycle. European Organization for Research and Treatment of Cancer (EORTC) QLQ-C15-PAL scale scores. The EORTC QLQ-C15-PAL is an abbreviated 15-item version of the EORTC QLQ-C30 (version 3.0) developed for palliative care. Wilcoxon signed ranks test repeat-measure analyses of variance were used to measure the change value from baseline value. Data has to be analysed following the corresponding EORTC manual http://www.eortc.be/qol/files/SCManualQLQ-C15-PAL.pdf and the overall quality of life assessment is contained in 0 to 100 where a higher value represents a better state. | Through study completion, an average of 5 cycles for PM1183 in cohort A and 9.5 cycles in cohort B were observed (1 cycle =3 weeks) |

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Focused Assessment With Sonography in Trauma Study Overview ================= Brief Summary ----------------- The study evaluates the knowledge and attitude about Focused Assessment with Sonography in Trauma examination among medical students and medical staff in Poland. Official Title ----------------- Prepared for Focused Assessment With Sonography in Trauma Examination? Conditions ----------------- Trauma, Ultrasonography Intervention / Treatment ----------------- * Other: Survey Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Give voluntary consent to participate in the study Exclusion Criteria: not meet the above criteria Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Intervention/Treatment | | --- | |Other: Survey|Survey about Knowledge and Attitude About Focused Assessment With Sonography in Trauma| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Results of the Medical Knowledge Tool (Questionnaire) | Percentage of healthcare workers and medical students with appropriate knowledge assessed by 10- items questionnaire about basic information about Focused Assessment With Sonography in Trauma. For each correct answer participant receive 1 point (0-1 point scale). | 2 weeks | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- attitudes, knowledge, examination

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Schizotypal Personality Disorder Risperidone Study Overview ================= Brief Summary ----------------- Neurophysiological indices of self-monitoring were assessed in a group of patients with Schizotypal Personality Disorder (SPD) and a control group. Both groups were assessed after the administration of risperidone and placebo. Detailed Description ----------------- The electroencephalogram (EEG) was recorder while participants (SPD participants and controls) performed a behavioral task: the Eriksen Flanker Task. The continuous EEG was segmented, corrected for artifacts and averaged. A component of the event-related brain potential known as the error-related negativity (ERN) was identified and its amplitude quantified in microvolts. This procedure was conducted two hours after the administration of risperidone 1 mg and placebo (lactose) on two different experimental days and for each participant group (SPD patients and controls). The amplitude of the ERN after placebo was compared between groups to test for baseline (non-drug-induced) differences between patients and controls. The impact of risperidone on the amplitude of the ERN was compared between the two participant groups. Conditions ----------------- Schizotypal Personality Disorder Intervention / Treatment ----------------- * Drug: Risperidone * Drug: Placebo Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Schizotypal Personality Disorder Exclusion Criteria: Major Psychiatric Disorder Medical condition Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Basic Science Allocation: Non-Randomized Intervention Model: Crossover Assignment Masking: Double Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Schizotypal Personality Disorder<br>Schizotypal Personality Disorder (SPD) patients. They received two interventions: risperidone 1 mg and placebo (lactose). | Drug: Risperidone<br>* 1 mg Risperidone<br>Drug: Placebo<br>* Lactose Placebo<br>| | Experimental: Healthy controls<br>Control group consisting of healthy volunteers.They received two interventions: risperidone 1 mg and placebo (lactose). | Drug: Risperidone<br>* 1 mg Risperidone<br>Drug: Placebo<br>* Lactose Placebo<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Neurophysiological indices of self-monitoring (Error Related Negativity) | Amplitude of the Error Related Negativity was assessed prior to and 2 hours after treatment administration | During acute effects of pharmacological treatment (up to 2 hours) |

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Evaluation of the Effect of Sodium Bicarbonate Water on Blood Pressure in Normotensive Subjects Study Overview ================= Brief Summary ----------------- ROX_TENSIO18 is a randomised cross-over trial and the main objective is to evaluate the effect of daily consumption of sodium bicarbonate water for 15 days on blood pressure. Secondary objective are: Evaluation of the effect of daily consumption of sodium bicarbonate water on total salt intake Evaluation on blood pressure of the usual food groups that are the strongest contributors of salt intake. Detailed Description ----------------- Volunteers are normotensive subjects divided into two equivalent groups. Group A subjects will begin their first 15-day period with the consumption of St-Yorre mineral water. Group B will begin the first 15-day period by drinking tap water. After a washout period of 15 days, each group alternates with a new period of 15 days of water consumption monitoring: tap water for group A and mineral water St-Yorre for group B. For each period salt intake and blood pressure are measured.Three-day food records are also performed for both 15-days periods. Official Title ----------------- Evaluation of the Effect of Daily Consumption of Sodium Bicarbonate Water for 15 Days on Blood Pressure in Normotensive Subjects Conditions ----------------- Blood Pressure Intervention / Treatment ----------------- * Other: Sodium bicarbonate-rich mineral water Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Normal blood pressure between 90/60 and 140/90 mm Hg Usually drinks tap water; Knowing read and write French routinely, Possessing an internet connection at home, Possessing and knowing how to use a computer or tablet, Affiliated with a social security scheme Not Trust Having signed the informed consent letter Exclusion Criteria: Pregnant or lactating woman BMI greater than 35 kg / m² Heart failure History of cardiovascular disease Hypertension treated or untreated Renal failure. Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 65 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Basic Science Allocation: Randomized Intervention Model: Crossover Assignment Interventional Model Description: Group A subjects: first 15-day period drinking a sodium bicarbonate-rich mineral water Group B subjects: first 15-day period drinking tap water Washout period of 15 days Group A subjects: last 15-day period drinking tap water Group B subjects: last 15-day period drinking a Sodium bicarbonate-rich mineral water Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Group A : sodium bicarbonate-rich mineral water and tap water<br>First 15-days period with daily intake of 1.5l of sodium bicarbonate-rich mineral water. 15-days washout period Last 15-days period with daily intake of 1.5l of tap water. | Other: Sodium bicarbonate-rich mineral water<br>* St-Yorre, a sodium bicarbonate-rich mineral water, is a commercial mineral water that contains 4368 mg/l sodium bicarbonate. The study intends to evaluate the effect on blood pressure of the sodium bicarbonate intake due to this mineral water consumption.<br>* Other names: St-Yorre mineral water;| | Experimental: Group B : tap water and sodium bicarbonate-rich mineral water<br>First 15-days period with daily intake of 1.5l of tap water. 15-days washout period Last 15-days period with daily intake of 1.5l of sodium bicarbonate-rich mineral water. | Other: Sodium bicarbonate-rich mineral water<br>* St-Yorre, a sodium bicarbonate-rich mineral water, is a commercial mineral water that contains 4368 mg/l sodium bicarbonate. The study intends to evaluate the effect on blood pressure of the sodium bicarbonate intake due to this mineral water consumption.<br>* Other names: St-Yorre mineral water;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change from baseline mean number of systolic and diastolic blood pressure at 15 days | The primary endpoint is the difference between mean number of blood pressure of the volunteers drinking sodium bicarbonated-rich water during 15 days and the mean number of volunteers drinking tap water during 15 days. | Day 1 to Day 3 - Day 13 to Day 15- Day 31 to Day 33 - Day 43 to Day 45 | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Sodium intake | The sodium intake per day is assessed using two three-day food records and the ExSel test. | Day 1 to Day 15 - Day 31 to Day 45 | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Nutrition, Blood pressure, Sodium bicarbonate

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Hyperbaric Oxygen Therapy for Ulcerative Colitis Flares Study Overview ================= Brief Summary ----------------- Ulcerative colitis (UC) is a chronic inflammatory bowel disease associated with recurrent mucosal inflammation. Clinically, the disease is characterized by bloody diarrhea, abdominal pain, and constitutional symptoms such as fever and weight loss. Treatment strategies vary based on disease activity and target various aspects of the inflammatory cascade. Options include: anti-inflammatory drugs (mesalamine), immunosuppressive or modulatory medications (corticosteroids, thiopurines, cyclosporine) and biologic agents (Anti-TNF). Disease severity can be wide ranging, and nearly 25% of UC patients are hospitalized for acute severe disease. Of these patients, 30% will undergo colectomy after the acute episode, a quarter of which will experience post-operative complications. Although there has been great progress in treatment of UC over the past decade, even with the anti-TNF agent infliximab, the one-year remission rate for patients not responding to conservative management is barely 20%. Furthermore, corticosteroids have significant long-term consequences and immune suppressive drugs such as 6-mercaptopurine, azathioprine and infliximab have been associated with serious adverse events including life-threatening infections and lymphomas. With growing evidence that the pathogenesis of UC is multi-factorial and involves a complex interaction of genetic and environmental factors, newer treatment modalities are being evaluated to target the mucosal immune response and mucosal inflammatory regulatory system. Hyperbaric oxygen offers a promising new treatment option since it targets both tissue hypoxia and inflammation. Recent small scales studies evaluating the impact of hyperbaric oxygen treatment in acute ulcerative colitis flares demonstrated improved outcomes. The mechanisms underlying the improvement are not known. In this study, we will treat ulcerative colitis flares with hyperbaric oxygen and measure changes in both markers of tissue hypoxia and inflammation. We hypothesize that hyperbaric oxygen will (a) improve outcomes, and (b) show reductions in markers of both tissue hypoxia and inflammation. Official Title ----------------- Hyperbaric Oxygen Therapy for Moderate to Severe Ulcerative Colitis Flares: A Multi-Center Randomized Trial Conditions ----------------- Colitis, Ulcerative Intervention / Treatment ----------------- * Other: Hyperbaric Oxygen Therapy Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Hospitalized patients with known or newly diagnosed moderate to severe ulcerative colitis (as defined by the Mayo score ≥6) Consented within the first 48 hours of initiating IV steroids Risk score of >3 points (pts) Mean stool frequency/24 hrs (<4 = 0 pts, 4-6 = 1 pt, 7-9 = 2 pts, >9 = 4 pts) Colonic Dilation = 4pts Hypoalbuminemia (< 3mg/dL) = 1 pts Mayo endoscopic sub-score >2 (moderate to severe) Age >18 and able to make their own medical decisions Exclusion Criteria: Complication requiring urgent surgical intervention (in the opinion of the investigators) Clinically significant cardiac, renal, neurological, endocrine, respiratory or hepatic impairment in the opinion of the investigator, including but not limited to: Pulmonary (COPD with CO2 retention; Previous/current imaging showing hyperinflation/air trapping/bullous disease/blebs (opinion of investigators), Current pneumothorax or previous spontaneous pneumothorax, Bronchogenic cyst(s)) Cardiac (Uncontrolled HTN (systolic >160 or diastolic >100), Unstable angina or myocardial infarction within the previous 3 months, Ejection fraction < 35%, Current or previous amiodarone use, ICD in place, Pacemaker in place not approved for chamber use) Hematological/Oncological (Current chemotherapeutic drug use, and past history of bleomycin use,Hereditary Spherocytosis, Sickle cell anemia) Gastrointestinal and Infectious Disease (Known or suspected Crohn's disease, Previous infection with mycobacterium, fungus, HIV, Hepatitis B or C, Severe gastrointestinal or systemic infection (opinion of investigator), Current capsule endoscopy or previously non-retrieved capsule Endocrinology (Uncontrolled hyperthyroidism) Neurological and Psychological (Vagal or other nerve stimulators, Uncontrolled seizure disorder, Medications or medical conditions that lower seizure threshold (opinion of the investigator), Drug or alcohol abuse/dependence,Current treatment for alcohol cessation with disulfiram, Current or recent (within past week) use of baclofen) Head and Neck (Previous middle ear damage, surgery or infection(s) which may increase the risk for needing ear tubes (opinion of the investigator),Current or previous retinal detachment or optic neuritis, Retinal or vitreous surgery within the past 3 months) Implanted devices not on the approved list for use with HBOT Women who are pregnant or nursing. Women with childbearing potential were required to use effective birth control if not surgically sterile or postmenopausal for >2 years. Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Crossover Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: 5 Days Hyperbaric Therapy<br>Patients will be enrolled and follow an identical medical treatment algorithm. At day 3 responders (based on partial Mayo score) will be re-randomized in a 1:1 fashion to complete 5 total days of HBOT (1 session per day) or to stop after 3 days of HBOT. Non-responders will be entered into an open label arm to complete 5 total days of HBOT. | Other: Hyperbaric Oxygen Therapy<br>* Hyperbaric oxygen (HBO) provides 100% oxygen at a pressure above atmospheric pressure (typically twice to three times standard sea level pressure (2.0-3.0 ATA)). This dramatically increases the amount of oxygen dissolved in blood plasma, which in turn increases oxygen delivery to tissues. This effect of hyperbaric oxygen is used clinically to treat acute hypoxia in crush injuries, severed limbs, and failing skin grafts<br>| | Active Comparator: 3 Days Hyperbaric Therapy<br>Patients will be enrolled and follow an identical medical treatment algorithm. At day 3 responders (based on partial Mayo score) will be re-randomized in a 1:1 fashion to complete 5 total days of HBOT (1 session per day) or to stop after 3 days of HBOT. Non-responders will be entered into an open label arm to complete 5 total days of HBOT. | Other: Hyperbaric Oxygen Therapy<br>* Hyperbaric oxygen (HBO) provides 100% oxygen at a pressure above atmospheric pressure (typically twice to three times standard sea level pressure (2.0-3.0 ATA)). This dramatically increases the amount of oxygen dissolved in blood plasma, which in turn increases oxygen delivery to tissues. This effect of hyperbaric oxygen is used clinically to treat acute hypoxia in crush injuries, severed limbs, and failing skin grafts<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Impact of HBOT on clinical response/remission | Impact of HBOT on clinical response/remission to medical therapy as measured by the partial Mayo score at study day 5. | 5 Days | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | relative and absolute reduction in the Mayo score | Relative and absolute reduction in the Mayo score | Day 5, 10 | | Flair duration | time to reduction in mayo score | day 5, 10 | | Hospitalization duration | time in the hospital | day5, 10 | | proportion of patients requiring other therapy | Proportion who require cyclosporine, infliximab or colectomy during index flare | Day 5, 10 | | Relative and absolute change in inflammatory markers | Relative absolute change in inflammatory markers: ESR | day 10 | | Relative and absolute change in inflammatory markers | Relative absolute change in inflammatory markers: CRP | day 10 | | Relative and absolute change in inflammatory markers | Relative absolute change in inflammatory markers: fecal calprotectin | day 10 | | Relative and absolute change in inflammatory markers | Relative absolute change in inflammatory markers: interleukins | day 10 | | Relative and absolute change in gene expression | Relative absolute change in gene expression: VEGF | day 10 | | Relative and absolute change in gene expression | Relative absolute change in gene expression: HIF-1 | day 10 | | Relative and absolute change in gene expression | Relative absolute change in gene expression: HO-1 | day 10 | | microbiome composition | Describe the HBOT specific changes in the microbiome composition | day 10 | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Hyperbaric Oxygen Therapy

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Using Telephone Counselling to Improve Exercise Participation in Hematologic Cancer Survivors Study Overview ================= Brief Summary ----------------- This study evaluates the impact of a 12-week theory-based exercise telephone counselling program (versus a self-directed exercise group) on closing the exercise intention-behavior gap in a sample of hematologic cancer survivors. Detailed Description ----------------- Problem: Regular exercise participation improves quality of life and physical function for cancer survivors. Unfortunately, the most effective way of promoting exercise to cancer survivors has yet to be determined, and as a result, many survivors are inactive. Theory-based efforts have typically focused on promoting intentions to exercise, though we are now discovering that only about half of those who intend to exercise actually follow through on their intentions. This is known as the exercise intention-behavior gap. It also appears that survivors are more likely to follow-through on their intention to exercise when they report employing key behavioral and motivational strategies (i.e., creating detailed exercise plans, feeling capable and obligated to exercise, perceiving it to be beneficial and fun, and avoiding the temptation to participate in alternative activities) which may be promoted via telephone counselling. Objective: To determine whether a theory-based telephone counselling intervention focused on closing the exercise intention-behavior gap is feasible and can improve exercise levels, motivation, quality of life, and fatigue in hematologic cancer survivors. Methods: A two-armed randomized controlled trial will compare the efficacy of telephone counselling versus a control condition (self-directed with Canada's Physical Activity Guide). All participants will be asked to increase their exercise by at least 60 minutes per week. Hematologic cancer survivors who previously participated in an exercise survey study and indicated interest in participating in future exercise related research (N=407) will be contacted to participate in the current trial. Eligible participants will be randomized in a 1:1 ratio to either the telephone counseling group or a self-directed exercise group. Participants in the intervention arm will receive 12 weekly telephone counseling sessions aimed at helping survivors follow-through on their exercise intention. A sample of approximately N=66 hematologic cancer survivors will be recruited for this 12-week trial. Data will be collected via online surveys assessing changes in exercise levels, motivation, quality of life, and fatigue. Feasibility will be determined by eligibility percentage, recruitment percentage, adherence rate, assessment completion rate, adverse events, and ratings of program acceptability. Official Title ----------------- Improving Quality of Life in Hematologic Cancer Survivors by Closing the Exercise Intention-Behavior Gap: a Phase II Randomized Controlled Trial of a Theory-based, Telephone-delivered Exercise Counselling Intervention Conditions ----------------- Leukemia, Lymphoma, Lymphoma, Non-Hodgkin, Behavior, Health Intervention / Treatment ----------------- * Behavioral: Telephone counselling Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: The inclusion criteria for this study will be survivors who have had a histologically confirmed hematologic cancer, and who are between 18-80 years of age, living in Alberta, can speak and comprehend English, and willing to participate in a 12-week exercise telephone counseling intervention. Exclusion Criteria: Survivors reporting greater or equal to 150 minutes of moderate-to-vigorous exercise will be excluded because they will already be meeting the public health guidelines for exercise. Survivors planning to be away for more than 2 weeks during the intervention, or with major exercise contraindications will also be excluded. Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 80 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Supportive Care Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Telephone Counselling<br>Participants will be asked to increase their exercise by at least 60 minutes per week and will receive a copy of Canada's Physical Activity Guideline plus 12 weekly telephone counseling sessions aimed at helping survivors follow-through on their exercise intention. | Behavioral: Telephone counselling<br>* The intervention is a 12 week telephone counselling exercise program where participants will receive weekly telephone counselling that targets key theoretical behavior change constructs. Participants will also receive a copy of Canada's Physical Activity Guideline.<br>| | No Intervention: Control<br>Participants will be asked to increase their exercise by at least 60 minutes per week and will be self-directed, only receiving a copy of Canada's Physical Activity Guideline as standard of care. | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change from baseline in Exercise Levels | Exercise levels assessed using the Godin Leisure-Time Exercise Questionnaire | Baseline and within 7 days of completing the 12-week intervention | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change from baseline in Exercise Motivation | Exercise motivation assessed via validated questionnaires that align with the Multi-Process Action Control Framework | Baseline and within 7 days of completing the 12-week intervention | | Change from baseline in Quality of life | Quality of life assessed using the Short Form-36 (SF-36) questionnaire | Baseline and within 7 days of completing the 12-week intervention | | Change from baseline in Fatigue | Fatigue assessed using the Functional Assessment of Cancer Therapy: Fatigue (FACT-F) questionnaire | Baseline and within 7 days of completing the 12-week intervention |

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Safety, Immunogenicity and Efficacy of GSK S. Aureus Candidate Vaccine (GSK3878858A) When Administered to Healthy Adults (Dose-escalation) and to Adults 18 to 64 Years of Age With a Recent S. Aureus Skin and Soft Tissue Infection (SSTI) Study Overview ================= Brief Summary ----------------- Safety, immunogenicity and efficacy of GSK S. aureus candidate vaccine (GSK3878858A) when administered to healthy adults (dose-escalation) and to adults 18 to 64 years of age with a recent S. aureus skin and soft tissue infection (SSTI). In the dose-escalation safety lead-in phase in healthy adults safety and immunogenicity of 4 different compositions is assessed. After safety has been shown in this phase, in the second phase, proof of principle (PoP) phase of the study in adults with a recent SSTI safety, immunogenicity and efficacy of the final composition of the vaccine is assessed. Official Title ----------------- A Phase I/II, Observer-blind, Randomised, Placebo-controlled Study to Assess Safety, Immunogenicity and Efficacy of GSK S. Aureus Candidate Vaccine When Administered to Healthy Adults (Dose-escalation) and to Adults 18 to 64 Years of Age With a Recent S. Aureus Skin and Soft Tissue Infection (SSTI) Conditions ----------------- Infections, Soft Tissue Intervention / Treatment ----------------- * Biological: Sa-5Ag half dose non-adjuvanted * Biological: Sa-5Ag full dose non-adjuvanted * Biological: Sa-5Ag half dose adjuvanted * Biological: Sa-5Ag full dose adjuvanted * Biological: Placebo Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: All subjects must satisfy all the following criteria at study entry: Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits). Written or witnessed informed consent obtained from the subject prior to performance of any study specific procedure. Subject satisfying screening requirements. Subjects who, after the nature of the study has been explained to them, have shown adequate comprehension of the study procedures and knowledge of study. A male or female Dose escalation and safety lead-in phase: Aged between 18 and 50 years of age, inclusive, at the time of first vaccination. PoP phase: Aged between 18 and 64 years of age, inclusive, at the time of first vaccination. Female subjects of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy or post-menopause. Female subjects of childbearing potential may be enrolled in the study, if the subject: has practiced adequate contraception for 30 days prior to vaccination, has a negative pregnancy test on the day of enrolment, and has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series. Additional inclusion criteria only for subjects to be enrolled in the dose-escalation safety lead-in screening epoch: - Healthy subjects as established by medical history, clinical examination and laboratory assessment. Additional inclusion criteria only for subjects to be enrolled in the PoP screening epoch: - Healthy subjects as established by medical history and clinical examination before entering into the study with an ongoing SSTI suspected to be caused by S. aureus, as diagnosed by investigator (before randomization subjects have to be treated until clinical resolution of culture confirmed SSTI caused by S. aureus). SSTI must be amenable to microbiological culturing per standard clinical practice (i.e. recovery of drainage sample from abscess or suppurative cellulitis). OR - Healthy subjects as established by medical history and clinical examination before entering into the study with an ongoing S. aureus SSTI (i.e. S. aureus is the most likely cause), as confirmed by a S. aureus positive culture performed outside the study procedures and not earlier than 30 days prior to Informed Consent Form signature. Before randomisation subjects have to be treated until clinical resolution of the culture confirmed SSTI caused by S. aureus. These subjects will be enrolled whether they have or have not already started specific treatment of the infection. In case they have not started the treatment, this will be then given in compliance with the standard medical practice for the management of S. aureus SSTIs and the choice and judgment of the most appropriate treatment will be applied by the investigator, outside the study procedures. Exclusion Criteria: All subjects at study entry BMI >40 kg/m2 History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine Hypersensitivity to latex Recurrent history of uncontrolled neurological disorders or seizures History of potential immune-mediated disease (pIMD) Clinical conditions that in the investigator's opinion represent a contraindication to intramuscular vaccination and blood draws Known bleeding diathesis or any condition that may be associated with a prolonged bleeding time Use of any investigational or non-registered product (drug, vaccine or medical device) other than the study vaccine(s) within 30 days before the first dose of study vaccine(s)/placebo (Day -29 to Day 1), or during the study period Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 3 months prior to the first vaccine/placebo dose Cytotoxic therapy (e.g., medications used during cancer chemotherapy) Administration of long-acting immune-modifying drugs at any time during the study period (e.g. infliximab) Administration of immunoglobulins and/or any blood products or plasma derivatives within 3 months before the first dose of study vaccine or during the study period Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 15 days before the first dose and ending 15 days after the last dose of vaccine(s) administration with the exception of any non-adjuvanted influenza vaccine which may be administered ≥7 days before or after each study vaccination *In case an emergency mass vaccination for an unforeseen public health threat (e.g.: a pandemic) is organised by the public health authorities, outside the routine immunisation program, the time period described above can be reduced if necessary for that vaccine provided it is licensed and used according to its Product Information. Concurrently participating in another clinical study, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product (drug or medical device) Received a vaccine against S. aureus Pregnant or lactating female Female planning to become pregnant or planning to discontinue contraceptive precautions before 2 months after completion of the vaccination series History of chronic alcohol consumption and/or drug abuse Any study personnel or immediate dependents, family, or household member All subjects at the time of vaccination Any clinically significant hematological (hemoglobin level, white blood cell, lymphocyte, neutrophil, eosinophil, platelet count and red blood cell count) and/or biochemical (alanine aminotransferase [ALT], aspartate aminotransferase [AST], creatinine) laboratory abnormality Additional exclusion criteria applied only for dose-escalation safety lead-in Any active or ongoing illness at screening or time of injection History of any serious chronic or progressive disease according to the judgment of the investigator Additional exclusion criteria applied only for PoP at study entry Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination Major congenital defects, as assessed by the investigator Acute or chronic, clinically significant pulmonary, cardiovascular*, hepatic or renal functional abnormality, neoplasm, diabetes type 1 and uncontrolled diabetes type 2*, as determined by physical examination or laboratory screening tests * Note: Well-controlled type 2 diabetes mellitus (HbA1c <7%) and well-controlled arterial hypertension (blood pressure <140/90 mmHg) can be considered for inclusion in the study. Any behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, may interfere with the subject's ability to participate in the study Individuals at risk for severe or life-threatening SSTIs (e.g., lymphatic or venous insufficiency, liver and kidney disease, IV drug use, etc.) Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the subject due to participation in the study Additional exclusion criteria applied only for PoP at vaccination - Microbiological test results of drainage suggest that the SSTI etiology could be other than infection with S. aureus Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 64 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Prevention Allocation: Randomized Intervention Model: Sequential Assignment Masking: Quadruple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Half dose non-adj Group 1a<br>Subjects aged 18 to 50 at the time of first vaccination who receive 1 dose of Sa-5Ag (5 antigens of S. aureus) half dose, non-adjuvanted at Day 1. | Biological: Sa-5Ag half dose non-adjuvanted<br>* 1 dose of Sa-5Ag (5 antigens of S. aureus) half dose, non-adjuvanted at Day 1, administered intramuscularly.<br>| | Placebo Comparator: Placebo Group 1b<br>Subjects aged 18 to 50 at the time of first vaccination who receive 1 dose of placebo (saline) at Day 1. | Biological: Placebo<br>* One dose of placebo (saline solution for injection/ vial or prefilled syringe) at Day 1 for placebo groups 1 to 3 and a series of 2 doses of placebo given approximately 2 months apart (Days 1 and 61) for placebo groups 4 and 5, administered intramuscularly.<br>| | Experimental: Full dose non-adj Group 2a<br>Subjects aged 18 to 50 at the time of first vaccination who receive 1 dose of Sa-5Ag (5 antigens of S. aureus) full dose, non-adjuvanted at Day 1 | Biological: Sa-5Ag full dose non-adjuvanted<br>* 1 dose of Sa-5Ag (5 antigens of S. aureus) full dose, non-adjuvanted at Day 1, administered intramuscularly.<br>| | Placebo Comparator: Placebo Group 2b<br>Subjects aged 18 to 50 at the time of first vaccination who receive 1 dose of placebo (saline) at Day 1. | Biological: Placebo<br>* One dose of placebo (saline solution for injection/ vial or prefilled syringe) at Day 1 for placebo groups 1 to 3 and a series of 2 doses of placebo given approximately 2 months apart (Days 1 and 61) for placebo groups 4 and 5, administered intramuscularly.<br>| | Experimental: Half dose adj Group 3a<br>Subjects aged 18 to 50 at the time of first vaccination who receive 1 dose of Sa-5Ag (5 antigens of S. aureus) half dose, adjuvanted at Day 1. | Biological: Sa-5Ag half dose adjuvanted<br>* 1 dose of Sa-5Ag (5 antigens of S. aureus) half dose, adjuvanted at Day 1, administered intramuscularly.<br>| | Placebo Comparator: Placebo Group 3b<br>Subjects aged 18 to 50 at the time of first vaccination who receive 1 dose of placebo (saline) at Day 1. | Biological: Placebo<br>* One dose of placebo (saline solution for injection/ vial or prefilled syringe) at Day 1 for placebo groups 1 to 3 and a series of 2 doses of placebo given approximately 2 months apart (Days 1 and 61) for placebo groups 4 and 5, administered intramuscularly.<br>| | Experimental: Full dose adj Group 4a<br>Subjects aged 18 to 50 at the time of first vaccination who receive a series of 2 doses of S. aureus candidate vaccine (Sa-5Ag full dose adjuvanted) given approximately 2 months apart (Days 1 and 61) | Biological: Sa-5Ag full dose adjuvanted<br>* A series of 2 doses of S. aureus candidate vaccine (Sa-5Ag full dose adjuvanted) given approximately 2 months apart (Days 1 and 61), administered intramuscularly.<br>| | Placebo Comparator: Placebo Group 4b<br>Subjects aged 18 to 50 at the time of first vaccination who receive a series of 2 doses of placebo (saline) given approximately 2 months apart (Days 1 and 61). | Biological: Placebo<br>* One dose of placebo (saline solution for injection/ vial or prefilled syringe) at Day 1 for placebo groups 1 to 3 and a series of 2 doses of placebo given approximately 2 months apart (Days 1 and 61) for placebo groups 4 and 5, administered intramuscularly.<br>| | Experimental: Vaccine Group 5a<br>Subjects aged 18 to 64 at the time of first vaccination who receive a series of 2 doses of S. aureus candidate vaccine (Sa-5Ag full dose adjuvanted) given approximately 2 months apart (Days 1 and 61). | Biological: Sa-5Ag full dose adjuvanted<br>* A series of 2 doses of S. aureus candidate vaccine (Sa-5Ag full dose adjuvanted) given approximately 2 months apart (Days 1 and 61), administered intramuscularly.<br>| | Placebo Comparator: Placebo Group 5b<br>Subjects aged 18 to 64 at the time of first vaccination who receive a series of 2 doses of placebo (saline) given approximately 2 months apart (Days 1 and 61). | Biological: Placebo<br>* One dose of placebo (saline solution for injection/ vial or prefilled syringe) at Day 1 for placebo groups 1 to 3 and a series of 2 doses of placebo given approximately 2 months apart (Days 1 and 61) for placebo groups 4 and 5, administered intramuscularly.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Number of participants with solicited local adverse events (AEs) (any, grade 3) | The solicited local AE(s) assessed are pain, redness and swelling. Any = any solicited local AE, regardless of intensity; Grade 3 pain = Significant pain at rest, that prevents normal every day activities; Grade 3 redness/swelling = greater than or equal to (≥)100 mm diameter (greatest surface diameter in millimetres [mm]). | During 7 days after the first dose (Days 1 to 8) | | Number of participants with solicited local adverse events (AEs) (any, grade 3) | The solicited local AE(s) assessed are pain, redness and swelling. Any = any solicited local AE, regardless of intensity; Grade 3 pain = Significant pain at rest, that prevents normal every day activities; Grade 3 redness/swelling = greater than or equal to (≥)100 mm diameter (greatest surface diameter in millimeters [mm]). | During 7 days after the second dose (Days 61 to 68) | | Number of participants with solicited general AEs (any, grade 3) | The solicited general AE(s) assessed are headache, fatigue, nausea, vomiting, diarrhea, abdominal pain, myalgia, shivering and fever (temperature ≥ 38.0 degrees Celsius (°C)/100.4 degrees Fahrenheit (°F). Any = any solicited general AE regardless of intensity; Grade 3 headache/fatigue/nausea/abdominal pain/myalgia/shivering = Severe: Prevents daily activity. Grade 3 vomiting = Severe: 6 or more times in 24 hours or requires intravenous hydration. Grade 3 diarrhea = Severe: 6 or more loose stools in 24 hours or requires intravenous hydration. Grade 3 fever = body temperature greater than (>) 40.0°C/104°F. | During 7 days after the first dose (Days 1 to 8) | | Number of participants with solicited general AEs (any, grade 3) | The solicited general AE(s) assessed are headache, fatigue, nausea, vomiting, diarrhea, abdominal pain, myalgia, shivering and fever (temperature ≥ 38.0 degrees Celsius (°C)/100.4 degrees Fahrenheit (°F). Any = any solicited general AE regardless of intensity; Grade 3 headache/fatigue/nausea/abdominal pain/myalgia/shivering = Severe: Prevents daily activity. Grade 3 vomiting = Severe: 6 or more times in 24 hours or requires intravenous hydration. Grade 3 diarrhea = Severe: 6 or more loose stools in 24 hours or requires intravenous hydration. Grade 3 fever = body temperature greater than (>) 40.0°C/104°F. | During 7 days after the second dose (Days 61 to 68) | | Number of participants with unsolicited AEs (any, grade 3, related, related grade 3) | Any (independent from causality) unsolicited AEs regardless of intensity; Grade 3 unsolicited AEs = An AE which prevents normal, everyday activities. Such an AE would, for example, prevent attendance at work/school and would necessitate the administration of corrective therapy. Related unsolicited AEs = AEs assessed by the investigator to be causally related to vaccination. Grade 3 related unsolicited AEs = An AE which prevents normal, everyday activities. Such an AE would, for example, prevent attendance at work/school and would necessitate the administration of corrective therapy. | During 30 days after the first dose (Days 1 to 31) | | Number of participants with unsolicited AEs (any, grade 3, related, related grade 3) | Any (independent from causality) unsolicited AEs regardless of intensity; Grade 3 unsolicited AEs = An AE which prevents normal, everyday activities. Such an AE would, for example, prevent attendance at work/school and would necessitate the administration of corrective therapy. Related unsolicited AEs = AEs assessed by the investigator to be causally related to vaccination. Grade 3 related unsolicited AEs = An AE which prevents normal, everyday activities. Such an AE would, for example, prevent attendance at work/school and would necessitate the administration of corrective therapy. | During 30 days after the second dose (Days 61 to 91) | | Number of participants with serious AEs (SAEs) (any, grade 3, related, related grade 3) | Any (independent from causality) SAEs regardless of intensity; Grade 3 SAEs = SAE which prevents normal, everyday activities. Such an SAE would, for example, prevent attendance at work/school and would necessitate the administration of corrective therapy. Related SAEs = SAEs assessed by the investigator to be causally related to vaccination. Grade 3 related SAEs = SAE which prevents normal, everyday activities. Such an SAE would, for example, prevent attendance at work/school and would necessitate the administration of corrective therapy. | Throughout the study period [from Day 1 (day of vaccination) until Day 366 | | Number of participants with serious AEs (SAEs) (any, grade 3, related, related grade 3) | Any (independent from causality) SAEs regardless of intensity; Grade 3 SAEs = SAE which prevents normal, everyday activities. Such an SAE would, for example, prevent attendance at work/school and would necessitate the administration of corrective therapy. Related SAEs = SAEs assessed by the investigator to be causally related to vaccination. Grade 3 related SAEs = SAE which prevents normal, everyday activities. Such an SAE would, for example, prevent attendance at work/school and would necessitate the administration of corrective therapy. | Throughout the study period [from Day 1 (day of vaccination) until Day 426 | | Number of participants with potential immune-mediated diseases (PIMDs) (any, grade 3, related, related grade 3) | Any (independent from causality) PIMDs regardless of intensity; Grade 3 PIMDs = PIMD which prevents normal, everyday activities. Such an PIMD would, for example, prevent attendance at work/school and would necessitate the administration of corrective therapy. Related PIMDs = PIMDs assessed by the investigator to be causally related to vaccination. Grade 3 related PIMDs = PIMD which prevents normal, everyday activities. Such an PIMD would, for example, prevent attendance at work/school and would necessitate the administration of corrective therapy. | Throughout the study period [from Day 1 (day of vaccination) until Day 366 | | Number of participants with potential immune-mediated diseases (PIMDs) (any, grade 3, related, related grade 3) | Any (independent from causality) PIMDs regardless of intensity; Grade 3 PIMDs = PIMD which prevents normal, everyday activities. Such an PIMD would, for example, prevent attendance at work/school and would necessitate the administration of corrective therapy. Related PIMDs = PIMDs assessed by the investigator to be causally related to vaccination. Grade 3 related PIMDs = PIMD which prevents normal, everyday activities. Such an PIMD would, for example, prevent attendance at work/school and would necessitate the administration of corrective therapy. | Throughout the study period [from Day 1 (day of vaccination) until Day 426 | | Number of participants with haematological and biochemical laboratory abnormalities and changes from the baseline values | The number of participants having hematology and biochemistry results below, within or above the normal laboratory ranges, compared to baseline range indicator. | At Day 8 (7 days after the first dose) | | Number of participants with haematological and biochemical laboratory abnormalities and changes from the baseline values | The number of participants having hematology and biochemistry results below, within or above the normal laboratory ranges, compared to baseline range indicator. | At Day 68 (7 days after the second dose) | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Number of participants with at least one culture confirmed case of recurrent S. aureus SSTI | This key secondary outcome measure is to evaluate efficacy in terms of number of participants with at least one culture confirmed case of recurrent S. aureus SSTI starting 14 days after the second dose. | Starting from Day 75 (i.e.14 days after the second dose) up to Day 426 (12 months after the second dose). | | Number of participants with at least one culture confirmed case of recurrent S. aureus SSTI | This co-secondary outcome measure is to evaluate efficacy in terms of number of participants with at least one culture confirmed case of recurrent S. aureus SSTI starting 14 days after the first dose. | Starting from Day 15 (i.e. 14 days after the first dose) up to Day 426 (12 months after the second dose). | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- S. aureus, skin and soft tissue infection, first time in human, S. aureus vaccine

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Randomised Evaluation of COVID-19 Therapy (RECOVERY) in Children With PIMS-TS in Switzerland (SWISSPED-RECOVERY) Study Overview ================= Brief Summary ----------------- The study is to provide reliable estimates of the effect of study treatment on hospital length of stay through to 28 days after randomisation. The protocol describes an overarching trial design to provide reliable evidence on the efficacy of candidate therapies for children hospitalised with PIMS-TS. It is an adaptive pragmatic platform trial with an open-label randomisation. New trial arms can be added as evidence emerges that other candidate therapeutics should be evaluated. Detailed Description ----------------- In May 2020 a new COVID-associated inflammatory syndrome in children was identified, Paediatric Inflammatory Multisystem Syndrome - Temporally associated with SARS-CoV-2 (PIMS-TS). A rapid international consensus process identified the need to evaluate corticosteroids and intravenous immunoglobulin (IVIg) as initial therapies in PIMS-TS, and confirmed tocilizumab and anakinra as biological anti-inflammatory agents to be evaluated as a second line therapy. This Swissped-Recovery trial is a sister trial to the RECOVERY international trial with the implementation of the study at Swiss study sites. The protocol describes an overarching trial design to provide reliable evidence on the efficacy of candidate therapies for children hospitalised with PIMS-TS. It is an adaptive pragmatic platform trial with an open-label randomisation. New trial arms can be added as evidence emerges that other candidate therapeutics should be evaluated. Additional substudies can be added to provide more detailed information on side effects or sub-categorisation of patient types. Official Title ----------------- Randomised Evaluation of COVID-19 Therapy (RECOVERY) in Children With PIMS-TS in Switzerland (SWISSPED-RECOVERY) Conditions ----------------- Paediatric Inflammatory Multisystem Syndrome-Temporally Associated With SARS-CoV-2 (PIMS-TS) Intervention / Treatment ----------------- * Drug: Methylprednisolone sodium succinate 10 mg/kg intravenously * Biological: Human normal immunoglobulin (IVIg) Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Hospitalised children (aged <18 years old) SARS-CoV-2 infection associated disease (clinically suspected or laboratory confirmed) with evidence of single or multi-organ dysfunction (called Pediatric Multisystem Inflammatory Syndrome temporally associated with COVID-19 [PIMS-TS]). No medical history that might, in the opinion of the attending clinician, put the patient at significant risk if he/she were to participate in the trial Exclusion Criteria: Neonates/infants with a corrected gestational age of <= 44 weeks If the attending clinician believes that there is a specific contra-indication to one of the active drug treatment arms or that the patient should definitely be receiving one of the active drug treatment arms, then that arm will not be available for randomisation for that patient. Ages Eligible for Study ----------------- Minimum Age: 44 Weeks Maximum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: Overarching trial design with treatment arms that are both available at the hospital and not believed by the enrolling doctor to be contraindicated (e.g. by particular co-morbid conditions or concomitant medications). Treatment arms to be added or removed according to the emerging evidence. Main randomisation part A: Methylprednisolone 2 mg/kg for three days intravenous or orally vs corticosteroids methylprednisolone 10mg/kg intravenous for three days vs intravenous immunoglobulin. Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Methylprednisolone sodium succinate 10 mg/kg<br>Methylprednisolone sodium succinate 10 mg/kg intravenously once daily for 3 days (max 1 g per dose) | Drug: Methylprednisolone sodium succinate 10 mg/kg intravenously<br>* Methylprednisolone sodium succinate 10 mg/kg intravenously once daily for 3 days (max 1 g per dose)<br>| | Active Comparator: Human normal immunoglobulin (IVIg)<br>Human normal immunoglobulin (IVIg) 2g/kg intravenously as a single dose in line with guidance for dosing and administration in Kawasaki disease | Biological: Human normal immunoglobulin (IVIg)<br>* Human normal immunoglobulin (IVIg) 2g/kg intravenously as a single dose in line with guidance for dosing and administration in Kawasaki disease<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Hospital length of stay | effect of study treatment on hospital length of stay | Within 28 days after randomisation | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | All-cause mortality among patients | For each pairwise comparison with the 'no additional treatment' arm, the primary objective is to provide reliable estimates of the effect of study treatments on all-cause mortality. | Within 28 days and up to 6 months after randomisation | | Composite endpoint of death or need for mechanical ventilation or extracorporeal membrane oxygenation (ECMO) | Among patients not on invasive mechanical ventilation at baseline, the number of patients with a composite endpoint of death or need for invasive mechanical ventilation or ECMO. | Within 28 days and up to 6 months after randomisation | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- coronavirus-disease (COVID-19), SARS coronavirus 2 (SARS-CoV-2), tocilizumab, anakinra, Human normal immunoglobulin (IVIg), Methylprednisolone sodium succinate

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9-ING-41 Plus Retifanlimab and Gemcitabine/Nab-Paclitaxel in Patients With Advanced Pancreatic Adenocarcinoma Study Overview ================= Brief Summary ----------------- This trial examines how Pancreatic Adenocarcinoma reacts to the addition of 9-ING-41 and retifanlimab to the standard of care chemotherapy treatment, to see if using this combination will help and is able to effect disease progression. Detailed Description ----------------- Given the role of GSK-3β in immune regulation, the combination of GSK-3β inhibition with PD 1 inhibition may be expected to provide synergistic anti-tumor efficacy. The excellent safety profile of 9-ING-41, along with preclinical and clinical evidence of anti-tumor activity in pancreatic cancer, provides a strong rationale to evaluate the efficacy of 9-ING-41 in combination with a PD 1 inhibitor plus standard chemotherapy (gemcitabine/nab-paclitaxel) as frontline therapy for patients with advanced PDAC. The combination of 9-ING-41 and retifanlimab with gemcitabine/nab-paclitaxel has not previously been administered to human subjects. In the 1801 study, 9-ING- 41 has been administered in combination with various chemotherapy regimens including gemcitabine/nab-paclitaxel, with one 9-ING-41-related SAE (transient visual change) documented to date. Retifanlimab alone has been well-tolerated when administered for up to 2 years in patients with anal cancer. Overall, based on previous nonclinical and clinical experience, both of these agents appear to have an acceptable safety profile and do not appear to have significant overlapping toxicities. However, it is possible that when they are administered together and in combination with gemcitabine/nab-paclitaxel, more frequent or severe AEs, or new AEs not previously observed with any of these agents administered alone, may occur. It is not known if administration of 9-ING-41 and retifanlimab will act synergistically to provide increased anti-tumor activity compared to gemcitabine/nab-paclitaxel alone. Subjects in this study should not expect to benefit directly by their participation in the study. The data collected in this study may benefit future cancer patients. Official Title ----------------- A Phase 2 Study of 9-ING-41, a Glycogen Synthase Kinase 3-beta (GSK-3β) Inhibitor, Combined With Retifanlimab, a PD-1 Inhibitor, Plus Gemcitabine/Nab-Paclitaxel as Frontline Therapy for Patients With Advanced Pancreatic Adenocarcinoma (RiLEY) Conditions ----------------- Pancreatic Adenocarcinoma Intervention / Treatment ----------------- * Drug: 9-ING-41 * Drug: Retifanlimab * Drug: Gemcitabine * Drug: Abraxane Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Voluntarily written informed consent and willingness/ability to comply with the protocol requirements Has pathologically confirmed advanced, recurrent, or metastatic pancreatic cancer AND is previously untreated with systemic agents in the advanced/metastatic setting. Must have at least 1 measurable lesion per RECIST v1.1. Lesions that are radiated should not count as target lesions unless there is evidence of growth post radiation on a subsequent scan prior to trial enrollment. Must have available archived tumor tissue at study entry (metastatic tissue preferred to primary tissue) Adequate bone marrow function: absolute neutrophil count (ANC) ≥ 1000/mL; hemoglobin ≥ 8.5 g/dL, platelets ≥ 100,000/mL. Adequate liver function: transaminases (aspartate aminotransferase/ alanine aminotransferase, AST/ALT) and alkaline phosphatase ≤ 2.5 x ULN (≤ 5 X the upper limit of normal (ULN) in the setting of liver metastasis or infiltration with malignant cells); bilirubin ≤ 1.5 x ULN. Adequate renal function: creatinine clearance CrCl > 60 mL/min measured or calculated by Cockcroft- Gault (C-G) equation (estimated glomerular filtration rate [eGFR] can also be used in place of CrCl). Serum amylase and lipase ≤ 1.5 x ULN Eastern Co-operative Oncology Group (ECOG) performance status (PS) 0 - 1 Has received the final dose of any of the following treatments/ procedures within the specified minimum intervals before first dose of study drug: Focal radiation therapy - 7 days Surgery with general anesthesia - 7 days Surgery with local anesthesia - 7 days Exclusion Criteria: Is pregnant or lactating. Is known to be hypersensitive to any of the components or metabolites of 9-ING-41 or to the excipients used in its formulation, or known sensitivity to one of the chemotherapeutic agents or to the PD-1 inhibitor. History of receiving prior treatment with any anti-PD-1, PD-L1 or PD-L2 agent. Has endocrine or acinar pancreatic carcinoma. Has not recovered from clinically significant toxicities as a result of prior anticancer therapy, except alopecia, anemia not requiring transfusion support and infertility. Recovery is defined as ≤ Grade 1 or baseline severity per Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 (v5.0). Has significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, or stroke within 6 months of the first dose of 9-ING-41, or cardiac arrhythmia requiring medical treatment detected at screening. Has had a myocardial infarction within 12 weeks of the first dose of 9-ING-41 or has electrocardiogram (ECG) abnormalities that are deemed medically relevant by the investigator or study medical coordinator. Has symptomatic rapidly progressive brain metastases or leptomeningeal involvement as assessed by computed tomography (CT) scan or magnetic resonance imaging (MRI). Patients with stable brain metastases or leptomeningeal disease or slowly progressive disease are eligible provided that they have not required new treatments for this disease in a 28-day period before the first dose of study drug, and anticonvulsants and steroids are at a stable dose for a period of 14 days prior to the first dose of study drug. Has had major surgery (not including placement of central lines) within 7 days prior to study entry or is planned to have major surgery during the course of the study (major surgery may be defined as any invasive operative procedure in which an extensive resection is performed, e.g., a body cavity is entered, organs are removed, or normal anatomy is altered). Has any medical and/or social condition that, in the opinion of the investigator would preclude study participation. Has received an investigational anti-cancer drug in the 14-day period before the first dose of study drug (or within 5 half-lives if longer) or is currently participating in another interventional clinical trial. Has a current malignancy other than pancreatic cancer. Known immunodeficiency syndrome or active autoimmune disease or requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (> 10 mg/day of prednisone or equivalent). Evidence of interstitial lung disease, history of interstitial lung disease, or active, noninfectious pneumonitis. Palliative radiation therapy administered within 1 week of first dose of study treatment or radiation therapy that is > 30 Gy within 6 months of the first dose of study treatment. Has received systemic antibiotics ≤ 7 days prior to the first dose of study drug. History of organ transplant, including allogeneic stem cell transplantation. Known hypersensitivity to another monoclonal antibody that cannot be controlled with standard measures (eg, antihistamines and corticosteroids). Known allergy or hypersensitivity to any component of retifanlimab or formulation components. Has received a live vaccine within 28 days of the planned start of study drug. Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: 9-ING-41 plus Retifanlimab plus Gem/Abraxane<br>intravenous (IV) infusion of nab-paclitaxel at a dose of 125 mg per square meter, followed by an infusion of gemcitabine according to the gemcitabine label at a dose of 1000 mg per square meter, on days 1, 8, 15 of a 28-day cycle. Retifanlimab 500 mg IV on day 1 of a 28-day cycle. (Retifanlimab will be administered following gemcitabine/nab-paclitaxel.) 9-ING-41 administered at a dose of 9.3 mg/kg by IV infusion twice weekly on Days 1 and 4 of each week of a 28-day cycle. (9-ING-41 will be administered following retifanlimab.) | Drug: 9-ING-41<br>* 9-ING-41 is a small molecule potent selective GSK-3β inhibitor<br>Drug: Retifanlimab<br>* Humanized, hinge-stabilized, IgG4κ monoclonal antibody that recognizes human PD-1.<br>* Other names: INCMGA00012;Drug: Gemcitabine<br>* cytotoxic chemotherapy agent<br>Drug: Abraxane<br>* cytotoxic chemotherapy agent<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Disease Control Rate (DCR) | Percentage of patients with stable disease for ≥ 16 weeks, Complete Response (CR), or Partial Response (PR) during treatment. Per RECIST v1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or nontarget) with reduction in short axis to <10 mm. Partial Response (PR): ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). | Up to 60 months (from enrollment) | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Overall Response Rate (ORR) | Percentage of patients with Complete Response (CR) or Partial Response (PR) per RECIST v1.1 Per RECIST v1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or nontarget) with reduction in short axis to <10 mm. Partial Response (PR): ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | Up to 60 months (from enrollment) | | Adverse Events and Serious Adverse Events | Number of participants with treatment-related adverse events (AE) and/or serious adverse events (SAE) as assessed by CTCAE v5.0. | Up to 60 months (from enrollment) | | Duration of response (DOR) | Median time from documentation of tumor response to disease progression. Per RECISIT v1.1, Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or nontarget) with reduction in short axis to <10 mm. Partial Response (PR): ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). | Up to 60 months (from enrollment) | | Progression-free survival (PFS) | Median time from study enrollment until objective tumor progression or death. Per RECISIT v1.1, Progressive Disease (PD) is ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression. | Up to 60 months (from enrollment) | | Overall survival (OS) | Median time from study entry to death from any cause. | Up to 60 months (from enrollment) | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- glycogen biosynthesis, Glycogen synthase kinase-3 (GSK-3), NF-κB pathway

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Detection of Upper Gastrointestinal (GI) Bleeding Using a Novel Bleeding Sensor Capsule -A Pilot Study Study Overview ================= Brief Summary ----------------- This is a multi-center, prospective, non-randomized, open-label, exploratory clinical investigation performed to evaluate safety and effectiveness of the PillSense System when used for detection of blood in the stomach of patients suspected to have an Upper Gastrointestinal Bleed (UGIB). Detailed Description ----------------- The PillSense System consists of the PillSense Capsule, an atraumatic, ingestible, and disposable capsule and PillSense Receiver, an external real-time monitor for results display. The PillSense Capsule is a non-invasive, single use device designed to detect blood in the stomach and wirelessly transmit the data to the external PillSense Receiver. The receiver is a handheld device which displays real-time information gathered from the capsule and clearly displays results, Blood Detected or No Blood Detected. All enrolled participants were admitted for suspected UGIB and were required to ingest a PillSense Capsule followed by esophagogastroduodenoscopy (EGD) within 1 hour of PillSense Capsule administration. All Patients underwent standard endoscopy following PillSense Capsule evaluation and results were compared with the PillSense System result, i.e., Blood Detected or No Blood Detected. The study was also designed to confirm transit of the PillSense Capsule through the GI tract and patient tolerability of the PillSense Capsule. Official Title ----------------- Detection of Upper Gastrointestinal (GI) Bleeding Using a Novel Bleeding Sensor Capsule -A Pilot Study Conditions ----------------- Upper Gastrointestinal Bleeding Intervention / Treatment ----------------- * Device: PillSense System Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Age 18 -80 years Ability to give written informed consent Clinical suspicion of bleeding Exclusion Criteria: Circulatory or hemodynamic instability with a clear need for urgent endoscopy or surgery (systolic blood pressure <100 mmHg,heart rate > 100 / min) Known current stenosis of the GI tract Subject is using a pacemaker or other implantable electrical device Dysphagia or difficulties in swallowing pills the size of the capsule History of achalasia or known esophageal dysmotility History of gastroparesis History of severe constipation (1 bowel movement per week or less) Patients who are currently pregnant or breastfeeding, or intend to become pregnant during the investigation Presence of psychological issues preventing participation Stomach bezoar History of Crohn disease History of diverticulitis History of bowel obstruction Suspected gastrointestinal tumor disease Planned MRI investigation (MRI needed before the capsule is excreted) Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 80 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Device Feasibility Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: PillSense System<br>The device is composed of an orally ingested sensor capsule and a wireless handheld receiver for real-time display of sensor data. The capsule contains a measuring slot for blood entry. The sensor capsule is used for diagnosis in patients with suspected acute bleeding in the upper gastrointestinal tract. | Device: PillSense System<br>* The PillSense capsule is a diagnostic capsule equipped with a sensor for in vivo detection of liquid blood and a paired PillSense receiver for result display.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Device feasibility | Ability of PillSense Capsule to detect the presence or absence of blood and send the results to the PillSense receiver | within 30 minutes | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Device sensitivity | Subjects with positive findings for blood based on PillSense and EGD | within 2 hours | | Device Specificity | Subjects with negative findings for blood based on PillSense and EGD | within 2 hours | | Safety | Number of patients that developed device-related adverse event (etc. retention, aspiration or bowel obstruction) | up to 3 weeks |

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A Study of LCL161 in Combination With Weekly Paclitaxel in Adult Patients With Advanced Solid Tumors Study Overview ================= Brief Summary ----------------- This is a dose escalation study that will assess the safety and efficacy of LCL161 in combination with weekly paclitaxel in adult patients with advanced solid tumors. Official Title ----------------- A Phase Ib Study of LCL161 in Combination With Weekly Paclitaxel in Adult Patients With Advanced Solid Tumors Conditions ----------------- Solid Tumors Intervention / Treatment ----------------- * Drug: LCL161 * Drug: Paclitaxel Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patients with breast cancer must have a histologically or cytologically confirmed diagnosis of disease that has metastasized or is resistant to therapy. Patients with ovarian cancer must have histological evidence of recurrent epithelial ovarian, fallopian tube or peritoneal cancer. Patients must have recovered or stabilized from all toxicities related to their previous treatment except for alopecia Male or female patients 18 years or older ECOG performance status 0-1 Life expectancy greater than 12 weeks Measurable disease as determined by RECIST v1.0 Patients must give written informed consent and comply with the protocol Exclusion Criteria: For patients with breast cancer: Concurrent Her2-directed or anti-estrogen therapy For patients with ovarian cancer: Primary refractory disease, defined as progression during initial treatment with a platinum- and taxane-containing regimen. Prior treatment with weekly paclitaxel. More than two chemotherapy regimens given in the relapse setting. Evidence of a documented bowel obstruction within six months of study entry Patients with unresolved peripheral neuropathy, nausea, vomiting, or diarrhea ≥ CTCAE Grade 2 Any concurrent severe and/or uncontrolled medical conditions that could increase the patient's risk for toxicity while in the study or that could confound discrimination between disease- and study treatment-related toxicities. Patients with impairment of GI function or GI disease that may significantly alter the absorption of LCL161 Patients who have undergone major surgery ≤ 3 weeks prior to starting study drug or who have not recovered from side effects of procedure. Pregnant or breast feeding (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive β-HCG laboratory test (> 5 mIU/mL). Known diagnosis of human immunodeficiency virus (HIV) infection or chronic active hepatitis B or C (HIV and hepatitis testing are not mandatory). Other protocol-defined inclusion/exclusion criteria may apply Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 100 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: LCL161 + Paclitaxel<br> | Drug: LCL161<br> <br> Drug: Paclitaxel<br> <br> | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Maximum tolerated dose (MTD)/RP2D of LCL161 when administered in combination with once weekly paclitaxel | | 24 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Safety and tolerability of the combination, including acute and chronic toxicities | | 24 months | | Pharmacokinetics of both LCL161 and paclitaxel when administered in combination (AUC0-∞, Cmax, tmax and other parameters as appropriate) | | 24 months | | Preliminary anti-tumor activity associated with this combination treatment | | 24 months | | Target inhibition, cell death, and cytokines in surrogate and tumor tissues | | 24 months | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- LCL161, solid tumors, paclitaxel

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Comparing Efficacy and Safety of Inhaled SNG001 to Placebo Study Overview ================= Brief Summary ----------------- When people with asthma get respiratory virus such as a cold or flu it often increases asthma symptoms. The investigators will test the study medication to find out if it can prevent the virus spreading from the nose to the lungs. SNG001 contains Interferon-beta that occurs naturally in the body. In this study, SNG001 will be given by a nebuliser. Detailed Description ----------------- The study will consist of a Pre-Treatment Phase into which subjects potentially eligible for the Treatment Phase will be recruited. Subjects will remain in the Pre-Treatment Phase until they experience respiratory virus symptoms at which time they will be further screened for eligibility for entry into the Treatment Phase. If eligible, subjects will be randomised 1:1 to receive SNG001 or placebo once daily for 14 days. Doses will be delivered by a CE marked breath actuated nebuliser (I-neb Philips Respironics). Subjects will be assessed for changes in changes in respiratory virus symptoms and asthma symptoms at home using a text message system, and via telephone questionnaire. Lung function will be measured both at home by the subjects (PEFR only) and in the clinic. Efficacy and safety will be monitored until at least 30 days post treatment. Official Title ----------------- A Randomised, Double-blind, Placebo-controlled Phase II Study, Comparing the Efficacy and Safety of Inhaled SNG001 to Placebo Administered to Asthmatic Subjects After the Onset of a Respiratory Viral Infection for the Prevention or Attenuation of Asthma Symptoms Caused by Respiratory Viruses Conditions ----------------- Asthma Intervention / Treatment ----------------- * Drug: Interferon beta 1a * Drug: Placebo Participation Criteria ================= Eligibility Criteria ----------------- Male or female aged 18 to 65 years of age at the time of screening. Symptoms of asthma for at least 2 years pri or to the Screening Visit, confirmed by a medical history and: ≥12% and 200mL bronchodilator reversibility at screening or documented in the past, OR, evidence of bronchial hyper-responsiveness at screening or documented in the past, OR, a documented hospital admission (including an Accident and Emergency admission) for asthma since the age of 18, OR. documented evidence that they have attended their GP surgery, out-of-hours clinic (or alternative health care provider) for worsening of asthma symptoms, since the age of 18 Must answer Yes to the question Does a cold make your asthma worse? To have had at least one asthma exacerbation suspected to have been caused by a respiratory virus in the last 24 months which required the use of oral steroids and/or additional treatment with antibiotics on one or more occasion. Must be taking regular inhaled corticosteroids. Pre-bronchodilator FEV1 ≥ 40 % predicted at screening. Post-bronchodilator FEV1 ≥ 50 % predicted at screening. Provide written informed consent. Females of childbearing potential must be using a medically acceptable adequate form of birth control and agree to maintain this usage throughout the duration of and four weeks post the Treatment Phase of the study. Motivation (in the Investigators opinion) to complete all study visits, the ability to communicate well with the Investigator and be capable of understanding the nature of the research and its treatment including its risks and benefits. Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 65 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Placebo Comparator: Placebo<br>Placebo once daily for 14 days | Drug: Placebo<br>* Placebo (excipients of the SNG001 solution only)<br>| | Experimental: SNG001<br> | Drug: Interferon beta 1a<br>* SNG001, IFN-β1a solution for inhalation<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | S-ACQ | To evaluate the superiority of inhaled SNG001 compared to placebo administered to asthmatic subjects after the onset of a respiratory viral infection for the prevention or attenuation of asthma symptoms caused by respiratory viruses in the modified intention to treat (mITT) population as measured by change from Baseline to Day 8 in the Shortened-Asthma Control Questionnaire (symptoms plus short-acting β2 agonist. - change from Baseline to Day 8 in the Shortened-Asthma Control Questionnaire | Baseline - Day 8 | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Asthma Index | To evaluate the superiority of inhaled SNG001 compared to placebo administered to asthmatic subjects after the onset of a respiratory viral infection for the prevention or attenuation of asthma symptoms caused by respiratory viruses in the mITT population as measured by peak score of the Asthma Index (Sorkness et al, 2008) in the 14 day period following first administration of study drug (measured from 24 hours post first dose to 24 hours post last dose taken). | Day 1-14 | | S-ACQ | To evaluate the superiority of inhaled SNG001 compared to placebo administered to asthmatic subjects after the onset of a respiratory viral infection for the prevention or attenuation of asthma symptoms caused by respiratory viruses in the per protocol (PP) population as measured by change from Baseline to Day 8 in the Shortened-Asthma Control Questionnaire. | Baseline - Day 8 | | Asthma Index | To evaluate the superiority of inhaled SNG001 compared to placebo administered to asthmatic subjects after the onset of a respiratory viral infection for the prevention or attenuation of asthma symptoms caused by respiratory viruses in the PP population as measured by peak score of the Asthma Index in the 14 day period following first administration of study drug (measured from 24 hours post first dose to 24 hours post last dose taken). | 14 days | | Sever Exacerbation | To evaluate the superiority of inhaled SNG001 compared to placebo administered to asthmatic subjects after the onset of a respiratory viral infection for the prevention or attenuation of asthma symptoms caused by respiratory viruses as measured by the proportion of subjects experiencing a severe exacerbation (Appendix 2) in the mITT population during the 14 days following first administration of study drug. | Day 1-14 | | Lung Function | To compare inhaled SNG001 to placebo administered to asthmatic subjects after the onset of a respiratory viral infection for the prevention or attenuation of decreases in lung function (AUC FEV1 and PEFR) caused by respiratory viruses in the mITT population during the 14 day dosing period. | Day 1-14 | | Viral Load | To compare the effect of inhaled SNG001 to placebo when administered to asthmatic subjects on viral load on Days 4 and 7 in sputum. | Days 4 and 7 | | Safety | To evaluate the safety of inhaled SNG001 when administered to asthmatic subjects. | Day 1-14 | | Concomitant Medications | To compare the frequency of use of concomitant medications in relation to conditions of the respiratory tract during the study Treatment Phase in asthmatic subjects receiving inhaled SNG001 compared to placebo. | Day 1-28 | | Pharmacokinetic | To gain information on the pharmacokinetic profile of inhaled SNG001 administered to asthmatic subjects during a respiratory virus infection. | Day 1-14 | | Pharmacodynamic | To gain information on the pharmacodynamic profile of inhaled SNG001 administered to asthmatic subjects during a respiratory virus infection. | Day 1-14 | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- asthma

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Observational Study of Ibrutinib Use in CLL Study Overview ================= Brief Summary ----------------- IB-RU-SCOPE is a routine-clinical practice oriented cohort observational study of ibrutinib efficacy and safety in approx. 70 patients with chronic lymphocytic leukemia in the Russian Federation Detailed Description ----------------- Ibrutinib is approved in Russia for treatment of CLL patients both in first line and in relapsed/refractory setting. There is a discrepancy in reported ibrutinib toxicity profile, efficacy and tolerability between registrational clinical trials and observational studies, which to some extent may be explained by patient selection in the former. IB-RU-SCOPE is a first routine-clinical practice oriented cohort observational study of ibrutinib in CLL in Russia. The study is designed to include all previously untreated and relapsed/refractory CLL patients older than 18 years with active disease, who have recently started or are about to start ibrutinib (both as monotherapy and in combination), and to follow them to a minimum of 18 and a maximum of 36 months. The study is being conducted in approx. 10 Russian hematological centers and aims to include approx. 70 CLL patients. Official Title ----------------- Analysis of Ibrutinib Efficacy and Safety in the Treatment of Chronic Lymphocytic Leukemia Patients in Routine Clinical Practice Conditions ----------------- Chronic Lymphocytic Leukemia Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Age older than 18 years. Diagnosis of chronic lymphocytic leukemia, established according to iwCLL criteria (Hallek et al., 2018). Presence of indications for initiating treatment as listed in iwCLL guidelines (Hallek et al., 2018) before start of ibrutinib therapy. Treatment with ibrutinib per instructions for medical use of the drug, approved in the Russian Federation, is planned or this therapy has been started within 7 days before enrolment in the study (date of signing of informed consent). Simultaneously, the patient has not received ibrutinib as one of the previous lines of treatment. Informed consent signed by the patient. Exclusion Criteria: 1. Presence of contraindications for the use of ibrutinib in accordance with the instructions, approved in the Russian Federation for the medical use of the drug, namely: known hypersensitivity to ibrutinib (e.g. with anaphylactic and anaphylactoid reactions); pregnancy and the period of breastfeeding; age under 18 years; severe renal dysfunction (creatinine clearance <30 mL/min), incl. need for hemodialysis; severe liver dysfunction (Child-Pugh class C); concomitant use with strong inducers of the isoenzyme CYP3A (e.g., carbamazepine, rifampicin, phenytoin and drugs, containing Hypericum perforatum extract); concomitant use with warfarin, other vitamin K antagonists, fish oil and vitamin E preparations. Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Frequency of adverse events (including serious adverse events) | In order to evaluate ibrutinib toxicity, all adverse events (AEs), which will occur in study patients, will be collected and analyzed. CTCAE v4.03 criteria and iwCLL criteria will be used for grading of non-hematologic and hematologic AEs, respectively. Frequencies of AEs of all grades will be calculated and reported. | 3 years | | Average duration of treatment with ibrutinib | Time from the first dose of ibrutinib to treatment discontinuation (e.g. due to AEs or CLL progression) will be measured in all study patients. Mean value will be then calculated and reported. This will provide a context, necessary for interpetation of other results (such as toxicity and efficacy measures). results (such as toxicity and efficacy measures). | 3 years | | Proportion of patients requiring dose reduction and/or discontinuation of therapy due to causes not related to CLL progression. | In order to evaluate tolerability of ibrutinib in CLL patients in routine clinical practice, all cases of ibrutinib dose reduction and/or drug discontinuation due to causes not related to CLL progression will be collected and analyzed. Proportion of patients, not tolerating full dose of ibrutinib will be then calculated and reported. | 3 years | | Dynamics of QoL indicators assessed by EORTC QLQ-C30 (version 3.0) questionnaire during treatment | Patients will complete EORTC QLQ-C30 (version 3.0) questionnaires every 3 months during the sudy. Data from questionnaires will be subsequently extracted as numerical values and analyzed according to recommended protocol to estimate changes in patient's quality of life (QoL) during treatment. As a result, either improvement, decline or no change in QoL will be shown | 3 yers | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- CLL, chronic lymphocytic leukemia, ibrutinib

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Does Saline Injection Around Phrenic Nerve Reduce Incidence of Diaphragmatic Paresis Following Interscalene Block? Study Overview ================= Brief Summary ----------------- Hemi-diaphragmatic palsy is a common undesirable effect of interscalene block, with an incidence of up to 100%. Mechanism of palsy is thought to be related to spread of local anaesthetic anterior to the anterior scalene muscle. We hypothesize that by injecting saline in this anatomical location prior to performing an interscalene block the incidence of phrenic palsy will be reduced. Detailed Description ----------------- Patients will be randomised to either group S (saline group) or group C (conventional group) by computer generated random numbers and allocation will be enclosed in sealed envelope. Anaesthetist performing and/or supervising the block will be the only personnel who will be aware of the randomisation. Patients will be blinded to the study group. Intraoperative management of the case will be done by an anaesthetist blinded to the study group. Outcome measurements will be recorded by study observers blinded to the group allocation. ISB protocol Following written informed consent, the patient will have routine monitors attached (ECG, Pulse oximeter and non-invasive blood pressure). Intravenous access will be secured and patients will be placed in 45 degree head-up position for the block with head turned to the non-operative side. Intravenous sedation with Midazolam (2 mg) and fentanyl (50 to 100 microgram) will be administered to all patients prior to the block. The ultrasound machine will be positioned on the side opposite to the block. Skin will be prepped with 2% Chlorhexidine (Chloraprep) following which the block will be performed under strict aseptic precautions with the anesthetist wearing a mask and sterile gloves. The high frequency linear probe (sonosite) will be aligned transversely across the neck at the interscalene level to identify C5 and C6 nerve roots. 2% lidocaine will be used for skin infiltration and stop before block performed prior to insertion of block needle. In plane posterior approach will be used with a 50 mm short bevel block needle (Braun) advanced through middle scalene muscle. Following this, the technique differs between the two groups. In group C, the needle tip will then be positioned between C5 and C6 nerve roots. At this location, 15 ml of 0.25% levobupivacaine will be injected in 5 ml increments with intermittent aspiration. The needle tip will not be repositioned unless the patient complaints of paraesthesia. In group S, at the same level chosen for interscalene block, needle tip will be positioned anterior to anterior scalene muscle. At this location 10 ml 0.9% saline will be injected. This will then be followed by repositioning of needle between roots of C5 and C6 where 15 ml of 0.25% levobupivacaine will be injected in 5 ml increments with intermittent aspiration. The needle tip will not be repositioned unless the patient complaints of paraesthesia. Intra-operative procedure Following performance of the block, all patients will receive protocolised general anaesthetic. Anaesthesia will be induced with 2-3 mg per kg of propofol, followed by rocuronium 0.6mg/kg for muscle relaxation. Anaesthesia will be maintained with inhaled sevoflurane (MAC 1 end tidal concentration) along with air and oxygen mixture to deliver an inspired oxygen concentration of 40%. Antibiotics will be given as per hospital protocol prior to incision. In the absence of contraindications, all patients will receive intravenous paracetamol 1g and parecoxib 40 mg as a part of multimodal analgesia regimen. All patients will also receive intravenous dexamethasone 8 mg and ondansetron 4mg for post-operative nausea and vomiting prophylaxis. Further doses of fentanyl in 25 microgram increments will be administered by the anaesthetist if the heart rate increases by more than 15% of baseline values obtained prior to induction. Patients will be reversed by suggamadex. If at least two twitches are present during TOF measurement 2 mg/kg dose will be administered. If less than 2 twitches are present, 4 mg/kg dose will be administered. Post-operative procedure: Following transfer to recovery unit, if patient reported pain score by numerical rating score was >3, morphine 2 mg increments will be given intravenously by the recovery staff. This will be repeated every 5 minutes till the pain score is <4. In patients needing more than 10 mg of morphine in the recovery, anaesthetist will be requested to review the patient. Post-operatively, in the absence of contraindications, all patients will be prescribed regular paracetamol 1g, 6 hourly and celecoxib 200 mg, 12 hourly. For breakthrough pain, oxynorm 10 mg as needed once every 4 hours will be prescribed. Anti-emetics (ondansetron 4 mg, 8 hourly and Cyclizine 50 mg, 8 hourly) will be prescribed for all patients to be administered as required. Patient will also be asked about presence or absence of subjective feeling of dypnoea and report satisfaction of overall anaesthetic management (numerical rating scale 0-10) prior to discharge from recovery. Diaphragm palsy and PFT assessment Diaphragm assessment and bed side spirometry will be done at two time points. First measurement (time point 1) will be done at the baseline as soon as the patient arrives in the induction room. This will be done prior to administration of any sedative agents or regional block. Second assessment (time point 2) will be done post-operatively once the patients are deemed to be ready for discharge from recovery back to the ward. For diaphragmatic paresis assessment, patients will be placed in supine position and curvilinear ultrasound probe (2-5 MHz) will be used. Diaphragm will be identified as hyperechoic line by subcostal approach using liver and spleen as acoustic windows. Patients will be requested to take deep breaths and M mode will be used to measure the excursion of diaphragm. Diaphragmatic paresis will be documented when there is more than 75% reduction in the excursion compared to baseline or if there was paradoxical movement of the diapragm. Bedside assessment will be done by radiologist blinded to the study group. Bedside spirometry assessments will be done with patients sitting up. They will be requested to make maximum inspiratory effort and blow as hard and fast in to the device. Best reading from three repeated measurements will be recorded. Official Title ----------------- Does Saline Injection Around Phrenic Nerve Reduce Incidence of Diaphragmatic Paresis Following Interscalene Block? Conditions ----------------- Phrenic Nerve Palsy Intervention / Treatment ----------------- * Procedure: Saline * Drug: Levobupivacaine Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patients undergoing surgery on shoulder, humerus, or clavicle Exclusion Criteria: Patient refusal Allergy to local anaesthesia Severe coagulopathy Contralateral phrenic nerve palsy Local infection Moderate to severe pulmonary dysfunction (GOLD II, II, IV) Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 80 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Supportive Care Allocation: Randomized Intervention Model: Parallel Assignment Masking: Triple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Group S (saline group)<br>In plane posterior approach will be used with a 50mm short bevel block needle (Braun), advanced through the middle scalene muscle. At the location chosen for interscalene block the needle tip will be positioned anterior to the anterior scalene muscle. At this point 10ml of 0.9% saline will be injected. This will be followed by repositioning of the needle between roots C5 and C6 where 20 ml of 0.25% levobupivicaine will be injected in 5ml increments with intermittent aspiration. | Procedure: Saline<br>* At the location chosen for interscalene block the needle tip will be positioned anterior to the anterior scalene muscle. At this point 10ml of 0.9% saline will be injected.<br>Drug: Levobupivacaine<br>* the needle tip will then be positioned between C5 and C6 nerve roots. At this location, 20 ml of 0.25% levobupivacaine will be injected in 5 ml increments with intermittent aspiration. The needle tip will not be repositioned unless the patient complaints of paraesthesia<br>| | Active Comparator: Group C (control group)<br>In plane posterior approach will be used with a 50mm short bevel block needle (Braun), advanced through the middle scalene muscle. The needle tip will be positioned between roots C5 and C6 where 20 ml of 0.25% levobupivicaine will be injected in 5ml increments with intermittent aspiration. | Drug: Levobupivacaine<br>* the needle tip will then be positioned between C5 and C6 nerve roots. At this location, 20 ml of 0.25% levobupivacaine will be injected in 5 ml increments with intermittent aspiration. The needle tip will not be repositioned unless the patient complaints of paraesthesia<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Rate of diaphragmatic paresis recorded in the post-operative period identified by ultrasound assessment | Diaphragmatic paresis will be documented with greater than 75% reduction in excursion compared to baseline | 4 hours | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | FEV1 | Forced expiratory volume in 1 second (FEV1) | 4 hours | | FVC | Forced vital capacity (FVC) | 4 hours | | PEFR | Peak expiratory flow rate (PEFR) will be assessed and compared to baseline | 4 hours | | Pain control | Intra-operative fentanyl consumption, post-operative morphine consumption in 24 hours, pain scores (numerical 1-10) on arrival in recovery and at 24 hours post operatively | 24 hours post-opertive | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- forced expiratory volume in 1 second, forced vital capacity, peak expiratory flow rate, interscalene block, diaphragmatic paresis

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Effect of Medicago Sativa on Oral Glucose Tolerance in Healthy Adults Study Overview ================= Brief Summary ----------------- Previous preclinical investigations have found that Medicago sativa promotes the decrease of glucose concentrations. To evaluate the acute effect of Medicago sativa administration on glucose tolerance, insulin secretion, and insulin sensitivity in healthy individuals. Detailed Description ----------------- A randomized, double-blind, placebo-controlled, two-period, cross-over clinical trail will be carrie out in 15 healthy, sedentary individuals of both genders, who meet the following inclusion criteria: 25 to 40 years of age, normal fasting plasma glucose (≤ 5.5 mm/L), blood pressure (<130/90 mmHg), body mass index of 25 to 29.9 kg/m2, no taking any medication known to affect glucose tolerance, nondrinkers and nonsmokers. No pregnant, and lactation estate for female participants. They will be select from the same neighborhood and socioeconomic status. After a fasting blood sample patients will be assigned at random-order through a closed-envelope selection, to receive one of two possible sequences during which they received either single oral doses of Medicago sativa or homologated placebo in 1,500 mg and were crossover with a difference of at least 7 days washout interval. Thirty minutes after each intervention patients underwent a 75-g oral glucose tolerant test (OGTT). Area under the curve of glucose and insulin, phases of insulin secretion, and insulin sensitivity will be calculate for each treatment period. Official Title ----------------- Effect of Acute Administration of Medicago Sativa on Glucose Tolerance, Insulin Secretion and Insulin Sensitivity in Normoglycemic, Overweight Adults Conditions ----------------- Glucose Tolerance Intervention / Treatment ----------------- * Drug: Medicago Sativa * Dietary Supplement: Placebo Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Fasting plasma glucose ≤99 mg/dL. Two hours postload plasma glucose (100 a 139 mg/dL). Body mass Index: 25 -39.9 kg/m2. body weight stable over the last 3 months. Women in follicular phase of the menstrual cycle (days 3 to 8 of the cycle) at the time of laboratory tests. Sedentary. Nonsmokers. Body weight unchanged upper to 5% for at least 3 moths before the study. Exclusion Criteria: Women in pregnancy and/or breastfeeding Physical or mental disability that makes it impossible to perform the intervention. Diagnosis of hypertension or heart failure. Untreated thyroid disease. Consumption of oral agents or other medications or supplements with proven properties that modify the behavior of glucose and lipids (oral hypoglycemic agents, insulin, lipid-lowering). Diagnosis of liver disease or elevation twice of the upper normal value of liver enzymes. Diagnosis of renal disease or creatinine >1.5 mg/dL. Diagnosis of prediabetes: Fasting plasma glucose ≥100 mg/dL and/or 2h-OGTT ≥140mg/dL and/or glycated hemoglobin A1c (A1C) between 5.7 - 6-4 %. Diagnosis of Type 2 Diabetes Mellitus (T2DM): Fasting glucose ≥ 126 mg / dL and/or 2h-OGTT ≥ 200 mg/dL . Total Cholesterol ≥ 280 mg/dL. Triglycerides ≥ 300 mg/dL. Known allergy to calcined magnesia or Medicago sativa. Ages Eligible for Study ----------------- Minimum Age: 30 Years Maximum Age: 40 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Crossover Assignment Masking: Triple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Medicago sativa<br>1,500 mg unique dose, 30 min before the oral glucose tolerance test. | Drug: Medicago Sativa<br>* Single oral doses of Medicago sativa (1,500 mg), 30 min before before the oral glucose tolerance test.<br>* Other names: Lucerne;| | Placebo Comparator: Placebo<br>1,500 mg unique dose, 30 min before the oral glucose tolerance test. | Dietary Supplement: Placebo<br>* Single oral doses of placebo (1,500 mg), 30 min before before the oral glucose tolerance test.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Fasting plasma glucose (FPG) | Glucose concentration after overnight fasting (10 to 12-h) determined by spectrophotometry methods. Expressed in mmol/L. | After the acute administration of placebo and Medicago sativa. 15 days wash period between them. | | 2 hour oral glucose tolerance test (2h-PG) | Glucose concentration after 75-g oral dextrose load, determined by spectrophotometry methods. Expressed in mmol/L | After the acute administration of placebo and Medicago sativa. 15 days wash period between them. | | First Phase of Insulin Secretion | calculated as 1283 + 1.829 x insulin 30' (mmol/L) - 138.7 x glucose 30' + 3.772 x insulin 0' (pmol/L). | After the acute administration of placebo and Medicago sativa. 15 days wash period between them. | | Total Insulin Secretion | Insulinogenic index calculated as ΔAUC insulin /(ΔAUC glucose | After the acute administration of placebo and Medicago sativa. 15 days wash period between them. | | Insulin sensitivity | Matsuda index (insulin sensitivity) calculated as [10,000/square root of (glucose 0' X insulin 0')] (mean glucose X mean insulin during 2h-OGTT)] | After the acute administration of placebo and Medicago sativa. 15 days wash period between them. | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Body Weight | Measured with minimal clothing and bare feet | At baseline of the study | | Body Mass Index (BMI) | Calculated with the Quetelet index | At baseline of the study | | Waist circumference (WC) | Measured with a flexible tape in them id point between the lowest rib and the iliac crest and is expressed in centimeters. | At baseline of the study | | Systolic blood pressure (SBP) | Evaluated with a digital sphygmomanometer with the subject sited down on a chair after a resting period of 5 minutes on three occasions. The mean of the three measures was considered as the value of systolic blood pressure expressed on mmHg | At baseline of the study | | Diastolic Blood pressure (DBP) | Evaluated with a digital sphygmomanometer with the subject sited down on a chair after a resting period of 5 minutes on three occasions. The mean of the three measures was considered as the value of diastolic blood pressure expressed on mmHg | At baseline of the study | | Total Cholesterol (TC) | Determined after overnight fasting (10 to 12-h), determined by spectrophotometric methods. Expressed in mmol/L. | At baseline of the study | | Triglycerides (TG) | Determined after overnight fasting (10 to 12-h), evaluated by colorimetric method, expressed on mmol/L. | At baseline of the study | | High Density Lipoprotein Cholesterol (HDL- C) | Determined after overnight fasting (10 to 12-h), evaluated by colorimetric method, expressed on mmol/L. | At baseline of the study | | Low Density Lipoprotein Cholesterol (LDL-C) | Determined after overnight fasting (10 to 12-h), calculated with the Friedewald equation LDL-C (mmol/L) = TC (mmol/L) - HDL-C (mmol/L) - [TG (mmol/L)/2.2] and very low-density lipoprotein (VLDL) for the proportion of TG (mmol/L)/2.2. Expressed in mmol/L. | At baseline of the study | | Very Low Density Lipoprotein (VLDL) | Estimated by standardized techniques | At baseline of the study | | Levels of aspartate aminotransferase in blood | Estimated by standardized techniques | At baseline of the study | | Levels of alanine aminotransferase in blood | Estimated by standardized techniques | At baseline of the study | | Levels of creatinine in blood | Estimated by standardized techniques | At baseline of the study | | Levels of uric acid in blood | Estimated by standardized techniques | At baseline of the study | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Medicago sativa, Insulin secretion, Insulin Sensitivity

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The Comparison of Oxidative Stress Between Inhalation Anesthetics Study Overview ================= Brief Summary ----------------- Oxidative stress is an unavoidable event during cardiac surgery. Isoprostanes have been demonstrated to be a reliable biomarker for the evaluation of oxidative stress in vivo.The aims of this study are(1)to develop an accurate liquid chromatography-tandem mass spectrometry methods for the detection of urinary isoprostane isomers in samples collected from healthy volunteers(for method quality control) and patients receiving a cardiac surgery (2)to investigate the change of isoprostanes after cardiopulmonary bypass(CPB) (3)to investigate the effect of different anesthetics on isoprostanes. Detailed Description ----------------- Enhanced production of oxygen free radicals can lead to the generation of oxidative stress, which is harmful to human tissue and organs. Reactive oxygen species are released abruptly during some surgical procedures, and they are the major causes of ischemia-reperfusion injuries.Isoprostanes have been demonstrated to be a reliable biomarker for the evaluation of oxidative stress in vivo. Therefore, accurately monitoring and avoiding the occurrence of oxidative stress during surgery is an important clinical issue. Isoprostanes are a series of prostaglandin-like compounds produced by non-enzymatic peroxidation of arachidonic acid.The aims of this study are(1)to develop an accurate liquid chromatography-tandem mass spectrometry methods for the detection of urinary isoprostane isomers in samples collected from patients receiving a cardiac surgery (2)to investigate the change of isoprostanes after cardiopulmonary bypass (3)to investigate the effect of different anesthetics on isoprostanes during surgery. Official Title ----------------- The Comparison of Oxidative Stress Between Inhalation Anesthetics Conditions ----------------- Oxidative Stress, Cardiac Surgery Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: patients receiving cardiac valve surgery in ASA II-III physical status Exclusion Criteria: trauma, infection, low ejection fraction (less than 25%), liver cirrhosis, or acute renal failure, and emergency surgery Ages Eligible for Study ----------------- Minimum Age: 25 Years Maximum Age: 80 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | cardiac surgery with CPB<br> | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | isoprostanes isomer as marker of oxidative stress | | one day | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- isoprostanes, mass spectrometry

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Mindfulness Mobile App to Reduce Adolescent Substance Use Study Overview ================= Brief Summary ----------------- Substance-abusing youth - especially those who are involved in the juvenile justice system - are at higher risk than nonusers for mental health problems, including depression, conduct problems, personality disorders, suicidal thoughts, attempted suicide, and completed suicide. The proposed Phase II project aims to develop and test the efficacy of a mobile app, called Rewire, that is geared toward helping high risk adolescent substance users reduce or quit their substance use. The Rewire app is based on the primary substance use cessation components tested in our previous work with juvenile justice-involved adolescents and on intervention components shown to be central to smoking cessation; it applies a mindfulness approach as the guiding framework for the intervention. Detailed Description ----------------- There is growing evidence that interventions based on mindfulness have been an efficacious intervention for a variety of problems, including substance use among adolescents. We propose to adapt and test the feasibility and efficacy of a smart phone application (app) intervention prototype that would help adolescent substance users reduce or quit their substance use through the development of stress reduction, emotion regulation, and mindfulness skills. During the development process, 20 high-risk adolescents will be recruited for participation in focus groups and usability testing of early versions of the app; their initial reactions to content and functionality will help guide final iterations. Rewire is a twelve module program, and each module consists of a teaching component and a practice component. Modules take 5 minutes or less to complete. Module topics include developing an awareness of mind and body states, mindful decision making, and maintaining sobriety. In this study, the Rewire app will be evaluated with 400 high risk adolescents that are involved in the juvenile justice system; the first 20 adolescents will be involved in the development process and the remaining 380 participants will be randomly and equally assigned to the Rewire condition (n = 190) or the Department of Youth Services standard treatment condition (n = 190). Youth will be assessed at baseline and will be instructed to attempt to reduce substance use with a target quit date of 28 days in the future. The Rewire group will receive instructions for using the app in the 28 days following baseline. All youth will complete 1 and 3 month followups. Assessments will consist of online surveys asking about substance use, emotion regulation, family demographics, and mindfulness practices. The Rewire group will also be asked for their thoughts and opinions on the app. Biochemical verification of self-reported substance use, a urine sample, will be collected at each interview. Official Title ----------------- Mindfulness Mobile App to Reduce Adolescent Substance Use Conditions ----------------- Adolescent Drinking, Adolescent Problem Behavior Intervention / Treatment ----------------- * Behavioral: Rewire app users Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: any gender, age 13-18 recent involvement with juvenile justice system documented substance use English speaking living in the community (e.g., with biological/adoptive/foster parents) Exclusion Criteria: non-English speaking Ages Eligible for Study ----------------- Minimum Age: 13 Years Maximum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: This study will recruit 400 adolescents to test an app designed to increase mindfulness skills and reduce substance use. Participants will be randomly assigned in equal numbers to the intervention group (and will use the app) or the control group. Masking: Single Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Intervention<br>This group will be asked to use the Rewire app daily in the month following the baseline assessment. This group will also receive services as usual from the Department of Youth Services. | Behavioral: Rewire app users<br>* Use of the Rewire app involves completing 12 modules and 12 practice sessions over 30 days.<br>| | No Intervention: Services as usual<br>This group will receive services as usual from the Department of Youth Services. | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in Adolescent Use of Cigarettes and E-Cigarettes | Decrease in nicotine use (i.e., frequency of use and amount consumed) as measured by Youth Substance Use Interview | Baseline, 1 month (treatment completion), 3 months | | Change in Adolescent Use of Alcohol | Decrease in alcohol use (i.e., frequency of use and amount consumed) as measured by Youth Substance Use Interview | Baseline, 1 month (treatment completion), 3 months | | Change in Adolescent Use of Marijuana | Decrease in marijuana use (i.e., frequency of use and amount consumed) as measured by Youth Substance Use Interview | Baseline, 1 month (treatment completion), 3 months | | Change in Adolescent Use of Other Recreational Substances | Decrease in substance use as measured by the Youth Substance Use Interview | Baseline, 1 month (treatment completion), 3 months | | Change in Emotion Regulation | Increased awareness of and control over emotions as measured by the Difficulties in Emotion Regulation Questionnaire | Baseline, 1 month (treatment completion), 3 months | | Change in Mindfulness Behavior | Increase in Mindfulness Behavior as measured by the Five Facet Mindfulness Questionnaire | Baseline, 1 month (treatment completion), 3 months | | Change in Attitude toward Substance Use | Increased awareness of normative beliefs and consequences related to drug use as measured by the Adolescent Attitudes Questionnaire | Baseline, 1 month (treatment completion), 3 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Evaluate efficacy and feasibility of Rewire app in Substance Use Cessation among High-Risk Adolescents | Usability and satisfaction data will be assessed using participant ratings of ease of use, perceived benefits, and likeability. System log-in data will be used to measure frequency of use. | 1 month (treatment completion) | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Adolescent, Alcohol, Marijuana, Mindfulness

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Corneal Collagen Crosslinking and Intacs for Keratoconus and Ectasia Study Overview ================= Brief Summary ----------------- This study will determine the efficacy of corneal collagen crosslinking (CXL) combined with Intacs for the treatment of keratoconus and corneal ectasia. The goal of CXL is to decrease the progression of keratoconus, while Intacs has been shown to decrease corneal steepness in keratoconus. This study will attempt to determine the relative efficacy of the two procedures either performed at the same session versus CXL performed 3 months after Intacs. Detailed Description ----------------- The purpose of this is to ascertain the possible additive effect of the two treatments to both improve the quality of the corneal optics (i.e. improve corneal topography regularity) and to stabilize the cornea. Previous investigations have shown that Intacs surgery, indeed, does improve corneal topography and improve contact lens tolerance and spectacle corrected visual acuity, as well as uncorrected visual acuity in some patients. Investigations of CXL have shown the procedure not only to decrease keratoconus progression, but also to decrease the steepness of the cone and improve uncorrected and best corrected visual acuity in some cases. Since the mechanism of improvement differs between the procedures, this suggests a potential additive effect of the two on the patient's ultimate visual outcome. Thus, the patient would be afforded two potential benefits: (1) the potential of a more robust visual outcome and (2) stabilization of the keratoconic cornea on the longer term. Official Title ----------------- Randomized Study of Safety and Effectiveness of Corneal Collagen Crosslinking and Intacs for Treatment of Keratoconus and Corneal Ectasia Conditions ----------------- Keratoconus, Corneal Ectasia Intervention / Treatment ----------------- * Drug: Riboflavin Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: 21 years of age or older Having a diagnosis of keratoconus or corneal ectasia after corneal refractive surgery (e.g., LASIK, photorefractive keratectomy [PRK], or epi-LASIK) Subjects who meet the manufacturer's nomogram recommendations for Intacs segments Topography consistent with keratoconus or post-surgical corneal ectasia. BSCVA worse than 20/20 (<55 letters on ETDRS chart) Exclusion Criteria: Eyes classified as either normal, atypical normal, or keratoconus suspect on the severity grading scheme. Corneal pachymetry ≤ 400 microns at the thinnest point measured by Pentacam in the eye(s) to be treated when the isotonic riboflavin solution is used or ≤ 300 microns when the hypotonic riboflavin us used, provided that the corneal thickness after treatment with the hypotonic riboflavin solution is > 400 microns. Corneal pachymetry ≤ 450 microns at the proposed insertion site for the Intacs Previous ocular condition (other than refractive error) in the eye(s) to be treated that may predispose the eye for future complications History of corneal disease History of chemical injury or delayed epithelial healing in the eye(s) to be treated. Pregnancy (including plan to become pregnant) or lactation during the course of the study A known sensitivity to study medications Subjects with nystagmus or any other condition that would prevent a steady gaze during the CXL and Intacs treatment or other diagnostic tests. Subjects with a current condition that, in the investigator's opinion, would interfere with or prolong epithelial healing. Ages Eligible for Study ----------------- Minimum Age: 21 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Intacs combined with CXL<br>Intacs placement followed by collagen crosslinking with UV light and riboflavin | Drug: Riboflavin<br>* Corneal epithelium removed followed by riboflavin drop administration every 2 minutes for 30 minutes followed by UV light exposure with additional riboflavin administration every 2 minutes for 30 minutes. Subjects will be randomized to receive Intacs placement either immediately before CXL or 3 months before CXL.<br>* Other names: Cornea Collagen Crosslinking;| | Active Comparator: Intacs followed by CXL<br>Intacs placement, to be followed by corneal collagen crosslinking with UV light and riboflavin 3 months later | Drug: Riboflavin<br>* Corneal epithelium removed followed by riboflavin drop administration every 2 minutes for 30 minutes followed by UV light exposure with additional riboflavin administration every 2 minutes for 30 minutes. Subjects will be randomized to receive Intacs placement either immediately before CXL or 3 months before CXL.<br>* Other names: Cornea Collagen Crosslinking;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Maximum keratometry | | 1 year | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Best Corrected Visual Acuity | | 1 year | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- keratoconus, corneal ectasia, collagen crosslinking, riboflavin, cornea, ultraviolet

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JNJ-40346527 in Treating Participants With Relapsed or Refractory Acute Myeloid Leukemia Study Overview ================= Brief Summary ----------------- This phase II trial studies how well edicotinib (JNJ-40346527) works in treating participants with acute myeloid leukemia that has come back or does not respond to treatment. JNJ-40346527 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Detailed Description ----------------- PRIMARY OBJECTIVE: Evaluate preliminary efficacy of JNJ-40346527 in participants with relapsed/refractory AML. I. Best objective response rate (> PR). SECONDARY OBJECTIVES: Assess safety and survival associated with JNJ-40346527 to treat participants with relapsed/refractory AML. Assess the duration of disease response associated with JNJ-40346527. I. Overall incidence of treatment-related and non-treatment related toxicity. II. Duration of response. III. 12-month event-free survival. IV. 12-month overall survival. EXPLORATORY OBJECTIVES: I. Evaluate the pharmacokinetics of JNJ-40346527 and effective inhibition of CSF-1R in marrow aspirates using plasma inhibitory assays, with established CSF-1R-sensitive cell lines. II. Identify the effect of JNJ-40346527 on leukemia cells and the immune microenvironment. III. Identify and quantify the specific subpopulation of cells that express CSF-1R in participants and correlate these with clinical response to JNJ-40346527. IV. Analyze the frequency of mutations using genomic deoxyribonucleic acid (DNA) from leukemia participants to determine if there is a genetic signature that predicts response to JNJ-40346527. V. Using ribonucleic acid (RNA) sequencing (RNAseq), identify an expression signature in CSF-1R+ cells that predicts patient response. VI. Evaluate the effect of JNJ-40346527 on immune cell populations (cytotoxic T cells, etc.) and phospho-signaling proteins by mass cytometry (CyTOF) analysis in pre- and post-treatment samples in order to identify biomarkers that predict patient response and prioritize potential combination strategies for future clinical trials. VII. Determine how leukemia cells change in response to CSF-1R inhibition by assessing cells collected pre- and post-treatment using an ex vivo sensitivity to a panel of small molecule inhibitors to determine what new drug sensitivities may emerge in AML cells after CSF-1R inhibition. OUTLINE: Participants receive JNJ-40346527 orally (PO) twice a day (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, participants are followed up within 2 weeks, at 4-6 weeks until death or minimum of 12 months. Official Title ----------------- A Phase 2 Open-Label Study of the CSF-1R Inhibitor JNJ-40346527 in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML) Conditions ----------------- Recurrent Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia Intervention / Treatment ----------------- * Drug: Edicotinib * Other: Pharmacokinetic Study Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: 1. Ability to understand and the willingness to sign a written informed consent document. 2. Age >= 18 years at time of informed consent. Both men and women and members of all races and ethnic groups will be included. 3. Morphologically documented relapsed/refractory AML as defined by World Health Organization (WHO) criteria after at least 1 prior therapy for AML with the exception of hydroxyurea, and not felt to have curative treatment options per treating physician, or the patients themselves are unwilling to consider curative treatment options. 4. Sufficient and viable bone marrow aspirate or peripheral blood collection to use for the ex vivo sensitivity assay. 5. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2. 6. Women must not be pregnant or breastfeeding. Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days prior to start of study drug administration. 7. Participants must agree to use an adequate method contraception. 8. Must be able to take oral medications. 9. Adequate organ function as defined by the following: Serum creatinine =< 2 x the upper limit of normal (ULN), or glomerular filtration rate > 20 ml/min as calculated by Cockcroft-Gault formula. Serum potassium, magnesium, and calcium (corrected for albumin) within institutional normal limits or can be corrected with supplementation. Total serum bilirubin =< 2.5 x ULN. Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) =< 2.5 x ULN. Exclusion Criteria: 1. Diagnosis of acute promyelocytic leukemia (APL, or AML M3 subtype). 2. Active central nervous system involvement with AML. 3. Concurrent active malignancy with expected survival of less than 1 year. For example, candidates with treated skin cancers, prostate cancer, breast cancer, etc. without metastatic disease are candidates for therapy since their expected survival exceeds that of relapsed or refractory AML. All subjects with concurrent malignancies will be reviewed by the principal investigator (PI) prior to enrollment. 4. Clinically significant graft versus host disease (GVHD) or active GVHD requiring initiation or escalation of treatment within 28-day screening period. 5. Clinically significant coagulation abnormality, such as disseminated intravascular coagulation. 6. Participants who are currently receiving any other investigational agents. 7. Previous treatment with CSF-1R kinase inhibitor or CSF-1R blocking antibody. 8. Known clinically significant liver disease defined as ongoing drug-induced liver injury, chronic active hepatitis C (HCV), chronic active hepatitis B (HBV), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, portal hypertension, or history of autoimmune hepatitis. 9. Untreated HIV or active hepatitis C detectable by polymerase chain reaction (PCR), or chronic hepatitis B (patients positive for hepatitis B core antibody who are receiving intravenous immunoglobulin (IVIG) are eligible if hepatitis B [HepB] polymerase chain reaction [PCR] is negative). 10. Known history of cerebrovascular accident, myocardial infarction, or intracranial hemorrhage within 2 months of enrollment. 11. Clinically significant surgery within 2 weeks of enrollment. 12. Per PI discretion, active infection that is not well controlled by antibacterial or antiviral therapy. 13. Cancer-directed therapy within 2 weeks prior to starting treatment, with the exception of hydroxyurea, which is allowed to control white blood cell count. Hydroxyurea will be weaned as soon as clinically feasible. 14. Unwillingness to receive infusion of blood products. 15. Drugs that affect the CYP3A4 systems are allowed and essential for cancer patients, including anti-fungals but should be used with caution. 16. Patients with uncontrolled white blood cell count (defined as > 50 K/cu mm not controlled with hydrea). Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Treatment (JNJ-40346527)<br>Participants receive JNJ-40346527 PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Drug: Edicotinib<br>* Given PO<br>* Other names: JNJ-40346527;Other: Pharmacokinetic Study<br>* Correlative studies<br>* Other names: PK Study;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Best Objective Response Rate | An objective response is defined as achievement of a PR or any type of CR (CR, CRm, CRc, CRi) during a participant's first 2 cycles of study drug. Each participant's best disease response designation (amended from the IWG criteria specified by Cheson, 2003 JCO) during the first 2 cycles will be used when computing the best objective response rate. This rate will be reported alongside an exact confidence interval for each arm separately. | first 2 cycles of study drug | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Incidence of Treatment-related and Non-treatment Related Adverse Events Per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 | The overall incidence of treatment-related and non-treatment-related toxicity (including serious and non-serious AEs). See the Adverse Event module of the Results section for a tabular summary of each toxicity event and associated system organ class. | Start of study drug until 30 days after the last dose of study drug (while the participant remains on-study), which amounted to an average of 31 days for the 3 enrolled participants | | Duration of Response | For participants that achieve at least a partial response (PR), the length of time between start date of this response and progression. | achievement of >=PR through end of study | | Event-free Survival | Defined for all patients of a trial; measured from the date of entry into a study to the date of relapse from PR or CR or CRi, progression, or death from any cause; patients not known to have any of these events are censored on the date they were last examined. The Kaplan-Meier method will be used to estimate event-free survival. | study enrollment until last on-study disease assessment | | Overall Survival | Defined for all patients of a trial; measured from the date of entry into a study to the date of death from any cause; patients not known to have died at end of study are censored on the date they were last known to be alive. The Kaplan-Meier method will be used to estimate overall survival. | From study enrollment until end of participant follow-up (i.e., death or last contact), with the protocol specifying that [p]articipants will be followed … until death |

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The Effect of Erigeron Injection on Acute Cerebral Infarction Serum VEGF, MMP-9 and EPC Levels Study Overview ================= Brief Summary ----------------- To study the effects of Erigeron Injection on human serum VEGF, MMP-9 and EPC levels after acute cerebral infarction,test is made by random double-blind controlled.patients with acute cerebral infarction were divided randomly into erigeron injection+aspirin group,aspirin group,and health people. The main indexes are the serum level of VEGF, MMP-9 and EPC.The review is made by the reference to NIHSS and so on. So, Erigeron Injection have the function of promoting angiogenesis in multiple targets through this test. Detailed Description ----------------- OBJECTIVE: To study the effects of Erigeron Injection on human serum VEGF, MMP-9 and EPC levels after acute cerebral infarction. METHOD: 40 patients with acute cerebral infarction(in accordance with the inclusion criteria) were divided randomly into erigeron injection+aspirin group,aspirin group,and 20 health people. Erigeron injection+aspirin group and aspirin group drew peripheral blood on the prior treatment,the posttreatment 1th, 3th and 7th day,and tested the level of VEGF, MMP-9 and EPC.Tested the health people one time. Official Title ----------------- The Effect of Erigeron Injection on Acute Cerebral Infarction Serum VEGF, MMP-9 and EPC Levels Conditions ----------------- Cerebral Infarction Intervention / Treatment ----------------- * Drug: Erigeron Injection * Drug: placebo Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: patients aged no younger than 18yrs attack within 72 hours NIHSS score in the 2-25 points Ischemic Stroke occurred for the first time, or with a history of stroke disease but without sequelae Signed the informed consents Exclusion Criteria: patients aged younger than 18yrs Patients with tumor, coronary heart disease, valvular heart disease, psoriasis, rheumatism, hematologic diseases, infertility, varieties of acute inflammation Patients with severe cognitive impairment Refused to cooperate or been unable to cooperation for neurological disorders Cerebral hemorrhage or hemorrhagic cerebral infarction Unstable vital signs dued to massive cerebral infarction Patients with serious heart, liver and renal insufficiency Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Erigeron Injection<br>Erigeron Injection, 30ml,qd,i.v., for 7 days | Drug: Erigeron Injection<br>* Erigeron Injection, 30ml, iv, qd, for 7days<br>| | Placebo Comparator: placebo<br>normal saline, 500ml,i.v.,qd, for 7 days | Drug: placebo<br>* normal saline, 500ml,i.v.,qd, for 7 days<br>* Other names: normal saline, 500ml,i.v.,qd, for 7 days;| | No Intervention: health volunteers<br>health volunteers, no drug to be given. | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | the serum level of VEGF,MMP-9 and EPC | | 0-7days | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | National Institute of Health of stroke scale | | 0-7days | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- promoting angiogenesis in multiple targets, herbal medicine, traditional chinese medicine, random clinical trial

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Evaluating PVI Using CMR Study Overview ================= Brief Summary ----------------- Using state of the art cardiac magnetic resonance imaging techniques, characterization of ablation lesions in the early phase after pulmonary vein isolation ablation in atrial fibrillation patients, and relate findings to the ablation scar at 3 months follow up and atrial fibrillation-free survival at 1 year. Official Title ----------------- CMR Characterization of Ablation Lesions Following Pulmonary Vein Isolation Conditions ----------------- Atrial Fibrillation Intervention / Treatment ----------------- * Procedure: MRI Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Adult patients (age ≥18 years old) Paroxysmal or persistent AF meeting guideline criteria. Anticipated PVI using index-guided radiofrequency ablation techniques. Availability of LGE-CMR images within 3 months before anticipated PVI. Exclusion Criteria: History of catheter ablation History of cardiac surgery. History of chest radiation therapy Estimated glomerular filtration rate (eGFR) <45 ml/min/kg Known (or suspected) allergic reaction to gadolinium Contraindications for CMR (such as claustrophobia, certain implants, devices, high body mass index). Inability to schedule CMR <48h after PVI Long-term use of anti-inflammatory medication, except for the use of nonsteroidal anti-inflammatory drugs Autoimmune disease or chronic inflammatory illness. Pregnancy of breast feeding Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Diagnostic Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Other: PVI<br> | Procedure: MRI<br>* MRI prior to PVI, acutely after PVI, and 3 months after PVI<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Ablaton scar | The correlation between ablation lesion characteristics in the early phase after PVI and ablation scar at 3 months follow up. | 3 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | AF recurrence | The relation between ablation lesion characteristics and AF recurrence at 1 year after the ablation procedure | 1 year |

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SS1P and Pentostatin Plus Cyclophosphamide for Mesothelioma Study Overview ================= Brief Summary ----------------- Background: Malignant mesothelioma is a form of cancer that develops on the protective lining that covers the body's internal organs. It most often occurs on the lining of the lungs and chest wall or the lining of the abdomen. There is no known cure for malignant mesothelioma, so researchers are searching for new ways to treat it. Mesothelin is a protein that is found in mesothelioma and other types of cancer cells. An experimental cancer drug called SS1P is designed to attack cells that have mesothelin while leaving healthy cells alone. Researchers want to test how effective SS1P is when it is given with pentostatin and cyclophosphamide. These drugs help suppress the immune system and may make the SS1P more effective. Objectives: - To study the effectiveness of SS1P plus two drugs that suppress the immune system to treat malignant mesothelioma. Eligibility: - Individuals at least 18 years of age who have malignant mesothelioma in the chest or abdomen. Design: Participants will be screened with a physical exam, medical history, and blood tests. They will also have imaging studies. The first treatment cycle will last 30 days. Up to three 21-day cycles of treatment will follow. In the first cycle, participants will have pentostatin on days 1, 5, and 9. They will have cyclophosphamide on days 1 through 12. They will have SS1P on days 10, 12, and 14. On the next three cycles, participants will have pentostatin on day 1.They will have cyclophosphamide on days 1 through 4. They will have SS1P on days 2, 4, and 6. Participants will have frequent blood tests and other studies. They will receive all four cycles of treatment as long as there are no severe side effects. Participants will have regular followup visits as directed by the study doctors. Detailed Description ----------------- BACKGROUND: Mesothelin is a cell surface glycoprotein present on normal mesothelial cells that is highly expressed in many human cancers including mesothelioma, lung and pancreatic adenocarcinoma. SS1 (dsFv) PE38 is a recombinant anti-mesothelin immunotoxin that has undergone phase I testing and has been evaluated in combination with pemetrexed and cisplatin for treatment of malignant pleural mesothelioma. SS1 (dsFv)PE38 is highly immunogenic and the majority of patients develop antibodies to it at end of one cycle. Pre-clinical studies demonstrate that SS1(dsFv)PE38 may be administered multiple times in combination with an immune-depleting regimen consisting of pentostatin and cyclophosphamide. OBJECTIVES: Mesothelioma Pilot Objective -To assess the safety, tolerability, and feasibility of a conditioning regimen of pentostatin and cyclophosphamide in combination with SS1(dsFv)PE38 -To monitor antibody formation to SS1(dsFv)PE38 and to assess the impact of the conditioning regimen on the formation of these antibodies Mesothelioma Positive Cancers Dose De-escalation Pilot Objective -To determine the safety profile and recommended phase 2 dose of SS1P (dsFv)PE38 in drug lot FIL129J01 using dosing regimen A in patients with mesothelioma, lung and pancreatic adenocarcinoma Phase 2 and Lung and Pancreatic Adenocarcinoma Expansion Pilot Objective -To evaluate objective tumor response in subjects with pleural mesothelioma, peritoneal mesothelioma, lung and pancreatic adenocarcinoma using Regimen A ELIGIBILITY: Patients with one of the following histologically confirmed malignancies: malignant pleural or peritoneal mesothelioma with epithelial or biphasic tumors having less than a 50% sarcomatoid component who have previously been treated on at least one platinum-containing chemotherapy regimen with progressive disease documented prior to study entry advanced (Stage IIIB/IV) lung adenocarcinoma who have had at least one prior chemotherapy for advanced disease. Patients who received an approved targeted therapy as first-line treatment should have also received chemotherapy prior to study entry. recurrent, locally advanced unresectable or metastatic adenocarcinoma of the pancreas. Measurable disease by modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria for pleural mesothelioma or by RECIST criteria for peritoneal mesothelioma, lung adenocarcinoma and pancreatic adenocarcinoma Adequate renal, hepatic and hematopoietic function No major surgery, radiotherapy, chemotherapy or biologic therapy within 28 days of therapy DESIGN: -During the mesothelioma pilot phase of this study, the first eleven mesothelioma patients enrolled in this study received a conditioning regimen of pentostatin on days 1, 5 and 9 of the first cycle and day 1 of subsequent cycles in combination with cyclophosphamide on days 1 through 12 of the first cycle and days 1 through 4 of subsequent cycles (Regimen A) while the next 8 mesothelioma patients received conditioning regimen of pentostatin on days 1, 5, 9, 13 and 17 of the first cycle and day 1 and 5 of subsequent cycles in combination with cyclophosphamide on days 1 through 20 of the first cycle and days 1 through 8 of subsequent cycles (Regimen B). SS1P was administered every other day for six days (3 doses) beginning on the day after the last pentostatin dose in each cycle for both regimens. In the mesothelin positive cancers dose de-escalation pilot study, a maximum of 12 patients with mesothelioma or lung or pancreatic adenocarcinoma will be enrolled in a 3+3 design to test up to 2 decreasing dose levels of SS1P administered in combination with cyclophosphamide and pentostatin on the Regimen A schedule for safety. In the phase 2 mesothelioma and pancreatic and lung adenocarcinoma pilot expansion portions of the study, a two-stage Minimax phase II trial design will be used to enroll up to 16 evaluable subjects with pleural mesothelioma (cohort 1), up to 10 evaluable subjects with peritoneal mesothelioma (cohort 2), up to 10 patients with lung adenocarcinoma (cohort 3)and up to 10 evaluable subjects with pancreatic adenocarcinoma (cohort 4) who will receive treatment on Regimen A. Treatment cycles will be repeated for up to four cycles if patients do not develop neutralizing antibodies, which will be assessed by a biological assay 14 and 20 days (+/- 2 days) following the first dose of SS1P in each cycle (corresponding to Days 24 and 30 of Cycle 1, and Days 16 and 22 of Cycles 2 through 4) Toxicity will be assessed by the Cancer Therapy Evaluation Program (CTEP) Version 4.0 of Common Terminology Criteria in Adverse Events (CTCAE) Tumor response assessments will be performed at the end of 2 cycles and at the end of treatment Tumor biopsies will be performed before treatment, after 2 cycles, and after the last cycle or at follow-up. Official Title ----------------- A Pilot/ Phase 2 Study of Pentostatin Plus Cyclophosphamide Immune Depletion to Decrease Immunogenicity of SS1P in Patients With Mesothelioma, Lung Cancer or Pancreatic Cancer Conditions ----------------- Mesothelioma, Adenocarcinoma of Lung, Pancreatic Neoplasms Intervention / Treatment ----------------- * Drug: Pentostatin * Drug: Cyclophosphamide * Biological: SS1(dsFv)PE38 - lot 073I0809 * Biological: SS1(dsFv)PE38 - lot FIL129J01 Participation Criteria ================= Eligibility Criteria ----------------- INCLUSION CRITERIA: Mesothelioma Cohorts (Cohorts 1 and 2 Only) Subjects must have histologically confirmed epithelial or biphasic mesothelioma not amenable to potentially curative surgical resection. However, patients with biphasic tumors that have a less than or equal to 50% sarcomatoid component will be excluded. The diagnosis will be confirmed by the Laboratory of Pathology / Center for Cancer Research (CCR) / National Cancer Institute (NCI). Patients must have had at least one prior chemotherapy regimen, with the Food and Drug Administration (FDA) approved regimen of a platinum-based therapy in combination with pemetrexed being preferred unless there was a specific contraindication for an individual patient. There is no limit to the number of prior chemotherapy regimens received. Total Bilirubin less than or equal to 1.5 X institutional upper limit of normal (ULN) INCLUSION CRITERIA: Lung Adenocarcinoma Cohort (Cohort 3) Only Subjects must have histologically confirmed advanced (Stage IIIB/IV) lung adenocarcinoma. The diagnosis will be confirmed by the Laboratory of Pathology/CCR/NCI. Patients must have had at least one prior therapy for advanced disease [platinum containing chemotherapy or one of the approved targeted therapies (an approved estimated glomerular filtration rate (EGFR) tyrosine kinase inhibitor (TKI) for EGFR mutant tumors or crizotinib and ceritinib for ALK translocated tumors)]. There is no limit to the number of prior chemotherapy regimens received. Mesothelin expression in at least 5% of cells as assessed in archival tumor tissue samples, determined by the immunohistochemistry (IHC) assay performed at Laboratory of Pathology / CCR / NCI. Archival samples must be available for eligibility. Total Bilirubin less than or equal to 1.5 X institutional upper limit of normal (ULN) INCLUSION CRITERIA: Pancreatic Cancer Cohort (Cohort 4) Only Subjects with recurrent, locally advanced unresectable or metastatic adenocarcinoma of the pancreas. The diagnosis will be confirmed by the Laboratory of Pathology/CCR/NCI. Patients must have had at least one prior chemotherapy for advanced disease. There is no limit to the number of prior chemotherapy regimens received. Total Bilirubin less than or equal to 2 X institutional upper limit of normal (ULN) INCLUSION CRITERIA: All Subjects Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan. See Section 11 for the evaluation of measurable disease. Patients must not have had major surgery, radiation therapy, chemotherapy, biologic therapy (including any investigational agents), or hormonal therapy (other than replacement), within 4 weeks prior to entering the study and must have evidence of stable or progressive disease to be eligible. Age greater than or equal to 18 years. Since the study diseases are extremely rare in children they are excluded from this study. Performance status (Eastern Cooperative Oncology Group (ECOG)) less than or equal to 1 Patients must have adequate organ and marrow function (as defined below). leukocytes less than or equal to 3,000/mm^3 absolute neutrophil count less than or equal to 1,500/mm^3 hemoglobin less than or equal to 9 g/dL platelets less than or equal to 90,000/ mm^3 total bilirubin See guidelines for individual cohorts in sections 3.1.1.3, 3.1.2.4 and 3.1.3.3 Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase (SGOT))/alanine aminotransferase (ALT)(serum glutamic-pyruvic transaminase (SGPT)) less than or equal to 3 X institutional upper limit of normal (ULN) (5x if liver function test (LFT) elevations due to liver metastases) creatinine less than or equal to 1.5 X institutional ULN OR --creatinine clearance greater than or equal to 45 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal, obtained through calculated or measured Creatinine Clearance Patients may be transfused to obtain a hemoglobin of less than or equal to 9 g/Dl. The effects of SS1(dsFv)PE38, pentostatin, and cyclophosphamide on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (barrier method of birth control; abstinence) for the duration of study therapy and for 3 months after the last dose of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. While hormonal methods of birth control are effective, we ask that female patients who are participating in the study cease hormonal forms of birth control, as these methods of birth control (birth control pills, injections, or implants) may affect the study drug. Patients must be off hormonal forms of birth control for at least 4 weeks prior to initiating the study. Ability to comply with intravenous administration schedule, and the ability to understand and the willingness to sign a written informed consent document. EXCLUSION CRITERIA: (All Subjects) Patients with symptomatic brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. However, patients who have had treatment for their brain metastases and whose brain metastatic disease status has remained stable for at least 4-6 weeks without steroids may be enrolled at the discretion of the principal investigator. Uncontrolled medical illness including, but not limited to, ongoing or uncontrolled, symptomatic congestive heart failure (American Heart Association (AHA) Class II or worse), uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Human immunodeficiency virus (HIV) positive patients will be excluded due to a theoretical concern that the degree of immune suppression associated with the treatment may result in progression of HIV infection. Patients with Hepatitis B and C will be excluded. Serum neutralization antibody assay shows greater than or equal to 75% neutralization of the SS1 (dsFv) PE38 activity at 200 ng/ml. Patients may not be receiving any other investigational agents. History of another invasive malignancy in the last two years. Adequately treated noninvasive, non-melanoma skin cancers as well as in situ carcinoma of the cervix will be allowed. Prior treatment with drugs of the immunotoxin class. Patients with tumor amenable to potentially curative therapy as assessed by the investigator. Pregnant women are excluded from this study because SS1(dsFv)PE38, pentostatin, and cyclophosphamide have the potential for teratogenic or abortifacient effects. The agents in the trial may also potentially be secreted in milk and therefore breastfeeding women should be excluded. Because of the potential of teratogenic or abortifacient effects women of childbearing potential and men must agree to use adequate contraception (barrier methods) before, during the study and for a period of 3 months after the last dose of the investigational agent. History of allergic reactions attributed to compounds of similar chemical or biologic composition to SS1(dsFv)PE38. INCLUSION CRITERIA: WOMEN AND MINORITIES -Both men and women and members of all races and ethnic groups are eligible for this trial. Every effort will be made to recruit women and minorities in this study. Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 99 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Mesothelioma Pilot Phase Regimen A<br>Drug: Pentostatin Regimen A: Cycle 1: 4 mg/m^2 on days 1, 5 and 9 of 30 day cycle Cycles 2-4: 4 mg/m^2 on day 1 of 21 day cycle Other Names: • Nipent Drug: Cyclophosphamide Regimen A:Cycle 1: 200 mg/day on days 1-12 of 30 day cycle Cycles 2-4: 200 mg/day on days 1-4 of 21 day cycle Other Names: • Cytoxan Drug: SS1 (dsFv)PE38 Regimen A: Cycle 1: 35 mcg/kg days 10, 12, and 14. Cycles 2-4: Days 2, 4, and 6, for a maximum of six treatment cycles. | Drug: Pentostatin<br>* Regimen A: Cycle 1: 4 mg/m^2 on days 1, 5 and 9 of 30 day cycle Cycles 2-4: 4 mg/m^2 on day 1 of 21 day cycle Regimen B: Cycle 1: 4 mg/m^2 or 2 mg/m^2 on days 1, 5, 9, 13 and 17 of 38 day cycle Cycles 2-6: 4 mg/m^2 on days 1 and 5 of 25 day cycle<br>* Other names: Nipent;Drug: Cyclophosphamide<br>* Regimen A:Cycle 1: 200 mg/day on days 1-12 of 30 day cycle Cycles 2-4: 200 mg/day on days 1-4 of 21 day cycle Regimen B:Cycle 1: 200 mg/day on days 1-20 of 38 day cycle Cycles 2-4: 200 mg/day on days 1-8 of 25 day cycle<br>* Other names: Cytoxan;Biological: SS1(dsFv)PE38 - lot 073I0809<br>* Regimen A: Cycle 1: Cycle 1: 35mcg/kg days 10, 12 and 14 Cycles 2-4: Days 2, 4 and 6, for a maximum of six treatment cycles Regimen B: Cycle 1: 35mcg/kg days 18, 20 and 22 Cycles 2-4: (Days 6, 8 and 10), for a maximum of six treatment cycles<br>Biological: SS1(dsFv)PE38 - lot FIL129J01<br>* Regimen A: Cycle 1: Cycle 1:35mcg/kg or 25 mcg/kg days 10, 12 and 14 Cycles 2-4: Days 2, 4 and 6, for a maximum of six treatment cycles<br>| | Experimental: Mesothelioma Pilot Phase Regimen B<br>Drug: Pentostatin Regimen B: Cycle 1: 4 mg/m^2 or 2 mg/m^2 on days 1, 5, 9, 13 and 17 of 38 day cycle Cycles 2-6: 4 mg/m^2 on days 1 and 5 of 25 day cycle Regimen B: Cycle 1: 4 mg/m^2 on days 1, 5, 9, 13 and 17 of 38 day cycle Cycles 2-6: 4 mg/m^2 on days 1 and 5 of 25 day cycle Other Names: • Nipent Drug: Cyclophosphamide Regimen B:Cycle 1: 200 mg/day on days 1-20 of 38 day cycle Cycles 2-4: 200 mg/day on days 1-8 of 25 day cycle Other Names: • Cytoxan Drug: SS1 (dsFv)PE38 Regimen B: Cycle 1: 35mcg/kg days 18, 20, and 22. Cycles 2-4: (Days 6, 8, and 10), for a maximum of six treatment cycles. | Drug: Pentostatin<br>* Regimen A: Cycle 1: 4 mg/m^2 on days 1, 5 and 9 of 30 day cycle Cycles 2-4: 4 mg/m^2 on day 1 of 21 day cycle Regimen B: Cycle 1: 4 mg/m^2 or 2 mg/m^2 on days 1, 5, 9, 13 and 17 of 38 day cycle Cycles 2-6: 4 mg/m^2 on days 1 and 5 of 25 day cycle<br>* Other names: Nipent;Drug: Cyclophosphamide<br>* Regimen A:Cycle 1: 200 mg/day on days 1-12 of 30 day cycle Cycles 2-4: 200 mg/day on days 1-4 of 21 day cycle Regimen B:Cycle 1: 200 mg/day on days 1-20 of 38 day cycle Cycles 2-4: 200 mg/day on days 1-8 of 25 day cycle<br>* Other names: Cytoxan;Biological: SS1(dsFv)PE38 - lot 073I0809<br>* Regimen A: Cycle 1: Cycle 1: 35mcg/kg days 10, 12 and 14 Cycles 2-4: Days 2, 4 and 6, for a maximum of six treatment cycles Regimen B: Cycle 1: 35mcg/kg days 18, 20 and 22 Cycles 2-4: (Days 6, 8 and 10), for a maximum of six treatment cycles<br>Biological: SS1(dsFv)PE38 - lot FIL129J01<br>* Regimen A: Cycle 1: Cycle 1:35mcg/kg or 25 mcg/kg days 10, 12 and 14 Cycles 2-4: Days 2, 4 and 6, for a maximum of six treatment cycles<br>| | Experimental: Phase 2 Peritoneal Mesothelioma Pilot Expansion Phase<br>Drug: Pentostatin Regimen B: Cycle 1: 4 mg/m^2 or 2 mg/m^2 on days 1, 5 and 9 of 38 day cycle Cycles 2-6: 4 mg/m^2 on day 1 and 5 of 25 day cycle Other Names: • Nipent Drug: Cyclophosphamide Regimen B:Cycle 1: 200 mg/day on days 1-20 of 38 day cycle Cycles 2-4: 200 mg/day on days 1-8 of 25 day cycle Other Names: • Cytoxan Drug: SS1(dsFv)PE38 Regimen B: Cycle 1: 35 mcg/kg or 25 mcg/kg days 18, 20 and 22. Cycles 2-4: Days 6, 8, and 10, for a maximum of six treatment cycles. | Drug: Pentostatin<br>* Regimen A: Cycle 1: 4 mg/m^2 on days 1, 5 and 9 of 30 day cycle Cycles 2-4: 4 mg/m^2 on day 1 of 21 day cycle Regimen B: Cycle 1: 4 mg/m^2 or 2 mg/m^2 on days 1, 5, 9, 13 and 17 of 38 day cycle Cycles 2-6: 4 mg/m^2 on days 1 and 5 of 25 day cycle<br>* Other names: Nipent;Drug: Cyclophosphamide<br>* Regimen A:Cycle 1: 200 mg/day on days 1-12 of 30 day cycle Cycles 2-4: 200 mg/day on days 1-4 of 21 day cycle Regimen B:Cycle 1: 200 mg/day on days 1-20 of 38 day cycle Cycles 2-4: 200 mg/day on days 1-8 of 25 day cycle<br>* Other names: Cytoxan;Biological: SS1(dsFv)PE38 - lot 073I0809<br>* Regimen A: Cycle 1: Cycle 1: 35mcg/kg days 10, 12 and 14 Cycles 2-4: Days 2, 4 and 6, for a maximum of six treatment cycles Regimen B: Cycle 1: 35mcg/kg days 18, 20 and 22 Cycles 2-4: (Days 6, 8 and 10), for a maximum of six treatment cycles<br>Biological: SS1(dsFv)PE38 - lot FIL129J01<br>* Regimen A: Cycle 1: Cycle 1:35mcg/kg or 25 mcg/kg days 10, 12 and 14 Cycles 2-4: Days 2, 4 and 6, for a maximum of six treatment cycles<br>| | Experimental: Phase 2 Pleural Mesothelioma Pilot Expansion Phase<br>Drug: Pentostatin Regimen A: Cycle 1: 4 mg/m^2 on days 1, 5 and 9 of 30 day cycle Cycles 2-4: 4 mg/m^2 on day 1 of 21 day cycle Other Names: • Nipent Drug: Cyclophosphamide Regimen A:Cycle 1: 200 mg/day on days 1-12 of 30 day cycle Cycles 2-4: 200 mg/day on days 1-4 of 21 day cycle Other Names: • Cytoxan Drug: SS1(dsFv)PE38 Regimen A: Cycle 1: 35 mcg/kg or 25 mcg/kg days 10, 12 and 14. Cycles 2-4: Days 2, 4, and 6, for a maximum of six treatment cycles. | Drug: Pentostatin<br>* Regimen A: Cycle 1: 4 mg/m^2 on days 1, 5 and 9 of 30 day cycle Cycles 2-4: 4 mg/m^2 on day 1 of 21 day cycle Regimen B: Cycle 1: 4 mg/m^2 or 2 mg/m^2 on days 1, 5, 9, 13 and 17 of 38 day cycle Cycles 2-6: 4 mg/m^2 on days 1 and 5 of 25 day cycle<br>* Other names: Nipent;Drug: Cyclophosphamide<br>* Regimen A:Cycle 1: 200 mg/day on days 1-12 of 30 day cycle Cycles 2-4: 200 mg/day on days 1-4 of 21 day cycle Regimen B:Cycle 1: 200 mg/day on days 1-20 of 38 day cycle Cycles 2-4: 200 mg/day on days 1-8 of 25 day cycle<br>* Other names: Cytoxan;Biological: SS1(dsFv)PE38 - lot 073I0809<br>* Regimen A: Cycle 1: Cycle 1: 35mcg/kg days 10, 12 and 14 Cycles 2-4: Days 2, 4 and 6, for a maximum of six treatment cycles Regimen B: Cycle 1: 35mcg/kg days 18, 20 and 22 Cycles 2-4: (Days 6, 8 and 10), for a maximum of six treatment cycles<br>Biological: SS1(dsFv)PE38 - lot FIL129J01<br>* Regimen A: Cycle 1: Cycle 1:35mcg/kg or 25 mcg/kg days 10, 12 and 14 Cycles 2-4: Days 2, 4 and 6, for a maximum of six treatment cycles<br>| | Experimental: Mesothelioma Positive Ca Dose De-escalation Pilot Regimen A<br>Drug: Pentostatin Regimen A: Cycle 1: 4 mg/m^2 on days 1, 5 and 9 of 30 day cycle Cycles 2-4: 4 mg/m^2 on day 1 of 21 day cycle Other Names: • Nipent Drug: Cyclophosphamide Regimen A:Cycle 1: 200 mg/day on days 1-12 of 30 day cycle Cycles 2-4: 200 mg/day on days 1-4 of 21 day cycle Other Names: • Cytoxan Drug: SS1(dsFv)PE38 Regimen A: Cycle 1: 35 mcg/kg or 25 mcg/kg days 10, 12 and 14. Cycles 2-4: Days 2, 4, and 6, for a maximum of six treatment cycles. | Drug: Pentostatin<br>* Regimen A: Cycle 1: 4 mg/m^2 on days 1, 5 and 9 of 30 day cycle Cycles 2-4: 4 mg/m^2 on day 1 of 21 day cycle Regimen B: Cycle 1: 4 mg/m^2 or 2 mg/m^2 on days 1, 5, 9, 13 and 17 of 38 day cycle Cycles 2-6: 4 mg/m^2 on days 1 and 5 of 25 day cycle<br>* Other names: Nipent;Drug: Cyclophosphamide<br>* Regimen A:Cycle 1: 200 mg/day on days 1-12 of 30 day cycle Cycles 2-4: 200 mg/day on days 1-4 of 21 day cycle Regimen B:Cycle 1: 200 mg/day on days 1-20 of 38 day cycle Cycles 2-4: 200 mg/day on days 1-8 of 25 day cycle<br>* Other names: Cytoxan;Biological: SS1(dsFv)PE38 - lot 073I0809<br>* Regimen A: Cycle 1: Cycle 1: 35mcg/kg days 10, 12 and 14 Cycles 2-4: Days 2, 4 and 6, for a maximum of six treatment cycles Regimen B: Cycle 1: 35mcg/kg days 18, 20 and 22 Cycles 2-4: (Days 6, 8 and 10), for a maximum of six treatment cycles<br>Biological: SS1(dsFv)PE38 - lot FIL129J01<br>* Regimen A: Cycle 1: Cycle 1:35mcg/kg or 25 mcg/kg days 10, 12 and 14 Cycles 2-4: Days 2, 4 and 6, for a maximum of six treatment cycles<br>| | Experimental: Phase 2 Pancreatic Adenocarcinoma Pilot Phase Regimen A<br>Drug: Pentostatin Regimen A: Cycle 1: 4 mg/m^2 on days 1, 5 and 9 of 30 day cycle Cycles 2-4: 4 mg/m^2 on day 1 of 21 day cycle Other Names: • Nipent Drug: Cyclophosphamide Regimen A:Cycle 1: 200 mg/day on days 1-12 of 30 day cycle Cycles 2-4: 200 mg/day on days 1-4 of 21 day cycle Other Names: • Cytoxan Drug: SS1(dsFv)PE38 Regimen A: Cycle 1: 35 mcg/kg or 25 mcg/kg days 10, 12 and 14. Cycles 2-4: Days 2, 4, and 6, for a maximum of six treatment cycles. | Drug: Pentostatin<br>* Regimen A: Cycle 1: 4 mg/m^2 on days 1, 5 and 9 of 30 day cycle Cycles 2-4: 4 mg/m^2 on day 1 of 21 day cycle Regimen B: Cycle 1: 4 mg/m^2 or 2 mg/m^2 on days 1, 5, 9, 13 and 17 of 38 day cycle Cycles 2-6: 4 mg/m^2 on days 1 and 5 of 25 day cycle<br>* Other names: Nipent;Drug: Cyclophosphamide<br>* Regimen A:Cycle 1: 200 mg/day on days 1-12 of 30 day cycle Cycles 2-4: 200 mg/day on days 1-4 of 21 day cycle Regimen B:Cycle 1: 200 mg/day on days 1-20 of 38 day cycle Cycles 2-4: 200 mg/day on days 1-8 of 25 day cycle<br>* Other names: Cytoxan;Biological: SS1(dsFv)PE38 - lot 073I0809<br>* Regimen A: Cycle 1: Cycle 1: 35mcg/kg days 10, 12 and 14 Cycles 2-4: Days 2, 4 and 6, for a maximum of six treatment cycles Regimen B: Cycle 1: 35mcg/kg days 18, 20 and 22 Cycles 2-4: (Days 6, 8 and 10), for a maximum of six treatment cycles<br>Biological: SS1(dsFv)PE38 - lot FIL129J01<br>* Regimen A: Cycle 1: Cycle 1:35mcg/kg or 25 mcg/kg days 10, 12 and 14 Cycles 2-4: Days 2, 4 and 6, for a maximum of six treatment cycles<br>| | Experimental: Phase 2 Lung Adenocarcinoma Pilot Expansion Phase Regimen A<br>Drug: Pentostatin Regimen A: Cycle 1: 4 mg/m^2 on days 1, 5 and 9 of 30 day cycle Cycles 2-4: 4 mg/m^2 on day 1 of 21 day cycle Other Names: • Nipent Drug: Cyclophosphamide Regimen A:Cycle 1: 200 mg/day on days 1-12 of 30 day cycle Cycles 2-4: 200 mg/day on days 1-4 of 21 day cycle Other Names: • Cytoxan Drug: SS1(dsFv)PE38 Regimen A: Cycle 1: 35 mcg/kg or 25 mcg/kg days 10, 12 and 14. Cycles 2-4: Days 2, 4, and 6, for a maximum of six treatment cycles. | Drug: Pentostatin<br>* Regimen A: Cycle 1: 4 mg/m^2 on days 1, 5 and 9 of 30 day cycle Cycles 2-4: 4 mg/m^2 on day 1 of 21 day cycle Regimen B: Cycle 1: 4 mg/m^2 or 2 mg/m^2 on days 1, 5, 9, 13 and 17 of 38 day cycle Cycles 2-6: 4 mg/m^2 on days 1 and 5 of 25 day cycle<br>* Other names: Nipent;Drug: Cyclophosphamide<br>* Regimen A:Cycle 1: 200 mg/day on days 1-12 of 30 day cycle Cycles 2-4: 200 mg/day on days 1-4 of 21 day cycle Regimen B:Cycle 1: 200 mg/day on days 1-20 of 38 day cycle Cycles 2-4: 200 mg/day on days 1-8 of 25 day cycle<br>* Other names: Cytoxan;Biological: SS1(dsFv)PE38 - lot 073I0809<br>* Regimen A: Cycle 1: Cycle 1: 35mcg/kg days 10, 12 and 14 Cycles 2-4: Days 2, 4 and 6, for a maximum of six treatment cycles Regimen B: Cycle 1: 35mcg/kg days 18, 20 and 22 Cycles 2-4: (Days 6, 8 and 10), for a maximum of six treatment cycles<br>Biological: SS1(dsFv)PE38 - lot FIL129J01<br>* Regimen A: Cycle 1: Cycle 1:35mcg/kg or 25 mcg/kg days 10, 12 and 14 Cycles 2-4: Days 2, 4 and 6, for a maximum of six treatment cycles<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Response Assessment | Response was assessed by the European Organization for Research and Treatment of Cancer (EORTC) modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Complete response (CR) is complete disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions. Progressive disease (PD) disease is at least a 20% increase in the sum of the LD of target lesions. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. | 52 months and 4 days | | Count of Participants With SS1P Antibody Formation | Development of antibodies following treatment with SS1P. The goal was to delay development of antibodies to SS1P so a patient could get a second cycle of therapy with SS1P. | On last day of last dosing cycle, end of cycle 1 (day 30) | | Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0) Who Were Administered SS1P and Pentostatin or Cyclophosphamide | Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. | Date treatment consent signed to date off study, approximately 64 months and 26 days | | Recommended Phase 2 Dose (RP2D) in Drug Lot FIL129J01 | Should any 2 patients within the first 3 to 6 patients experience treatment limiting toxicity requiring cessation of treatment prior to the conclusion of the first cycle, the maximum tolerated dose will have been exceeded and patients will be enrolled to the next lower dose. | Days 1, 3, and 5 of a 21 day cycle | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Overall Survival | The Kaplan-Meier was used to determine the probability of overall survival from on-study date until death or last follow-up (calculated from the date of study entry until the date of analysis). | 36 months | | Progression-free Survival | Defined as the time interval from the start of treatment to documented evidence of disease progression. Progressive disease is assessed by the European Organization for Research and Treatment of Cancer (EORTC) modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and is at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum on study LD (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. (Note: the appearance of one or more new lesions is also considered progression). | 36 months | | Duration of Response | DOR is assessed by the European Organization for Research and Treatment of Cancer (EORTC) modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria and is measured from the time measurement criteria is met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Complete response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to<10mm. partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive disease is at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum on study LD (this includes the baseline sum if that is the smallest on study). | up to 2.5 years | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Immune Therapy, Immunotoxin, T-Cell Depletion, Mesothelioma

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Discovery of Soluble Biomarkers for Pancreatic Cancer Using Innovative All-Patient Inclusive Methodology Study Overview ================= Brief Summary ----------------- Pancreatic ductal adenocarcinoma (PDAC) remains among cancers with a very poor prognosis (1-year survival <20%). Endoscopic ultrasound with fine needle aspiration (EUS/FNA) is the common examination for all patients with suspicious pancreatic mass. A method was recently developed : it preserves the sanitary sample, named EXPEL, which allows standard pathology examination and OMICS analyzes from the rinse liquid. After EUS/FNA in clinical practice, the content of the needle is rinsed in CytoLyt® preservative solution. After cytofiltration, this liquid is systematically discarded. Based on the EXPEL concept, we hypothesise that this all-patients inclusive approach (Modified EXPEL procedure) combined with the methodology to access proteomic and metabolomics information in these original samples will allow us to identify a series of clinically useful marker signatures that will ultimately be measurable, non-invasively, in the patient blood. Detailed Description ----------------- Clinical and pathological data will be prospectively collected to obtain 2 subgroups: PDAC and non-PDAC according to the final biopsy diagnosis. A combined quantitative analysis of the proteins and their peptides contained in CytoLyt® will be performed. ROC curves, AUC, sensitivity, specificity, positive predictive value and negative predictive value associated to biomarkers will be calculated to isolate combinations of diagnostic biomarkers. Candidate biomarkers will be validated by immunohistochemistry and multiple reaction monitoring. Prognostic biomarkers will be evaluated by generating 1-year overall survival curves and Cox regression. The present research, modeled on current practice, employs novel and holistic approach - PANEXPEL methodology - to establish a new repertoire of biomarkers for pancreatic cancer. We intent to provide a comprehensive proteomic and metabolomics biomarker signature that will be measurable in the patient blood using common clinical methods. The potential for translation from benchside to bedside is especially high due to the involvement of clinical teams. We expect to propose a combined, robust protein/metabolite biomarker signature that can be rapidly tested in the clinics. Necessary biological resources: Biological resources will include Cytolyt® and Blood Samples, accompanied by a signed Free and Informed Consent for each included patient. CytoLyt® fluid will be first processed by Pathology Dept. of the CHU for routine PDAC diagnosis. In essence, the samples are filtered, tissue fragments and cells are kept for analysis while flow-through is kept until the diagnosis is confirmed. Once this is completed, the samples will be transferred to the lab where the proteins found in the CytoLytR fluid will be precipitated and then solubilized. The protein extracts are stored at -80°C pending proteomic analysis. The remaining CytoLytR fluid supernatant is also stored at - 80°C to be used for metabolomics. Blood sample will be collected from each patient that underwent diagnostic biopsy. Dry tube for serum analysis 5 ml will be collected at the time of inclusion during the routine blood test (mandatory assessment pre-operative or pre-chemotherapy). The blood sample is centrifuged at 1500xg for 15 minutes while the resulting sera are aliquoted (500μl/aliquot; 4-5 aliquots per patient) and stored at -80°C. These samples will be stored at Biologic Resources Center (CRB Montpellier) that is labelled NF-S-96900 (AFNOR). The serum samples are intended for the validation phase (WP4) and will be exclusively dedicated to this study. Official Title ----------------- Discovery of Soluble Biomarkers for Pancreatic Cancer Using Innovative All-Patient Inclusive Methodology (PanEXPEL2) Conditions ----------------- Pancreatic Neoplasms Intervention / Treatment ----------------- * Diagnostic Test: Soluble Biomarkers dosage Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patient with pancreatic mass and suspicion of pancreatic ductal adenocarcinoma requiring endoscopic ultrasound with fine needle biopsy Exclusion Criteria: Vulberable person according to L1121-6 of Public health reglementation in France Pregnant women Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Intervention/Treatment | | --- | |Diagnostic Test: Soluble Biomarkers dosage|CytoLyt® fluid will be first processed for routine PDAC diagnosis. In essence, the samples are filtered, tissue fragments and cells are kept for analysis while flow-through is kept until the diagnosis is confirmed. Once this is completed, the samples will be transferred to the lab where the proteins found in the CytoLytR fluid will be precipitated and then solubilized. The protein extracts are stored at -80°C pending proteomic analysis. The remaining CytoLytR fluid supernatant is also stored at - 80°C to be used for metabolomics. Blood sample will be collected from each patient that underwent diagnostic biopsy. Dry tube for serum analysis will be collected at the time of inclusion during the routine blood test. The serum samples are intended for the validation phase (WP4) and will be exclusively dedicated to this study.| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Predictive value of each protein contained in Cytolyt® for the positive diagnosis of pancreatic ductal adenocarcinoma | Predictive value of each protein contained in Cytolyt® for the positive diagnosis of pancreatic ductal adenocarcinoma Correlation with positive diagnosis of pancreatic ductal adenocarcinoma and proteins quantity in Cytolyt® samples using ROC curves (sensibility/specificity: Area Under the Curve > 0.85) and binary logistic regression method with controlling for the effects of the co-variates (such as age, disease cTNM stage, and treatment details). | Baseline | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Disease-free survival | Disease-free survival (percentage of patients without recurrence) .Biomarkers that are prognostically significant on disease free or overall survival in patients with pancreatic cancer, identified using the survival analysis | One year | | Disease-free survival | Biomarkers that are prognostically significant on disease free or overall survival in patients with pancreatic cancer, identified using the survival analysis. Disease-free survival (DFS) (time from diagnosis to time of first radiological evidence of local, regional, or distant relapse, or death due to any cause) | One year | | Overall survival | Biomarkers that are prognostically significant on disease free or overall survival in patients with pancreatic cancer, identified using the survival analysis Overall survival at 1 year (percentage of patients alive) | One year | | Identification of prognostically significant biomarkers | Biomarkers that are prognostically significant on disease free or overall survival in patients with pancreatic cancer, identified using the survival analysis. Kaplan Meier analysis, logrank test and Cox's proportional hazards regression model to identify biomarkers that are prognostically significant (Hazard ratio (HR) and its 95% confidence interval (CI) | One year | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Biopsy, Fine-Needle, diagnostic imaging, Endosonography

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Prevention of Inappropriate ICD Shocks Study Overview ================= Brief Summary ----------------- The aim of the present study is to investigate whether increasing detection zones can effectively reduce inappropriate ICD therapies in primary prevention patients. Conditions ----------------- Inappropriate ICD Therapy, Appropriate ICD Therapy Intervention / Treatment ----------------- * Device: ICD programming Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: > 18 years Cardiomyopathy (ischemic or not) Current accepted indication for ICD implantation Exclusion Criteria: Previous device implantation Secondary prevention patients Pregnancy, Primary electrical disorders, Patient refusal, <1 year of expected mortality Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Prevention Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Sham Comparator: Conventional<br>Conventional ICD programming | Device: ICD programming<br> <br> | | Experimental: High-zone<br>High-zone ICD programming | Device: ICD programming<br> <br> | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | First total inappropriate therapy | Occurence of first total inappropriate therapy at 12-month follow-up | 12 months | | Occurence of first total appropriate therapy at 12-month follow-up | Occurence of first total appropriate therapy at 12-month follow-up | 12 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | All-cause mortality | Occurence of all-cause mortality at 12-month follow-up | 12 months | | Hospitalization for heart failure | Occurence of hospitalization for heart failure at 12-month follow-up | 12 months |

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Immunogene-modified T (IgT) Cells Against Glioblastoma Multiforme Study Overview ================= Brief Summary ----------------- This study aims to treat patients who have been diagnosed with brain cancer including glioblastoma multiforme (GBM). The treatment combines two different approaches to fight cancer: immune modulators and antigen-specific T cells. Immune checkpoint antibodies have been tested on various tumors with good outcomes. GBM is known to express increased levels of certain antigens that can be targeted by antigen-specific T cells. Thus, in this study, the gene-modified T cells specific for GBM antigens will be combined with immune modulatory genes to treat patients in dose escalation cohorts. Detailed Description ----------------- Background: Glioblastoma multiforme (GBM) is the most dangerous and aggressive form of brain cancer. Chimeric antigen receptor (CAR)-modified T cells have been shown to mediate long-term durable remissions in recurrent or refractory CD19+ B cell malignancies, and thus the CAR-T therapy approach is considered a promising treatment against GBM. Certain antigens are highly specific in GBM, such as epidermal growth factor receptor variant iii, EGFRviii. EGFRviii is a variant form of EGFR protein, and one of the potential target antigens in GBM. Alternative antigens such as GD2 and MucI have also been targeted as potential GBM antigens. Tumor microenvironment is known to suppressive anti-cancer immune responses. Many immune checkpoint inhibitors have demonstrated marked anti-tumor activities. Instead of infusing antibodies, this study aims to infuse antigen-specific T cells modified with immune modulatory genes (IgT) such as genes encoding immune checkpoint inhibitors. Combination of tumor targeting and immune modulatory activities, the IgT cells could target both the tumor cells and the tumor microenvironment. Official Title ----------------- Immunogene-modified Antigen-specific T (IgT) Cells for the Treatment of Glioblastoma Multiforme Conditions ----------------- Glioblastoma Multiforme of Brain, Glioblastoma Multiforme Intervention / Treatment ----------------- * Biological: Antigen-specific IgT cells Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: abilities to understand and the willingness to provide written informed consent; patients are ≥ 1 and ≤ 80 years old; recurrent glioblastoma or brain tumor patients with measurable tumors. Patients have received standard care of medication, such as gross total resection with concurrent radio-chemotherapy ( 54 - 60 Gy, TMZ). Patients must either not be receiving dexamethasone or receiving ≤ 4 mg/day at the time of leukopheresis; Malignant cells are target antigen positive confirmed by immunostaining, quantitative PCR or sequencing; karnofsky performance score (KPS) ≥ 60; life expectancy >3 months; satisfactory bone marrow, liver and kidney functions as defined by the following: absolute neutrophile count ≥ 1500/mm^3; hemoglobin > 10 g/dL; platelets > 100000 /mm^3; Bilirubin < 1.5×ULN; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 2.5×ULN; creatinine < 1.5×ULN; peripheral blood absolute lymphocyte count must be above 0.8×10^9/L; satisfactory heart functions; patients must be willing to follow the orders of doctors; women of reproductive potential (between 15 and 49 years old) must have a negative pregnancy test within 7 days of study start. Male and female patients of reproductive potential must agree to use birth control during the study and 3 months post study. Exclusion Criteria: a prior history of gliadel implantation 4 weeks before this study start or antibody based therapies; HIV positive; tuberculosis infection not under control; history of autoimmune disease, or other diseases require long-term administration of steroids or immunosuppressive therapies; history of allergic disease, or allergy to immune cells or study product excipients; patients already enrolled in other immune cell clinical study; patients, in the opinion of investigators, may not be eligible or not able to comply with the study. Ages Eligible for Study ----------------- Minimum Age: 1 Year Maximum Age: 80 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Intervention Model: Single Group Assignment Interventional Model Description: Patients with GBM will be treated with tumor targeting IgT cells expressing immune modulatory genes Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Antigen-specific IgT cells<br>Patients will receive non-myeloablative chemotherapy consisting of fludarabine and/or cyclophosphamide, followed by intravenous infusion of autologous IgT cells. A standard 3+3 escalation approach will be used to obtain the safe dosage of IgT cells. The tested IgT cell dosage ranges from 0.5×10^5 /kg to 2.5×10^7 /kg | Biological: Antigen-specific IgT cells<br>* Tumor antigen-specific IgT cells are infused intravenously or directly to the tumor location of the patients in a three-day split-dose regimen（day 0,10%; day1, 30%; day2, 60%）to complete a total targeted dose. Drug: cyclophosphamide 250 mg/m^2 d1-3; Drug: Fludarabine 25mg/m^2 d1-3<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Safety of infusion of autologous IgT cells with cyclophosphamide and fludarabine as lymphodepleting chemotherapy in patients with recurrent glioblastoma using the NCI CTCAE V4.0 criteria. | incidents of treatment related adverse events as assessed by CTCAE V4.0. | 2 years | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Treatment response rate of recurrent glioblastoma | Defined as the proportion of patients who achieved complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD). | 6 months | | Overall survival Rate | Percentage of participants with objective response as determined by the investigator based on Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) | 2 years | | Progression-free survival rate | Progression-free Survival (PFS) as determined by the investigator based on RECIST v1.1 | 2 years | | Persistence and proliferation of IgT cells in patients | IgT cell percentage in the peripheral blood by flow cytometry or qPCR | 2 years | | Production of specific immune check point modulatory proteins | Specific immune modulators in peripheral blood will be measured by ELISA | 2 years | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- CAR T, Gene Therapy, GBM, PD-L1, PD1

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Efficacy and Safety of JTT-705 300, 600 And 900mg in Comparison With Placebo in Patients With Type II Hyperlipidaemia Study Overview ================= Brief Summary ----------------- To demonstrate the effect of JTT-705 doses from 300 mg to 900 mg on the elevation of HDL-C and on the inhibition of CETP activity versus placebo, in patients presenting with mild dyslipidaemia. These objectives will be tested after 4 weeks of treatment. Official Title ----------------- A 4-Weeks Treatment, Randomised, Double-Blind, Parallel-Group Study Evaluating The Efficacy and Safety of JTT-705 300 to 900mg in Comparison With Placebo in Patients With Type II Hyperlipidaemia Conditions ----------------- Type II Hyperlipidaemia Intervention / Treatment ----------------- * Drug: Placebo * Drug: JTT-705 300mg * Drug: JTT-705 600mg * Drug: JTT-705 900mg Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patients with of Type II hyperlipidaemia Patients having lipid values as indicated below: HDL-C < 1.6 mmol/l TG < 4.5 mmol/l Male and females between 18 and 65 years old (If female must be post-menopausal, or pre-menopausal and surgically sterile or using an acceptable form of contraception) Exclusion Criteria: Body Mass Index (BMI) > 35 kg/m² Pregnant, breast feeding, or woman with child bearing potential without an effective method of contraception Concomitant use of medications identified in the protocol Ages Eligible for Study ----------------- Minimum Age: 22 Years Maximum Age: 65 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Placebo Comparator: 1<br>Placebo | Drug: Placebo<br>* Placebo tablet, 3 tablets, oral, once daily after breakfast<br>| | Experimental: 2<br>JTT-705 300mg | Drug: JTT-705 300mg<br>* JTT-705 tablet, 1 tablet, oral, once daily, after breakfast. Placebo tablet, 2 tablets, oral, once daily, after breakfast.<br>| | Experimental: 3<br>JTT-705 600mg | Drug: JTT-705 600mg<br>* JTT-705 tablet, 2 tablets, oral, once daily, after breakfast. Placebo tablet, 1 tablet, oral, once daily, after breakfast<br>| | Experimental: 4<br>JTT-705 900mg | Drug: JTT-705 900mg<br>* JTT-705 tablet, 3 tablets, oral, once daily, after breakfast<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | %change from baseline in HDL-C, Inhibition of CETP activity | | 4-weeks | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | %change from baseline in LDL-C and TC/HDL ratio | | 4-weeks | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- CETP Inhibitor, HDL-C, LDL-C, Apolipoprotein

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Advanced Approach to Arterial Stiffness Study Overview ================= Brief Summary ----------------- The aim of the 3A Study is to assess the role of MetS on the arterial mechanics and vascular health in different age groups using the Cardio Ankle Vascular Index (CAVI) of the Vasera system and the classic carotid-femoral Pulse Wave Velocity (PWV). Detailed Description ----------------- Hypothesis The aim of thie 3A study is to assess the role of MetS on the arterial mechanics and vascular health in different age groups using the Cardio Ankle Vascular Index (CAVI) of the Vasera system and the classic carotid-femoral Pulse Wave Velocity (PWV). STUDY OBJECTIVES Objectives Primary Objective: Assess the influence of MetS on CAVI values (primary study endpoint) in 3 different age groups (40-54, 55-69, 70-85 years) of a European population. Secondary Objectives Establish the CAVI values in a European population according to the clusters of (MetS) components i.e. cardiovascular risk factors: abdominal obesity, high triglycerides, low HDL cholesterol, elevated blood pressure (BP), systolic or diastolic, and elevated fasting glucose (and diabetes), as well as tobacco smoking. Assess the correlation between CAVI and the carotid-femoral PWV in the full population and in each age group; and compare the impact of MetS and its components on both the CAVI and PWV To establish, the relationship between cardiovascular risk factors and the evolution of arterial stiffness as evaluated by CAVI and carotid-femoral PWV over a 2-year follow-up period. To assess changes and predictive value of CAVI on organ damages and CV events during the follow-up period. To assess 24h ABPM and its correlations and variations with the CAVI and PWV in patients with MetS and/or its different components. This is a multinational European prospective longitudinal study. Official Title ----------------- Advanced Approach to Arterial Stiffness (AAA Study - Triple A Study) Conditions ----------------- Arterial Stiffness Intervention / Treatment ----------------- * Device: Cardio Ankle Vascular Index (CAVI) of the Vasera system VS1500N Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: All patients aged 40-85 with life expectancy over 2 years will be included. Patients will be stratified according to their age (3 groups: 40-54, 55-69, 70-85 years)) and the presence or not of MetS. Exclusion Criteria: Factors that may impair the quality of the CAVI and /or the PWV measurement or make PWV recording unreliable: known significant peripheral vascular disease with proximal artery stenosis, ankle brachial index < 0.9, or limb amputation; history of vascular surgery at the level of the carotid artery, femoral artery or aorta; body mass index > 40 kg/m²; atrial fibrillation and/or other major arrhythmia. Ages Eligible for Study ----------------- Minimum Age: 40 Years Maximum Age: 85 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Intervention/Treatment | | --- | |Device: Cardio Ankle Vascular Index (CAVI) of the Vasera system VS1500N|CAVI will be measured using the Vasera device (VS1500 n - Fukuda Denshi co, Japan). This device is easy to use and calculates automatically the CAVI. CAVI measurements will be performed according to the manufacturer Measurements will be performed after five to ten minute - period of rest in order to obtain a steady hemodynamic state and to limit measurements variability.| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Cardio-Ankle-Vascular Index | CAVI will be measured using the Vasera device (Fukuda Denshi co, Japan). This device is easy to use and calculates automatically the CAVI. CAVI measurements will be performed according to the manufacturer recommendations Measurements will be performed after five to ten minute - period of rest in order to obtain a steady hemodynamic state and to limit measurements variability. The details of the CAVI measurements are shown in a specific document, C.F. appendix Ankle Brachial Index (ABI): The Ankle Brachial Index (ABI) will be measured using the Vasera device (Fukuda Denshi co, Japan). This device will calculate the ABI automatically. ABI measurements will be performed according to the manufacturer recommendations Measurements will be performed after five to ten minute - period of rest in order to obtain a steady hemodynamic state and to limit measurements variability. | 2 years | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Pulse Wave Velocity | Measurement of PWV will be performed using a validated automatic device (Complior®, Sphygmocor®, and PulsePen®). The method of simultaneous recordings of the pulse waves from 2 different sites (carotid and femoral arteries) will be preferred. Because of the use of several devices, normalisation of the measurement values will be performed according to the European Experts recommendations. | 2 years | | Blood pressure Measurements | Blood pressure will be measured in clinic according to the European Society of Hypertension (ESH) guidelines. BP should be measured in a standardized fashion using equipment that meets certification criteria. | 2 YEARS | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- PWV, Cardio ankle vascular index, CAVI, pulse wave velocity, Non invasive arterial structure assessment

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Dynamic Evaluation of Ankle Joint and Muscle Mechanics in Children With Spastic Equinus Deformity Due to Cerebral Palsy Study Overview ================= Brief Summary ----------------- This research will lead to the first evaluation of intrinsic and dynamic joint and muscle mechanics of equinus in cerebral palsy. It would provide a direct cause and effect relationship between equinus and bone deformity. Mechanical insights to the pathophysiology of the targeted muscles will lead to better understanding and, thus, to a better medical and surgical management of equinus deformity. Secondary aim will provide an important insight whether key gait parameters can be exclusively relied upon for surgical treatment planning and evaluation. In a medium-term perspective, depending upon the results of this study, dynamic MRI of the ankle joint may serve as a guiding tool for fixed equinus surgery in case of cerebral palsy. Detailed Description ----------------- Equinus is the most common deformity in children with cerebral palsy. Spastic equinus is typically defined as the inability to dorsa-flex the foot above plantigrade, with the hindfoot in neutral position and the knee in extended position. Approximately 90% of the deformities in cerebral palsy occur in the ankle and foot region alone with the incidence of equinus being around 75%. Spastic equinus exhibits poor muscle control and muscle weakness around ankle and foot, resulting in bone deformities and gait abnormalities. Non-operative conservative management of equinus is typically undertaken up until 8 years in order to prevent recurrent equinus or overcorrection by avoiding high-growth phase of child's development for surgical intervention. Despite these precautions, long term follow-up studies report up to 48% of recurrence rate post-surgery. Recurrence surgery not only increases the economic burden on the society but also has a debilitating impact on children and their families. Previous research is focused on extrinsic risk factors such as CP type, demographic parameters, and clinical gait parameters for surgical recurrence and none assessed the dynamic impact of intrinsic bone deformity on ankle joint and muscle mechanics. A primary reason for this recurrence could be a lack of understanding of bone deformity that might be forcing the child to adapt altered ankle joint and muscle mechanics (bone kinematics, cartilage contact parameters, muscle strain) during dynamic activities. In fact, the surgical treatment of fixed equinus does not consider any bone corrections and focus on muscle release or lengthening only. Being a dynamic pathology, it is critical to understand the in vivo effect of weak ankle joint musculature on joint mechanics and the resultant bone deformity. However, no such efforts have been made so far in the literature. With the advent of technology, researchers have developed and validated dynamic magnetic resonance imaging techniques to analyze in vivo muscle and joint mechanics. Processing this data enables researchers to analytically track bones without having to identify specific points or anatomical landmarks and thus provides the ability to track muscle motion as well as skeletal motion. Thus properties such as bone kinematics, cartilage contact mechanics, musculotendon moment arms, muscle strain and tendon strain are available from these analyses. These techniques can be successfully employed in equinus research to evaluate ankle joint and muscle mechanics in vivo. Official Title ----------------- In Vivo Dynamic Evaluation of Ankle Joint and Muscle Mechanics in Children With Spastic Equinus Deformity Due to Cerebral Palsy: Implications for Recurrent Equinus. Conditions ----------------- Equinus Deformity Intervention / Treatment ----------------- * Radiation: MRI scanner * Other: Gait analysis Participation Criteria ================= Eligibility Criteria ----------------- Equinus cohort inclusion criteria: children between 7 and 14 years old with unilateral CP and GMFCS score of I or II with the presence of fixed equinus defined as a fixed limitation of dorsiflexion inferior to 0° Control cohort inclusion criteria: age and gender matched to equinus cohort no history of lower limb musculo-skeletal injury in past 6 months no history of lower limb musculoskeletal surgery in past six months no contraindications to MRI Equinus cohort exclusion criteria: history of lower limb musculo-skeletal surgery botulinum toxin injection in past 6 months contraindications to MRI Uncooperative patient who refused to sign the informed consent Patient unable to understand the protocol, under guardianship Patients not affiliated to the Social Security. Control cohort exclusion criteria: Uncooperative patient who refused to sign the informed consent Patient unable to understand the protocol, under guardianship Patients not affiliated to the Social Security. Ages Eligible for Study ----------------- Minimum Age: 7 Years Maximum Age: 14 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Prevention Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Equinus cohort<br>15 childrens who have a fixed equinus defined as a fixed limitation of dorsiflexion inferior to 0°. Interventions: MRI scanner and gait analysis | Radiation: MRI scanner<br>* This examination is divided in 2 parts: Passive movement: after placing the ankle joint in the fixture, each child will be asked to relax the lower limb musculature and then the fixture will be cyclically moved by a technician at a speed which does not trigger spasticity. Active movement: no technician will be present and children will be asked to perform voluntary plantar-dorsiflexion between the extreme positions on the beat of the metronome.<br>* Other names: MRI data on pediatric ankle joint;Other: Gait analysis<br>* For gait evaluation, each child will undergo a lower limb gait analysis in a motion analysis laboratory equipped with Camera system and 4 AMTI force plates Sixteen reflective markers will be placed on the lower limbs. Each child will walk bare foot and gait will be recorded during each of five 10-meter trials. A velocity of 1 m/s (+/- 10%) will be imposed using a stop watch in order to eliminate the influence of velocity on gait kinematics and kinematics while comparing across subjects. Each child will be allowed to walk for 5 minutes after attaching the reflective markers and before recording the gait data. In addition to the joint kinematics, joint powers and moments will be computed using an inverse dynamics method.<br>* Other names: Gait evaluation;| | Experimental: Control cohort<br>In this cohort, there will be 15 childrens with age and gender matched to equinus cohort and with no history of lower limb musculo-skeletal injury in past 6 months. Interventions: MRI scanner and gait analysis | Radiation: MRI scanner<br>* This examination is divided in 2 parts: Passive movement: after placing the ankle joint in the fixture, each child will be asked to relax the lower limb musculature and then the fixture will be cyclically moved by a technician at a speed which does not trigger spasticity. Active movement: no technician will be present and children will be asked to perform voluntary plantar-dorsiflexion between the extreme positions on the beat of the metronome.<br>* Other names: MRI data on pediatric ankle joint;Other: Gait analysis<br>* For gait evaluation, each child will undergo a lower limb gait analysis in a motion analysis laboratory equipped with Camera system and 4 AMTI force plates Sixteen reflective markers will be placed on the lower limbs. Each child will walk bare foot and gait will be recorded during each of five 10-meter trials. A velocity of 1 m/s (+/- 10%) will be imposed using a stop watch in order to eliminate the influence of velocity on gait kinematics and kinematics while comparing across subjects. Each child will be allowed to walk for 5 minutes after attaching the reflective markers and before recording the gait data. In addition to the joint kinematics, joint powers and moments will be computed using an inverse dynamics method.<br>* Other names: Gait evaluation;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Talocrural joint flexion, pronation, and internal rotations | Talocrural (talus relative to tibia) joint rotations and translations will be compared between two cohorts. | One year | | Subtalar joint flexion, pronation, and internal rotations | Subtalar (calcaneus relative to talus) joint rotations and translations will be compared between two cohorts. | one year | | Achilles tendon moment arm (MAAT) | MAAT is defined as a perpendicular 3D distance between Achilles' tendon line of action and the Medial-lateral Calcaneal axis. Using calcaneal kinematics, MAAT value for each time frame will be quantified and compared between two cohorts. | one year | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Ankle joint kinematics (joint angles) during walking | Walking gait parameters (ankle, knee, and hip joint angles) will be correlated with primary outcome measures | one year | | Knee joint kinematics (joint angles) during walking | Walking gait parameters (ankle, knee, and hip joint angles) will be correlated with primary outcome measures | one year | | Hip joint kinematics (joint angles) during walking | Walking gait parameters (ankle, knee, and hip joint angles) will be correlated with primary outcome measures | one year | | Talocrural joint contact area | Joint contact mechanics measures and will be compared between cohorts. | one year | | Talocrural joint contact centroid location | Joint contact mechanics measures and will be compared between cohorts. | one year | | Subtalar joint contact area | Joint contact mechanics measures and will be compared between cohorts. | one year | | Subtalar joint contact centroid location | Joint contact mechanics measures and will be compared between cohorts. | one year |

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Neurobiological Effects of Transcranial Direct Current Stimulation Treatment in Alcohol Use Disorder Study Overview ================= Brief Summary ----------------- Background: Alcohol Use Disorder (AUD) is a complex psychiatric disorder, involving several brain areas and neurocircuits. Transcranial Direct Current Stimulation (tDCS) allows to stimulate superficial areas of brain using a weak electrical current. Preliminary data suggest that tDCS may reduce alcohol craving and consumption. Objectives: The main outcome is to test if tDCS can reduce alcohol craving and use and to assess the changes in BDNF and pro-BDNF levels. Secondary outcomes are the assessment of other psychiatric dimensions (mood, behavioral and cognitive alterations) associated with prolonged alcohol use. Eligibility: Healthy, right-handed adults ages 18-65 who do have AUD (moderate to severe). Design: This is a randomized, double-blind, sham-controlled study with three phases: 1) a tDCS intensive treatment phase; 2) follow-up with weekly tDCS stimulation; 3) follow-up without tDCS stimulation. Participants will be screened with: Psychometric Scales Medical history Physical exam Urine tests and breathalyzer After being enrolled, baseline behavioral and laboratory data will be collected. In particular, participants will undergo: Psychometric Scales Venous blood sample (BDNF/proBDNF levels) Participants will be randomized to real or sham tDCS arm. The stimulation will be delivered daily for five days during the first week (intensive treatment phase) and then weekly for 3 months (follow-up with stimulation). During this period patient will be tested with a behavioral and psychometric evaluation.Therefore, participants will receive 3 follow-up monthly visits without tDCS stimulation, in which behavioral and psychometric data will be collected. Treatment includes: tDCS: The tDCS will be delivered with a stimulator connected to two sponge electrodes, soaked in a saline solution. The stimulation will be administered at a current intensity of approximately 1 mA, for the duration of 20 minutes. The anode will be placed on the right DLPFC, the cathode on the contralateral cortical area. BDNF/proBDNF levels: A venous blood sample will be collected before the first stimulation and after the last stimulation of the intensive-stimulation period (first week). The blood sample will be centrifuged within 20 minutes of sampling at 1000 × g for 15 minutes. Then, the serum will be aliquoted and stored at -80 ° C until analysis. Repeat of screening tests and questionnaires Urine toxicological screen and breathalyzer Detailed Description ----------------- Transcranial Direct Current Stimulation (tDCS) consists in the application on the scalp of electrodes (anode and cathode) delivering a direct current of low intensity that cannot be perceived by the stimulated subject. In recent years, tDCS stimulation has been increasingly used in psychiatric clinical research and in the addiction field. Although there are some studies showing the anti-craving action of tDCS in alcohol use disorder (AUD), there are some differences between the stimulation parameters used in these works. Furthermore, there is a lack in the international scientific literature of studies that have investigated the neurobiological basis of tDCS activity. This double-blind randomized sham-controlled trial consist in an intensive daily tDCS stimulation for the first week, then 3 months of follow up with tDCS stimulation (one tDCS stimulation/week) and then 3 months of follow up without tDCS stimulation. Psychometric evaluations will be performed at: baseline, end of the first week of stimulation, 2 weeks, 3 months, 6 months. A venous blood sample will be collected before the first stimulation and after the last stimulation of the intensive first week treatment. The primary outcome of the study is the evaluation of the short-term clinical efficacy of the application of tDCS in subjects with AUD, applying a anodal stimulation (1 mA) on the right Dorso-Lateral Prefrontal Cortex (DLPFC) for 20 minutes for 5 consecutive days. The results on some psychiatric psychometric scales (examine possible changes in mood, cognition and other psychiatric domains) will represent additional criteria. Another outcome is to assess the neuromodulation at the level of DLPFC evaluating the changes in serum levels of the brain-derived neurotrophic factor (BDNF) and its precursor (pro-BDNF). After screening and informed consent, participants will undergo active or sham tDCS for one week during the intensive treatment phase, and a maintenance intervention (twice a week for 3 months), during the tDCS follow-up phase. Following this phase, participants will be followed for further 3 months, during which no rTMS will be delivered but clinical and imaging data will be collected. Procedure: The project consists of: Screening Visit (baseline), phase 1 (intensive treatment phase), phase 2 (3 months- tDCS follow-up), phase 3 (3 months follow-up without rTMS). In the screening visit, a clinical interview to assess the eligibility of participant (following the inclusion and exclusion criteria) will be performed. The signature of the informed consent and the baseline clinical and cognitive data will be acquired. In Phase 1, all participants will be randomized in the active or sham arm. Participants will receive 20 minutes of anodal right DLPFC stimulation for 5 consecutive days. The assessor will evaluate the acute effect of treatment on craving , consumption and on the psychometric variable considered at the end of this phase. A venous blood sample will be collected before the first stimulation and after the last stimulation of the intensive-stimulation period to asses the BDNF and pro-BDNF level. In Phase 2, each participant will undergo the same treatment (active or sham) of the Phase 1 for three months receiving stimulation once per week. The same psychometric and behavioral data of the phase 1 will be collected monthly. During Phase 3 participants will not receive any tDCS stimulation. Also in this phase, the same psychometric and behavioral data of the phase 1 will be collected monthly. Official Title ----------------- Neurobiological Effects of Transcranial Direct Current Stimulation Treatment in Alcohol Use Disorder: a Sham-controlled Trial. Conditions ----------------- Alcohol Use Disorder (AUD), Alcohol Abuse, Alcohol Dependence, Alcohol-Related Disorders, Drug Abuse, Substance Use Disorders, Mental Disorder Intervention / Treatment ----------------- * Device: Active transcranial Direct Current Stimulation * Device: Sham transcranial Direct Current Stimulation Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: diagnosis of Alcohol Use Disorder (at least 12 months); drug free/stable psychopharmacological therapy (one month), with the exception of guidelines treatments for alcoholic abstinence (treatment-as-usual); any assumption of substances for at least 48 hours. Exclusion Criteria: presence of organic pathologies (capable of interfering with the safety of the procedure) in comorbidities; presence of intellectual disability; history of epileptic seizures (also in first degree relatives); score> 12 on the Young Mania Rating Scale (Y-MRS). Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 65 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: double blind, randomized, sham-controlled with a 1:1 allocation into 2 parallel arms Masking: Double Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Active tDCS<br>The intervention will be the stimulation with transcranial Direct Current Stimulation (tDCS). Each patient will undergo a 20 minutes session with anode placed on the right Dorso-Lateral Prefrontal Cortex (RDLPFC) and the cathode on the left DLPFC (LDLPFC); the tDCS will administrate a 1 mA stimulation. During the intensive treatment phase participant will undergo one stimulation/day for 5 consecutive days. After this, participants will receive one stimulation per week for 3 months with the same parameters. Device: tDCS device (E.M.S. Electromedical Systems, Bologna, Italy) with a maximum output of 5 mA and administered by two 25-cm2 sponge electrodes of rectangular shape. | Device: Active transcranial Direct Current Stimulation<br>* tDCS is a non-invasive brain stimulation technique. The investigators will use a BrainSTIM (EMS, Bologna, Italy)<br>* Other names: Active tDCS;| | Sham Comparator: Sham tDCS<br>The intervention will be the stimulation with sham transcranial Direct Current Stimulation (sham tDCS). The device will be set by staff member not involved with data collection analysis to ensure the blinding of assessors. The device will be set to give a weak amperage for the first and the last 20 second of stimulation to ensure the blinding of participant giving them a similar sensation experienced by the active tDCS participants without stimulate brain tissues. Device: tDCS device (E.M.S. Electromedical Systems, Bologna, Italy) with a maximum output of 5 mA and administered by two 25-cm2 sponge electrodes of rectangular shape. | Device: Sham transcranial Direct Current Stimulation<br>* tDCS is a non-invasive brain stimulation technique. The investigators will use a BrainSTIM (EMS, Bologna, Italy)<br>* Other names: Sham tDCS;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in BDNF level | BDNF levels will be evaluated by collecting a venous blood sample. BDNF is a member of the nerve growth factor (NGF) family of neurotrophic growth factors. Low levels of peripheral BDNF and NGF have been reported in mood disorders and other psychopathological conditions with normalization after antidepressant treatment or mood stabilization. The increase in serum levels of BDNF seems to reflect the concomitant activation of BDNF synthesis that accompanies the neuronal remodeling triggered by the suspension of alcohol intake and suggests that the synthesis of BDNF may have a role in the long-term maintenance of alcohol abstention. BDNF measurements will be calculated in pg/ml | Baseline and after tDCS treatment: one week | | Change in pro-BDNF | Pro-BDNF is the precursor of BDNF and it acts as a repository of mature BDNF and acts itself by inducing neuronal thinning. Pro-BDNF levels will be evaluated by collecting a venous blood sample. Pro-BDNF measurements will be calculated in ng/ml. | Baseline and after tDCS treatment: one week | | Change in pro-BDNF/BDNF ratio. | Pro-BDNF/BDNF ratio, seems to be a more specific measurement of the early changes in the metabolism of BDNF. Its level seems to correlate to more or less a neurotrophic and neuroprotective action of BDNF. | Baseline and after tDCS treatment: one week | | Change in alcohol consumption as assessed by Alcohol Timeline Follow Back (TLFB-Alcohol) | The TLFB is a calendar-based interview method in which the individual retrospectively identifies the days when alcohol was assumed, and the number of standard drinks consumed on those days. // Alcohol consumption will be assessed using the TimeLine Follow Back (TLFB). TLFB is an interview-based assessment. Using a calendar, participants are guided through the process of recalling and reporting daily alcohol consumption. TLFB provides measures of alcohol consumption per week, alcohol consuming days per week, heavy alcohol consuming days per week. | Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months | | Change in alcohol craving as assessed by the Visual Analog Scale for Craving (VAS 0-10 Craving) | Alcohol craving intensity will be assessed using a visual analog scale (VAS). Participants sign subjective feelings of craving on a 10 cm line marked from zero (null) to 10 (the most intense). | Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months | | Change in alcohol craving characteristics as assessed by the Brief Substance Craving Scale (BSCS) | Alcohol craving will be assessed using the Brief Substance Craving Scale (BSCS). The BSCS is a 16 item, self-report instrument assesses craving for substances of abuse over a 24 hour period. | Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months | | Absence of alcohol intoxication evaluated by breathalyzer | Alcohol consumption will be evaluated by breathalyzer. Breathalyzer measures breath alcohol concentration (BrAC) levels; the BrAC-data was interpreted as blood alcohol content (BAC). Semi-quantitative analyses are performed. The breathalyzer can differentiate five levels: negative (0 - 0.07 gr / L), low (0.07 - 0.3 gr / L), warn (0.31 - 0.5 gr / L), fall (0.51 - 0.8 gr / L), fall + (> 0.8 gr / L) | Baseline, before the stimulation each day of treatment, each meeting of follow-up | | Evaluation of craving subtype assessed by the Craving Typology Questionnaire (CTQ) | Alcohol craving subtype will be assessed using the Craving Typology Questionnaire (CTQ). It is a self-report questionnaire measuring three supposedly independent typologies of alcohol craving: relief, obsessive and reward craving. | Baseline | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Changes in Montgomery-Asberg Depression Scale (MADRS) Total Score | The MADRS is a 10-item scale that evaluates the core symptoms and cognitive features of clinical depression. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms. | Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months | | Change in substances consumption as assessed by Urine Drug Screen (UDS) | Substances consumption will be evaluated by Urine Drug Screen (UDS). Urine Drug Screen is a test to evaluate the presence of substances of abuse in urine samples. Quantitative analyses are not performed. Test may be positive or negative for the presence of substances of abuse. | Baseline, after tDCS treatment: one week and randomly at follow-up meetings | | Changes in the Frontal Assessment Battery (FAB) Total Score | Frontal Assessment Battery (FAB) is a short neuropsychological tool aimed at assessing executive functions. The FAB consists of six subtests, each exploring functions related to the frontal lobes: conceptualization (by means of a similarities task), mental flexibility (by means of a phonological fluency task), motor programming (by means of Luria's motor series), sensitivity to interference (by means of a conflicting instruction task), inhibitory control (by means of a go-no-go task), and environmental autonomy (by means of evaluation of prehension behavior). Each subtest score may range from 0 (min) to 3 (max); total score is from 0 (min) to 18 (max). Higher scores indicate better performance. | Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months | | Changes in Hamilton Rating Scale for Anxiety (HAM-A) Total Score | The HAM-A is a 14-item scale that assesses anxiety symptoms of anxiety such as anxious mood, tension or fears. Each item is scored on a 5-point scale, ranging from 0 (not present) to 4 (severe). Sum the scores from all 14 parameters gives the HAM-A Total Score which may range from 0 (min) to 56 (max). | Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months | | Changes in Hamilton Rating Scale for Depression (HAM-D) 21 items Total Score | The HAM-D is a 21-item scale that measures the severity of depressive symptoms and additional clinical information (diurnal variation, depersonalization/derealization, paranoid symptoms, and obsessive-compulsive symptoms). The severity of depression is divided into 4 categories as follows: 0-7 is considered as normal patients, 8-16 suggesting mild depression, 17-23 suggesting moderate depression and scores over 24 indicating severe depression. The total HDRS score ranged from 0 to a maximum of 52 points. | Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months | | Changes in Barratt Impulsiveness Scale - 11 (BIS-11) Total Score | The Barratt Impulsiveness Scale 11th version (BIS-11) is a 30-item scale that assesses impulsivity. The BIS-11 was developed to specifically measure impulsiveness, in contrast to other action-oriented traits such as sensation-seeking, extraversion, and risk taking. The total BIS-11 score ranged from 30 to a maximum of 120 points. Higher scale scores indicate higher levels of impulsiveness. | Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months | | Changes in Toronto Alexithymia Scale (TAS-20) Total Score | The TAS-20 is a self-report scale that assesses alexithymia. It is comprised of 20 items assessing three dimensions of alexithymia, i.e., Difficulty Identifying Feelings (DIF), Difficulty Describing Feelings (DDF), and Externally Oriented Thinking (EOT). Each of the twenty items is rated on a 5-point Likert scale. Increasing scores indicate higher degrees of alexithymia. The TAS-20 uses cutoff scoring: equal to or less than 51 = non-alexithymia, equal to or greater than 61 = alexithymia. Scores of 52 to 60 = possible alexithymia. | Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months | | Changes in Beck Depression Inventory-II scale (BDI-II) Total Score | The BDI-II is a 21-item self-report measure of depressive symptoms. Each of the 21 items corresponding to a symptom of depression is summed to give a single score for the Beck Depression Inventory-II (BDI-II). There is a four-point scale for each item ranging from 0 to 3. On two items (16 and 18) there are seven options to indicate either an increase or decrease of appetite and sleep. Cut-off score guidelines for the BDI-II are given with the recommendation that thresholds be adjusted based on the characteristics of the sample, and the purpose for use of the BDI-II. Total score of 0-13 is considered minimal range, 14-19 is mild, 20-28 is moderate, and 29-63 is severe. | Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months | | Evaluation of South Oaks Gambling Screen (SOGS) Total Score | The SOGS is a 20-item instrument to screen for probable pathological gambling. A cut score of 5 or more is typically used to indicate that the individual is a probable pathological gambler. | Baseline | | Changes in Leuven Affect and Pleasure Scale (LAPS) Total Score | The LAPS is a 16-item questionnaire to assess negative affect, positive affect, and hedonic tone. The 16-item scale comprises 3 subscales (negative affect, positive affect, hedonic tone) and 4 independent items (cognitive functioning, overall functioning, my life is meaningful, I feel happy). Patients rate their positive and negative moods, and hedonic tone from 0 to 10, where 0 is not at all, 1-3 are scores for a little bit, 4-6 are scores for moderately, 7-9 are scores for quite a bit and 10 represents very much. | Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months | | Changes in Gambling Symptom Assessment Scale (G-SAS) Total Score | The G-SAS is a 12-item self-rated scale designed to assess gambling symptom severity and change during treatment. Each 12-item scale has a score ranging from 0 - 4 (adjective anchors for 0 and 4 vary for each item). All items ask for an average symptom based on the past 7 days. Total score ranges from 0 - 48: extreme = 41 - 48, severe = 31 - 40, moderate = 21 - 30, mild = 8 - 20. | Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months | | Changes in Young Mania Rating Scale (YMRS) Total Score | The Y-MRS is a 11-item scale to assess manic symptoms based on the patient's subjective report of his or her clinical condition over the previous 48hours. Additional information is based upon clinical observations made during the clinical interview. YMRS cut-off values were minimal (13), mild (20), moderate (26), and severe (38) manic symptoms. | Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months | | Changes in Brief Psychiatric Rating Scale Expanded (BPRS-E) Total Score | The BPRS-E is a 24-item scale for assessing type, severity and change over time of 24 psychiatric symptoms. The presence and severity of psychiatric symptoms were rated on a Likert scale ranging from 1 (not present) to 7 (extremely severe). Thus, possible scores vary from 24 to 168 with lower scores indicating less severe psychopathology. | Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months | | Evaluation of Questionnaire of sensations related to Transcranial Electrical Stimulation (TES) Total Score | The TES is a short tool aimed at assessing any possible discomfort during the electrical stimulation (e.g., itching, pain or burning), the duration and the degree of intensity discomfort. | After each tDCS treatment: Every day first week, once a week in the next three months. | | Evaluation of Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES 8A) Total Score | A) The SOCRATES 8A is a 19-items scale that measures participants general level of motivation. SOCRATES 8A assess strengths and needs in the areas of treatment readiness, motivation of problem drinkers and drug users for change and to enter treatment. It provides scores on three subscales- Recognition, Ambivalence and Taking steps. | Baseline | | Changes in Iowa Gambling Test (IGT)Total Score | The IGT is a computer-administered neuro-psychological test to evaluate decision-making abilities. It consists of 100 card selections from four decks of cards divided into five distinct blocks of 20 trials each to examine participant's learning curve. A total score for the IGT is calculated by subtracting the total number of selections from the bad decks from the total number of selections from the good deck. A positive total score indicates advantageous decision-making, whereas a negative total score indicates disadvantageous decision-making. | Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months | | Changes in Stroop Color and Word Test (SCWT) Total Score | The SCWT evaluates attention, information processing speed, selective attention, cognitive flexibility and the ability to inhibit cognitive interference of simultaneous stimulus. The SCWT evaluates the reaction times to non-ambiguous stimuli and to ambiguous stimuli. | Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Alcohol Use Disorder, transcranial Direct Current Stimulation, Non-Invasive Brain Stimulation, Craving, Brain Derived Neurotrophic Factor, Pro-Brain Derived Neurotrophic Factor

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The Effect of Methylphenidate Versus Placebo on State Anxiety in Children With Attention Deficit Hyperactivity Disorder. Study Overview ================= Brief Summary ----------------- The purpose of the study is to explore the effect of methylphenidate on state anxiety in children with attention deficit hyperactivity disorder. Patient population: 30 children diagnosed with attention deficit hyperactivity disorder. The subjects will be of all racial, ethnical and gender categories, ranging from 8 to 18 years of age. Structure: the study is a randomized double blind crossover study. The subjects will complete a continuous performance test, the cambridge neuropsychological test automated Battery, before and after given methylphenidate or placebo on the first day of the study. On the second day of the study, the subjects will receive either methylphenidate or placebo based on what was given on the first day of the study and they will complete the same task. Official Title ----------------- A Double Blind Randomized Crossover Study of the Effect of Methylphenidate Versus Placebo on State Anxiety in Children With Attention Deficit Hyperactivity Disorder. Conditions ----------------- Attention Deficit Hyperactivity Disorder Intervention / Treatment ----------------- * Drug: Methylphenidate Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Attention deficit and hyperactivity disorder Children aged 8-18 years Exclusion Criteria: Pervasive developmental disorder Schizophrenia Bipolar disorder Current depressive episode Current Anxiety disorder Drug use during the past 6 months Ages Eligible for Study ----------------- Minimum Age: 8 Years Maximum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Diagnostic Allocation: Randomized Intervention Model: Crossover Assignment Masking: Quadruple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Methylphenidate<br>Methylphenidate 0.3 mg/kg per os is given before performing a continuous performance test. | Drug: Methylphenidate<br> <br> | | Placebo Comparator: Placebo<br>Placebo is given before performing a continuous performance test. | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | State anxiety | State anxiety will be measured by the Spielberger's state anxiety inventory | 1 year | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Cognitive function | Cognitive function will be measured by the cambridge neuropsychological test automated battery | 1 year | | Patient's perspective | Patient's perspective will be measured by questionnaires assessing treatment adherence issues and patient's view regarding the use of placebo. | 1 year | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Attention Deficit Hyperactivity Disorder, Methylphenidate, Placebo, State anxiety

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A Vignette-based Randomized Controlled Trial to Evaluate the Impact of Research Climate on Research Practices of Doctoral Students Study Overview ================= Brief Summary ----------------- This study aims to evaluate the impact of research climate on PhD students' research practice (i.e., an environment where their peer (i.e., a post-doc researcher) had detrimental practice in a similar situation) Detailed Description ----------------- PhD students are the next generation of researchers and will present the field in the future. However, several environmental factors might influence their research practice. In this study, the investigators will evaluate the impact of research climate on PhD students' research practice (exposure to an environment where their peers commit a detrimental practice). Objective: To evaluate the impact of research climate on PhD students' research practice Design: A randomized controlled trial Intervention: Participants will be shown two case vignettes describing dilemma situations in research reported with and without research climate factor. Participants: The participants will be PhD students in all biomedical disciplines. Sample size will be 300 participants Primary outcome: In each vignette, participants will have to indicate which solution they prefer on a semantic differential scale, rated from - 5 to -1 (preference for solution A) and from 1 to 5 (preference for solution B). Participants will be forced to make a choice between the 2 solutions. The primary outcome will be the mean preference score. This study is approved by ethics review regulations by INSERM (CEEI-IRB): IRB00003888 Official Title ----------------- A Vignette-based Randomized Controlled Trial to Evaluate the Impact of Research Climate on Research Practices of Doctoral Students Facing Dilemma Situations Conditions ----------------- The Study Focus on no Specific Condition Intervention / Treatment ----------------- * Other: Vignette with emphasis on research climate Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: PhD students in biomedical disciplines Exclusion Criteria: NA Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Other Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Vignette with research climate<br>Participants in this arm will receive vignettes describing a dilemma situation in research (e.g adding honorary author) with additional sentence describing research climate (i.e. an environment where their peer had detrimental practice in a similar situation) | Other: Vignette with emphasis on research climate<br>* A vignette describing a dilemma situation for a researcher (e.g. adding an honorary author) with or without a research environment factor (i.e. an environment where other researchers commit detrimental research practice)<br>| | Active Comparator: Vignette without research climate<br>Participants in this arm will receive vignettes describing a dilemma situation in research without the additional sentence describing research climate | Other: Vignette with emphasis on research climate<br>* A vignette describing a dilemma situation for a researcher (e.g. adding an honorary author) with or without a research environment factor (i.e. an environment where other researchers commit detrimental research practice)<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | mean preference score | In each vignette, participants will have to indicate which solution they prefer on a semantic differential scale, rated from - 5 to -1 (preference for solution A) and from 1 to 5 (preference for solution B). | Immediate assessment | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | proportion of students who chose the detrimental research practice (DRP) | Proportion of students rated from -5 to -1 for the DRP. | Immediate assessment |

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Extracorporeal Photopheresis and Early Cardiac Graft Vasculopathy Study Overview ================= Brief Summary ----------------- Heart transplantation is a golden standard for the treatment of terminal heart failure. The major cause of death in late posttransplant period is cardiac allograft vasculopathy (CAV). This posttransplant complication develops slowly over several years, and when diagnosed either by conventional coronary angiography or due to graft failure, it is often too advanced and difficult to treat since it is diffuse coronary artery disease. Therefore, early prevention of CAV is a subject of major interest in the transplant cardiology. Since CAV is associated with immune factors, immunomodulatory therapeutic options, like extracorporeal photopheresis are lately being investigated. Unlike conventional coronary angiography, optical coherence tomography (OCT) is able to detect the development of CAV in the earliest phase, i.e. even in the first post-transplant year. In our study, we plan to investigate the prophylactic effect of extracorporeal photopheresis in the early development of cardiac graft vasculopathy detected by OCT. Detailed Description ----------------- Introduction Heart transplant is golden standard in the treatment of terminal heart failure. Although patients' survival improved due to new advanced surgical techniques and the use of modern immunosuppressants, the posttransplant period of these patients is still fraught with complications and associated with reduced life expectancy compared to healthy individuals. Morbidity and mortality in the early post-transplant period are mainly associated with infections, acute graft rejection, multiorgan failure, and unspecified graft failure. In the late posttransplant period, the main cause of death is cardiac allograft vasculopathy (CAV). It should be emphasized that 30% of patients after 5 years and 50% after 10 years have angiographic changes in coronary arteries. Unlike atherosclerosis in the native heart that is typically focal, noncircumferential and usually localized in proximal segments of coronary arteries, CAV is a diffuse disease with concentric intimal hyperplasia and thickening of microvasculature media. It is a multifactorial disease caused by the immune, but also other non-immune factors: cellular and humoral (antibody-mediated) graft rejection, donor-specific anti-HLA antibodies, CMV infection, and hypercholesterolemia. The pathophysiology of immune-mediated development of CAV is based on T-cell and vascular endothelial interaction. According to the previously known association between graft rejection and development of coronary vasculopathy, routine clinical follow-up of transplanted patients includes regular myocardial biopsies with pathohistological analysis for cellular and humoral rejection. Although CAV sometimes develops rapidly, it is usually slowly progressive disease associated with the development of chronic humoral graft rejection. Since symptoms and signs of CAV are usually absent or atypical (due to afferent and efferent graft denervation), early diagnosis is extremely important. For that reason, according to current recommendations of International Society for Heart and Lung Transplantation (ISHLT), regular periodic coronary angiographies are being performed. Nowadays, modern transplant centers, besides classical coronary angiography, perform intravascular ultrasound (IVUS) for coronary artery imaging. It provides a measurement of intimal thickness and today it is the gold standard in early detection of vasculopathy. However, due to the better spatial resolution of coronary artery layers, especially the intimal layer, in comparison to IVUS, optical coherence tomography (OCT) is started to use more often in the detection of CAV. Despite many efforts, there are still no effective measures for CAV prevention. Out of all examined options, statin therapy and use of mTOR inhibitors as a part of the immunosuppressive regimen is providing best, but still not effective enough. Since the development of CAV is associated with various immune factors, immunomodulatory therapeutic options are being investigated. One of those options is extracorporeal photopheresis. It is an immunoregulatory method that divides patients' peripheral blood into two fractions: leukocyte-rich and leukocyte-poor fraction. The first fraction is immediately returned in circulation, and another one is exposed to UVA irradiation to achieve the immunomodulatory effect, i.e. increase in regulatory T-cell activity. This reduces rejection and graft vasculopathy as a result of an excessive immune response to the transplanted organ. The positive effect of this therapeutic method on CAV development was confirmed in one small study where pathomorphological changes of coronary arteries were detected using IVUS. Moreover, maintenance immunosuppressive therapy in study patients included a combination of cyclosporin and azathioprine, inferior to contemporary immunosuppressive combinations. Hypothesis Extracorporeal photopheresis, along with other standard methods of treatment after heart transplantation significantly reduces the development of cardiac allograft vasculopathy as detected with optical coherence tomography. Materials and methods: This is a controlled prospective study of de novo heart transplant patients followed at the the Department for intensive care unit, arrhytmias and transplantation cardiology at University Hospital Center Zagreb. We plan to enroll 25 consecutive patients after heart transplant after signing an informed consent form. All patients will be treated with standard immunosuppressive protocol and have a standard follow-up with regular biopsies. The number of patients (12-13) determined by chance will receive additional treatment with extracorporeal photopheresis (ECP) according to a predetermined protocol. During the first post-transplant year, these patients will undergo 10 ECP treatments, each pair of treatment given on two consecutive days. Complete blood count, electrolytes and coagulation parameters are performed prior to the procedure. Since psoralen application can cause photosensitivity, patients are advised to avoid sun exposure for 24 hours. The procedure will be performed in the Department for transfusion and transplantation biology at University Hospital Center Zagreb. All patients included in the study will undergo two coronary angiographies with OCT imaging - the initial within the first three months after heart transplantation, and the second 12 months after heart transplantation. Ilumien Optis System platform with Dragonfly Optis Imaging catheter will be used to acquire high-resolution images. OCT images acquired at basal and control will be used for statistical analysis of ECP effect on the development of cardiac allograft vasculopathy. OCT acquisition will be performed in all three major coronary arteries. The analysis will be performed in a blinded fashion. For quantification of intimal tissue hyperplasia, we will measure maximal and median intimal thickness, maximal and mean intima area, as well as volumetric indices including intimal volume, plaque volume, and plaque index. These parameters will be normalized to measured segment length. Qualitative intimal tissue analysis will be performed as well. All plaques in the acquired segments will be characterized and sized according to luminal presentation and mapped for serial assessment. During the study, we will collect patients' medical history data, anthropometric measurements, and laboratory tests results. According to the standard protocol of myocardial biopsies and pathological analysis, results regarding graft rejection will be used in the comparative analysis of photopheresis efficacy. Official Title ----------------- Extracorporeal Photopheresis for the Prevention of Early Cardiac Allograft Vasculopathy Detected by Optical Coherence Tomography Conditions ----------------- Cardiac Allograft Vasculopathy, Heart Transplant Rejection Intervention / Treatment ----------------- * Procedure: Extracoropreal photopheresis Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: age >18 and <65 primary orthotopic heart transplant early photopheresis adequate intravenous approach signed informed consent Exclusion Criteria: aphakia psoralen hypersensitivity active retinal disease - photosensitive diseases splenectomy L <2000; Hb <70 g/L coagulopathy Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 65 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Prevention Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: Patients are randomized after heart transplant into two groups. Those randomized for extracorporeal photopheresis undergo 10 procedures during first year, in addition to standard follow-up. Patients in the control group are treated and followed-up according to standard protocol of our transplant center. Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Photopheresis<br>Patients who sign informed consent form undergo prophylactic extracorporeal photopheresis after heart transplant according to predetermined protocol | Procedure: Extracoropreal photopheresis<br>* Patients who sign informed consent form undergo prophylactic extracorporeal photopheresis after heart transplant according to predetermined protocol<br>| | No Intervention: No prophylactic photopheresis<br>Standard post-transplant protocol without prophylactic extracorporeal photopheresis | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Prevention of cardiac allograft vasculopathy detected by optical coherence tomography | It will be measured as the mean change in maximal intimal thickness (mm) between matched slices and the mean change in intimal volume (mm3) between matched coronary segments from baseline to month 12. Intima-to-media border will be identified as sharp line between first bright layer (intima) and first dark layer (media) of vessel wall. OCT will be performed during the patient's angiogram at baseline (1-3 months after transplantation) and again at one year after transplantation. An attempt will be made to get OCT image of all three coronary arteries. Two independent experienced angiographers, who will be blinded to clinical data, will review the baseline and follow-up image acquisition sequences to accurately match the coronary segments. We will compare the mean change of maximal intimal thickness (mm) and/or the mean change of intimal volume (mm3) between patients who underwent extracorporeal photopheresis (ECP) to those who did not undergo ECP. | One year | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Number of patients with angiographically detected coronary artery disease | Angiographically detected CAV is defined as any new luminal irregularity or new stenosis ≥50% on control coronary angiography at 12 months interval. We will compare the incidence of angiographically detected transplant vasculopathy defined as newly occurring angiographic luminal irregularities or ≥50% stenosis between patients who underwent extracorporeal photopheresis (ECP) to those who did not undergo extracorporeal photopheresis (ECP). | 1 year | | Number of patients with acute cellular rejection | Patients will be monitored for acute rejection by routine surveillance endomyocardial biopsy at 1, 2, 4, 6, 9 and 12 months after heart transplantation. Graft rejection will be as an acute cellular rejection with histopathology grade ≥1B according to the 1990 International Society of Heart and Lung Transplantation classification and ≥2R according to the 2004 R grading system. For patients with multiple episodes of rejection, the time to the first event will be counted as the censored outcome. A 1-year cumulative total rejection score (TRS) will be assigned as grade 0=0, grade 1A=0.5, grade 1B=1, grade 2=1.5, grade 3A=2, grade 3B=2.5, grade 4=3, or as grade 0R=0, grade 1R = 1, grade 2R=2, grade 3R=3, and normalized by dividing the cumulative scores with the total number of biopsies performed during the 1-year period. We will compare the incidence of acute cellular rejection between patients who underwent ECP to those who did not undergo ECP. | 1 year | | Number of patients with antibody-mediated rejection | Patients will be monitored for antibody-mediated rejection (AMR) by routine surveillance endomyocardial biopsy at 1, 6 and 12 months within the first year after heart transplantation. It will be defined as either positive immunopathologic finding (the presence of C4d deposition in capillaries in the fresh-frozen biopsy sample), positive histopathologic finding or both. We will compare the incidence of antibody-mediated rejection between patients who underwent extracorporeal photopheresis (ECP) to those who did not undergo extracorporeal photopheresis (ECP). | 1 year | | Number of patients with positive donor specific antibodies | Patients will be monitored for de novo donor specific antibodies (DSA) by routine laboratory surveillance using Luminex assay at 1, 6 and 12 months within the first year after heart transplantation. Positive DSA will be defined as donor-specific antibody with mean fluorescence intensity (MFI) ≥ 2000. We will compare the incidence of positive de novo donor specific antibodies between patients who underwent extracorporeal photopheresis (ECP) to those who did not undergo extracorporeal photopheresis (ECP). | 1 year | | Left ventricular function expressed as ejection fraction (%) and plasma levels of NT-proBNP | Left ventricular systolic function will be assessed by echocardiography and expressed as ejection fraction (%), as well as plasma levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) (ng/L) measured at month 12. We will compare left ventricular ejection fraction and NT-proBNP plasma concentration at month 12 between patients who underwent extracorporeal photopheresis (ECP) to those who did not undergo extracorporeal photopheresis (ECP). | 1 year | | Levels of T-lymphocyte subsets, B-lymphocytes, and NK cells in peripheral blood evaluated by the flow cytometry technique | Peripheral blood samples will be taken just before transplantation, and then before 6th and 9th ECP cycle. Sample will be taken before leukapheresis and analyzed for WBC, hematocrit, mononuclear cells (MNC), and platelet counts. Number of T-lymphocyte subsets (CD3+, CD3+4+, CD3+8+, CD4+8+ ratio) B-lymphocytes (CD 19+), and NK cells (CD56+) in patient's peripheral blood will be taken according to schedule. The levels of T, B lymhocytes and NK cells will be evaluated by the flow cytometry technique (Becton Dickinson, Facs Calibur, USA). The values of lymphocyte subsets will be expressed as percentages and absolute counts (cells/μl). | 1 year | | Number of patients with adverse events - safety assesments | Safety will be assessed by the number of patients with adverse events including: death, all infections (pneumonia, CMV viremia/infection, urinary tract infection, wound infection, sepsis…), CMV viremia/infection, indwelling venous access catheters related bacteremia, indwelling venous access catheters related thrombosis. CMV will be documented as infection (viremia) and disease (viremia with clinical symptoms and signs). | 1 year | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Heart transplant, vasculopathy, extracorporeal photopheresis, prevention, optical coherence tomography

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Immune Response to C.Difficile Infection Study Overview ================= Brief Summary ----------------- The protocol aims to address the basic mechanisms of Clostridium difficile pathogenesis by identifying how a Th 17 response impacts severity of C. difficile infection and how Type II immunity protects the gut from Clostridium difficile toxin-induced damage. This could lead to new and effective approaches to the treatment or prevention of Clostridium difficile colitis that act downstream of fecal microbiota transplants (FMT) or next generation probiotics. Successful fecal microbial transplantation will restore protective immunity to recurrent C.difficile infection. Detailed Description ----------------- The study includes one cohort of hospitalized patients with acute CDI who may require diagnostic colonoscopy, a second cohort of outpatients with recurrent CDI scheduled for FMT and a third cohort of inpatients with past history of CDI without recurrence. Blood samples and discarded stool samples for research will be obtained from adult hospitalized patients. Biopsies and brushing samples for research will be obtained from patients requiring diagnostic colonoscopies for clinical care. Follow-up will include phone contact at 60-90 days to determine relapse or mortality in acute CDI patients. Blood and colonic biopsies and brushing samples will be obtained from patients undergoing FMT for recurrent CDI and again after 60 days from convalescent patients. Blood and biopsies taken for research purposes at each colonoscopy will be analyzed for: cytokines and chemokines, gene expression analysis, immunohistochemistry and high dimensional flow-cytometry. Official Title ----------------- Clostridioides Difficile and Immune Responses in Acute CDI and Fecal Microbiota Transplant Conditions ----------------- Clostridium Difficile Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: -Acute CDI cohort Acute CDI diagnosis including PCR positive fecal samples Optional diagnostic colonoscopy for clinical care FMT cohort At least one relapse or recurrence of C. difficile infection Eligible for fecal microbiota transplant (FMT) Past CDI cohort Past CDI diagnosis and current PCR negative fecal samples Optional diagnostic colonoscopy for clinical care Exclusion Criteria: Acute CDI cohort: Unwilling to have research biopsies and brushings at time of diagnostic colonoscopy; Unwilling to provide blood and stool samples (discarded stool from UVA lab) for research Unwilling to participate in follow-up phone call at 60-90 days Concurrent participation in another clinical trial. This exclusion does not apply to participation in IRB-HSR #200046 and non-interventional research studies. Concurrent participation in non-interventional research studies is allowed. Clinical contraindication to colonoscopy or conscious sedation Pregnancy Inability to give informed consent unless a legally authorized representative (LAR) is available Incarceration HIV infection FMT cohort: Unwilling to have research biopsies and brushings and stool samples at time of colonoscopy with FMT for clinical care and research sigmoidoscopy at Day 60 Unwilling to provide blood samples for research Concurrent participation in another clinical trial This exclusion does not apply to participation in non-interventional research studies. Concurrent participation in non-interventional research studies is allowed. Clinical contraindication to sigmoidoscopy or conscious sedation Pregnancy Inability to give informed consent Incarceration HIV infection Neutropenia (<1000 PMNs/µl blood) Past CDI Control cohort: Unwilling to have research biopsies and brushings at time of diagnostic colonoscopy; Unwilling to provide blood and stool samples (discarded stool from UVA lab) for research Concurrent participation in another clinical trial. This exclusion does not apply to participation in IRB-HSR #200046 and non-interventional research studies. Concurrent participation in non-interventional research studies is allowed. Clinical contraindication to colonoscopy or conscious sedation Pregnancy Inability to give informed consent unless a legally authorized representative (LAR) is available Incarceration HIV infection Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Acute CDI cohort<br>Hospitalized patients diagnosed with Acute CDI | | | FMT cohort<br>Patients undergoing FMT for recurrent CDI | | | Past CDI Control Cohort<br>Hospitalized patients with past CDI diagnosis without recurrence | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Adaptive immune response | Assessment of adaptive immunity including Th1, Th2 and TH17 immune response | 0-60 days post enrollment | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Changes in gut health | Association of biomarkers in stool and biopsy specimens with CDI outcome | 0-60 days post enrollment | | Gene expression of immune cells in colon | Profiling colonic gene expression and mucosal immune pathways in CDI | 0-60 days post enrollment | | Microbiome | Tissue 16s rDNA | 0-60 days post enrollment | | Immunohistochemistry | Changes in mucosal immunity following FMT | 0-60 days post enrollment | | Antibody response to C. difficile infection | IgG and IgA to C. difficile antigens in plasma and stool | 0-60 days post enrollment | | High dimensional flow-cytometry | Profiling of immune cells in blood and biopsy | 0-60 days post enrollment |

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HEM iSMART-D: Trametinib + Dexamethasone + Chemotherapy in Children With Relapsed or Refractory Hematological Malignancies Study Overview ================= Brief Summary ----------------- HEM-iSMART is a master protocol which investigates multiple investigational medicinal products in children, adolescents and young adults (AYA) with relapsed/refractory (R/R) ALL and LBL. Sub-protocol D is a phase I/II trial evaluating the safety and efficacy of trametinib in combination with dexamethasone, cyclophosphamide and cytarabine in children and AYA with R/R ped ALL/LBL whose tumor present with alterations in the RAS-RAF-MAPK pathway. Detailed Description ----------------- HEM-iSMART is a master protocol with sub-protocols. The overarching objective is that introducing targeted therapy using a biomarker driven approach for treatment stratification may improve the outcome of children with R/R acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) It is characterized by a shared framework that allows for the investigation of multiple IMPs and generate pivotal safety and efficacy evidence within the sub-protocols to establish and define the benefits and risks of new treatments for children with R/R leukemia. Sub-Protocol D within HEM-iSMART, is a phase I/II, multicenter, international, open-label clinical trial designed to evaluate the safety, tolerability, pharmacokinetics (PK) and efficacy of trametinib in combination with dexamethasone, cyclophosphamide and cytarabine in children, adolescents and young with R/R ALL and LBL. Patients with actionable alterations in the RAS-RAF-MAPK pathway will be eligible for sub-protocol D including but not limited to KRAS, NRAS, HRAS, FLT3, PTPN11, MAP2K1, MP2K1 hotspot mutations, cCBL; NF1 del. Official Title ----------------- International Proof of Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory HEMatological Malignancies in Children, Subprotocol D: Trametinib + Dexamethasone + Cyclophosphamide and Cytarabine in Pediatric Patients With Relapsed or Refractory Hematological Malignancies Conditions ----------------- Acute Lymphoblastic Leukemia, in Relapse, Lymphoblastic Lymphoma (Precursor B-Lymphoblastic Lymphoma/Leukaemia) Recurrent, Lymphoblastic Lymphoma (Precursor T-Lymphoblastic Lymphoma/Leukaemia) Recurrent, Lymphoblastic Lymphoma (Precursor B-Lymphoblastic Lymphoma/Leukaemia) Refractory, Lymphoblastic Lymphoma (Precursor T-Lymphoblastic Lymphoma/Leukaemia) Refractory Intervention / Treatment ----------------- * Drug: Trametinib * Drug: Dexamethasone * Drug: Cyclophosphamide * Drug: Cytarabine * Drug: Intrathecal chemotherapy Participation Criteria ================= Eligibility Criteria ----------------- Inclusion criteria Children between 1 year (≥ 12 months) and 18 years of age at the time of first diagnosis and less than 21 years at the time of inclusion. Patients under 6 years old must weigh at least 7 kg at the time of enrollment. Patients over 6 years old must weigh at least 10 kg at the time of enrollment. Performance status: Karnofsky performance status (for patients >12 years of age) or Lansky Play score (for patients 12 years of age) ≥ 50% (Appendix I). Written informed consent from parents/legal representative, patient, and age-appropriate assent before any study specific screening procedures are conducted, according to local, regional or national guidelines. Patients must have had molecular profiling and flow-cytometric analysis of their recurrent or refractory disease at a time-point before the first inclusion into this trial (see section 9.1 of this protocol for detailed description of the molecular diagnostics required). Drug response profiling and methylation is highly recommended but not mandatory. Patients with molecular profiling at first diagnosis lacking molecular diagnostics at relapse or refractory disease may be allowed to be included after discussion with the sponsor. Patients whose tumor present RAS pathway activating mutations including but not limited to KRAS, NRAS, HRAS, FLT3, PTPN11, MAP2K1, MP2K1 hotspot mutations, cCBL; NF1 del, as detected by molecular profiling. Adequate organ function: RENAL AND HEPATIC FUNCTION (Assessed within 48 hours prior to C1D1) : Serum creatinine ≤ 1.5 x upper limit of normal (ULN) for age or calculated creatinine clearance as per the Schwartz formula or radioisotope glomerular filtration rate ≥ 60 mL/min/1.73 m2. Direct bilirubin ≤ 2 x ULN (≤ 3.0 × ULN for patients with Gilbert's syndrome). Alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) ≤ 5 x ULN; aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase/SGOT ≤ 5 x ULN. Note: Patients with hepatic disfunction related to the underling disease can be eligible even if they do not fulfill the aforementioned values for hepatic transaminases. In these cases, patients need to be discussed with the sponsor to confirm the eligibility. CARDIAC FUNCTION: Shortening fraction (SF) >29% (>35% for children < 3 years) and/or left ventricular ejection fraction (LVEF) ≥50% at baseline, as determined by echocardiography or MUGA. Absence of QTcF prolongation (QTc prolongation is defined as >450 msec on baseline ECG, using the Fridericia correction), or other clinically significant ventricular or atrial arrhythmia. Exclusion Criteria Pregnancy or positive pregnancy test (urine or serum) in females of childbearing potential. Pregnancy test must be performed within 7 days prior to C1D1. Sexually active participants not willing to use highly effective contraceptive method (pearl index <1) as defined in CTFG HMA 2020 (Appendix II) during trial participation and until 6 months after end of antileukemic therapy. Breast feeding. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter drug absorption of oral drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome) in case of oral IMPs. Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to the study drugs, or drugs chemically related to study treatment or excipients that contraindicate their participation, including conventional chemotherapeutics (i.e. cytarabine and cyclophosphamide, intrathecal agents) and corticoids. Known active viral hepatitis or known human immunodeficiency virus (HIV) infection or any other uncontrolled infection. Severe concomitant disease that does not allow treatment according to the protocol at the investigator's discretion. Subjects unwilling or unable to comply with the study procedures. Previous treatment with trametinib. Current use of a prohibited medication or herbal preparation or requires any of these medications during the study. See Section 7 and Appendix III for details. Drugs inducing QTc changes (prolongation of the QT interval or inducing Torsade de Points) are not permitted. Unresolved toxicity greater than NCI CTCAE v 5.0 ≥ grade 2 from previous anti-cancer therapy, including major surgery, except those that in the opinion of the investigator are not clinically relevant given the known safety/toxicity profile of the study treatment (e.g., alopecia and/or peripheral neuropathy related to platinum or vinca alkaloid based chemotherapy) (Common Terminology Criteria for Adverse Events (CTCAE) (cancer.gov). Active acute graft versus host disease (GvHD) of any grade or chronic GvHD of grade 2 or higher. Patients receiving any agent to treat or prevent GvHD post bone marrow transplant are not eligible for this trial. Received immunosuppression post allogenic HSCT within one moth of study entry. History or current evidence of retina vein occlusion (RVO) or central serous retinopathy are excluded. Wash-out periods of prior medication: CHEMOTHERAPY: At least 7 days must have elapsed since the completion of cytotoxic therapy, with the exception of hydroxyurea, 6-mercaptopurine, oral methotrexate and steroids which are permitted up until 48 hours prior to initiating protocol therapy. Patients may have received intrathecal therapy (IT) at any time prior to study entry. RADIOTHERAPY: Radiotherapy (non-palliative) within 21 days prior to the first dose of drug. Palliative radiation in past 21 days is allowed. HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT): Autologous HSCT within 2 months prior to the first study drug dose; Allogeneic HSCT within 3 months prior to the first study drug dose. IMMUNOTHERAPY: At least 42 days must have elapsed after the completion of any type of immunotherapy other than monoclonal antibodies (e.g. CAR-T therapy) MONOCLONAL ANTIBODIES AND INVESTIGATIONAL DRUGS: At least 21 days or 5 times the half-life (whichever is shorter) from prior treatment with monoclonal antibodies or any investigational drug under investigation must have elapsed before the first study drug. SURGERY: Major surgery within 21 days of the first dose. Gastrostomy, ventriculo-peritoneal shunt, endoscopic ventriculostomy, tumor biopsy and insertion of central venous access devices are not considered major surgery. Ages Eligible for Study ----------------- Minimum Age: 1 Year Maximum Age: 21 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Sub-study D<br>Trametinib + dexamethasone + cyclophosphamide and cytarabine. Each cycle lasts 28 days. Cycle 1: Trametinib is given orally continuously once a day in tablets or oral formulation depending on the age and weight of the patient. Dexamethasone is given intravenously (IV)/orally on days 1 to 5. Cyclophosphamide is given IV on day 3. Cytarabine is given IV in two blocks of 4 days each one week apart from day 5. Cycle 2 and subsequent cycles: Trametinib is given orally continuously once a day in tablets or oral formulation depending on the age and weight of the patient. Dexamethasone is given intravenously (IV)/orally on days 1 to 5. Cyclophosphamide is given IV on day 1. Cytarabine is given IV in two blocks of 4 days each one week apart from day 3. Patients in dose level -1, receive only 1 block of cytarabine per cycle. All patients receive age adapted intrathecal chemotherapy. | Drug: Trametinib<br>* Oral<br>Drug: Dexamethasone<br>* Oral/ Intravenous<br>Drug: Cyclophosphamide<br>* Intravenous<br>Drug: Cytarabine<br>* Intravenous<br>Drug: Intrathecal chemotherapy<br>* IT: Methotrexate +/- prednisone/hydrocortisone/cytarabine according to the degree of central nervous involvement<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Phase I: Maximum tolerated dose (MTD) / Recommended phase 2 dose (RP2D) | Defined as the highest dose level tested at which 0/6 or 1/6 patients experiences dose limiting toxicities (DLT) during course 1 with at least 2 patients experiencing DLT at the next higher dose | 3 years | | Phase II: Best Overall Response Rate (ORR) | For patients with leukemia: CR and MRD response after 1 cycle of treatment. This includes determination of CR, CRp, CRi and minimal residual disease (MRD) negativity rate in patients suffering from overt morphological relapse of T-ALL at time of enrolment (morphological disease (M2/M3)), and the MRD negativity rate in those that entered with high-MRD levels but in morphological CR. These results will together be presented as a composite endpoint Overall Response rate (ORR). MRD negativity will be defined as ≤1x10-4 as generated by multi-parameter flow cytometry. For patients with lymphoma: Response in LBL patients is defined as CR, PR, minor response (MR) as defined in International pediatric NHL response criteria. In case of bone-marrow involvement MRD will be taken into account. For patients with lymphoma: Response in LBL patients is defined as CR, PR, minor response (MR) as defined in International pediatric NHL response criteria | 6 years | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Overall survival (OS) | Defined as time from C1D1 until death of any cause. | 7 years | | Event-free survival (EFS) | Defined as time from C1D1 to the first event (subsequent relapse after CR (including molecular reappearance), death of any cause, failure to achieve remission (CR, CRp or CRi), or secondary malignancy) | 7 years | | Cumulative incidence of relapse (CIR) | Estimate of the risk, that a patient will develop a relapse over a specified period of time. | 7 years | | Number of patients proceeding to hematopoietic stem cell transplantation (HSCT) after the experimental therapy | The rate of those proceeding to subsequent allogenic HSCT | 7 years | | Cumulative overall response rate (ORR) | Defined as the CR, CRp, CRi and MRD negativity rates after more than 1 cycle of treatment. | 7 years | | Rate of dose limiting toxicities (DLTs) | Number of participants with dose limiting toxicities (DLTs) | 7 years | | Peak Plasma Concentration (Cmax) | Estimation of trametinib CMAX | 6 years | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Acute lymphoblastic leukemia, Lymphoblastic lymphoma, Biomarker driven clinical trial, Trametinib, Chemotherapy, Relapse, Refractory, Children, Adolescents, Young adults

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Vietnamese Caregiver Intervention Study Study Overview ================= Brief Summary ----------------- The purpose of this study is to develop and implement a culturally-appropriate intervention to reduce stress in Vietnamese dementia caregivers. A pilot intervention will be done to test the feasibility and acceptability of the intervention in a community setting. This will be done by randomly assigning a family triad (primary caregiver, secondary caregiver, and their care recipient) into an active intervention or a control condition and monitoring findings at baseline, post-intervention, and at three months.The intervention will consist of multiple components -enhanced psycho-education that includes discussion of Alzheimer's Disease (AD) and cultural impacts on beliefs about dementia and caregiving, management of problem behaviors, facilitation of support seeking, and mindful Tai Chi. A secondary caregiver who the primary caregiver identifies as providing him/her with the most support will be invited to join all components, but the intervention will be flexible depending on caregivers' needs/preferences. The care recipient is not required to join the sessions but will be able to if he/she or the family wishes. During the intervention, community partners will provide respite care for the care recipient. Detailed Description ----------------- Twenty-four (24) caregivers, the identified secondary caregiver, and a care recipient will be randomly assigned into the active intervention or a control condition: 16 triads in the intervention condition, 8 in the control. For the primary caregivers: Primary caregivers will attend six weekly intervention sessions lasting 2 hours each. Based on previous Randomized Controlled Trials (RCTs) of a successful behavior change (i.e., smoking cessation) intervention in Vietnamese using only 2-3 sessions, six sessions were chosen as a middle ground. In the first 45 minutes, primary caregivers and a secondary caregiver (who the primary caregiver identifies) will participate in family psycho-education delivered by a Master's level trained, bilingual facilitator. Each group will consist of no more than four dyads (4 different groups totaling 16 dyads). The curriculum will be adapted based on what the Alzheimer's Association and REACH II have successfully used as well as what the University of California (UC) Davis Alzheimer's Disease Center (ADC) has implemented. The sessions will cover the following: a clinical model of dementia and helping family members come to a shared understanding of the nature and cause of dementia. The innovative component is a discussion of cultural values typical of individuals in Vietnamese and American cultures and how this can influence perceptions of dementia and caregiving strategies. This is important because it will help family members who disagree on the etiology of dementia and strategies for care to empathize with each other's perspective. Subsequent sessions will help caregivers learn skills and develop self-efficacy in dealing with patient symptoms, accessing resources (e.g., in-home support), and gaining family support in culturally-congruent ways. Facilitating the use of formal and informal support is a critical piece as Vietnamese caregivers may be looking for basic and concrete assistance rather than help in coping with caregiving. The last part of the intervention is mindful Tai Chi that was chosen for several reasons. In a recent review and meta-analysis, Tai Chi showed beneficial effects on depression, anxiety, stress management, and self-efficacy. Second, Tai Chi is rooted in East Asian traditions and philosophies that promote balance and healing of the mind and body, thus addressing holistic beliefs Vietnamese have about wellness. An RCT of Tai Chi recently was successfully completed in Vietnam, demonstrating its growing acceptance in the Vietnamese population. The protocol will be adapted to meet caregivers' needs and highlight meditation that involves accepting stressful circumstances, thus capitalizing on emotion regulation strategies. For the care recipients: Care recipients will receive the Montreal Cognitive Assessment (MoCA) measure to assess their mental status at baseline. The purpose of the Quality of Life - Alzheimer's Disease (QoL-AD) measure is to assess the caregiver intervention affects the care recipient's quality of life. The total time to complete these questionnaires is about 30 minutes per session. Participants not randomized to the active intervention will receive educational materials/pamphlets on dementia and occasional phone-calls by research assistants to maintain contact, as is the standard of care in most caregiver intervention studies. Including a control condition will allow for mirroring of the actual larger trial as closely as possible, and also ascertain the feasibility of randomization. Official Title ----------------- A Culturally-Relevant Approach to Reducing Dementia Caregiver Stress in an Underserved Population Conditions ----------------- Alzheimer's Disease (Incl Subtypes), Cognitive Impairment Intervention / Treatment ----------------- * Behavioral: Enhanced psycho-education about dementia and caregiving Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Caregivers will be included if they (a) are Vietnamese; (b) are age 21+; (c) speak Vietnamese and/or English (d) provide day-to-day, hands on care to a family member with Alzheimer's disease (AD) or cognitive impairment related to AD (e) have at least one family member who will also participate in the intervention; (f) volunteer informed consent; (g) are physically able to participate; and (g) expect to stay in the Sacramento area for the duration of the study Care recipients will be included if they are (a) Vietnamese; (b) are age 21+; (c) have reported Alzheimer's disease (AD) or cognitive impairment related to AD; (d) have at least one caregiver who is participating in the intervention (e) volunteer informed consent or surrogate consent, and (f) expect to stay in the Sacramento area for the duration of the study Exclusion Criteria: If the care recipient expresses dissent to participation or to the use of surrogate consent, then he/she will be excluded from the study. Ages Eligible for Study ----------------- Minimum Age: 21 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Supportive Care Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: Families will then be randomized (as a team) to either the active intervention or the control condition. Caregivers in the active intervention will then be scheduled for six weekly intervention sessions, lasting about 2 hours each. Following the completion of the sessions, primary caregivers will complete assessment measures (that they completed at baseline) immediately after the intervention (post) and at three months. This is expected to take one hour for each assessment. Primary caregivers assigned to the control condition will also complete these assessment measures around the same those in the active intervention complete them. These caregivers will also have the option of participating in the active intervention after the three-month follow up. Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Active Intervention<br>Six weekly intervention sessions (2 hours, each) that include enhanced psycho-education and discussion of AD and cultural impacts on beliefs about dementia and caregiving, management of problem behaviors, facilitation of support seeking, and mindful Tai Chi. | Behavioral: Enhanced psycho-education about dementia and caregiving<br>* Enhanced psycho-education re dementia and caregiving helping family members come to shared understanding of the nature and cause of dementia. Discussion of cultural values in Vietnamese and American cultures and how this can influence perceptions of dementia and caregiving strategies will help family members who disagree on the etiology of dementia and strategies for care to empathize with each other's perspective. Other sessions will teach skills to develop self-efficacy in dealing with patient symptoms, to access resources (e.g., in-home support), and to gain family support in culturally-congruent ways. Mindful Tai Chi is rooted in East Asian traditions and philosophies that promote balance and healing of the mind and body, thus addressing holistic beliefs Vietnamese have about wellness.<br>* Other names: mindful Tai Chi;| | No Intervention: Control<br>Participants will receive educational materials/pamphlets on dementia and occasional phone-calls by research assistants to maintain contact, as is the standard of care in most caregiver intervention studies. | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Randomization | % of eligible dyads who agree to randomization | assessed once all 3-month follow-ups are complete | | Retention | Retention in both arms of the study; Note: no formal assessment tool will be used - this will be assessed via number of participants retained | assessed once all 3-month follow-ups are complete | | Caregiver Intervention Adherence | % of dyads engaging in the initial session, % completing at least 3 sessions, and % completing all sessions | assessed at end of study, once all 3-month follow-ups are complete | | Treatment Fidelity | Extent to which the facilitator adheres to the intervention protocol, as measured by a self-report checklist, with a goal of 85% adherence to key elements | assessed once all 3-month follow-ups are complete | | Administration of Study Measures | % of baseline, post-, and 3-month assessments completed (considering length of assessments and completeness of collected data | assessed at end of study, once all 3-month follow-ups are complete | | Acceptability | Assessed through a questionnaire and interview assessing the perceptions of the intervention by primary and secondary caregivers, CBO staff/administrators, and interventionists. | 2 years | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Alzheimer's Disease Knowledge Scale (ADKS) | This scale assesses knowledge about AD. The scale has 30 statements. Subjects are asked to rate each statement as True or False. | Baseline, 6-weeks (Post-intervention), 3 months post-intervention | | Caregiver Self-Efficacy | Asks the caregiver about how confident in their ability to keep up their own activities and also respond to caregiving situations. The Scale includes 10 items, and asks caregivers to rate their confidence in handling situations on a scale from 1 to 10. | Baseline, 6-weeks (Post-intervention), 3 months post-intervention | | Center for Epidemiological Studies Depression (CES-D) scale | This is a self-report depression scale that asks how many times during the past week a person has felt symptoms of depression. There are 20 items. | Baseline, 6-weeks (Post-intervention), 3 months post-intervention | | Zarit Burden Inventory (ZBI) | This is a caregiver self-report measure that contains 22 items. Each item on the interview is a statement which the caregiver is asked to endorse using a 5-point scale. Response options range from 0 (Never) to 4 (Nearly Always). | Baseline, 6-weeks (Post-intervention), 3 months post-intervention | | Quality of Life - Alzheimer's Disease (QoL-AD) | The QOL-AD is a brief, 13-item measure designed specifically to obtain a rating of the patient's Quality of Life from both the patient and the caregiver. It was developed for individuals with dementia, based on patient, caregiver, and expert input, to maximize construct validity, and to ensure that the measure focuses on quality of life domains thought to be important in cognitively impaired older adults. It uses simple and straightforward language and responses & includes assessments of the individual's relationships with friends and family, concerns about finances, physical condition, mood, and an overall assessment of life quality. | Baseline, 6-weeks (Post-intervention), 3 months post-intervention | | Perceived Stress Scale | This scale asks subjects about how often they have felt or thought about 10 items during the past month. | Baseline, 6-weeks (Post-intervention), 3 months post-intervention | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Caregiver, Vietnamese, Alzheimer's Disease

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Trial Assessing the Effect of Preoperative Furosemide on Intraoperative Blood Pressure Study Overview ================= Brief Summary ----------------- The purpose of this study is to determine whether continuing or discontinuing furosemide (a diuretic) on the day of elective noncardiac surgery for those who take furosemide on a chronic basis, causes more intraoperative hypotension (low blood pressure) during surgery. Our hypothesis is that the usual practice of continuing furosemide on the day of surgery would contribute to more hypotension during surgery than discontinuing furosemide. Detailed Description ----------------- A significant proportion of patients who undergo surgery take medications on a chronic basis. Little is known about the effects of these medications on the successful conduct of anesthesia and surgery. Diuretics like furosemide may contribute to low blood pressure during surgery, an outcome associated with cardiovascular complications. However, many patients are recommended to take their diuretics on the day of surgery. We wished to determine if preoperative administration of furosemide contributes to intraoperative hypotension compared to placebo. Comparison: We conducted a randomized, double blind placebo controlled trial to compare the effect of furosemide with that of placebo on intraoperative hypotension using intraoperative blood pressure recordings in patients who take furosemide chronically and were undergoing noncardiac surgery. Official Title ----------------- Randomized Controlled Trial Assessing the Effect of Preoperative Furosemide on Intraoperative Blood Pressure Conditions ----------------- Hypertension, Hypotension, Edema, Congestive Heart Failure Intervention / Treatment ----------------- * Drug: furosemide * Drug: placebo Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: All adults referred to preoperative assessment clinics by surgeons for elective non-cardiac surgery who routinely take furosemide. Participants must also be able to give informed consent Exclusion Criteria: Less than 18 years of age Have comorbid conditions with which brief periods of hypotension may be particularly harmful such as: 1) pregnancy; 2) baseline hypotension (systolic <100 mmHg at the preoperative assessment clinic); 3) autonomic dysfunction; 4) severe aortic stenosis. Patients who take furosemide only on an 'as needed basis' rather than 'regularly'. Those patients who take less than 10 mg of furosemide daily Those patients who are undergoing local anesthetic only surgical procedures Patients who are unwilling or unable to give informed consent. Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Prevention Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: 1<br>furosemide | Drug: furosemide<br>* for patients on chronic furosemide therapy, patients are randomized to furosemide (at their previous dose) or placebo (given in identical form to ensure masking)<br>| | Placebo Comparator: 2<br>placebo | Drug: placebo<br>* patients will be given placebo capsules (identical to experimental arm in color) at the equivalent dose as to their chronic furosemide therapy.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Proportion of patients developing hypotension during the operative period. Hypotension is defined based on blood pressure criteria (systolic BP <90 mmHg or 35% drop in mean arterial pressure) (or vasopressor treatment during surgery). | | hospital stay | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Patients will be followed up for the duration of their hospital stay for the following endpoints: (1) Development of congestive heart failure exacerbation | | hospital stay | | (2) Total cardiovascular complications: composite of acute myocardial infarction, angina, stroke/TIA, arrhythmia, congestive heart failure or cardiac death. | | hospital stay | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- anesthesia, hypotension, furosemide, blood pressure, peripheral edema, diuretic, surgery, congestive heart failure

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Immunotherapy After Transplantation for Skin Cancer Prevention in Organ Transplant Recipients Study Overview ================= Brief Summary ----------------- This clinical trial aims to investigate the efficacy of Calcipotriol ointment combined with 5-FU cream in Organ Transplant Recipients (OTRs) to determine if it can stimulate the immune cells against actinic keratoses precancerous skin lesions after transplantation and prevent cutaneous squamous cell carcinoma (SCC) in long-term. Detailed Description ----------------- The main goal of this investigator-initiated clinical trial is to determine the efficacy of topical calcipotriol combined with 5-fluorouracil (5-FU) treatment in OTRs on immunosuppressive medications with precancerous skin lesions called actinic keratoses (AKs) and a history of non-melanoma skin cancer in order to eliminate AKs and prevent squamous cell carcinoma (SCC) development. SCC is the most common cutaneous malignancy seen after transplantation, with a 65-250fold greater incidence in organ transplant recipients (OTRs) compared to the general population. This increased risk is due to the systemic immunosuppression caused by anti-rejection medications, which are indispensable for protecting against allograft loss. Our previous findings have established the efficacy of calcipotriol in combination with 5-FU in inducing an antitumor immunity against AKs in immunocompetent patients. This SCC risk reduction is accompanied by the induction of robust T cell immunity and TRM cell formation against AKs. Calcipotriol is a FDA-approved low calcemic vitamin D analogue for the treatment of psoriasis. Topical 5-FU is a standard chemotherapy for AKs. Based on our previous findings demonstrating the synergistic impact of TSLP induction by calcipotriol in combination with the cytotoxic effects of 5-FU that leads to a robust T cell immunity against early skin carcinogenesis in immunocompetent patients, we aim to determine whether this efficacy is maintained in OTRs on immunosuppressive therapy and its effect on SCC prevention in long-term after transplantation. Official Title ----------------- Calcipotriol Plus 5-Fluorouracil Immunotherapy for Skin Cancer Prevention in Organ Transplant Recipients Conditions ----------------- Immunotherapy, Cutaneous Squamous Cell Carcinoma, Actinic Keratoses, Organ Transplant Recipients, Skin Cancer Intervention / Treatment ----------------- * Drug: Calcipotriol Only Product in Cutaneous Dose Form * Drug: Vaseline * Drug: Topical 5FU Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Solid organ transplant recipients with AKs and a history of non-melanoma skin cancer in one year prior to enrollment into the study. The target population includes post-transplant OTRs. Presence of four to fifteen clinically typical, visible, and discrete AKs in 25 cm2 on any of the four anatomical sites: scalp, face, right upper extremity and left upper extremity. The period between the first visit and transplantation is minimum 4 weeks and maximum 12 months. Age of at least 18 years Ability and willingness of the patient to participate in the study (Informed consent will be obtained) Exclusion Criteria: Treatment area is within 5 cm of an incompletely healed wound or a suspected basal cell or squamous cell carcinoma. Treatment area contained hypertrophic and hyperkeratotic lesions, cutaneous horns, or lesions that had not responded to repeated cryotherapy. Patients with history of hypercalcemia or vitamin D toxicity. Female participants must be either of non-reproductive potential (i.e., post-menopausal by history of age > 50 years old and no menses for >1 year without an alternative medical cause; OR history of hysterectomy, history of bilateral tubal ligation, or history of bilateral oophorectomy) OR must have a negative serum pregnancy test within 7 days prior to study registration. Patients with DPD (Dihydropyrimidine Dehydrogenase) deficiency (due to their higher risk of 5-FU toxicity). Ages Eligible for Study ----------------- Minimum Age: 50 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: Parallel Assignment Masking: Triple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Topical Calcipotriol ointment plus 5-Fluorouracil cream<br>Topical Calcipotriol 0.0025% ointment plus 5-Fluorouracil 2.5% cream will be administered by the participants to their face, scalp and upper extremities twice a day for 6 consecutive days. | Drug: Calcipotriol Only Product in Cutaneous Dose Form<br>* Calcipotriene is a form of vitamin D. It works by inducing thymic stromal lymphopoietin cytokine expression in the skin.<br>* Other names: Topical Calcipotriene ointment;Drug: Topical 5FU<br>* 5-FU is a chemotherapy that causes the death of proliferating tumor cells. Topical preparation of this drug is being used.<br>* Other names: Topical 5-fluorouracil;| | Placebo Comparator: Topical vaseline plus 5-Fluorouracil 2.5% cream<br>Topical Vaseline plus 5-Fluorouracil 2.5% cream will be administered by the participants to their face, scalp and upper extremities twice a day for 6 consecutive days. | Drug: Vaseline<br>* Placebo<br>* Other names: Petrolatum;Drug: Topical 5FU<br>* 5-FU is a chemotherapy that causes the death of proliferating tumor cells. Topical preparation of this drug is being used.<br>* Other names: Topical 5-fluorouracil;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | The changes in baseline number of AKs on treated anatomical sites in post-transplant OTRs | The changes in baseline number of AKs on treated anatomical sites in post-transplant OTRs quantified based on participants' medical records and photographs in test versus control group | 8 weeks after treatment | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | The changes in the number of SCC on treated anatomical sites in post-transplant OTRs | The changes in number of SCC on treated anatomical sites in post-transplant OTRs quantified based on participants' medical records, photographs and pathology results in test versus control group | 1, 2 and 4 years after treatment | | The changes in the magnitude of TSLP, CD3+, CD4+ and CD8+ TRM cell infiltrates in in the AK and normal skin after transplantation | The changes in the magnitude of TSLP, CD3+, CD4+ and CD8+ TRM cell infiltrates in OTRs after transplantation compared to before transplantation in test versus control group. | at one day after 6-day treatment and at one year post-treatment | | The changes in immune infiltrate (CD3+, CD4+ and CD8+ TRM cell) in any SCC that develops after treatment | The changes in immune infiltrate in any SCC that develops after calcipotriol plus 5-FU versus Vaseline plus 5-FU treatment for up to 4 years post-transplant. | up to 4 years after treatment | | Number of Participants with Treatment Related Adverse Events | Adverse events will be assessed including any local skin reactions like itching and rash | From the start of treatment until 30 days after the end of treatment, up to 2 months | | Number of participants with any proven rejection of the graft in OTRs | Number of participants with any biopsy proven acute rejection of the graft after treatment with calcipotriol plus 5-FU compared to test group. | From the start of treatment until 30 days after the end of treatment | | The changes in erythema extent and intensity scores (0-4) of the treated anatomical sites | The changes in erythema extent and intensity scores of the treated anatomical sites in test versus control group in post-transplant OTRs. Treated skin will be evaluated for any sign of irritation including erythema, crusting or ulceration using a clinical erythema scale. (No erythema=0, mild erythema=1, sever erythema with minimal scaling=2, sever erythema with significant scaling=3, sever erythema with scaling, crusting, itching and burning=4) | at one day after the completion of a 6-day treatment | | The changes in response to treatment (AKs number) between treated anatomical sites | The changes in response to topical calcipotriol plus 5-FU versus Vaseline plus 5-FU between treated anatomical sites | at one day after treatment and one year after treatment | | The changes in SCC prevention (number of SCC) on the untreated anatomical sites (i.e., trunk and lower extremities) of OTRs | The changes in efficacy of a twice daily 6-day treatment with topical calcipotriol plus 5-FU (test) versus Vaseline plus 5-FU (control) before transplantation in preventing SCC on the untreated anatomical sites (i.e., trunk and lower extremities) of OTRs. | at one, two and four years post-transplant. | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Squamous Cell Carcinoma, Actinic keratoses, Calcipotriol ointment, 5-FU cream, Prevention, Organ Transplant Recipients, Immunotherapy

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Vascular Post Market Review Study Overview ================= Brief Summary ----------------- The primary objective of this study is to confirm that properties of CardioCel provide operative benefit to surgeons when compared to Dacron, CorMatrix, and all other bovine pericardium not treated with proprietary ADAPT engineering. Detailed Description ----------------- ENDPOINTS OR experience: suturability, handling, hemostasis, compliance to recipient vessel, blood loss, OR time. In-hospital survival MAE (Stroke, MI, death) 1 Month duplex US scan 6 month duplex US scan Secondary Efficacy Endpoints 1. Less than 50% stenosis at 6 months (PSV <150 cm/s) Safety Endpoint Incidence of CardioCel related Major Adverse Cardiac Events (MACE) at 6 months, defined for this study as: Structural CardioCel failure - aneurysm/dilation Vasculitis Leak or pseudoaneurysm Dehiscence Thromboembolism Thrombosis Haemolysis Reoperation and explant Review endpoints at 6 months to confirm results meet the expectations of the Principal Investigator. BACKGROUND Rationale for Study: CardioCel's unique strength, pliability, resistance to degradation and calcification make it a promising alternative to synthetic fabrics or other xenographic materials incompletely decellularized or detoxified (aldehyde removal). Device Description: Tissue-engineered CardioCel pericardium is manufactured from bovine spongiform encephalopathy-free pericardium (37). Manufacturing consists of several tissue-engineering processes, which include steps to remove lipids, cells and cell remnants, nucleic acids (DNA, RNA) and Gal epitopes. In addition, cross-linking is achieved with an ultra-low engineered glutaraldehyde concentration to minimise glutaraldehyde cytotoxicity levels (Admedus Ltd. proprietary). Cytotoxicity is further reduced by the ADAPT® anti-calcification process and a non-glutaraldehyde sterilisation and storage solution. CardioCel is US FDA cleared for the repair of cardiac and vascular defects, including intra-cardiac defects; septal defects, valve and annulus repair, great vessel reconstruction, peripheral vascular reconstruction, suture line buttressing and pericardial closure. STUDY DESIGN This is a prospective, non-randomized, single arm study. SCHEDULE OF ASSESSMENTS/DATA COLLECTION ENROLLMENT: 10 subjects to be enrolled per site DURATION OF ENROLLMENT: Patients will be followed for 6 months after CEA procedure. SCREENING A pre-screening procedure may be performed to determine whether the patient meets the inclusion/exclusion eligibility selection criteria. A pre-screened patient will be asked to sign the informed consent form before any study-specific tests or procedures are performed. Subject screening numbers will be assigned at this visit and subjects will be evaluated for eligibility criteria. BASELINE Informed consent will be obtained from all subjects who are potential trial candidates prior to commencement of any study related procedures. The following baseline data will be collected for all subjects prior to procedure: Patient demographics Standard of care Physical Examination Vital Signs (Blood pressure and heart rate only) Medical history (for cardiovascular risk factors) Standard of care Clinical Lab tests Final confirmation of Inclusion/Exclusion Criteria IMPLANT PROCEDURE Patients will undergo a CEA with patch arterioplasty. Patients will be managed according to standard pre-operative, operative, and postoperative care. The following OR Experience data will be collected for all subjects: Suturability Handling Hemostasis Compliance to recipient vessel Blood loss OR time In-hospital survival MAE (Stroke, MI, death) FOLLOW-UP VISITS Patients will return for follow-up visits that will include a carotid duplex ultrasound at 1 and 6 months. Follow-up visits may also include a physical examination and adverse event review. The following follow-up data will be collected for all subjects: Standard of care physical examination 1 Month duplex US scan- Duplex US scanning for velocity, calibre, occlusion/lesion status 6 month duplex US scan- Duplex US scanning for velocity, calibre, occlusion/lesion status MAE (Stroke, MI, death) and AE review at each visit STATISTICAL ANALYSIS & DATA MANAGEMENT: Principal Investigator plans to follow patients for 6 months and create report (white paper) on OR experiences and 6 month follow-up. The study is a direct observation of 6 month follow-up for patients undergoing CEA with patch arterioplasty. No control group is included in the study, and no comparative analysis is planned. DATA MONITORING Internal monitoring will be conducted periodically. CRF's, source documents, informed consent forms, and study deviations will be included; these findings will be reported to the PI. Deviations will be documented and reported according to IRB policy. Regulatory documents will be audited by the Baylor Research Institute Department of Research Compliance upon request. Official Title ----------------- Vascular Post Market Review Conditions ----------------- Carotid Endarterectomy Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Scheduled for carotid endarterectomy (CEA) with patch arterioplasty Expected lifespan of over 24 months Age over 18 years Exclusion Criteria: Revision of previous CEA arterioplasty Active infection Cerebral ischemic event (completed stroke) within 30 days of planned surgery Pregnant or breastfeeding Concomitant surgical or endovascular procedure being performed Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | 6 Month Duplex US Report to Measure Material Quality | The 6 month duplex US report will measure peak velocity and flow through the repaired carotid artery, caliber, and occlusion/lesion status as per normal parameters used in post-CEA scans. | Up to 6 months post CEA | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | OR Data and Surgeon Feedback During the Procedure | The OR data from the procedure including blood loss and how long it took to achieve hemostasis in addition to surgeon feedback on bleeding, handling, and suturing of the material will be collected on a source worksheet. | procedure |

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Safety Study of R(+)Pramipexole to Treat Early Alzheimer's Disease Study Overview ================= Brief Summary ----------------- By doing this study, researchers will examine the safety and tolerability of R-pramipexole in participants with Alzheimer's disease. This study will also examine the body and brain's response to the study drug by measuring the amount of injury to the cells (oxidative stress) in the blood and spinal fluid and brain imaging before and after treatment. Detailed Description ----------------- Subjects will be recruited from the Univ of Kansas Alzheimer's Center and will provide informed consent about participating. R(+)-pramipexole will be provided as Good Manufacturing Practice powder and taken as a liquid and start at one teaspoon (5 ml) twice a day for a total dose of 100 mg/day. After 4 weeks, the dose will double (two teaspoons twice a day, or a total of 200mg/day). Four weeks later the dose will be increased again to 2 1/2 teaspoons twice a day (total of 300mg/day) where it will remain for the remaining 16 weeks of study treatment. Prior to each increase, participants and their study partners will be interviewed regarding any possible side effects or problems. These findings will be discussed with Dr. Burns prior to increasing the study drug dose. The dose will only increase if the participant is not having side effects. Primary Outcome Measure: 1.Number of Patients with Adverse Events [Time Frame: Every 2 months] [Safety Issue: Yes] Labwork will be performed every two months. There will be frequent contact with subjects to assess for adverse events. Secondary Outcome Measures: Reduction of Oxidative Stress [Time Frame: Baseline and at 24 weeks after taking study drug] [Safety Issue: No] A lumbar puncture (spinal tap) will be performed to collect cerebral spinal fluid, which will be assayed for isoprostane levels before and after treatment. Changes in cerebral glucose metabolism [Time Frame: Baseline and at 24 weeks after taking drug] [Safety Issue: No] Positron Emission Tomography Scan will be performed. Changes in cerebral glucose metabolism as a proxy for mitochondrial respiration will be assayed at baseline and 24 weeks. Correlations will be sought with assays of oxidative stress reduction to see if greater reductions in brain oxidative stress are reflected in elevations of cortical 2-fluorodeoxyglucose. Effects on Cognitive Performance [Time Frame: Baseline and then 6 months thereafter] [Safety Issue: Yes] Quantitative assessment of cognitive status will be taken at baseline and at end of 6 month dosing period. Official Title ----------------- Safety/Tolerability and Effects on Cognitive Impairment, Impaired Cerebral Cortical Metabolism and Oxidative Stress of R(+)Pramipexole Administered to Subjects With Early Alzheimer's Disease Conditions ----------------- Alzheimer's Disease Intervention / Treatment ----------------- * Drug: R-pramipexole Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Informed consent provided by the participant or the participant's legally acceptable representative Age 55 years or older Possible/probable Alzheimer's Disease (AD) Community dwelling with a caregiver able and willing to accompany the participant on all visits, if necessary. Caregiver must visit with the subject >5 times per week. Rosen Modified Hachinski score of 4 or less Imaging Study (CT or MRI) compatible with AD or age-related changes (absence of significant abnormalities that may explain cognitive decline, such as multiple lacunar infarcts or a single prior infarct >1 cubic cm, microhemorrhages or evidence of a prior hemorrhage > 1 cubic cm, evidence of cerebral contusion encephalomalacia, aneurysm, vascular malformation, or space occupying lesion such as an arachnoid cyst or brain tumor). Adequate visual and auditory abilities to perform all aspects of the cognitive and functional assessments Exclusion Criteria: Significant neurological disease, other than AD, that may affect cognition Current clinically-significant systemic illness that is likely to result in deterioration of the patient's condition or affect the patient's safety during the study. History of clinically-evident stroke Clinically-significant infection within the last 30 days Myocardial infarction or symptoms of active coronary artery disease (e.g., angina) in the last two years. Uncontrolled hypertension within the last 6 months. History of cancer within the last 5 years (except non-metastatic basal or squamous cell carcinoma) History of drug or alcohol abuse as defined by DSM-IV criteria within the last 2 years Insulin dependent diabetes mellitus Significant pain or musculoskeletal disorder that would prohibit participation in metabolic testing Ages Eligible for Study ----------------- Minimum Age: 55 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: R(+)pramipexole<br>Each study participant will be given the active study drug, R-pramipexole. There is no placebo arm. | Drug: R-pramipexole<br>* R-pramipexole will be taken as a liquid and start at one teaspoon (5 ml) twice a day for a total dose of 100 mg/day. After 4 weeks, the dose will double (two teaspoons twice a day, or a total of 200mg/day). Four weeks later the dose will be increased again to 2 1/2 teaspoons twice a day (total of 300mg/day) where it will remain for the remaining 16 weeks of study treatment. Prior to each increase, participants and their study partners will be interviewed regarding any possible side effects or problems. These findings will be discussed with the physician prior to increasing the study drug dose. The dose will only increase if the participant is not having side effects.<br>* Other names: Dexpramipexole;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Number of Patients With Adverse Events | Labwork will be performed every two months. There will be frequent contact with subjects to assess for adverse events. | 6 months | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Safety, Tolerability, R(+)Pramipexole, Alzheimer's

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Impact of an Educational Tool on Quality of Life and Anxiety in Parents of Children With Nut Allergy Study Overview ================= Brief Summary ----------------- The number of young children with food allergy, in particular with nut allergy, is increasing worldwide. A diagnosis of nut allergy can cause much anxiety in parents. They worry about their child being exposed to nuts in foods when outside the home. This anxiety can lead to these young children being restricted from taking part in normal childhood activities. Last year, the investigators conducted a study Recording accidental allergic reactions in children's and teenagers (ReAACT) in which they surveyed over 500 children with food allergy attending our clinic, in order to learn more about their participation in social activities and their practices in relation to eating outside the home. In the present study, the investigators wish to build upon these results through using the findings to develop a programme to help to lessen the fear and anxiety experienced by parents of young children with newly diagnosed nut allergy. The investigators imagine that knowledge of how other families with children who have food allergy participate in activities involving food outside of the home might help newly diagnosed families. The investigators would like to know if parents of young children newly diagnosed with nut allergy would benefit from hearing this information. In order to do this, the investigators have developed a short online programme that parents can take part in, in their own homes. Content will focus on the day to day social activities of children with food allergy, based on the findings of the REAACT study. To help the investigators to measure the effectiveness of this programme on reducing anxiety and improving quality of life, they are asking all volunteer participants to complete 4 questionnaires. Two of these questionnaires will ask a parent to indicate 1) the impact of their child's nut allergy on their quality of life and 2) on their child's quality of life. The third questionnaire will ask about their level of anxiety. The fourth questionnaire will ask about their emotions and the coping strategies they use in the context of their child's food allergy. Participants will be randomized into 2 groups. Group 1 will take part in the online education session along with the usual education provided by the allergy team. The questionnaires will be completed online using only a study identifier number. This will ensure anonymity throughout the study. The only personal information that will be asked is parent's age group, whether they are a mother or father, their child's age and gender and whether they have any other allergies. Two weeks following the online educational session, Groups 1 and 2 will again complete the online questionnaires. The research question is to determine if the online educational session is effective at decreasing anxiety and improving quality of life in parents of young children with nut allergy. The outcomes are health related quality of life and level of anxiety. It is hoped that the findings will positively support parents, children and their families in Ireland who are living and managing nut allergy on a daily basis. Detailed Description ----------------- Over 4% of children in Ireland have a food allergy. Many studies report that parents and children with food allergy have a decreased quality of life (QOL). However maternal anxiety and parental overprotection even in the absence of FA can lead to childhood anxiety. Children with FA are at risk of exclusion from social activities and overly restrictive lifestyles as parents attempt to minimise risk and their own anxiety by avoiding food related activities. The investigator's department carried out a prospective observation study collecting data on lifestyle practice of food allergic children between 2-16 years attending their services and the rate of accidental allergic reactions (AARs) over 1 year (Recording accidental allergic reactions in children with food allergy: REAACT). Most children in REACCT (which represents 25% of the return waiting list population) are attending social activities and visiting food venues. Caregivers can be influenced by high profile media cases which often report fatal AARs occurring in food establishments and during social activities such as parties. The psychological theories of availability heuristic (people make judgements on the likelihood of an event on how easily a case comes to mind) and base case neglect (erroneously judge the likelihood of a situation by failing to consider all relevant data, instead, focusing on new information) can help explain how heavy reporting of rare severe/fatal AAR cases in the media can increase anxiety among vulnerable parents and children leading to social exclusion and avoidance of visiting eateries. Conversely, there is no reporting of the thousands of food allergic children and families who successfully manage their food allergies and manage to navigate events such as eating out and social activities where food is an integral part. Hence, it is likely that families newly diagnosed with nut allergy are not aware of how other families with established nut allergy behave on a day to day basis. A primary goal of the allergy clinic is to promote safe, age appropriate, social interaction and eating out behaviors. Therefore, the investigators are interested in finding out whether awareness of the successful management by a greater number of families with nut allergy in Ireland, would impact on level of anxiety and health related quality of life of those newly diagnosed with nut allergy? The investigators hypothesize that providing newly diagnosed children and their parents with information on how other Irish children with established food allergies behave in situations involving food will have a positive impact on their quality of life and level of anxiety and promote living with risk rather than living with fear. Specifically, they aim to assess the effectiveness of a psycho-educational intervention (illustrating the routine practices of food allergic children regarding social activities and eating out) on disease-specific quality of life and level of anxiety of newly diagnosed parents and children. A randomized control trial will be performed comparing quality of life, anxiety and self efficacy in parents who receive the intervention versus those that do not. These parents will have a young child with a newly diagnosed nut allergy. Official Title ----------------- Impact of an Educational Tool on Quality of Life and Anxiety in Parents of Young Children With Newly Diagnosed Nut Allergy Conditions ----------------- Child Allergy, Food Allergy Intervention / Treatment ----------------- * Behavioral: living with food allergy educational booklet Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Parents of children between 6 and 36 months Parent of children with a new diagnosis of a nut allergy defined as a clinical reaction with a skin prick test (SPT) of >3mm or sensitised with a SPT of >7mm. Exclusion Criteria: Parents who already had a child with a food allergy as parents would have well established coping mechanisms Participation in another research project Their food allergic child had another chronic condition that might cause anxieties in social environments. Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Supportive Care Allocation: Randomized Intervention Model: Parallel Assignment Masking: Single Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: educational Booklet<br>Receive intervention- educational booklet describing the day to day social activities and eating out habits of children with established food allergy in Ireland | Behavioral: living with food allergy educational booklet<br>* An educational booklet giving information on social and eating out habits as well as reaction rates in food allergy Irish children.<br>| | Active Comparator: Routine education<br>This group will receive routine education in the allergy group. | Behavioral: living with food allergy educational booklet<br>* An educational booklet giving information on social and eating out habits as well as reaction rates in food allergy Irish children.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Primary outcome 1 | Change in score in each group on Food allergy Quality of Life Questionnaire (FAQLQ) parental proxy form | 4 weeks | | Primary outcome 2 | Change in score in each group on Food Allergy Quality of Life (FAQOL) parental burden form | 4 weeks | | Primary outcome 3 | Change in score in each group on Stait and Trait anxiety inventory (STAI) | 4 weeks | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Secondary score | Change in score on Self efficacy in Food Allergy Questionnaire (SEFAQ) | 4 weeks | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- educational intervention, Food allergy, Quality of Life, anxiety, self efficacy, maternal education, booklet

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A Study of Combination Therapies With or Without Pembrolizumab (MK-3475) and/or Chemotherapy in Participants With Advanced Esophageal Cancer (MK-3475-06A) Study Overview ================= Brief Summary ----------------- This is a phase I/II multicenter, open-label umbrella platform study that will evaluate the safety and efficacy of investigational agents with pembrolizumab, plus chemotherapy or lenvatinib, for the treatment of participants with advanced esophageal cancer who have failed 1 prior line of therapy and have not been previously exposed to programmed cell death 1 protein (PD-1)/ programmed cell death ligand 1 (PD-L1) based treatment. With protocol amendment 5 (effective: 17-November-2023), enrollment in study arms Pembrolizumab plus MK-4830 plus Chemotherapy and Pembrolizumab plus MK-4830 plus lenvatinib is discontinued. Detailed Description ----------------- The master protocol is MK-3475-U06. Official Title ----------------- A Phase 1/2 Open-Label, Umbrella Platform Design Study of Investigational Agents With or Without Pembrolizumab (MK-3475) and/or Chemotherapy in Participants With Advanced Esophageal Cancer naïve to PD-1/PD-L1 Treatment (KEYMAKER-U06): Substudy 06A. Conditions ----------------- Esophageal Squamous Cell Carcinoma (ESCC) Intervention / Treatment ----------------- * Biological: Pembrolizumab * Biological: Coformulation favezelimab/pembrolizumab * Biological: MK-4830 * Drug: Lenvatinib * Drug: Irinotecan * Drug: Paclitaxel Participation Criteria ================= Eligibility Criteria ----------------- The main inclusion and exclusion criteria include but are not limited to the following: Inclusion Criteria: Histologically or cytologically confirmed diagnosis of metastatic or locally advanced unresectable ESCC Has experienced investigator documented radiographic or clinical disease progression on one prior line of standard therapy. Has an evaluable baseline tumor sample (newly obtained or archival) for analysis Has adequately controlled blood pressure (BP) with or without antihypertensive medications Participants who have adverse events (AEs) due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have ≤Grade 2 neuropathy are eligible Exclusion Criteria: Direct invasion into adjacent organs such as the aorta or trachea Has experienced weight loss >10% over approximately 2 months prior to first dose of study therapy Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication Known additional malignancy that is progressing or has required active treatment within the past 3 years, except basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ that has undergone potentially curative therapy Known active central nervous system (CNS) metastases and/or carcinomatous meningitis Active autoimmune disease that has required systemic treatment in past 2 years History of human immunodeficiency virus (HIV) infection History of Hepatitis B or known active Hepatitis C virus infection History of allogenic tissue/solid organ transplant Clinically significant cardiovascular disease within 12 months from first dose of study intervention Participants with known gastrointestinal (GI) malabsorption or any other condition that may affect the absorption of lenvatinib Has risk for significant GI bleeding, such as: Has had a serious nonhealing wound, peptic ulcer, or bone fracture within 28 days prior to allocation/randomization Has significant bleeding disorders, vasculitis, or has had a significant bleeding episode from the GI tract within 12 weeks prior to allocation/randomization Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Pembrolizumab plus chemotherapy<br>Participants will receive pembrolizumab intravenously plus chemotherapy (investigator's choice of irinotecan or paclitaxel) at specified doses on specified days for a total treatment duration of up to approximately 2 years. | Biological: Pembrolizumab<br>* 200 mg administered via intravenous (IV) infusion every 3 weeks (Q3W)<br>* Other names: KEYTRUDA®;Drug: Irinotecan<br>* 180 mg/m^2 administered via IV infusion on day 1 of every 14-day cycle.<br>Drug: Paclitaxel<br>* 80-100 mg/m^2 administered via IV infusion on Days 1, 8 and 15 of every 28 day cycle<br>| | Experimental: Coformulation Favezelimab/Pembrolizumab plus Chemotherapy<br>Participants will receive coformulation of favezelimab/pembrolizumab administered intravenously plus chemotherapy (investigator's choice of irinotecan or paclitaxel) at specified doses on specified days for a total treatment duration of up to approximately 2 years. | Biological: Coformulation favezelimab/pembrolizumab<br>* 800 mg favezelimab + 200 mg pembrolizumab administered via IV infusion on day 1 and then Q3W<br>* Other names: MK-4280A;Drug: Irinotecan<br>* 180 mg/m^2 administered via IV infusion on day 1 of every 14-day cycle.<br>Drug: Paclitaxel<br>* 80-100 mg/m^2 administered via IV infusion on Days 1, 8 and 15 of every 28 day cycle<br>| | Experimental: Pembrolizumab plus MK-4830 plus Chemotherapy<br>Participants will receive pembrolizumab intravenously plus MK-4830 plus chemotherapy (investigator's choice of irinotecan or paclitaxel) at specified doses on specified days for a total treatment duration of up to approximately 2 years. | Biological: Pembrolizumab<br>* 200 mg administered via intravenous (IV) infusion every 3 weeks (Q3W)<br>* Other names: KEYTRUDA®;Biological: MK-4830<br>* 800 mg administered via IV infusion Q3W<br>* Other names: anti-immunoglobulin-like transcript 4 (ILT4);Drug: Irinotecan<br>* 180 mg/m^2 administered via IV infusion on day 1 of every 14-day cycle.<br>Drug: Paclitaxel<br>* 80-100 mg/m^2 administered via IV infusion on Days 1, 8 and 15 of every 28 day cycle<br>| | Experimental: Pembrolizumab plus MK-4830 plus lenvatinib<br>Participants will receive pembrolizumab intravenously plus MK-4830 plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years. | Biological: Pembrolizumab<br>* 200 mg administered via intravenous (IV) infusion every 3 weeks (Q3W)<br>* Other names: KEYTRUDA®;Biological: MK-4830<br>* 800 mg administered via IV infusion Q3W<br>* Other names: anti-immunoglobulin-like transcript 4 (ILT4);Drug: Lenvatinib<br>* 20 mg administered via oral capsules each day<br>* Other names: LENVIMA®;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Number of Participants Experiencing a Dose-limiting Toxicity (DLT) During Safety Lead-in Phase | A DLT is defined as any drug-related adverse event (AE) according to the National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) Version 5.0, observed during the DLT evaluation period that results in a change to a given dose or a delay in initiating the next cycle. | Up to approximately 3 weeks | | Number of Participants Experiencing an Adverse Event (AE) During Safety Lead-in Phase | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. | Up to approximately 3 Weeks | | Number of Participants Who Discontinue Study Treatment Due to an AE During Safety Lead-in Phase | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. | Up to approximately 3 weeks | | Objective Response Rate (ORR) | ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented. | Up to approximately 119 weeks | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Progression-Free Survival (PFS) | PFS is defined as the time from allocation to the first documented progressive disease (PD) as assessed by RECIST 1.1 or death due to any cause, whichever occurs first. PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR will be presented. | Up to approximately 216 weeks | | Duration of Response (DOR) | For participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by BICR will be presented. | Up to approximately 216 weeks | | Overall Survival (OS) | OS is defined as the time from the date of allocation to death from any cause. | Up to approximately 216 weeks | | Number of Participants Experiencing at Least One Adverse Event (AE) During the Efficacy Phase | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. | Up to approximately 216 weeks | | Number of Participants Who Discontinue Study Treatment Due to An AE During the Efficacy Phase | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. | Up to approximately 104 weeks | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Esophageal cancer, Programmed Cell Death 1 (PD1, PD-1), Programmed Cell Death 1 Ligand 1 (PDL-1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL-2, PD-L2)

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Sympathetic Activity in Patients With End-stage Renal Disease on Peritoneal Dialysis Study Overview ================= Brief Summary ----------------- Hypothesis: Patients starting peritoneal dialysis with a glucose-based regimen have high sympathetic activity in response to an increase in leptin and insulin. Converting patients from a regimen of only glucose containing dialysate to a regimen with non-glucose-based solution, icodextrin, will reduce the insulin and leptin levels and will reverse dialysis-induced increases in sympathetic activity. Detailed Description ----------------- Cardiovascular mortality remains higher among patients treated with peritoneal dialysis as compared to patients treated with hemodialysis. Sympathetic hyperactivity is considered a significant emerging risk factor for cardiovascular mortality among patients with ESRD (End-Stage Renal Disease). Sympathetic activity, via its hemodynamic effects and trophic effects, and in interaction with RAAS (Renin Angiotensin Aldosterone System), does play a major role in cardiac and vascular remodelling, development of LVH and vascular hypertrophy, as well as progression to CHF. Glucose-based dialysate induces hyperinsulinemia and hyperleptinemia. We propose that hyperleptinemia induced by glucose-based peritoneal solution is a significant contributing factor to sympathetic hyperactivity in ESRD patients treated with PD, and could be prevented by non-glucose-based PD solution such as icodextrin-based. Adult patients with ESRD starting PD as their first renal replacement therapy modality will be studied. Patients will be recruited 1-3 weeks prior to starting PD treatment. At baseline, specific studies for microneurography (MSNA), fasting plasma insulin, leptin, catecholamines and brain natriuretic peptide (BNP) will be performed. EKG will be recorded and digitized for further assessment of heart rate variability using power spectral analysis. Extracellular fluid volume status will be assessed by bioelectrical impedance. Central vascular volume will be assessed from inferior vena cava (IVC) by heart ultrasound. Consequently 24-h ambulatory blood pressure monitoring(ABPM)and a 24-h urine collection for urea clearance and creatinine clearance will be done. All participants into the study will receive a PD treatment for 6 weeks with standard glucose-based PD solution Dianeal. The specific studies are repeated at 6 weeks.Then, patients will be randomized to one of the two groups (arms). One group will continue with Dianeal PD solution for another 12 weeks. The other group will receive Dianeal during the day and Extraneal, icodextrin or non-glucose based solution, during the night only, for the next 12 weeks. The specific studies are repeated at 12 weeks after randomization (18 weeks of PD treatment). Official Title ----------------- Effects of Non-Glucose-Based Peritoneal Dialysis Solution EXTRANEAL on Changes in Leptin Levels and Sympathetic Activity Induced by Conventional Glucose-Based Dialysate DIANEAL in Patients on Peritoneal Dialysis Conditions ----------------- End-stage Renal Disease (ESRD), Kidney Disease Intervention / Treatment ----------------- * Other: DIANEAL * Other: EXTRANEAL Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Adult (age 18 years and older) Patients with end-stage renal disease(ESRD)/chronic kidney disease(CKD)stage 5 Exclusion Criteria: Diabetes Mellitus Acute coronary syndrome in the past 6 months Cardiac arrhythmias (2nd and 3rd degree heart block or premature ventricular complexes in Lown classes 4 or 5) Symptoms suggestive of obstructive or central sleep apnea (with a score of > 10 on Epworth sleepiness scale) Patients taking Clonidine Body mass index (BMI) > 34 Patients unable to give consent Pregnant women Patients with leg injury involving nerve damage Patients taking anticoagulant medication Patients with significant bleeding disorder or liver disorder Hemoglobin <1.05 g/dl at the time of initiation of therapy patients with unilateral or bilateral nephrectomy Planned kidney transplant in the next 4 months Life expectancy under 6 months Oliguria (urine output less than 400 ml per day) Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Single Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: DIANEAL<br>One group of patients will start peritoneal dialysis with the glucose-based solution (DIANEAL) for 6 weeks, then will continue with the same type of solution for another 12 weeks. | Other: DIANEAL<br>* Weeks 1 to 6 (6 weeks): CAPD (Continuous Ambulatory Peritoneal Dialysis)patients will receive three 4-6 hour dwells of DIANEAL during the day and one 8-10-hour dwell of DIANEAL during the night CCPD (Continuous Cycler Peritoneal Dialysis)patients will receive one-two 4-6 hour dwells of DIANEAL during the day and three to seven 2-4-hour dwells of DIANEAL during the night Weeks 7 to 18 (12 weeks): *same regimen as weeks 1 to 6, for both CAPD and CCPD patients<br>* Other names: Dextrose-based PD solution;| | Active Comparator: EXTRANEAL<br>The other group of patients will start peritoneal dialysis with the glucose-based solution (DIANEAL) for 6 weeks, then will continue with DIANEAL solution during the day and the non-glucose-based solution, EXTRANEAL, during the night | Other: EXTRANEAL<br>* Weeks 1 to 6 (6 weeks): CAPD (Continuous Ambulatory Peritoneal Dialysis)patients will receive three 4-6 hour dwells of DIANEAL during the day and one 8-10-hour dwell of DIANEAL during the night CCPD (Continuous Cycler Peritoneal Dialysis)patients will receive one-two 8-12-hour dwells of DIANEAL during the day and three to seven 2-4-hour dwells of DIANEAL during the night Weeks 7 to 18 (12 weeks): CAPD (Continuous Ambulatory Peritoneal Dialysis)patients will receive three 4-6 hour dwells of DIANEAL during the day and one 8-10-hour dwell of EXTRANEAL during the night CCPD (Continuous Cycler Peritoneal Dialysis)patients will receive one-two 8-12-hour dwells of DIANEAL during the day and one 8-12-hour dwell of EXTRANEAL during the night<br>* Other names: Icodextrin-based PD solution;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Changes in muscle sympathetic nerve activity(MSNA) | Muscle sympathetic nerve activity(MSNA) is measured by microneurography at baseline (before starting peritoneal dialysis) 6 weeks of PD 18 weeks of PD(12 weeks after randomization) MSNA increases on a glucose-based dialysis regimen and may decrease by adding non-glucose-based solution | 6 weeks on PD and 18 weeks on PD | | Changes in leptin levels | Plasma leptin increases on a glucose-based peritoneal dialysis regimen and may decrease by adding non-glucose-based solution to the dialysis regimen | 6 weeks on PD and 18 weeks on PD | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Changes in blood pressure as assessed from 24-hour ambulatory blood pressure monitor (ABPM) | Blood pressure will be assessed with 24-hour ABPM at baseline, 6 weeks on PD and 18 weeks after starting peritoneal dilaysis. Summary measures of each day and night period include average systolic and diastolic BP as well as % nocturnal dipping. These summary measures can predict cardiovascular events more accurately than casual BP measures | 6 weeks on PD and 18 weeks on PD | | Changes in extracellular volume assessed by bioelectrical impedance (BIA) | Bioelectrical impedance directly measures extracellular fluid volume and total body water. The test is based on the ability to detect differences in the conductive properties of a cell by measuring its resistance (impedance) to electrical current. The technique is reliable for tracking sequential changes in extracellular fluid volume. | 6 weeks on PD and 18 weeks on PD | | Changes in heart rate variability | During the microneurography testing, EKG is recorded. Heart rate and heart rate variability(HRV) will be analyzed from EKG data at baseline, 6 weeks and 18 weeks after starting dialysis. | 6 weeks on PD and 18 weeks on PD | | Changes in central intravascular volume assessed by cardiac ultrasound | Central intravascular volume will be assessed by measuring inferior vena cava (IVC) diameter during cardiac ultrasound at baseline, 6 weeks and 18 weeks on dialysis treatment | 6 weeks on PD and 18 weeks on PD | | Changes in plasma catecholamines levels | *Plasma catecholamines (epinephrine and norepinephrine) increase on a glucose-based peritoneal dialysis regimen and may decrease by adding non-glucose-based solution to the dialysis regimen | 6 weeks on PD and 18 weeks on PD | | Changes in BNP (Brain Natriuretic Peptide)levels | *Brain Natriuretic Peptide (BNP)increases on a glucose-based peritoneal dialysis regimen and may decrease by adding non-glucose-based solution to the dialysis regimen | 6 weeks on PD and 18 weeks on PD | | Changes in plasma insulin levels | *Plasma insulin increases on a glucose-based peritoneal dialysis regimen and may decrease by adding non-glucose-based solution to the dialysis regimen | 6 weeks on PD and 18 weeks on PD | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Peritoneal Dialysis, Dialysis Solutions, Artificial Kidney, Renal Replacement Therapy, Renal Dialysis, Sympathetic Nervous System, Leptin, Icodextrin

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To Evaluate Efficacy and Safety of Parsaclisib Plus Either Rituximab or Obinutuzumab in R/R Follicular Lymphoma (FL) and Marginal Zone Lymphoma (MZL) (CITADEL-302) Study Overview ================= Brief Summary ----------------- This is a Phase 3, double-blind, randomized, placebo-controlled, multicenter study of parsaclisib plus investigator's choice of either rituximab or obinutuzumab versus placebo plus investigator's choice of rituximab or obinutuzumab for the treatment of participants with R/R FL or MZL. The Participants will be stratified in a 1:1 randomization ratio by investigator's choice of rituximab or obinutuzumab prior to randomization, time since last antilymphoma therapy (≤ 2, > 2 years), and disease histology (MZL or FL) . Official Title ----------------- A Phase 3, Double-Blind, Randomized, Placebo-Controlled Study of Parsaclisib Plus Investigator's Choice of Either Rituximab or Obinutuzumab in Participants With Relapsed or Refractory Follicular Lymphoma and Marginal Zone Lymphoma Conditions ----------------- Follicular Lymphoma ( FL), Marginal Zone Lymphoma (MZL) Intervention / Treatment ----------------- * Drug: parsaclisib * Drug: rituximab * Drug: obinutuzumab Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Male and female participants aged 18 years or older (Japan, aged 20 years or older). Histologically confirmed Grade 1, 2, or 3a FL or nodal MZL, splenic MZL, or extra nodal MZL Prior systemic treatment with at least 1 anti-CD20 mAb (either as monotherapy or in combination as chemoimmunotherapy) Documented disease that has relapsed or progressed or was refractory after the most recent prior systemic therapy. Note: Participants must not be refractory to anti-CD20 mAb Radiographically (CT, MRI) measurable lymphadenopathy per the Lugano criteria for response assessment (Cheson et al 2014). ECOG PS of 0 to 2 Adequate organ functions including hematopoiesis, liver, and kidney Willingness to avoid pregnancy or fathering children Exclusion Criteria: Women who are pregnant or breastfeeding. Known histological transformation from indolent NHL to an aggressive NHL (eg, diffuse large B-cell lymphoma). Presence of CNS lymphoma (either primary or secondary) or leptomeningeal disease. Prior treatment with PI3K inhibitors. Inadequate washout of immunosuppressive therapy, anticancer medications and investigational drugs. Significant concurrent, uncontrolled medical condition, including, but not limited to, renal, hepatic, hematological, GI, endocrine, pulmonary, neurological, cerebral, cardiac, infectious, or psychiatric disease. Known HIV infection. HBV or HCV infection: Participants positive for HBsAg or anti-HBc will be eligible if they are negative for HBV-DNA; these participants must receive prophylactic antiviral therapy. Participants positive for HCV antibody will be eligible if they are negative for HCV-RNA. History of other malignancy within 2 years of study entry. Any condition that would, in the investigator's judgment, interfere with full participation in the study. Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Triple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Treatment Group A<br>Participants will be administered with parsaclisib in combination with investigator choice of rituximab or obinutuzumab. | Drug: parsaclisib<br>* parsaclisib will be administered once daily at 20 mg for 8 weeks followed by 2.5 mg once daily.<br>* Other names: INCB050465;Drug: rituximab<br>* rituximab will be administered intravenously on select days as per protocol.<br>Drug: obinutuzumab<br>* obinutuzumab will be administered intravenously on select days as per protocol.<br>| | Placebo Comparator: Treatment Group B<br>Participants will be administered with placebo in combination with investigator choice of rituximab or obinutuzumab | Drug: rituximab<br>* rituximab will be administered intravenously on select days as per protocol.<br>Drug: obinutuzumab<br>* obinutuzumab will be administered intravenously on select days as per protocol.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Progression Free Survival (PFS) in R/R FL and MZL participants | Defined as the time from the date of randomization until the first documented disease progression as determined by IRC based on the Lugano criteria for response assessment (Cheson et al 2014) or death from any cause, whichever occurs first. | 62 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Progression Free Survival (PFS) in R/R FL participants | Defined as the time from the date of randomization until the first documented disease progression as determined by IRC based on the Lugano criteria for response assessment (Cheson et al 2014) or death from any cause, whichever occurs first. | 62 months | | Overall Response Rate (ORR) | Defined as the proportion of participants with a CR or PR as determined by IRC based on the Lugano criteria for response assessment (Cheson et al 2014). | 62 months | | Overall Survival (OS) | Defined as the time from the date of randomization until death from any cause. | 10 years | | Progression Free Survival (PFS) in R/R MZL participants | Defined as the time from the date of randomization until the first documented disease progression as determined by IRC based on the Lugano criteria for response assessment (Cheson et al 2014) or death from any cause, whichever occurs first. | 62 months | | Complete Response Rate (CRR) | Defined as the proportion of participants with a CR as determined by IRC based on the Lugano criteria for response assessment (Cheson et al 2014). | 62 months | | Duration of Response (DOR) | Defined as the time from the date of first documented evidence of CR or PR until the first documented disease progression or death from any cause, whichever occurs first, among participants who achieve an objective response as determined by IRC based on the Lugano criteria for response assessment (Cheson et al 2014). | 62 months | | Disease Control Rate (DCR) | Defined as the proportion of participants who achieve best overall response of CR, PR, or SD (Cheson et al 2014) as determined by IRC. | 62 months | | Event Free Survival (EFS) | Defined as the time from the date of randomization to the first documented disease progression as determined by radiographic disease assessment provided by IRC, the initiation of a new antilymphoma therapy, or death from any cause, whichever occurs first. | 62 months | | Time To Next antiLymphoma Therapy (TTNLT) | Defined as the time from the date of randomization to the first documented administration of a new antilymphoma therapy. | 62 months | | Progression-Free Survival on next antilymphoma therapy (PFS2) | Defined as the time from the date of randomization to the first documented disease progression as reported by the investigator after the initiation of a new antilymphoma therapy, death from any cause, or start of a third antilymphoma therapy since randomization in the study, whichever occurs first. | 62 months | | Number of Treatment Emergent Adverse Events (TEAE's) | Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment. | 62 months | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- parsaclisib, Relapsed/Refractory, obinutuzumab, rituximab

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Multicenter Retrospective Observatory of Patients With Acute Myeloid Leukemia to Core Binding Factor Study Overview ================= Brief Summary ----------------- Acute Core Binding Factor leukemias represent a specific category of acute myeloid leukemias that share prognostic factors, a specific mutational profile, and a favorable response to chemotherapy. Their management now follows the reference pattern from the French trial CBF-2006 closed to inclusions since November 2010. This includes intensive chemotherapy and intensification by allogeneic marrow transplant depending on the residual disease measured by RT qPCR . These leukemias have not been the subject of multicenter clinical trials since that date. The results of this treatment regimen need to be evaluated. Known prognostic factors such as signaling mutations, clonal interference or residual disease follow-up (MRD) will be analyzed and updated in this recent cohort. The interaction between residual disease and mutational profile will be evaluated on the prognosis. Treatment with gemtuzumab-ozogamycin and first-line allogeneic transplantation will be investigated, depending on prognostic factors including associated mutations and residual disease. The course and early treatment of molecular relapses will be analyzed. The treatment and prognosis of cytological relapses will be described with in particular the role of tyrosine kinase inhibitors and therapeutic intensification. Detailed Description ----------------- NOT PROVIDED Official Title ----------------- Multicenter Retrospective Observatory of Patients With Acute Myeloid Leukemia to Core Binding Factor Conditions ----------------- Acute Myeloblastic Leukemia Core Binding Factor Intervention / Treatment ----------------- * Other: NOT PROVIDED Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patients over 18 years old Diagnosis of acute myeloid leukemia with CBF confirmed by cytogenetics (karyotype and / or FISH): t (8; 21), inv (16) or t (16; 16) and / or molecular biology (RUNX1-RUNX1T1 fusions or CBFB-MYH11) Initial management by intensive chemotherapy, hypomethylants or targeted therapies Exclusion Criteria: - Opposition expressed to research Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Intervention/Treatment | | --- | |Other: NOT PROVIDED|NOT PROVIDED| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Event-free survival (EFS) | | December 2010 to December 2020 | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | - Complete remission rate (CR / CRp) | | December 2010 to December 2020 | | - Overall survival (OS), relapse free survival (DFS) +/- censored with allogeneic transplant | | December 2010 to December 2020 | | - Cumulative incidence of relapse (CIR) +/- censored at allograft | | December 2010 to December 2020 | | - Second complete remission rate, OS, EFS, DFS and CIR post-relapse | | December 2010 to December 2020 | | -Prognostic impact on OS, CR, EFS, DFS and CIR of recurrent somatic mutations | | December 2010 to December 2020 | | - Interaction between mutations and MRD on OS, CR, EFS, DFS and CIR | | December 2010 to December 2020 | | - Cumulative incidence of molecular relapse. | | December 2010 to December 2020 | | - Prognostic impact on OS, CR, EFS, DFS, CIR and post-relapse survival of using first-line GO and relapsing | | December 2010 to December 2020 |

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Preparing for Eating Disorders Treatment Through Compassionate Letter-Writing Study Overview ================= Brief Summary ----------------- Compassion-focused therapy (CFT) seeks to lower shame and help people develop compassion for personal distress and shortcomings. There is increasing evidence to support the benefits of incorporating CFT-based interventions into the treatment of eating disorders (EDs). Building on the investigators' prior research, this study will examine the effects of a two-week CFT-based self-compassion letter-writing intervention on patients with eating disorders. Participants will be recruited from the wait-list of patients scheduled to begin treatment at the outpatient St. Joseph's Healthcare Hamilton Eating Disorders Program, and will be randomly assigned to the two-week letter-writing intervention or to a control group. Results will inform the integration of new empirically-derived interventions into ED treatments to improve the currently dismal rates of ED recovery. Detailed Description ----------------- The study consists of two phases. In phase one, participants will be randomly assigned to a two-week daily letter-writing intervention condition or a two-week control condition; phase one will occur two to four weeks prior to the start date of group ED treatment. Participants will complete a brief set of online questionnaires pre-, mid-, and post- two-week condition (i.e. baseline, after one week, and after two weeks). Following these two weeks of intervention/control condition, all participants will complete a 25-week group treatment program as scheduled by the Eating Disorders Program. For phase two of the study, participants will be asked to complete questionnaires after 5 weeks, after 11 weeks, and post-group treatment. Data that is routinely collected as part of patients' clinical care pre- and post-treatment (i.e. on the first day and last week of group treatment) will also be collected. Official Title ----------------- Preparing for Eating Disorders Treatment Through Compassionate Letter-Writing Conditions ----------------- Eating Disorders, Anorexia Nervosa, Bulimia Nervosa, Binge-Eating Disorder, Compassion Intervention / Treatment ----------------- * Other: Self-compassionate letter-writing intervention Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: DSM-5 diagnosis of anorexia nervosa, bulimia nervosa, or binge eating disorder Eligible to start group eating disorders treatment at St. Joseph's Eating Disorder Program 17 years of age or older Exclusion Criteria: None Ages Eligible for Study ----------------- Minimum Age: 17 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: Half of the study participants (n=80) will be placed into the self-compassionate letter-writing intervention group, and half of the study participants (n=80) will be placed into a control group. Masking: Single Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Self-compassionate letter-writing intervention<br>An online self-compassionate letter-writing task once per day (10-20 minutes each) for 2 weeks | Other: Self-compassionate letter-writing intervention<br>* Participants in this condition will be asked to engage in an online self-compassionate letter-writing task once per day (10-20 minutes each) for 2 weeks.<br>| | No Intervention: Control condition<br> | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Weight- and Body-Related Shame and Guilt Scale (WEB-SG) | Self-report questionnaire with 12 questions on a 5-point Likert scale (scored 0-4). Total scores range from 0-48, with higher decrease in score indicative of a better outcome (i.e. higher decrease in levels of shame and guilt). | Change from baseline to post-2 weeks of intervention/control condition | | Self-compassion Scale (short form; SCS-SF) | Self-report questionnaire with 12 questions on a 5-point Likert scale (scored 1-5). Total scores range from 12-60, with higher increase in score indicative of a better outcome (i.e. higher increase in levels of self-compassion). | Change from baseline to post-2 weeks of intervention/control condition | | Readiness to Change Eating Behaviours | Self-report questionnaire with 3 questions on a 10-point Likert scale (scored 1-10). Total scores range from 3-30, with higher increase in score indicative of a better outcome (i.e. higher increase in readiness to change disordered eating behaviours). | Change from baseline to post-2 weeks of intervention/control condition | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Eating Disorder Examination Questionnaire (EDE-Q) | Self-report questionnaire with 28 questions, collecting two types of data. The EDE-Q collects frequency data of eating disorder behaviours. The EDE-Q also has four subscales assessing the severity of four aspects of ED psychopathology. These subscales are scored using 7-point Likert scales (scored 0-6). Higher decreases in scores are indicative of a better outcome (i.e. higher decreases in eating disorder symptomatology). | Change from day 1 to week 25 of group eating disorder treatment | | Clinical Impairment Assessment (CIA) | Self-report questionnaire with 16 questions on a 4-point Likert scale (scored 0-3). Total scores range from 0-48, with higher decrease in score indicative of a better outcome (i.e. higher decrease in clinical impairment). | Change from day 1 to week 25 of group eating disorder treatment |

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Preoperative Exercise Training for Pelvic Floor in Urinary Incontinence Post RALP Study Overview ================= Brief Summary ----------------- The aim of the study is to investigate how posology and typology of preoperative strengthening training of Pelvic Floor Muscle before RALP surgery can affect the postoperative urinary incontinence. 120 subjects undergoing RALP (Robotic-assisted laparoscopic prostatectomy) will be recruited. The amount of urinary leakage for 48h after 45-55 days post-surgery (Pad Test 48h) will be assessed. Urinary symptoms (IPSS and ICIQ-SF) and their impact on quality of life (index of quality of life 0-6) will be also evaluated. Data will be collected preoperatively (about 30-40 days before surgery) and at 45-55- days after surgery. Detailed Description ----------------- The male urinary incontinence is one of the possible complications following radical prostatectomy surgery. It represents one of the main problems with great impact on quality of life, physical activity or social well being. Previous studies define strengthening exercises for the pelvic floor as the most effective conservative approach for postoperative continence recovery. However, the effect of a preoperative exercises training is still controversial. To date, studies evaluating the influence of a preoperative rehabilitation program in postoperative urinary incontinence to varying of exercises posology (number of daily repetitions) and of the exercises typology (isometric exercises VS functional exercises) have still not been published. The aim of this clinical study is to investigate possible changes concerning the urinary incontinence in subjects undergoing a robotic-assisted laparoscopic prostatectomy, to varying of posology and typology of preoperative exercises. 120 subjects undergoing a RALP (Robotic-assisted laparoscopic prostatectomy) will be recruited. The inclusion criteria will be: RALP surgery planned after approximately 30-40 days from the preoperative session, objectivity of Pelvic Floor Muscle recruitment and contraction at manual perineal testing during preoperative session. Subjects with urinary incontinence before surgery, patients receiving radiotherapy treatment before surgery or patients who have had previous urogenital surgery shall be excluded from the study. Moreover, subjects with cognitive and/or psychiatric deficits and subjects with concurrent neurological conditions, internal conditions or disorders of the musculoskeletal system, which may affect the functional or motor recovery, will be excluded from the study. The recruited patient will be randomized and stratified by age in 4 groups according to exercise posology and typology and 4 different exercise protocols will be administered according Group of intervention. The primary outcome is to quantify the amount of the urinary leakage for 48h after 45-55 days post-surgery (Pad Test 48h). The secondary outcome is to evaluate urinary symptoms (IPSS and ICIQ-SF) and their impact on quality of life (index of quality of life 0-6), through self-assessment questionnaires compiled during preoperative session (about 30-40 days before surgery) and after 45-55- days (follow-up). At the end of the data collection, a verification of normality and homogeneity of demographic variables and of outcome measures will be proceeded. Any differences between groups will be investigated through ANOVA test for mixed models with possible post-hoc analysis. Official Title ----------------- The Influence of Typology and Posology of Exercise for the Preoperative Strengthening Training of Pelvic Floor in Urinary Incontinence Post RALP Conditions ----------------- Urinary Incontinence Intervention / Treatment ----------------- * Other: Exercise Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: On the list for RALP (Robotic-assisted laparoscopic prostatectomy) surgery expected 30-40 days before preoperative session Objectivity of Pelvic Floor Muscle recruitment and contraction at manual perineal testing during pre-operative session Exclusion Criteria: Incontinence before surgery Radiotherapy treatment before surgery Previous urogenital surgery Simultaneous presence of neurological disorders, internal conditions or disorders of the musculoskeletal system that may affect the functional or motor recovery. Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 90 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: 120 subjects on the list for RALP surgery will be recruited and randomized into 4 groups. Subjects will be evaluated during the preoperative session (T0) and about 45-55 days before the surgery (T1). The initial assessment shall provide for the compilation of two self-assessment questionnaires concerning urinary symptoms: IPSS (International Prostatic Symptoms Score) and ICIQ-SF (International Consultation on Incontinence Questionnaire- Short Form). Furthermore, the impact of quality of life of patient (index of quality of life 0-6) will be evaluated, in order to give a numerical indicator to the patient's perception about its condition. The same questionnaires will be given by a physiotherapist during follow-up session (T1) before 45-55 days post-surgery, when the amount of urinary incontinence through PAD test 48h will be evaluated, that provides for the weighing of used pad by patient during 48 hours before the session. Masking: Double Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Isometric strenghtening 1<br>once a day (1RI): patients in this group will have to play 20 tonic contractions of Pelvic Floor Muscle with a duration of 5 seconds each, performed in supine position), in sitting position and in standing position. | Other: Exercise<br>* Four type of exercises will be delivered to patients. These exercises differ for posology and typology.<br>| | Experimental: Isometric strenghtening 2<br>twice a day (2RI): patients in this group will have to play the same typology of exercises in the same way just described (see above), but twice a day (in the morning and in the evening). | Other: Exercise<br>* Four type of exercises will be delivered to patients. These exercises differ for posology and typology.<br>| | Experimental: Functional strenghtening 1<br>once a day (1RF): patients in this group will have to play 10 times the postural passage from supine position to sitting position on a bed and 10 times the postural passage from sitting position to erect position (STS), maintaining the contraction of Pelvic Floor Muscle during the execution of each functional act. In sequence, starting from erect position, they will have to play 10 trunk flexion bending their knees (as to pick up an object on the ground), maintaining the contraction of Pelvic Floor Muscle during the execution of each functional movement. | Other: Exercise<br>* Four type of exercises will be delivered to patients. These exercises differ for posology and typology.<br>| | Experimental: Functional strenghtening 2<br>twice a day (2RF): patients in this group will have to play the same typology of exercises in the same way just described (see above), but twice a day (in the morning and in the evening). | Other: Exercise<br>* Four type of exercises will be delivered to patients. These exercises differ for posology and typology.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Pad test 48h | Change in weighing of pad during 48 hours at 45 days | 45 days after surgery | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in International Prostatic Symptoms Score (IPSS) | IPSS evaluates the entity of urinary symptoms. It ranges from 0 (no symptoms) to 35 (severe symptoms). A higher value represents a worse outcome. The results is obtained summing the items of the scale. | Between before surgery (T0) and at 45 days after surgery (T1) | | International Consultation Incontinence Questionnaire - Short Form (ICIQ-SF) | ICIQ-SF evaluates the severity of urinary incontinence during the last week. The score ranges from 0 to 21, where higher score indicates higher severity. The results is obtained summing the items of the questionnaire. | Between before surgery (T0) and at 45 days after surgery (T1) | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Urinary, Exercise, Posology

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Cardiac Function and Morphology Evaluated by Magnetic Resonance Imaging in Growth Hormone Deficiency and Acromegaly Study Overview ================= Brief Summary ----------------- To test the hypothesis that both lack and excess of growth hormone (GH) is associated with cardiac abnormalities. Cardiac function and morphology will be evaluated by MRI before and after treatment. Detailed Description ----------------- It is an open prospective noninterventional clinical study. Treatment and follow-up will be according to usual guidelines, and will be unaffected by inclusion in the study. GHD patients will be treated with daily subcutaneous GH injections. Patients with acromegaly will be treated with either transsphenoidal surgery or by medical treatment with long acting somatostatin analogues, dopamine agonist, GH antagonist or combinations of these treatment modalities. Patients will be examined by Cardiac MRI before treatment and after one year of treatment. Official Title ----------------- Impact of Growth Hormone on Serum N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) and on Cardiac Function and Morphology Evaluated by Magnetic Resonance Imaging in Growth Hormone Deficiency and Acromegaly Conditions ----------------- Growth Hormone Deficiency, Cardiac Function Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Peak GH below 6.0 ng/mL during Pyridostigmine-GHRH test. Nadir GH above 0.4 ng/mL and elevated levels of IGF-I during oral glucose tolerance test Exclusion Criteria: Contraindications for magnetic resonance scan Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 70 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | GH<br>Patients with GHD | | | Pegvisomant and Somatostatin analogues<br>Acromegaly | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Changes in cardiac function i relation to changes in the activity of the GH-axis | | | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- The GH-system and cardiac function

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Clinical Trial for Assessment of Safety and Efficacy of a Echinacea/Sage Spray Compared to a Chlorhexidine/Lidocaine Spray in the Treatment of Acute Sore Throats Study Overview ================= Brief Summary ----------------- The aim of the study is to show non-inferiority of an echinacea/sage spray compared to a chlorhexidine/lidocaine-spray in the treatment of acute sore throat during five days of treatment. Main outcome parameter is the non-inferiority in number of responders between the two treatment groups. A responder is defined as a reduction by 50% of the total baseline score taken prior to treatment start. The symptoms are assessed with a symptom score. Detailed Description ----------------- Further secondary parameters are : Responders during at day 4 and 5, single symptom scores during 1 to 5 days of observation, pain at begin and end (100mm VAS), assessment of efficacy by physician and patient, consumption of rescue medication Assessment of safety by physician and patient, frequency of adverse events Official Title ----------------- Multicentric Randomized Double Blind Double Dummy Placebo Controlled Clinical Trial for Assessment of Safety and Efficacy of a Echinacea/Sage Spray in Comparison to a Chlorhexidine/Lidocaine Spray in the Treatment of Acute Sore Throats Conditions ----------------- Pharyngitis Intervention / Treatment ----------------- * Drug: chlorhexidine/lidocaine * Drug: echinacea/sage Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Age > 12 years; Acute pharyngitis or tonsillitis with symptoms of throat pain and inflammation of the pharynx and/or tonsils; Onset of sore throat less than 72 hours before inclusion ; A Tonsillopharyngitis Severity Score ≥6; Written informed consent. Exclusion Criteria: Analgesics <12 hours; Antibiotics <24 hours; t Topical throat pain medication <4 hours; Systemic corticosteroids within the last month; Symptoms of primary bacterial pharyngitis or secondary bacterial infection; Serious illness such as tumors; allergy to one of the ingredients; pregnancy or lactation; Hypersensitivity to ibuprofen; Participation in another clinical trial in the previous 30 days. Ages Eligible for Study ----------------- Minimum Age: 12 Years Maximum Age: 75 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: 2<br>Drug: Echinacea/sage patients received additionally a placebo-spray for the synthetical comparator (chlorhexidine/lidocaine) as the study was double dummy blinded. Patients had to apply spray every 2 hours with two puffs to the pharyngeal area up to a maximum of 10 times daily. Treatment duration was until illness was resolved or for a maximum of 5 consecutive days. Arms: 1 | Drug: echinacea/sage<br> <br> | | Active Comparator: 1<br>Drug: Chlorhexidine/lidocaine patients received additionally a placebo-spray for the synthetical comparator (echinacea/sage) as the study was double dummy blinded. Patients had to apply spray every 2 hours with two puffs to the pharyngeal area up to a maximum of 10 times daily. Treatment duration was until illness was resolved or for a maximum of 5 consecutive days. | Drug: chlorhexidine/lidocaine<br> <br> | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | comparison of responder of the two treatment groups after the first, second, and third days. A responder is defined as a reduction by 50% of the total baseline score taken prior to treatment start. | | first three days of treatment | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Comparison of response rates after 4th and 5th days of treatment; VAS throat pain; amount rescue medication used; global assessment efficacy Frequency of adverse events, global assessment of tolerability | | five days of treatment | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Sore throats,, Pharyngitis, Acute

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DNA Adductomics for Colorectal Cancer Investigation Study Overview ================= Brief Summary ----------------- This project seeks to identify DNA-adducts in colon tissue from different groups of patients with CRC scheduled for complete or partial colon resections. Other patients scheduled for resection of the colon serve as controls. In addition, surrogate samples such as white blood cells are investigated for the presense of adducts while blood plasma and urine are investigated for the presense of DNA-repair products. Detailed Description ----------------- Colorectal cancer (CRC) develops as a result of multiple genetic mutations causing normal intestinal epithelium to transform into a colorectal carcinoma. Genetic mutations may be caused by many different genetic events including chemical damage to the DNA nucleosides. These chemical modifications are due to both exogenous compounds coming from diet, environment and gut microbiota, or endogenous compounds produced by our own metabolic processes like inflammation and oxidative stress. Such genetic alteration is thought to be the starting event leading to development of sporadic CRC. However, there is little understanding on which DNA nucleoside modifications are associated with increased risk of CRC and their mechanism of action. The study of these DNA nucleoside modifications has been addressed in the recent years by a new research field, called DNA adductomics. DNA adductomics uses the new advanced high resolution mass spectrometry (HRMS) instrumentations for identifying the complexes that are formed between toxic compounds and DNA, namely DNA adducts. Some studies have been previously identified DNA adducts in CRC with older technology. However, there is not a real evidence on which DNA adducts are related to sporadic CRC, hereditary non polyposis colorectal cancer (HNPCC) and other diseases such as familial adenomatous polyposis (FAP) which turns into CRC with a 95% risk before the age of 35. The lack of more recent human studies in DNA adductomics is mainly due to the lack of appropriate analytical methods. Developing such methods requires sufficient sample material and the amount of sample in a colon biopsy is too low to be used for method development. In this study, colon epithelial tissue obtained by resection of colon during surgery will be used for developing a more sensitive method, possibly allowing DNA adduct analysis from biopsies in future studies. In order to ascertain that the developed method can differentiate the level of DNA-adducts between inherited CRC, sporadic CRC and non-CRC subjects, also materials from other groups coming to the hospital for colon resections will be obtained. By analyzing the materials obtained in a case-control manner, we might also be able to resolve whether some of the DNA adducts differ between the different CRC cases or in comparison with cancer-free subjects. This knowledge should provide a preliminary basis for suggesting prevention and intervention approaches to reduce morbidity and mortality from CRC. However, in case-control studies, a proper selection of the subjects should be carried out by assuring gender and age balance between the control group and the CRC group. This will be difficult in the first part of the current study since 1) there is limited possibility of obtaining resected colon from healthy subjects 2) CRC incidence rates are markedly higher in men than in women, and 3) different types of CRC develop at different ages. It is also obvious that a method relying on analyses of colon resections would have a limited application in preventive medicine. A solution to these issues may be the use of appropriate surrogate samples like blood, faeces and urine. Indeed, since DNA lesions may be removed from the genome by the DNA repair system, they are often excreted in urine, in faeces, or in blood. In order to know whether we may substitute tissues with surrogate samples, we will explore whether there is a correlation between DNA-repair product level in surrogate samples and DNA adducts in colon tissues. Substituting colon tissues with surrogates, or developing a sensitive method for DNA analysis from biopsies, would allow an easier collection of the samples, giving the possibility, in the future, of performing large and controlled clinical studies as well as less invasive sampling from patients. This could allow to confirm a causal relationship between specific DNA-adducts and CRC, providing real advances in prevention and intervention approaches. Finally, after the identification of the DNA adducts and DNA-repair products possibly associated with CRC, it will be important to identify the real cause of DNA adducts formation. Our final purpose is therefore identifying which life-style, dietary or environmental factors are possibly associated with the DNA adducts and DNA-repair products identified in colon and surrogate samples, respectively. For this purpose, we will perform a metabolic profiling of serum, urine and faeces, a microbial profiling of faeces, and we will correlate it with basic information on patient life styles about smoking, alcohol consumption and intake of red meat, e.g. factors suspected to influence risk of colonic diseases. Establishing a causal relationship between specific DNA-adducts and CRC or other colonic diseases, and understanding the causes for DNA adducts formation, will not only yield much richer insights into the molecular defects but will also result in advances in prevention and intervention approaches. Official Title ----------------- Novel DNA Adductomics Methodological Developments for Research in Colon Cancer Conditions ----------------- Colorectal Cancer, Familial Adenomatous Polyposis, Hereditary Non-polyposis Colon Cancer, Lynch Syndrome Intervention / Treatment ----------------- * Other: resectomy of the colon Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patients with either FAP, Lynch syndrome, other HNPCC, sporadic colorectal cancer, ulcerative colitis or other conditions who are scheduled for whole or partial resection of their colon Exclusion Criteria: Any condition that makes the investigator or hospital personnel doubt that voluntary participation isfeasible. Patients who are not able to understand and sign the informed consent form for any reason, including lack of a sufficient period of time to consider their participation. Patients who are below 18 years of age. Patients who donated blood to a blood bank within 3 months prior to their operation. Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | CRC<br>Patient affected by any sporadic colorectal cancer | Other: resectomy of the colon<br>* The patient scheduled for colon resectomy are included in the study<br>| | FAP<br>Patients affected by familial adenomatous polyposis coli | Other: resectomy of the colon<br>* The patient scheduled for colon resectomy are included in the study<br>| | HNPCC<br>Patient affected by hereditary non polyposis colorectal cancer | Other: resectomy of the colon<br>* The patient scheduled for colon resectomy are included in the study<br>| | Lynch<br>patient affected by lynch syndrome | Other: resectomy of the colon<br>* The patient scheduled for colon resectomy are included in the study<br>| | others<br>Patients affected by ulcerative colitis, chron disease, diverticulitis and other colon diseases, which represent the control | Other: resectomy of the colon<br>* The patient scheduled for colon resectomy are included in the study<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | DNA adductome in CRC and other diseases | Identification of DNA adducts in colon tissue from CRC and other diseases | During surgery | | Correlation of DNA adduct and DNA repair products | Correlation of DNA adduct in colon tissues and DNA repair products in surrogate samples | Baseline (Before surgery) | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Correlation of DNA adducts with microbiota | Correlation of DNA adduct in colon tissues with microbiota and microbiota metabolites in faeces | Baseline (Before surgery) | | Correlation of DNA adducts with CRC causes | Correlation of DNA adduct in colon tissues with metabolism in serum and urine | Baseline (Before surgery) |

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Study to Evaluate the Safety and Efficacy of a Proprietary Joint Health Dietary Supplement in Subjects With Joint and Connective Tissue Pain Study Overview ================= Brief Summary ----------------- This study is designed to evaluate the effectiveness of a proprietary nutritional supplement that contains Krill Oil (KO), astaxanthin (AX) and hyaluronic acid (HA) to reduce pain and discomfort in participants, compared to an inert placebo (palm oil) control and to a positive control (glucosamine-chondroitin). The purpose of the study is to determine if the combination of KO, AX, and HA will benefit participants with joint pain. Official Title ----------------- A Double-Blinded, Placebo Controlled, Human Clinical Study to Evaluate the Safety and Efficacy of a Proprietary Joint Health Dietary Supplement in Subjects With Joint and Connective Tissue Pain Conditions ----------------- Joint Pain Intervention / Treatment ----------------- * Dietary Supplement: Joint Health Product * Dietary Supplement: Placebo * Dietary Supplement: Glucosamine / Chondroitin Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Subjects must be able and willing to give Informed Consent. Subjects must not have taken anti-inflammatory drugs or supplements for 5 days prior to their initial C-RP blood test, and must refrain from taking these products for the duration of the study. Subjects will be required to refrain from taking other pain-reducing agents during the course of the study. This will ensure that the effects observed in the study are the effects of the supplement only, and not of other anti-inflammatory agents Subjects must have had knee or hip joint or muscle pain on most days of the previous month; should not have morning stiffness for more than 30 minutes; and should experience stiffness after resting. Subjects must have persistent pain in the knee or hip joints or connective tissue with a pain assessment score of at least 5, but not more than 9 using the WOMAC Pain Assessment and Pain Intensity Rating scale. Subjects must be available for and willing to attend all evaluation visits. Subjects must be willing to take/use the test Krill Oil compositions in place of current pain relief medications. Subjects may not be on any steroid-based therapies. Subjects must have access to a telephone for calling into the Clinical Center as part of test product compliance. Subjects must be willing to use appropriate birth control for duration of trial (if appropriate) Subjects must be willing to limit consumption of fatty fish for one week prior to and during the study Subjects must be willing to refrain from taking any other nutritional supplements related to immune function or pain reduction during the course of this study. Exclusion Criteria: Subjects must not be taking remission-inducing drugs such as methotrexate. Subjects whose joint pain is not in their knees. Subjects who are not willing to forego the use of anti-inflammatory and anti-pain medications or supplements for the duration of the study. Subjects who know that their joint pain is due to osteoarthritis or rheumatoid arthritis. Women who are pregnant, breastfeeding, or planning to become pregnant during the course of the trial Clinical evidence or known history of severe cardiac, pulmonary, gastrointestinal, renal, hepatic or neurological disorders. History of allergy to aspirin or NSAlDs. Subjects who have undergone total knee replacement in the contra-lateral knee within 6 months prior to the screening visit. Subjects who have received an intra-articular corticosteroid injection in a lower joint during the three (3) months prior to the baseline visit. Subjects with isolated lateral compartment disease defined by joint space loss in the lateral compartment only. Subjects who have received chondrocyte transplants in any lower extremity joint. Subjects with co-morbid conditions that restrict knee function. Treatment with corticosteroids before washout period Patients with infectious arthritis or gout Unstable medical conditions. Use of omega fatty acid supplements within two weeks of this study Clinically significant abnormal laboratory results at baseline Participation in a clinical research trial within 30 days prior to randomization Allergy, especially from crustaceans, or sensitivity to study supplement ingredients Individuals cognitively impaired and/or who are unable to give Informed Consent Any other health or mental condition that in the Investigator's opinion may adversely affect the subject's ability to complete the study or its measures or that may pose significant risk to the subject Subjects taking Inflammatory medications, cardiovascular medications, hypotensive medications, blood thinners Presence of auto immune diseases, other diseases of the immune systems, gastrointestinal diseases, i.e. Irritable bowel syndrome, or disorders of lipid metabolism. Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 80 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Triple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Joint Health Product<br> | Dietary Supplement: Joint Health Product<br>* Krill oil, Astaxanthin, Hyaluronic Acid Formulation, 353 mg per day; Softgel capsule<br>* Other names: FlexPro MD;| | Placebo Comparator: Placebo<br> | Dietary Supplement: Placebo<br>* Palm oil Softgel capsule<br>| | Active Comparator: Glucosamine / Chondroitin<br> | Dietary Supplement: Glucosamine / Chondroitin<br>* Glucosamine 1500 mg, Chondroitin 1200 mg per day<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | WOMAC Change | Change in Clinical Coordinator administered pain assessment and pain intensity evaluation over 56 days as determined by the Western Ontario and McMaster Universities Osteoarthritis Index™© (WOMAC) | Days: 0, 14, 28 and 56 | | VAS Change | Change in Self-administered Visual Analogue Pain Assessment and Pain Intensity Rating Scale (VAS) over 56 days | Days: 0, 7, 14, 28, 35, 42 and 56 | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Blood Chemistry CBC Change | Change in CBC and differentials over 56 days | Days: 0, 14, 28 and 56 | | Blood Chemistry hs-CRP Change | Change in hs-CRP over 56 days | Days: 0, 14, 28 and 56 |

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Naldebain® Extended-release Injection After Cesarean Section in Pain Management Study Overview ================= Brief Summary ----------------- Cesarean section is one of the surgeries most commonly leading to postoperative severe acute pain. It was reported that the mean worst pain intensity reached to 6.14 one day after cesarean section in Germany. Inadequate pain management may result in the cardiorespiratory complications, late recovery, and postoperative chronic pain. According to a series of pain management article published in the Lancent in 2019, the incidence of post-cesarean section chronic pain was 55%, including 12% of severe chronic pain. Extended-release dinalbuphine sebacate, a prodrug of nalbuphine, is a novel analgesic developed in Taiwan and the indication is moderate to severe postoperative pain. After intramuscular injected, dinalbuphine sebacate will be released to blood stream and immediately hydrolyzed. In Taiwan, dinalbuphine sebacate has been used for alleviating pain after several types of surgeries, such as colorectal surgery, orthopaedics, gynecology and obstetrics. However, few post-marketing studies investigated the efficacy and safety of dinalbuphine sebacate. Detailed Description ----------------- This is an observational, prospective, single arm study. This study is aimed to investigate the efficacy and safety of dinalbuphine sebacate in subjects undergoing cesarean section. Written informed consent are obtained before subjects participate in the study. Eligible subjects will be visited twice daily during stay in hospital. Pain intensity, consumption of analgesics, adverse reaction, and the residues of dinalbuphine sebacate and nalbuphine in milk will all be analyzed. Official Title ----------------- Naldebain® Extended-release Injection After Cesarean Section in Pain Management: a Prospective Observational Study Conditions ----------------- Post Operative Pain, Caesarean Section, Analgesia Intervention / Treatment ----------------- * Drug: Dinalbuphine sebacate Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Female aged 20 to 45 years. Going to have cesarean section and use dinalbuphine sebacate to alleviate postoperative pain. Cesarean section scheduled between the 34th and 41st week of gestation. ASA I or II. Willing to comply with study protocol and give written informed consent. Exclusion Criteria: With contraindication to opioids. Chronic use or abuse of opioids. Underlying disease which contribute to abnormal lactation, such as mastitis. Diagnosed with gestational diabetes mellitus and administration of insulin is required. Diagnosed with pre-eclampsia or eclampsia. Unsuitable for participation judged by investigator. Ages Eligible for Study ----------------- Minimum Age: 20 Years Maximum Age: 45 Years Sexes Eligible for Study ----------------- Female Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | DS group<br>Subjects going to receive dinalbuphine sebacate for post-cesarean section pain. | Drug: Dinalbuphine sebacate<br>* After giving the birth, subjects are intramuscularly injected with a single dose of 150 mg of dinalbuphine sebacate (DS). DS is a prodrug of nalbuphine. After injeciton, DS are released to blood stream and hydrolyzed immediately. The onset of action is 12 to 24 hours and the analgesic effect can last about 5 to 7 days.<br>* Other names: NALDEBAIN;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Incidence of complication | Analgesic-related complication occurring in the period of hospital stay will be recorded, such as dizziness, nausea, vomiting, and injection site reaction. | Within 5 days after injection of dinalbuphine sebacate | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Post-cesarean section pain intensity | Pain intensity is assessed by numerical rating scale (NRS) twice daily during stay | Within 5 days after delivery | | Consumption of analgesics | Analgesics consumed during stay of hospital are recorded. | Within 5 days after delivery | | Concentration of nalbuphine in breast milk | Dinalbuphine sebacate is a prodrug of nalbuphine. After intramuscular injection, dinalbuphine sebacate are slowly released to blood stream and immediately hydrolyzed. The breast milk is collected twice daily within 5 days after cesarean section, and tested by HPLC. | Within 5 days after delivery | | Concentration of dinalbuphine sebacate in breast milk | Dinalbuphine sebacate is a prodrug of nalbuphine. After intramuscular injection, dinalbuphine sebacate are slowly released to blood stream and immediately hydrolyzed. The breast milk is collected twice daily within 5 days after cesarean section, and tested by HPLC. | Within 5 days after delivery | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Dinalbuphine Sebacate, NALDEBAIN, Extended-release analgesics

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A Cytomegalovirus-Directed Vaccine (CMV-alphaDC1) for Preventing Cytomegalovirus Infection or Reactivation in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation Study Overview ================= Brief Summary ----------------- This phase Ib trial evaluates the safety and most effective dose of a cytomegalovirus (CMV) pp65 peptide-loaded alpha-type-1 polarized dendritic cell (CMV-alphaDC1) vaccination in patients who are undergoing an allogeneic hematopoietic stem cell transplant. CMV is an opportunistic infection that can occur or reactivate after allogeneic hematopoietic stem cell transplant as a result of immunosuppression. The CMV-alphaDC1 vaccine is made of white blood cells that have been exposed to molecules called cytokines, as well as CMV proteins. Introducing these dendritic cells to the patients immune system may activate an immune response to CMV, protecting against infection or reactivation. Detailed Description ----------------- PRIMARY OBJECTIVES: I. Determine the safety of cytomegalovirus (CMV) pp65 peptide loaded alpha-type 1 polarized dendritic cell (CMV-alphaDC1) vaccination after allogeneic hematopoietic cell transplantation (alloHCT). II. Determine the immunogenicity of CMV-alphaDC1 vaccination after alloHCT. SECONDARY OBJECTIVES: I. Evaluate the effect of CMV-alphaDC1 vaccination after alloHCT on late CMV reactivation. II. Evaluate the effect of CMV-alphaDC1 vaccination after alloHCT on non-relapse mortality (NRM). EXPLORATORY OBJECTIVES: I. Assess the effect of CMV-alphaDC1 vaccination on T cell subsets. II. Assess the effect of CMV-alphaDC1 vaccination on T cell receptor diversity. OUTLINE: On day 0, patients undergo standard of care hematopoietic stem cell infusion. Patients receive CMV-alphaDC1 vaccine intradermally on days 28, 42, 56, and 70. After completion of study treatment, patients are followed up at days 84, 100, 180, and 365. Official Title ----------------- A Phase 1b Safety and Immunogenicity Study of Cytomegalovirus (CMV) Directed Type 1 Polarized Dendritic Cell Vaccination (αDC1) After Allogeneic Hematopoietic Cell Transplantation (alloHCT) for Hematologic Malignancies Conditions ----------------- Cytomegaloviral Infection, Hematopoietic and Lymphoid System Neoplasm Intervention / Treatment ----------------- * Procedure: Allogeneic Hematopoietic Stem Cell Transplantation * Procedure: Biospecimen Collection * Biological: CMV pp65 Peptide-loaded Alpha-type-1 Polarized Dendritic Cell Vaccine Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Recipient age >= 18 years of age The recipient is CMV seropositive The recipient is planned to receive an allogeneic peripheral blood stem cell graft The recipient is planned to receive fludarabine, melphalan, and total body irradiation for the transplant conditioning regimen The recipient is planned to receive micro-dose methotrexate, tacrolimus, and mycophenolate mofetil for acute graft versus host disease (GvHD) prophylaxis The recipient has an expected hematopoietic cell transplantation-comorbidity index (HCT-CI) score of 4 or less based upon the data available at the time of eligibility assessment The recipient must understand the investigational nature of this study and has signed an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedures The donor is CMV seronegative or seropositive The donor is 8/8 human leukocyte antigen (HLA) (DR-B1, A, B, C) matched to the recipient The donor is willing and able to donate peripheral blood mononuclear cells in addition to peripheral blood stem cells The donor is willing to sign informed consent Exclusion Criteria: The recipient is CMV seronegative The recipient is planned to receive T cell depletion in vivo (anti-thymocyte globulin [ATG], alemtuzumab, post-transplant cyclophosphamide) or ex vivo (alpha-beta T cell depleted or CD34+ selected grafts) as acute GvHD prophylaxis The graft source is cord blood or bone marrow The donor or recipient has HLA DRB1*0301 or DRB1*1501 alleles The recipient has a very high disease risk index (DRI) based upon the data available at the time of eligibility assessment The recipient has a medical, behavioral, or social condition which in the opinion of the investigators would preclude compliance with the study Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Prevention Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Treatment (CMV-alphaDC1)<br>Patients undergo standard of care allogeneic hematopoietic stem cell transplant on day 0 and receive CMV-alphaDC1 vaccine intradermally on days 28, 42, 56, and 70. | Procedure: Allogeneic Hematopoietic Stem Cell Transplantation<br>* Undergo standard of care allogeneic hematopoietic stem cell transplant<br>* Other names: Stem Cell Transplantation, Allogeneic;Procedure: Biospecimen Collection<br>* Correlative studies<br>* Other names: Specimen Collection;Biological: CMV pp65 Peptide-loaded Alpha-type-1 Polarized Dendritic Cell Vaccine<br>* Given intradermally<br>* Other names: Cytomegalovirus pp65 Peptide Loaded Alpha-type 1 Polarized Dendritic Cell Vaccine;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Incidence of dose limiting toxicities | For each dose level of cytomegalovirus (CMV) pp65 peptide loaded alpha-type 1 polarized dendritic cell (CMV-alphaDC1) vaccination that is tested. Will be summarized by dose level using frequencies and relative frequencies. | Up to 2 years | | Number of multifunctional CMV antigen specific T cells | The number of multifunctional CMV antigen specific T cells will be determined by flow cytometry before and after vaccination with CMV-alphaDC1. Assessed by the change in the number of CMV specific T cells before and after treatment, which is compared using a one-sided paired t-test. The number of CMV specific T cells will be summarized before and after treatment using the appropriate descriptive statistics, with the mean change estimated using a 90% confidence interval. | At days 28 (before vaccination), 42 (before vaccination), 56, 70, 84, 100, 180, 365 | | Number of CMV pp56 reactive T cells | The number of CMV pp65 reactive T cells will be determined by cytokine secretion (such as IFN-gamma) with ELISPOT before and after vaccination with CMV-alphaDC1. Assessed by the change in the number of CMV specific T cells before and after treatment, which is compared using a one-sided paired t-test. The number of CMV specific T cells will be summarized before and after treatment using the appropriate descriptive statistics, with the mean change estimated using a 90% confidence interval. | At days 28 (before vaccination), 42 (before vaccination), 56, 70, 84, 100, 180, 365 | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Incidence of late CMV reactivation after allogeneic hematopoietic stem cell transplant | Will be summarized by dose level using the appropriate descriptive statistics; with estimates of rates obtained by 95% Jeffrey's prior confidence intervals. | From day 85 to 365 | | Incidence of non-relapse mortality after allogeneic hematopoietic stem cell transplant | Will be summarized by dose level using the appropriate descriptive statistics; with estimates of rates obtained by 95% Jeffrey's prior confidence intervals. | Up to 2 years |

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A Notch Signalling Pathway Inhibitor for Patients With Advanced Breast Cancer (0752-014) Study Overview ================= Brief Summary ----------------- An investigational study to determine the safety/tolerability, and efficacy of a notch signaling pathway inhibitor in patients with metastatic or locally advanced breast cancer and other advanced solid tumors. Official Title ----------------- A Phase I Study of MK0752, a Notch Inhibitor, in Patients With Metastatic or Locally Advanced Breast Cancer and Other Solid Tumors Conditions ----------------- Advanced Breast Cancer, Other Solid Tumors Intervention / Treatment ----------------- * Drug: Comparator: MK0752, Notch Inhibitor * Drug: Comparator: MK0752, Notch Inhibitor - 450 mg * Drug: Comparator: MK0752, Notch Inhibitor - 3 days on, 4 off * Drug: Comparator: MK0752, Notch Inhibitor - 1 day on, 6 off * Drug: Comparator: MK0752, Notch Inhibitor - 3 days on, 4 off 350 mg Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Women or men greater than or equal to 18 years of age ECOG status less than or equal to 2 (a measurement to determine your ability to perform daily activities) In Parts I, III, and IV, patient must have a histologically confirmed, metastatic or locally advanced solid tumor that has failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist. There is no limit on the number of prior treatment regimens In Part II, only breast cancer patients are eligible In Part V, only patients with Numb negative breast cancer (i.e., tumor shows Numb immunoreactivity in less than 10% of the neoplastic cells assessed) are eligible Patient has recovered from and is at least 2 weeks from previous antineoplastic therapy, including chemotherapy, biological therapy (including Herceptin), hormonal therapy, radiotherapy, or surgery Exclusion Criteria: Patient has had an investigational treatment in the preceding 21 days Uncontrolled congestive heart failure or myocardial infarction (heart attack) within 3 months of study start History of hepatitis B or C or HIV Patient has the presence of clinically apparent central nervous system metastases or carcinomatous meningitis. Patients with CNS metastases who have completed a course of radiotherapy and are clinically stable in the judgment of the investigator are eligible Patients with currently active second malignancy, other than non-melanoma skin cancer, should not be enrolled. Patients are not considered to have a currently active malignancy if they have completed therapy for prior malignancy and are considered by their physician to be at <30% risk of relapse Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Part I - Arm 1<br> | Drug: Comparator: MK0752, Notch Inhibitor<br>* Dose escalating beginning with rising dose levels of 300, 450, and 600 mg/day in a continuous dosing schedule.<br>| | Experimental: Part II - Arm 1<br> | Drug: Comparator: MK0752, Notch Inhibitor - 450 mg<br>* Dose 450 mg capsules daily for 28 day cycles.<br>| | Experimental: Part III - Arm 1<br> | Drug: Comparator: MK0752, Notch Inhibitor - 3 days on, 4 off<br>* Dose escalating in a repeating intermittent dosing schedule of 3 days on and 4 days off at rising dose levels of 450, 600, 800, 1000, 1200, and 1400 mg/day.<br>| | Experimental: Part IV - Arm 1<br> | Drug: Comparator: MK0752, Notch Inhibitor - 1 day on, 6 off<br>* Dose escalating in a repeating intermittent dosing schedule of 1 day on/6 days off at rising dose levels of 600, 900, 1200, 1500, 1800, 2400, 3200 mg/day once weekly and then increase at 33% increments.<br>| | Experimental: Part V - Arm 1<br> | Drug: Comparator: MK0752, Notch Inhibitor - 3 days on, 4 off 350 mg<br>* Dose 350 mg capsules daily intermittent 3 days on/4 days off dosing. THIS DOSING SCHEDULE IS NO LONGER UNDER INVESTIGATION<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Safety and tolerability; MTD will be established | | Day 1 to Day 28 | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Overall tumor/disease response will be evaluated using RECIST criteria, radiographic and clinical evaluations | | radigraphic evaluation = every 56 days | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Advanced Breast Cancer, Solid Tumors, Advanced Solid Tumors

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Auditory Training and Hearing Aid Satisfaction Study Overview ================= Brief Summary ----------------- Although hearing aids are the most common treatment for hearing loss, and have the potential to help seniors stay active and productive, almost 50% of them who receive hearing aids rarely if ever use them, a state of affairs sometimes referred to as the hearing aid in the drawer syndrome. clEAR's customized auditory brain training has been shown to be effective in improving adults' abilities to recognize speech, in reducing their perceptual effort associated with listening with a hearing loss, and in increasing their confidence to engage in everyday conversations. In the proposed research, we will determine whether older adults who receive hearing aids for the first time report higher satisfaction with their new hearing aids and have longer daily use time as a result of having completed clEAR's auditory brain training program for new hearing aid users. Detailed Description ----------------- Auditory training as the potential to dramatically affect older persons' adjustment to a new hearing aid and to maximize the benefits they receive from wearing one. In turn, by wearing hearing aids, they experience easier and more successful communication patterns. They enhance their ability to engage in everyday conversations and will be able to become more socially involved with their family and friends. In this study we will try to determine the extent to which web-based clEAR auditory brain training, with concomitant support from a clEAR in-house audiologist, affects satisfaction with new hearing aids and increases daily use time. The study will include thirty adults over the age of 60 years who have received hearing aids for the first time. After an adjustment period, half will complete clEAR's auditory brain training program right away and the other half will complete it after a delay period, and both will complete a control condition. To establish the level of feasibility and clinical utility. We will measure hearing aid satisfaction, benefit ratings, and hearing aid use time. Official Title ----------------- Auditory Brain Training to Enhance Satisfaction and Usage of New Hearing Aids by Older Adults Conditions ----------------- Hearing Impairment, Sensorineural Intervention / Treatment ----------------- * Behavioral: Auditory Brian Training Games/Activities Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Must be a native English speaker Must have a mild to severe bilateral sensorineural hearing loss Must be a candidate for new hearing aid(s) (have never used hearing aids) Exclusion Criteria: Cognitive impairment or any factors that would prohibit a participant from completing questionnaires Cognitive or speech production factors that would prohibit a participant from repeating words during a speech perception test. Ages Eligible for Study ----------------- Minimum Age: 60 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Health Services Research Allocation: Non-Randomized Intervention Model: Single Group Assignment Interventional Model Description: All participants experience the same interventions and assessments. Subjects are divided into either early or late intervention groups. Masking: Single Arms and Interventions | Intervention/Treatment | | --- | |Behavioral: Auditory Brian Training Games/Activities|Game-based activities that encourage listening to words and sentences in noisy situations. Participants will receive subscriptions to the clEAR online auditory training activities and recommended protocol for those who recently received new hearing aids.| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in Hearing Aid Satisfaction After Auditory Training | The Client Orientated Scale of Improvement (COSI), a subjective measure of improvement on self-defined goals. The scale is relative to a baseline assessed before wearing hearing aids. For each goal participants select from a scale of improvement including Worse (-1), No Difference (0), Slightly Better (+1), Better (+2), and Much Better (+3). Positive values between one and three indicate improvement, negative values indicate that the self-defined goals got worse, and zero is no improvement. COSI scores were assessed before and after participants used the Amptify DTx. The outcome measure reported is the difference between scores before and scores after using the Amptify DTx. | Three weeks after hearing aid fitting and after completing the four week training protocol. | | Change in Hearing Aid Satisfaction After Auditory Training | The International Outcome Inventory for Hearing Aids (IOI-HA) is a hearing aid satisfaction questionnaire that averages a series of seven questions on a five-point scale (0-5 possible points of improvement). IOI-HA scores were assessed before and after participants used the Amptify DTx. The outcome measure reported is the difference between scores before and scores after using the Amptify DTx. Higher values between 1 and 5 indicate more relative satisfaction. | Three weeks after hearing aid fitting and after completing the four week training protocol. | | Change in Hearing Aid Satisfaction After Auditory Training | Abbreviated Profile of Hearing Aid Benefit (APHAB) is common clinical questionnaire for determining hearing aid benefit using a series of 24 questions on a seven-point scale (A-G; the scale is then converted to percent of time from 1% (Never) to 99% (Always) and 50% means half of the time). Hearing aid benefit is calculated as the difference between the performance with a hearing and and performance without a hearing aid. More positive values indicate more benefit. | Three weeks after hearing aid fitting and after completing the four week training protocol. | | Change in Hearing Aid Satisfaction After Auditory Training | The Speech, Spatial and Qualities of Hearing Scale (SSQ-12) is a subjective tool or assessing the quality of the sound from a hearing aid using a 12-item questionnaire. Questions focus on how well the participant could hear in various situations. The responses range on a scale from Not At All (0) to Perfectly (10). Higher values indicate better sound quality. | Three weeks after hearing aid fitting and after completing the four week training protocol. | | Change in Hearing Aid Satisfaction After Auditory Training | Daily use (in hours/day) is logged by the participant. Improvement is indicated by an increase in the amount of time the participant uses the hearing aid each day. | Three weeks after hearing aid fitting and after completing the four week training protocol. | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in Percent Words Correct on Speech Perception Measures After Auditory Training | The NU-6 is a standard clinical assessment of word discrimination. Lists consist of 50 words in quiet and were presented through the Amptify DTx while wearing the hearing aid. NU-6 scores are in percent words correctly identified. Scores reported here are the difference between scores measured before and after completing the Amptify DTx. | At the time of hearing aid fitting (baseline), three weeks after hearing aid fitting, and after completing the four week training protocol. | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Auditory Training

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PEGI to Improve Shared Decision-Making for Breast Reconstruction Study Overview ================= Brief Summary ----------------- The purpose of this study is to determine the effectiveness of a pre-consultation decision support workshop for breast reconstruction after breast cancer, in facilitating the decision-making process, compared to routine pre-surgical education. Detailed Description ----------------- Postmastectomy breast reconstruction is becoming increasingly utilized in breast cancer patients to provide surgical restoration of the breast mounds. The breast reconstruction discussions can be highly complex, as there are many different techniques, timing, and complications that are unique to each procedure. However ¼ of women report being dissatisfied with some component of their cancer or reconstructive care. Failure of the physician to provide adequate information about treatment options is the most frequent source of cancer patient dissatisfaction and breast reconstruction patients have expressed a need for further information regarding the complex decision to pursue breast reconstruction. In such scenarios of complex medical decision-making, decision support techniques may be an effective solution to information provision and shared decision-making. As a result, the investigators developed a pre-consultation educational group intervention delivered in a group setting for women considering breast reconstruction, with the aims to fill an existing information-gap, promote high-quality decision-making and enhance decision self-efficacy and other decision measures. This study will evaluate the educational group intervention. Official Title ----------------- Pre-consultation Educational Group Intervention to Improve Shared Decision-Making for Postmastectomy Breast Reconstruction Conditions ----------------- Breast Cancer Intervention / Treatment ----------------- * Behavioral: pre-consultation educational group intervention Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patients > 18 years of age. Seeking consultation for delayed Post Mastectomy Breast Reconstruction, or prophylactic mastectomy and immediate Post Mastectomy Breast Reconstruction for breast cancer prevention. Exclusion Criteria: Chest wall or atypical breast malignancy that require chest wall reconstruction. Active invasive or in situ breast cancer. Consultation for breast revision or nipple reconstruction only. Patient cannot read or write in English. Cognitive impairment or uncontrolled psychiatric diagnosis. Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- Female Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Supportive Care Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Educational group intervention<br>The pre-consultation educational group intervention will be 2 hours in duration on the morning of the consultation and will be facilitated by a dedicated social worker from psycho-oncology. | Behavioral: pre-consultation educational group intervention<br>* Incorporates the key components of shared decision-making and decision support with the philosophy of delivering supportive care to cancer patients. Surgeon (40 mins): treatment options for breast reconstruction with indications/ contraindications, advantages / disadvantages, expected post-operative course, aesthetic result and complications with probabilities Registered nurse (20 mins): preparing for surgery, postoperative recovery and how to navigate the health care system Social worker (30 mins): values clarification exercise Breast reconstruction patient volunteers (30 mins) questions and answers about their personal experience<br>| | No Intervention: Standard Care<br>Routine pre-consultation education | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Decisional Conflict Scale | Decision conflict scale measures personal perceptions of uncertainty in choosing options and has been demonstrated to be valid and responsive to change. The decisional conflict scale is a 16-item 5-response instrument that reports a score from 0 - 100 with higher scores indicating more conflict (items are summed, divided by 16 and multiplied by 25). | Change from baseline decision conflict at 1 week after surgical consultation | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- breast cancer, breast reconstruction, shared decision making, decision support intervention

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A Trauma-Informed Approach for Positive Youth Development for Montana Students Study Overview ================= Brief Summary ----------------- Given the prevalence of suicide and mental health issues in rural Montana, this project is intended to help mitigate stressors that may contribute to poor behavioral and mental health in high school-aged children. The immediate goal is to measure physical and mental health outcomes in adolescents resulting from a trauma-informed yoga intervention designed to foster positive youth development and student success. It builds on feasibility study for year one in which 19 experimental condition participants engaged in an 8-week yoga program. Detailed Description ----------------- mental and physical health issues (17). Stressors deriving from low socioeconomic status and/or traumatic childhood experiences such as abuse or neglect are exacerbated by today's educational culture, where mandated practices such as standardized testing and post-graduation plans are cited as primary causes for stress in adolescents' lives (4). In Montana, the childhood abuse/neglect rate was 8.3 per 1000 children in 2015, which indicates a 56.8% increase from 2014 (16); nationally, in the same year the abuse/neglect rate was 9 per 1000 children (15). Childhood trauma tends to cluster in areas of high poverty; in Livingston Public Schools in rural southwestern Montana, for instance, 52% of students were eligible for free and reduced-price lunch in 2016, which is the same as the national rate (4; 40). In Livingston, 13.2% of residents are listed as living in poverty, which is slightly above the 12.3% national rate (53). These unfortunate but common childhood stressors can result in significant public health issues including poor mental health, suicidality, substance abuse, juvenile offenses, and autoimmune disease (8). Despite Livingston being on par with national childhood poverty and abuse trends, the suicide rates in Livingston are triple the national average (42). Substance abuse among minors in Montana, which is often comorbid with mental health issues and suicidality, is prevalent; according to a 2015 report by the office of adolescent health, 38% of Montana high schoolers reported having used marijuana at least once, 20% self-reported using alcohol before age 13, and 30% reported using e-cigarettes (36). Given the prevalence of suicide and mental health issues in rural Montana, this project is intended to cultivate positive coping skills to buffer the negative effects of stressors among school-aged children. Because of the geographic isolation and resulting lack of resources for many schools in Montana, there is a need for innovative and novel school- and community-centered interventions in order to address the varied health needs of rural adolescents. According to research, yoga and mindfulness can have a positive impact on youth development (6; 7; 13; 14). The second year of this pilot study prepares the way for a robust intervention by examining efficacy of this intervention modality compared to a control group in a collaborative school setting, basing the framework of the study on the tenets of community-based participatory research (16). Existing validated measures of efficacy using physical and mental health measures will be used to generate student, teacher, and parent reports of perceived strengths and difficulties, along with measures of anxiety and depressive symptomology. Secondary outcomes of school performance also will be assessed. Efficacy of the intervention will be ascertained through observational and qualitative data obtained utilizing participant, school, and community partner interviews; quantitative feedback will also be gathered from community and school stakeholders to evaluate program outcomes. From this data analysis, decisions regarding any necessary modifications to experimental design and program implementation will be made for third year of the study, which will lead to an expansion to middle level students within the same school district. Aim 1: Pilot test a trauma-informed yoga intervention for 15-18 year-old male and female high school students. H1: Students who participate in the pilot intervention will demonstrate improved mental health as measured by a decrease in depressive and anxiety symptomology at the conclusion of the study (week 8) as compared to participants in the control group. H2: Students who participate in the pilot intervention will demonstrate improved physical health as measured by a decreased resting heart rate, improved sleep patterns, and reduced cortisol levels at the conclusion of the study (week 8) as compared to participants in the control group. Aim 2: Evaluate the study's school-community-academic partnership at the conclusion of the program using a mixed methods survey. The CAB will meet monthly to determine program adjustments. Survey administration and data analysis will occur in summer 2021. The PI will share results with the CAB to determine areas for program refinement and assess need for study continuation or expansion into multiple schools for year 3. H3: Findings from the partnership evaluation will be used to refine the community engagement component of the study in Year 3. This data will be used to determine intervention and program efficacy in order to indicate areas for revision and refinement in year 3 of this study; the data will also inform future implementation plans for program expansion to the middle school level within the same school district. Official Title ----------------- A Trauma-Informed Approach for Positive Youth Development for Montana Students Conditions ----------------- Depression, Anxiety, Suicidal Ideation, Stress, Trauma Intervention / Treatment ----------------- * Other: Trauma-Informed Yoga Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Freshmen enrolled in a health and wellness/physical education class at a rural Montana High School Exclusion Criteria: None Ages Eligible for Study ----------------- Minimum Age: 14 Years Maximum Age: 19 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Supportive Care Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Experimental Yoga Group<br>35 freshman students enrolled in a health and wellness/physical education class at a rural Montana high school | Other: Trauma-Informed Yoga<br>* 8 weeks of twice weekly trauma-informed yoga for 45 minutes per session<br>| | No Intervention: Control Group (No Yoga Intervention)<br>20 freshman students enrolled in a health and wellness/physical education class at a rural Montana high school | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in Salivary Cortisol Levels | Students will provide a saliva sample in which cortisol levels will be analyzed through salivary assay kits (through Salimetrics.com). Samples will be collected on the first day of the intervention, halfway through the intervention, and on the last day of the intervention to determine if the intervention has changed cortisol levels. A biostatistician will provide analysis and conclusion of these samples at the conclusion of the study; the mean change pre vs. post is provided here. Negative change indicates improvement in stress levels. | Week 1 and. Week 6 | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Patient Health Questionnaire for Adolescents | This 9 item questionnaire is designed to evaluate severity of depressive symptoms in adolescents. It is scored on a Likert scale from 0 (not at all) to 3 (nearly every day) on items linked to depression indicators. The minimum score is a 0 and the maximum score is a 27, and a negative change in score from pre- to post-assessment indicates an improvement in symptomology. Pre and post-intervention means are reported here. | Baseline and 6 weeks | | Generalized Anxiety Disorder-7 Anxiety Scale | This 7 item questionnaire is based on a Likert scale of 0 (not at all) to 3 (nearly every day) for items related to anxiety disorders. The lowest score is a zero and the maximum score is a 21. A negative change in score from pre- to post-assessment indicates an improvement in symptomology. Pre and post-intervention means are reported here. | Baseline and 6 weeks | | Connor-Davidson Resilience Scale (CD-RISC) | The CD-RISC 10 is a unidimensional self-reported scale consisting of 10-items measuring resilience. Respondents rate items on a 5-point Likert scale, ranging from 0 (not true at all) to 4 (true nearly all the time). Each item has a minimum score of 0 and a maximum score of 4. Possible scores range from 0-100. A higher score indicates higher resilience. Pre and post-intervention means are reported here. | Baseline and 6 weeks |

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Automated Breast Ultrasound Screening Study Overview ================= Brief Summary ----------------- Women with dense breasts (BIRADS 3 or 4) with a BIRADS category 1 or 2 mammogram are asked to participate in a automated volume breast ultrasound scanner. The study evaluates prospectively the changes in recall rate, positive biopsy rate, cancer detection rate when BIRADS category 3 lesions are given a 1 year follow-up recommendation. Detailed Description ----------------- Women with dense breasts (BIRADS 3 or 4) with a BIRADS category 1 or 2 mammogram are asked to participate in a automated volume breast ultrasound scanner. If the women agrees to participate and sign informed consent she undergoes an automated whole breast scan. The scan is interpreted independent of the mammogram. Scans are assigned a BIRADS category score of 1, 2, 3,or 0. BIRADS category 3 lesions are reported as no evidence of malignancy and a 1 year follow-up is recommended. BIRADS category 0 lesions are requested to have a hand held ultrasound including elastography. Follow up is then determined by BIRADS score and elastography results of hand held ultrasound. The study evaluates prospectively the changes in recall rate, positive biopsy rate, cancer detection rate when BIRADS category 3 lesions are given a 1 year follow-up recommendation. Official Title ----------------- Automated Breast Ultrasound Screening in Women With Dense Breasts (BIRADS 3 or 4) and BIRADS Category 1 or 2 Mammogram Assigning BIRADS 3 Lesions to Yearly Follow-up Conditions ----------------- Breast Cancer Intervention / Treatment ----------------- * Procedure: Breast ultrasound Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Women age >18 scheduled for routine screening mammogram. Women with Density 3 or 4 and BIRADS category 1 or mammogram are asked to participate in study Exclusion Criteria: Inability to give informed consent Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 80 Years Sexes Eligible for Study ----------------- Female Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Intervention/Treatment | | --- | |Procedure: Breast ultrasound|automated whole breast ultrasound| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Decreased recall rate for screening breast ultrasound while maintaining cancer detection rate | | 3 years | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Increased positive biopsy rate | | 3 years | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Breast Cancer, Automated whole breast ultrasound, BI-RADS category 3 lesions

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Tow Techniques of Adductor Canal Block for Analgesia After Total Knee Replacement Study Overview ================= Brief Summary ----------------- This study compares the tow technique of continues adductor canal block for total knee replacement surgery. Half participants will receive catheterization at the entrance of the adductor canal, while the other half will receive catheterization at the middle point of the adductor canal. Official Title ----------------- Ultrasound-guided Continuous Adductor Canal Block for Analgesia After Total Knee Replacement: Comparison of Block at the Entrance and Middle of the Canal Conditions ----------------- Total Knee Arthroplasty, Analgesia, Nerve Block Intervention / Treatment ----------------- * Procedure: ultrasound-guided short-axis placement of catheter at the entrance of the adductor canal * Procedure: ultrasound-guided long-axis placement of catheter at the middle of the adductor canal Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: 18-80 years Knee-arthroscopy Written consent ASA I-III BMI 19-35 Exclusion Criteria: Unable to communicate with the investigators (e.g., a language barrier or a neuropsychiatric disorder). coagulopathy or on anticoagulant medication Allergic reactions toward drugs used in the trial History of substance abuse Infection at injection site Can not be mobilised to 5 meters of walk pre-surgery Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 80 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Supportive Care Allocation: Randomized Intervention Model: Parallel Assignment Masking: Triple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: entrance placement of adductor canal catheter<br> | Procedure: ultrasound-guided short-axis placement of catheter at the entrance of the adductor canal<br>* Ultrasound probe is placed at the entrance of the adductor canal in short axis ，insertion of a PAJUNK Contiplex S catheter with the tip of the catheter located at the entrance of the canal<br>| | Experimental: middle point placement of adductor canal catheter<br> | Procedure: ultrasound-guided long-axis placement of catheter at the middle of the adductor canal<br>* Ultrasound probe is placed at the middle of the adductor canal in long axis with the caphelad end of the probe aligned with the entrance of the canal. insertion of a PAJUNK Contiplex S catheter with the tip of the catheter located at the middle of the canal<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | cumulative sulfentanil consumption at 24 hours after surgery | | 24 hours after surgery | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | the strength of quadriceps femoris | Quadriceps strength was assessed on a 0-5 scale as per the Medical Research Council Scale quadriceps motor strength(0 = no voluntary contraction possible, 1 = muscle flicker, but no movement of limb, 2 = active movement only with gravity eliminated, 3 = movement against gravity but without resistance, 4 = movement possible against some resistance and 5 = normal motor strength against resistance) | 0,2,4,8,24,48 hours postoperatively | | The pain scores at rest determined by the numeric rating scale (NRS, 0-10) | 11-point numerical rating scale (NRS; 0, no pain; 10, maximum pain imaginable). | at 0,2,4,8,24,48 hours postoperatively | | The pain scores on adduction of the keen determined by the numeric rating scale (NRS, 0-10) | 11-point numerical rating scale (NRS; 0, no pain; 10, maximum pain imaginable). | at 0,2,4,8,24,48 hours postoperatively | | incidence of postoperative nausea and vomiting (PONV) | | within 48 hours after surgery | | Patient satisfaction with anesthesia | Patient satisfaction with anesthesia was assessed using a 5-point scale (5, very satisfied; 4, satisfied; 3, neither satisfied nor dissatisfied; 2, dissatisfied; 1, very dissatisfied) | within 5th day after surgery | | complications | Record complications including catheter dislodgment, puncture point infection, leakage,falling down,et al. | within 3days after surgery | | cumulative sulfentanil consumption at other time points after surgery | | 2,4,8,48 hours postoperatively | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- adductor canal block

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A Study Assessing 13-valent Pneumococcal Conjugate Vaccine in Healthy Chinese Subjects Study Overview ================= Brief Summary ----------------- This study will assess the safety and tolerability of a single dose of 13-valent Pneumococcal Conjugate Vaccine for approximately 1 month after vaccination sequentially in healthy Chinese adults aged 18 through 55 years, followed by children aged 3 through 5 years, and then infants aged approximately 2 months. Official Title ----------------- A Phase 1 Open-label Study to Assess the Safety and Tolerability of a Single Dose of 13-valent Pneumococcal Conjugate Vaccine in Healthy Chinese Adults, Children and Infants Conditions ----------------- Pneumococcal Infection Intervention / Treatment ----------------- * Biological: 13-valent Pneumococcal Conjugate Vaccine * Biological: 13-valent Pneumococcal Conjugate Vaccine * Biological: 13-valent Pneumococcal Conjugate Vaccine Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Age at the time of enrollment is: 18 through 55 years (before the fifty sixth birthday) for Group 1. 3 through 5 years (before the sixth birthday) for Group 2. 42 to 98 days for Group 3. Healthy subject as determined by medical history, physical examination, and judgment of the investigator. Exclusion Criteria: Previous vaccination with licensed or investigational pneumococcal vaccine. Previous anaphylactic reaction to any vaccine or vaccine-related component. Contraindication to vaccination with pneumococcal vaccine. Ages Eligible for Study ----------------- Minimum Age: 42 Days Maximum Age: 55 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Basic Science Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Group 1<br>Adults aged 18 through 55 years (before the fifty sixth birthday) | Biological: 13-valent Pneumococcal Conjugate Vaccine<br>* suspension in prefilled syringe for intramuscular injection, 0.5 mL, only one dose<br>| | Experimental: Group 2<br>Children aged 3 through 5 years (before the sixth birthday) | Biological: 13-valent Pneumococcal Conjugate Vaccine<br>* suspension in prefilled syringe for intramuscular injection, 0.5 mL, only one dose<br>| | Experimental: Group 3<br>Infants aged approximately 2 months (42 to 98 days) | Biological: 13-valent Pneumococcal Conjugate Vaccine<br>* suspension in prefilled syringe for intramuscular injection, 0.5 mL, only one dose<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Number of participants reporting Adverse Events | | Baseline to Month 1 | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- 13vPnC, Healthy subjects, China

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Therapeutic Drug Monitoring of Ixekizumab in Psoriasis Patients Study Overview ================= Brief Summary ----------------- Biologics, such as ixekizumab, are currently the most effective treatment option for patients with moderate-to-severe psoriasis. But they are costly for health care systems and prescribed according to a 'one dose fits all' dosing regimen, leading to potential over- and undertreatment. Within this study the investigators aim to investigate the predictive value of early serum trough levels of ixekizumab and determine the therapeutic window of ixekizumab in psoriasis patients. Detailed Description ----------------- Patients will be included after siging informed consent. After inclusion, patients will continue on standard dosing schedule of ixekizumab (i.e. one loading dose of 2 subcutaneous injections (160 mg) at week 0, followed by one subcutaneous injection (80 mg) every 2 weeks for 12 weeks, and then one subcutaneous injections (80 mg) every 4 weeks). During each study visit, blood will be taken in order to quantify Ctroughs and/or anti-drug antibodies towards ixekizumab. In addition, the Psoriasis Severity and Area Index (PASI) and the Investigator's Global Assessment (IGA) score will be evaluated by a physician. Patients complete the Dermatology Life Quality Index (DLQI) and European quality of life EQ-5D instrument at each visit. Official Title ----------------- Evaluation of the Predictive Value of Early Serum Trough Concentrations and Anti-drug Antibodies of Ixekizumab and the Development of Concentration-response Curve of Ixekizumab for Psoriasis Patients Conditions ----------------- Psoriasis Vulgaris Intervention / Treatment ----------------- * Procedure: Venapuncture * Other: Patient questionnaires Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Participants must have a clinical or histological diagnosis of chronic plaque-type psoriasis Participants must sign an ICF indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study Exclusion Criteria: Participants who have currently a predominant nonplaque form of psoriasis Participants who are pregnant, nursing or planning a pregnancy Participants who are unable or unwilling to undergo multiple venapunctures Participants who are treated according to a different dosing schedule than standard dosing of ixekizumab Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Intervention Model: Single Group Assignment Interventional Model Description: A prospective, open label, non-randomized study Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Other: Standard of care - ixekizumab<br>Patient will continue to receive ixekizumab according to standard of care dosing regimen, i.e. loading dose first (160 mg) at week 0; 80 mg every 2 weeks until week 12, then 80 mg every 4 weeks | Procedure: Venapuncture<br>* Blood samples will be collected to determine the serum trough levels and anti-drug antibodies of ixekizumab<br>Other: Patient questionnaires<br>* The study participant will complete the Dermatology Quality of Life Index (DLQI) and EQ5D5L questionnaires at each study visit.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Predictive value of early serum trough concentrations of ixekizumab | Prediction of the clinical response (PASI) at week 12 and/or week 24 based on serum trough concentrations measurements taken from week 0, 1, 2, 3 and/or 4. | Week 0 until week 24 of treatment | | Predictive value of early anti-drug antibodies of ixekizumab | Prediction of the clinical response (PASI) at week 12 and/or week 24 based on anti-drug antibodies measurements taken from week 0, 1, 2, 3 and/or 4. | Week 0 until week 24 of treatment | | The development of a therapeutic window of ixekizumab in psoriasis | Defining a therapeutic window for ixekizumab based on serum trough levels corresponding with adequate clinical response. | Week 0 until week 52 of treatment | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | DLQI | The DLQI (Dermatology Life Quality Index) (range 0-30) is a dermatology specific quality of life (QoL) instrument designed to assess the impact of the disease on participant's QoL. It is a ten item questionnaire that, in addition to evaluated overall QoL, can be used to assess six different aspects that may affect QoL: 1) symptoms and feelings, 2) daily activities, 3) leasure, 4) work or school performances, 5) personal relationships, and 6) treatment. The scoring of each question is as follows: Very much - scored 3; A lot - scored 2; A little - scored 1; Not at all - scored 0; Not relevant - scored 0; Question 7, 'prevented work or studying' - scored 3. The DLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. | Week 0 until week 52 of treatment | | EQ5D5L | The 5-level EQ-5D version (EQ-5D-5L) was introduced by the EuroQol Group in 2009 to improve the instrument's sensitivity and to reduce ceiling effects. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems (level 1), slight problems (level 2), moderate problems (level 3), severe problems (level 4) and extreme problems (level 5). The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state, which is the outcome result. There is no minimum or maximum score since the the 5 digit-number is a non-numeric variable. | Week 0 until week 52 of treatment | | EQ VAS | The EQ VAS (Visual Analogue Scale) (range 0-10) records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS can be used as a quantitative measure of health outcome that reflect the patient's own judgement. Minimum score is 0%, max. score is 100%. Lower values mean 'worse health the patient can imagine', higher values mean 'better health the patient can imagine'. | Week 0 until week 52 of treatment | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Psoriasis, Therapeutic drug monitoring, Ixekizumab

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The Effect of Cognitive Function as Measured by Repeated Cognitive Measures After 12 Weeks Treatment With Donepezil Study Overview ================= Brief Summary ----------------- The purpose of this study is to determine if there is improvement or measurable change in cognition after only one month of treatment with donepezil when using a computerized test battery. The results at one month will be compared with the results at 3 months to evaluate this. Official Title ----------------- A Randomised, Double-blind, Placebo-controlled, Parallel Design, Multicentre Study in Patients With Mild to Moderate Alzheimer's Disease to Investigate the Effect on Cognitive Function as Measured by Repeated CogState Testing in Relation to Effects on Traditional Cognitive Measures After 12 Weeks Conditions ----------------- Alzheimer's Disease Intervention / Treatment ----------------- * Drug: Donepezil * Drug: Donepezil * Drug: Placebo to match Aricept Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Clinical diagnosis of probable AD according to NINCDS-ADRDA criteria. The patient should live with an appropriate caregiver at home, or in a community dwelling. A caregiver should be capable of accompanying the patient to clinic visits or attending study visits in the patient's home. Patient and caregiver should understand, speak, and read local language. Exclusion Criteria: Significant neurological disease or dementia other than AD, e.g., mixed dementia, frontotemporal dementia, and Parkinson's Disease. Females of child bearing potential Impaired vision or hearing Ages Eligible for Study ----------------- Minimum Age: 55 Years Maximum Age: 85 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Basic Science Allocation: Randomized Intervention Model: Parallel Assignment Masking: Triple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: 1<br>5 mg Donepezil (first 14 days), 10 mg Donepezil (next 70 days) | Drug: Donepezil<br>* 5 mg capsule, orally, once daily, first 14 days of treatment<br>* Other names: Aricept;Drug: Donepezil<br>* 10 mg, orally, once daily, for remaining 70 days of treatment<br>* Other names: Aricept;| | Placebo Comparator: 2<br> | Drug: Placebo to match Aricept<br>* Placebo capsule, orally, 84 days of treatment<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | CogState Computerized Neurological Test Battery | | Tl. of 25 times: 10 times between Days 3-14, 5 times between Days 36-42, 5 times between Days 64-70, four times between Days 92-97, 1 time on Day 98 | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Neuropsychological Test Battery (NTB) | | Tl. of 5 times: Once between Days 1-2, Once anytime between Days 3-14, Once anytime between Days 36-42, Once anytime between Days 64-70, Once between Days 92-97 | | Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog) | | Tl. of 5 times: Once between Days 1-2, Once anytime between Days 3-14, Once anytime between Days 36-42, Once anytime between Days 64-70, Once between Days 92-97 | | Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) | | Tl. of 4 times: Once anytime between Days 3-14, Once anytime between Days 36-42, Once anytime between Days 64-70, Once between Days 92-97 | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Patients with Mild to Moderate Alzheimer's Disease

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Interactive Gentle Yoga in Improving Quality of Life in Patients With Stage I-III Breast Cancer Undergoing Radiation Therapy Study Overview ================= Brief Summary ----------------- This pilot clinical trial studies interactive gentle yoga in improving quality of life in patients with stage I-III breast cancer undergoing radiation therapy. Interactive gentle yoga may improve the quality of life in patients with breast cancer undergoing radiation therapy. Detailed Description ----------------- PRIMARY OBJECTIVES: I. To determine the feasibility of implementing a 6-week biweekly yoga intervention delivered by multi-point videoconferencing in breast cancer patients undergoing radiation therapy. SECONDARY OBJECTIVES: I. To obtain preliminary data on changes in depression, anxiety, fatigue, sleep quality pre- and post-intervention in women with breast cancer undergoing radiation therapy. II. To obtain preliminary data on acute effects of the yoga classes on fatigue and distress. OUTLINE: Participants undergo 12 sessions of cancer-adapted integral yoga classes using an internet-based videoconferencing platform. Integral yoga includes postures, deep relaxation, breathing practices and meditation to create a profound experience of peace and well-being. Participants take part in study classes from home (or other location that is convenient for the participant and that allows them to access the internet-based classes) with two-way interaction with group instructors and members alike over 75 minutes twice weekly for 6 weeks during radiation therapy. Participants are encouraged to complete additional yoga practice sessions outside of the twice weekly study sessions. After completion of study, participants are followed up at 1 week. Official Title ----------------- Convenient and Live Movement (CALM): Feasibility of Interactive Gentle Yoga for Women With Breast Cancer Conditions ----------------- Depression, Anxiety Disorder, Ductal Breast Carcinoma in Situ, Fatigue, Stage IA Breast Cancer, Stage IB Breast Cancer, Stage II Breast Cancer, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer Intervention / Treatment ----------------- * Procedure: yoga therapy * Other: internet-based intervention * Other: questionnaire administration Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Participants must be newly diagnosed with a histologically or cytologically confirmed breast cancer stage I-III (ductal carcinoma in situ [DCIS] is allowed) Participants must have a score >= 8 on the depression subscale of the Hospital Anxiety and Depression Scale [HADS], indicating clinically significant depressive symptoms Participants must be: >= 2 weeks post-surgery for women who have had a lumpectomy, a lumpectomy with an axillary node dissection or a mastectomy without reconstruction OR >= 4 weeks post-surgery for women who have had mastectomy with reconstruction Participants must be scheduled to begin the standard 6-week course of radiation therapy (RT) within 4 weeks Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 For the duration of RT, participants must have access to an existing broadband internet connection and a computer (laptop or desktop; tablets are not sufficient) with a full-sized computer screen and the following specifications: Windows® 8, RT, 7 Vista, XP or 2003 Server or Mac operating system (OS)® X 10.6 (Snow Leopard®) or newer Internet Explorer ® 7.0 or newer, Firefox® 4.0 or newer, Safari 3.0 or newer or Chrome or newer (available for free download) Participants must be able to understand written/spoken English since the yoga classes will be taught in English Ability to understand and the willingness to sign an institutional review board (IRB)-approved written informed consent document Exclusion Criteria: Participants who have practiced yoga regularly (defined as at least once per week on average) in the past 3 months Participants who have regularly (defined as 4 or more days per week) engaged in vigorous physical activity (i.e., causes heavy breathing, sweating, rapid fatigue; can be sustained for short periods, like running or swimming strongly) over the past 4 weeks Participants who are being treated with a shortened course of radiation therapy (i.e. Canadian fractionation less than 5 weeks, partial breast radiation therapy) Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- Female Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Supportive Care Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Supportive care (internet-based integral yoga intervention)<br>Participants undergo 12 sessions of cancer-adapted integral yoga classes using an internet-based videoconferencing platform. Integral yoga includes postures, deep relaxation, breathing practices and meditation to create a profound experience of peace and well-being. Participants take part in study classes from home (or other location that is convenient for the participant and that allows them to access the internet-based classes) with two-way interaction with group instructors and members alike over 75 minutes twice weekly for 6 weeks during radiation therapy. Participants are encouraged to complete additional yoga practice sessions outside of the twice weekly study sessions. | Procedure: yoga therapy<br>* Undergo integral yoga intervention with videoconferencing<br>* Other names: yoga;Other: internet-based intervention<br>* Undergo integral yoga intervention with videoconferencing<br>Other: questionnaire administration<br>* Ancillary studies<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Recruitment rates, calculated as the number of women enrolled divided by the number of women who screened eligible for the study | | Up to week 7 | | Retention rates, calculated as the proportion of enrolled women who complete all study measures at each time point | | Up to week 7 | | Adherence, measured by the total number of yoga classes attended by each participant | | Up to week 7 | | Participants' acceptability of the intervention, including ratings of ease/difficulty of use of the videoconferencing and participating in group classes from home using the device | The proportions and 95% confidence intervals will be calculated. Descriptive statistics will be computed. | Up to week 7 | | Feedback regarding the participants' experience in the study | Qualitative analysis of open-ended feedback on strengths and weaknesses of the yoga intervention and teacher, use of the multi-point videoconferencing device will be performed. | Up to week 7 | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in depression as measured by HADS | Computed using a mixed model analysis to account for the repeated measures on each subject. | Baseline up to 7 weeks | | Change in anxiety as measured by HADS | Computed using a mixed model analysis to account for the repeated measures on each subject. | Baseline up to 7 weeks | | Change in fatigue as measured by visual analogue scale and Functional Assessment of Cancer Therapy-Fatigue | Computed using a mixed model analysis to account for the repeated measures on each subject. Assessed by calculating the difference in the post and pre scores for each session, and then examining whether there is a time effect using a mixed model. | Baseline up to 7 weeks | | Change in sleep quality as measured by Pittsburgh Sleep Quality Inventory | Computed using a mixed model analysis to account for the repeated measures on each subject. | Baseline up to 7 weeks |

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Comparison of Two Silicone Hydrogel Toric Contact Lenses Study Overview ================= Brief Summary ----------------- The purpose of this research study is to compare the performance of two different types of Alcon soft toric study contact lenses to obtain information on study lens orientation. Official Title ----------------- Axis Orientation Comparison of Two Silicone Hydrogel Toric Contact Lenses Conditions ----------------- Astigmatism Intervention / Treatment ----------------- * Device: Lotrafilcon B toric contact lenses with HYDRAGLYDE * Device: Lotrafilcon B toric contact lenses Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Successful wear of soft contact lenses for vision correction in both eyes during the past 3 months for a minimum of 3 days per week and 8 hours per day Astigmatism Requires contact lenses Best corrected visual acuity of 20/25 or better in each eye Other protocol-specified inclusion criteria may apply Exclusion Criteria: Any eye condition that contraindicates contact lens wear, as determined by the Investigator Any eye surgery that contraindicates contact lens wear, as determined by the Investigator Other protocol-specified exclusion criteria may apply Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Other Allocation: Randomized Intervention Model: Crossover Assignment Masking: Double Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Other: AOHG toric, then AO toric<br>Lotrafilcon B toric contact lenses with HYDRAGLYDE, followed by lotrafilcon B toric contact lenses, as randomized. Each product worn in both eyes for approximately 30 minutes, with a 30-45 minute washout between the removal of Pair 1 and insertion of Pair 2. | Device: Lotrafilcon B toric contact lenses with HYDRAGLYDE<br>* Silicone hydrogel soft contact lenses for astigmatism<br>* Other names: AOHG for Astigmatism;Device: Lotrafilcon B toric contact lenses<br>* Silicone hydrogel soft contact lenses for astigmatism<br>* Other names: AO for Astigmatism;| | Other: AO toric, then AOHG toric<br>Lotrafilcon B toric contact lenses, followed by lotrafilcon B toric contact lenses with HYDRAGLYDE, as randomized. Each product worn in both eyes for approximately 30 minutes, with a 30-45 minute washout between the removal of Pair 1 and insertion of Pair 2. | Device: Lotrafilcon B toric contact lenses with HYDRAGLYDE<br>* Silicone hydrogel soft contact lenses for astigmatism<br>* Other names: AOHG for Astigmatism;Device: Lotrafilcon B toric contact lenses<br>* Silicone hydrogel soft contact lenses for astigmatism<br>* Other names: AO for Astigmatism;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Percentage of Lenses With Axis Orientation Within ±30 Degrees From the 90 Degree Axis (Ideal Location) | Each lens was classified based on whether the absolute difference between the axis location and 90° was less than or equal to 30° (ie, lens axis located between the 60° and 120° axis inclusive). Inferential testing was not planned for this primary effectiveness endpoint. | Day 1, 10 minutes after lens insertion, each product | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Astigmatism, Axis orientation

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Identification of Biomarkers for Obstructive Sleep Apnoea Syndrome Study Overview ================= Brief Summary ----------------- Untreated Obstructive Sleep Apnea Syndrome (OSAS) has long-term complications, namely metabolic imbalances (obesity, dislipidemia, type 2 diabetes mellitus). Until now, no molecular markers for this physiopathological connection have been identified. This project aims to determine non-invasive biomarkers that may allow better comprehension of the metabolic consequences of OSAS, as well as assess the effect of Continuous positive airway pressure (CPAP) on these metabolic parameters. This project will integrate the clinical, metabolic, genetic/proteomic and biologic systems to further explore the mechanisms behind OSAS, as well as the effect of the treatment with CPAP. Official Title ----------------- Obstructive Sleep Apnoea and Associated Metabolic/Cardiovascular Disorders: Understanding Mechanisms Towards Early Diagnosis and Prognosis Conditions ----------------- Obstructive Sleep Apnoea Syndrome Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Male 25-60 years Mild/Moderate/Severe OSAS Exclusion Criteria: Female Other sleep disorders Previous CPAP therapy Type 1 diabetes mellitus Familiar Dyslipidemia Severe organ pathology Acute disease Ages Eligible for Study ----------------- Minimum Age: 25 Years Maximum Age: 60 Years Sexes Eligible for Study ----------------- Male Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | CPAP<br>Patients with moderate/severe OSAS will be treated with CPAP | | | Control<br>Patients with snoring will not be subject to treatment with CPAP | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Percentage of patients with clinical improvement | Treatment efficacy of CPAP will be assessed at the end of treatment through a clinical observation. | 6 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Frequency of occurence of biomarkers | Using Mass Spectrometric Immunoassay, we will identify which biomarkers have a positive association with long-term treatment effect. | 6 months | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- NOVA MEDICAL SCHOOL, CPAP, OSAS, CEDOC (Centro de Estudos de Doenças Crónicas), FCM (Faculdade de Ciências Médicas), UNL (Universidade Nova de Lisboa, FCT (Fundação para a Ciência e Tecnologia)

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Bendamustine and Bortezomib Combination Therapy in Indolent Non-Hodgkin's Lymphoma(NHL) Study Overview ================= Brief Summary ----------------- The purpose of this study is to determine whether the combination of bendamustine and bortezomib in patients with indolent Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia is safe and tolerable. Detailed Description ----------------- Bendamustin and bortezomib have been shown to be effective in the treatment of patients with indolent Non-Hodgkin's Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL). Both compounds appear not to be cross-resistant with prior therapy. Therefore, it is of interest to combine bendamustine and bortezomib in this patient population. Preliminary results from patients with multiple myeloma showed that the combination of bendamustine and bortezomib is efficacious and well tolerated. However, there are so far no data on this combination in patients with NHL or CLL. Official Title ----------------- Weekly Bendamustine and Bortezomib Combination Therapy in Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma or B-CLL: A Single-Center Phase 2 Study Conditions ----------------- Lymphoma, Non-Hodgkin Intervention / Treatment ----------------- * Drug: Bendamustine * Drug: Bortezomib Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Symptomatic recurrent or refractory indolent NHL or B-CLL Adequate organ and bone marrow function Karnofsky greater than 50% Exclusion Criteria: Candidates for autologous stem cell transplantation Secondary high grade lymphoma Concurrent severe medical condition Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Bendamustine and Bortezomib<br>Combination Chemotherapy of Bendamustine and Bortezomib as described in the intervention section | Drug: Bendamustine<br>* starting with 60 mg/m^ 2, IV, dose escalation, weekly d1,8,15 q5w<br>* Other names: Ribomustin, SDX-105;Drug: Bortezomib<br>* weekly 1.5mg/m^2, IV, d1,8,15,22 q5w<br>* Other names: Velcade;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Optimal Bendamustine Dosage for Further Studies | | Three weeks after treatment termination | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Lymphoma, Non-Hodgkin, Low-Grade

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Preoperative Lymph Node Staging With EBUS-TBNA in Clinical N0 Non Small-cell Lung Cancer Study Overview ================= Brief Summary ----------------- The introduction of modern staging systems has increased the detection of small peripheral lung cancers at an early stage [1]. Stage I non-small-cell lung cancers (NSCLCs) are confined to the lung without lymph node involvement, and surgical resection is currently considered the standard therapeutic approach. Nodal staging is initially performed non-invasively with computer tomography (CT) and positron emission tomography (PET) scans followed by minimally invasive staging with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) when CT and/or PET are suggestive of mediastinal nodal involvement. Lobectomy with radical lymphadenectomy is currently considered the treatment of choice for early-stage lung cancer. Several studies demonstrated that primary invasive non- small-cell lung carcinomas > 2.0 cm were twice as likely to have nodal metastases as carcinomas ≤ 2.0 cm, emphasizing that small lung cancers had less lymph node involvement and confirming a better survival. In our pilot study [18] published in 2011 in the European Journal of Thoracic Surgery, no nodal involvement was observed in any of the 62 patients with pulmonary nodule size less than 10 mm, in 20 out of 120 patients (17%) with nodule size 11-20 mm, and in 9 out of 37 tumors (24%) 21-30 mm in size (p = 0.0007). These patients could be spared radical lymph node dissection if deemed not essential, thereby reducing operative risks, postoperative morbidity, and surgery time. A preoperative diagnostic determination to establish the size and correct staging of the tumor is mandatory for appropriate selection of candidates, avoiding unnecessary surgery. Detailed Description ----------------- BACKGROUND AND RATIONALE The introduction of modern staging systems such as computed tomography (CT) and positron emission tomography/CT (PET/CT) with fluorodeoxyglucose (FDG) has increased the detection of small peripheral lung cancers at an early stage [1]. Stage I non-small-cell lung cancers (NSCLCs) are confined to the lung without lymph node involvement, and surgical resection is currently considered the standard therapeutic approach. Lobectomy with radical lymphadenectomy is currently considered the treatment of choice for early-stage lung cancer, irrespective of tumor size or its metabolic features on PET. However, the new TNM classification recently demonstrated that very small lung cancers may be less aggressive than others [2], suggesting a less aggressive surgical approach to reduce morbidity. According to the new TNM classification (8th edition), the overall 5-year survival rate for pathological stage IA NSCLC was 85%, ranging from 80% to 90% for T1a and T1c tumors respectively, compared with 64% for stage IB tumors [2]. Among patients with stage I cancer, tumor size may affect outcome and drive survival, as confirmed by different studies [7-12]. Several studies demonstrated that primary invasive non- small-cell lung carcinomas > 2.0 cm were twice as likely to have nodal metastases as carcinomas ≤ 2.0 cm, emphasizing that small lung cancers had less lymph node involvement, and confirming a better survival [11-15]. Based on that, Ishida et al. and then Konaka et al. have already demonstrated the absence of lymph node involvement in sub-centimeter lung cancers and the feasibility to omit lymph node dissection in those cases [15,16]. However, Zhoua et al. recommended systematic nodal dissection in the presence of sub-centimeter disease, finding nodal metastases in 15% of NSCLC < 1 cm, but also including higher tumor stages such as stage II and III in their study without performing PET scan as part of the preoperative staging [17]. In our pilot study [18] published in 2011 in the European Journal of Thoracic Surgery, no nodal involvement was observed in any of the 62 patients with pulmonary nodule size less than 10 mm, in 20 out of 120 patients (17%) with nodule size 11-20 mm, and in 9 out of 37 tumors (24%) 21-30 mm in size (p = 0.0007). All 55 patients with nodule SUV < 2.0 and all 26 non-solid lesions were pN0 (respectively, p = 0.0001 and p = 0.03). So we adopted cut-offs of 10 mm for nodule diameter and 2.0 as peak SUV to distinguish patients with nodal involvement from those without. These patients could be spared radical lymph node dissection if deemed not essential, thereby reducing operative risks, postoperative morbidity, and surgery time. A preoperative diagnostic determination to establish the size and correct staging of the tumor is mandatory for appropriate selection of candidates, avoiding unnecessary surgery. Data have demonstrated that positron emission tomography (PET-FDG) is a reliable tool versus CT in evaluating both solitary pulmonary nodules and lymph node involvement [3]. Standard nodal staging is initially performed non-invasively with PET followed by minimally invasive staging with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) when PET is suggestive of mediastinal nodal involvement. In fact, EBUS-TBNA is a minimally invasive procedure with a high yield for lymph node staging of lung cancer [4]. EBUS-TBNA allows access to the paratracheal lymph node stations (levels 2R, 2L, 4R, 4L), the subcarinal lymph node (level 7), hilar, interlobar, and lobar lymph nodes (levels 10, 11, and 12). Previous studies, including systematic reviews and meta-analyses, and more recently Yasufuku et al. have demonstrated a major impact of EBUS-TBNA on management of patients with non-small cell lung cancer (NSCLC), with a diagnostic yield comparable to mediastinoscopy [5,6]. Annema et al. have recently confirmed that the sensitivity of endosonography is similar to that of mediastinoscopy (85% vs 79%, respectively), and associated with a lower complication rate (1% vs 6% for mediastinoscopy), so concluding that endosonography should be the first step for mediastinal nodal staging [19]. In patients without evidence of mediastinal nodal metastasis on PET and CT, the need for EBUS-TBNA becomes less clear. The most recent American College of Chest Physicians (ACCP) evidence-based guidelines recommend minimally invasive mediastinal staging with a needle technique in patients with a central tumor or nodal hilar disease (N1) on PET/CT. This is based on the increased prevalence of N2 disease in this group, but this is a grade 1C recommendation, that is based on low quality evidence. In patients with peripheral tumors and no evidence of mediastinal or hilar nodal disease on PET/CT, invasive staging is not recommended. Concerns have been raised regarding these recommendations given that the prevalence of occult nodal metastasis in patients with N0 disease by PET/CT appears to be higher than previously reported, with recent studies showing values as high as 17-22% [20,21]. EBUS-TBNA may provide an attractive option to increase staging accuracy. However, sensitivity of EBUS-TBNA in patients with clinical N0/N1 disease on PET/CT is unclear and largely based on retrospective studies [22,23]. The only prospective study published by Leong et al. [24] demonstrated that a significant proportion of patients with N0/N1 disease by PET/CT had N2 disease (20%) and EBUS-TBNA was able to identify a substantial fraction of these patients, thus improving diagnostic accuracy compared with PET/CT alone. Sensitivity of EBUS-TBNA however appears lower compared with historical data from patients with larger volume mediastinal disease [5,6,26]. TRIAL OBJECTIVES Hypotheses: In selected series the overall sensitivity of EBUS varies from 80-90% (88%) but for clinical N0/N1 drops to 40-49%. About 24% of patients with early stage lung cancer > 2 cm and less than 5 cm (T1b,c and T2a,b N0 PET-) would be N+ , whereas none of the T1a (less or equal than 1 cm) NSCLC would be upstaged considering the absence of N+ [19]. From reference 19 pT size ALL pN+ <10 mm 62 0 ( 0%) 11-20 mm 120 20 (17%) >20 mm 37 9 (24%) 7. OVERALL DESIGN AND PLAN OF TRIAL 7.1 Design of the study All patients clinical stage I and II will be undergone EBUS-TBNA for the staging of hilar and mediastinal lymph nodes. All patients will be undergoing robotic (RATS) or videothoracoscopic (VATS) lobectomy plus radical lymph node dissection following the Society of Thoracic Surgery (STS) guideline. All lymph nodes previously sampled with EBUS-TBNA will be compared with those harvested during surgery. Statistical analysis Observed (Surgery) pN- pN+ Predicted EBUS Negative TN FN UPSTAGING = (FN+TP)/total patients Positive FP TP SENSITIVITY is defined as the ration of TP/ (TP+FN) A sample size of 12 upstaged patients will achieve 80% power to detect a difference of sensitivity >38.4% assuming that the sensitivity under the null hypothesis is 49% (results of the meta-analysis by Leong et al, 2018 [22]), and that the actual sensitivity is >88% (95.6% in the study by Guarize et al, 2018 [25]) using a two-sided binomial test. N° Upstaging EBUS Upstaging Surgery Sensitivity Leong 2017 Meta-analysis 15% (6- 24%) n/a 49% Naur 2017 167 6% (10/167) 10%(12/115) 43% (10/21) Ong 2015 220 8% (18/220) 27%(27/100) 36.7% * Shingyoji 2014 113 6% (7/113)** 17.6% (20/113) 35% (7/20) Vial 2018 75 8% (6/75) 20% (15/75) 40% (6/15) Assuming that the proportion of patients with pathological pN+ (upstaging) is 24%, a total sample of 50 patients will be necessary to be enrolled in the study. This hypothesis will be rejected if 2 or more FN are observed among the 12 upstaged patients. ETHICAL CONSIDERATIONS Patient protection The responsible investigator will ensure that this study is conducted in agreement with the Declaration of Helsinki. The protocol will be approved by the Local Ethics Committee. Subject identification A sequential identification number will be automatically attributed to each subject/patient registered in the trial. This number will identify the subject/patient and must be included on all case report forms. Informed consent The investigator must provide to each subject/patient both oral and written information about the Trial and must ensure that the subject is fully informed about the aims of the trial, procedures, potential risks, any discomforts and expected benefits. The subject/patient must agree that his/her data will be processed and stored in an anonymous form for evaluation of this trial and any later overviews and that his /her data may also be transferred in an anonymous form to third parties. It must be emphasized that participation is voluntary and that the subject has the right to withdraw from the Trial at any time without prejudice. A physician must obtain the subject's voluntary, personally signed (and dated) Informed Consent prior to any Trial - related procedure. DATA SUBMISSION We will conduct the trial according to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) guidelines. Case report forms Data will be collected as for trial specific case report forms. Signing and submitting forms All forms should be signed by the Principal Investigator or designee. Data management Data collected in this trial will be sent to the Data Management Office of the European Institute of Oncology. The Data Management Center will process the data and will generate queries and forms requests. The statistician will perform the data analysis. Authorization log The Principal Investigator (PI) should identify the other members of the Clinical Trial Team who are supervised by the PI and approved to provide information in case report form (CRF), queries, etc. Subject/Patient identification log As per GCP, subjects/patients have the right to confidentiality. Therefore, no subject'/patients' names should be used in CRFs or any other documentation transmitted to the data management. Item that are used to identify a subject/patient include initials of subjects/patient's name, date of birth, registration number. ADMINISTRATION RESPONSABILITIES The Chairmen of the study will be responsible for writing the protocol, reviewing all case report forms and documenting their review on evaluation forms, the contents of the reports, and for publishing the study results. They will also generally be responsible for answering all clinical questions concerning eligibility, treatment and the evaluation of the subjects/patients. PROPERTY OF DATA AND PUBLICATION POLICY Property of data is of European Institute of Oncology. The main results of the clinical trial will be published in a peer-reviewed scientific journal. The final publication will be written by the Study Chairman or by one or more co-investigators of the study. All publications, abstracts or presentations including data related to the present trial will be submitted for review to the Chair of the study prior to submission. Trials results will not be released before data maturity has been reached for the primary endpoint of the trial. Official Title ----------------- Preoperative Lymph Node Staging by EBUS-TBNA in Clinical N0 Non Small-cell Lung Cancer Conditions ----------------- Non Small Cell Lung Cancer Intervention / Treatment ----------------- * Procedure: Endobronchial ultrasound transbronchial needle aspiration lymph node staging Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Suspected or proven non-small cell lung cancer (NSCLC) clinical stage I and II (diameter > 1 cm and less than 5 cm, no pleura invasion) clinical N0M0 (8th TNM) All patients have to be staged by total body CT scan and PET-FDG Negative preoperative staging at hilar and mediastinal level at CT and CT/PET (PET negative and lymph node short axis < 1 cm at CT scan) Age between 18 and 75 years old Exclusion Criteria: NSCLC smaller or equal than 1 cm Unfit for bronchoscopy or surgical resection Evidence of locally advanced or metastatic disease Prior chemotherapy or radiotherapy for this malignancy Other malignancy within the past 5 years except for not melanoma skin cancer, superficial bladder cancer or carcinoma in situ of the cervix Previous surgical treatment for lung cancer Multiple lung tumors Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 75 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Diagnostic Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: EBUS-TBNA procedure<br>Single arm protocol. Invasive mediastinal staging with EBUS-TBNA in clinical N0 NSCLC patients candidate to surgical resection with systematic lymphadenectomy. | Procedure: Endobronchial ultrasound transbronchial needle aspiration lymph node staging<br>* EBUS-TBNA in clinical N0 NSCLC patients<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Assessment of the sensitivity of EBUS-TBNA in lymph node staging for early stage lung cancer | A sample size of 12 upstaged patients will achieve 80% power to detect a difference of sensitivity >38.4% assuming that the sensitivity under the null hypothesis is 49% (results of the meta-analysis by Leong et al, 2018 [22]), and that the actual sensitivity is >88% (95.6% in the study by Guarize et al, 2018 [25]) using a two-sided binomial test. | 17 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Assessment of concordance between EBUS-TBNA and surgery | Evaluation of diagnostic accuracy of both procedure in predicting the presence of lymph node metastasis | 17 months | | Assessment of lymph node upstaging by EBUS and surgery | Predictive false negative and pathological upstaging for both procedures | 17 months | | Assessment of the complication rates | Evaluation of the incidence of any type of complication in EBUS-TBNA procedures | 17 months | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- EBUS-TBNA, NSCLC, Interventional bronchoscopy, Lung cancer

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Microendoscopic Discectomy Vs Transforaminal Endoscopic Lumbar Discectomy Vs Open Discectomy Study Overview ================= Brief Summary ----------------- In our study, a multicenter randomized controlled，single blind trial will be performed to evaluate the effectiveness and safety of these three procedures for the treatment of symptomatic lumbar disc herniation. Detailed Description ----------------- Lumbar disc herniation (LDH) is one of the most common diseases in the department of orthopedics, which produced medical and economic burdens to families and society. In spite, the majority of the patients with disc herniation can be relieved or even cured via conservative treatment; there are still a considerable number of invalid patients who eventually still need to be undergoing a surgical operation treatment. Three main methods for intervertebral disc surgery are adopted in our routine work. One procedure is Open Discectomy (OD), which has been always a gold standard for treatment of LDH. And the other two procedures are Microendoscopic Discectomy (MED) and Transforaminal Endoscopic Lumbar Discectomy (TELD) respectively. MED and TELD have been developed as alternatives to OD. OD can compress the nerve root or spinal cord through removal of the protrusion. However, it destroys the rear structure of spine, causing segmental instability and long-term distress. Compared with OD, MED and TELD procedures are smaller incisions or less dissection (or both), lower blood loss, less postoperative pain, shorter hospitalisation and earlier return to work. However, the steep learning curves of MID inhibit the development of surgery specialists; for example, optimal surgical management requires many years of experience. These deficiencies need more educational effort at a higher priority than accorded so far. There are inconsistent outcomes about the efficacy and safety in the previous studies; all of the recent researches do not yield conclusive results. Official Title ----------------- Microendoscopic Discectomy Vs Transforaminal Endoscopic Lumbar Discectomy Vs Open Discectomy for the Treatment of Lumbar Disc Herniation Conditions ----------------- Lumbar Disc Herniation Intervention / Treatment ----------------- * Procedure: open discectomy * Procedure: microendoscopic discectomy * Procedure: transforaminal endoscopic lumbar discectomy Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: All forms of disc herniation were included in the study History of concordant radicular leg pain refractory to conservative treatment for longer than 6 months Leg pain must be greater than back pain Exclusion Criteria: cauda equine syndrome, progressive neurologic deficit, bilateral lower extremity symptoms, low back pain more than leg pain Systemic infection or localized infection at the anticipated entry needle site combined with lumbar infection, fracture of lumbar vertebra, tumor, Ⅱ°and above spondylolisthesis, lumbar spinal stenosis, lumbar scoliosis is larger than 15 degree with severe heart, brain, lungs, and other organs disease or mental illness History of opioid abuse or patients currently on long acting opioid History of the operation on lumbar Pregnancy Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 75 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Single Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: open discectomy<br>patients diagnosed as lumbar disc herniation undergoing open simple discectomy(OD) | Procedure: microendoscopic discectomy<br>* Microendoscopic discectomy combines standard lumbar microsurgical techniques with endoscope, enabling surgeons to successfully address free-fragment disc pathologic factors and lateral recess stenosis.<br>Procedure: transforaminal endoscopic lumbar discectomy<br>* transforaminal endoscopic lumbar discectomy removes the intervertebral disc portion through the intervertebral foramen<br>| | Active Comparator: microendoscopic discectomy<br>patients diagnosed as lumbar disc herniation undergoing microendoscopic discectomy(MED) | Procedure: open discectomy<br>* The open discectomy, will be performed under general anesthesia in the prone position with horizontal. The level of the spine indicated for surgical treatment will be identified with the aid of fluoroscopy. An incision is made about the dorsal disc level involved with dissection of the paravertebral muscles on the side of disc herniation. After laminectomy and resection of part of the yellow ligament, partial discectomy is done under direct vision.<br>Procedure: transforaminal endoscopic lumbar discectomy<br>* transforaminal endoscopic lumbar discectomy removes the intervertebral disc portion through the intervertebral foramen<br>| | Active Comparator: transforaminal endoscopic discectomy<br>patients diagnosed as lumbar disc herniation undergoing transforaminal endoscopic lumbar discectomy(TELD) | Procedure: open discectomy<br>* The open discectomy, will be performed under general anesthesia in the prone position with horizontal. The level of the spine indicated for surgical treatment will be identified with the aid of fluoroscopy. An incision is made about the dorsal disc level involved with dissection of the paravertebral muscles on the side of disc herniation. After laminectomy and resection of part of the yellow ligament, partial discectomy is done under direct vision.<br>Procedure: microendoscopic discectomy<br>* Microendoscopic discectomy combines standard lumbar microsurgical techniques with endoscope, enabling surgeons to successfully address free-fragment disc pathologic factors and lateral recess stenosis.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Oswestry Disability Index(ODI) | Oswestry Disability Index (ODI) -> The Oswestry Disability Index (ODI) is one of the principal condition-specific outcome measures used in the management of spinal disorders. The ODI is the most commonly outcome measures in patients with low back pain. Each of the 10 items is scored from 0 - 5. The maximum score is therefore 50. If the FIRST statement is marked, the section score = 0, If the LAST statement is marked, it = 5. 0 is the best outcome and 50 is the worst The ODI is the most commonly outcome measures in patients with low back pain. Each of the 10 items is scored from 0 - 5. The maximum score is therefore 50. If the FIRST statement is marked, the section score = 0, If the LAST statement is marked, it = 5. 0 is the best outcome and 50 is the worst outcome | up to 104 weeks | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | visual analogue scale(VAS) | Pain Score - Visual Analog Scale (VAS) -> minimum value=0 and maximum value=10, higher values represent a worse outcome and zero is a better outcome | up to 104 weeks | | The generic health survey on the Short Form-36(SF-36) | The scale was used to evaluate the quality of life | up to 104 weeks | | Complications survey | Complications of surgery including mortality and common: thrombosis; surgical site and other infections; recurrent disc herniation; dural tear; nerve root injury | up to 104 weeks |

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Antiresorptive Effect of Treatment With Risedronate and Vitamin D in Postmenopausal Patients Study Overview ================= Brief Summary ----------------- Osteoporosis is defined as a systemic disease of bone mineralization, characterized by a decrease in bone mineral density that causes bone fragility and increases the risk of fractures during menopause. Recently, a high prevalence of hypovitaminosis D has been found worldwide, which could trigger a state of secondary hyperparathyroidism that can worsen the state of postmenopausal patients with osteoporosis. An open-label, clinical trial was conducted in Mexican women with postmenopausal osteopenia-osteoporosis to determine the efficacy of the combined treatment with risedronate and high-dose vitamin D in improving bone mineral density, hyperparathyroidism, and hypovitaminosis D. Detailed Description ----------------- Participants were selected from the climacteric clinic of the regional hospital 1ro de Octubre-Instituto de Seguridad y Servicios Sociales para Los Trabajadores del Estado (ISSSTE), Mexico. All participants voluntarily accepted to be part of the study and provided written informed consent.This study was approved by the institutional ethical committee of the hospital with registration number COFEPRIS 17 CI 09005135 with the internal registration number 118.2021. Every participant was clinically examined. Their metabolic state was assessed by considering height, weight, body mass index (BMI) and the percentage of Hb1Ac. 33 patients were included among 40 to 78 years with the diagnosis of postmenopausal osteoporosis with associated hyperparathyroidism, hypovitaminosis D or both conditions. All the patients were treated for 6 months with 35 mg of risedronate and 2800 IU of vitamin D once a week, with additional daily supplementation of 4000 IU of vitamin D. Statical analysis was performed using PAST 3.0 and GraphPad Prism 8.4.3. software. Some statical parameters, such as arithmetic median (µ), and standard deviation (S.D.) were calculated using Excel-Word. Graphics were constructed with GraphPad Prism 8.4.3 and tables were done in Excel-Word. The assigned α value for this study was <0.05. Official Title ----------------- Risedronate With High-dose Vitamin D Resolves Hyperparathyroidism and Hypovitaminosis D But Not Osteoporosis in Mexican Postmenopausal Patients Conditions ----------------- Postmenopausal Osteoporosis, Hypovitaminosis D, Hyperparathyroidism Intervention / Treatment ----------------- * Drug: Risedronate * Drug: Vitamin D Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Participants with a diagnosis of postmenopausal osteoporosis or osteopenia. Participants with a diagnosis of hyperparathyroidism or hypovitaminosis D. Participants who accepted to participate and that provided informed consent. Exclusion Criteria: Participants with oncological pathologies. Participants with recent fractures. Participants with gastric intolerance or hypersensitivity to the drugs. Participants were under treatment with another antiresorptive or bone-forming drug, or if they were receiving treatment with thiazide diuretics, lithium, teriparatide or glucocorticoids. Participants with Addison's disease, pheochromocytoma or depressive disorders. Ages Eligible for Study ----------------- Minimum Age: 40 Years Maximum Age: 78 Years Sexes Eligible for Study ----------------- Female Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Intervention Model: Single Group Assignment Interventional Model Description: 33 participants between 40 and 78 years old with a diagnosis of postmenopausal osteoporosis or osteopenia with associated hyperparathyroidism, hypovitaminosis or both conditions were selected. All participants were treated for 6 months with risedronate 35 mg and vitamin D 2800 IU once a week, with additional daily vitamin D supplementation of 4000 IU. Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Postmenopausal Osteopenia-osteoporosis patients<br>All participants were treated for 6 months with risedronate 35 mg and vitamin D 2800 IU once a week, with additional daily vitamin D supplementation of 4000 IU. | Drug: Risedronate<br>* Participants received risedronate 35 mg once a week for 6 months.<br>* Other names: SERALIS®;Drug: Vitamin D<br>* Participants received 2,800 IU of vitamin D once a week, with additional daily supplementation of 4,000 IU of vitamin D<br>* Other names: Generic;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Remission of hyperparathyroidism | Remission of hyperparathyroidism was considered when serum parathyroid hormone [PTH] values were below 45 pg/mL. | 6 months | | Remission of hypovitaminosis D | Remission of hypovitaminosis D was considered when serum 25-hydroxy vitamin D [25(OH)D] was above 29 pg/ml. | 6 months | | Remission of osteopenia | Osteopenia remission was considered when densitometry T-score values were below -1. | 6 months | | Remission of Osteoporosis | Osteoporosis remission was considered when densitometry T-score values were below -2.4. | 6 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change from baseline serum calcium at 6 months | Calcium was evaluated as a bone mineralization marker. | 6 months | | Change from baseline serum phosphorus at 6 months | Phosphorus was evaluated as a bone mineralization marker. | 6 months | | Change from baseline urinary calcium at 6 months | Urinary calcium was evaluated as an indirect marker of bone demineralization. | 6 months | | Change from bone resorption biomarker at 6 months | Alkaline Phosphatase was evaluated as a bone resorption biomarker. | 6 months | | Fracture Risk Assessment Tool (FRAX®) for hip fracture | Fracture Risk Assessment Tool (FRAX®) for hip fracture was used to determine the 10-year probability of hip fracture. When the predicted risk was greater than 3% was considered a high risk for hip fracture, and when it was lower than 3%, it was considered a low risk for hip fracture. | 6 months | | Fracture Risk Assessment Tool for major osteoporotic fracture (FRAX® Mo) | Fracture Risk Assessment Tool for major osteoporotic fracture (FRAX® Mo) was used to determine the 10-year probability of major osteoporotic fracture (clinical spine, forearm, hip or shoulder fracture). When the predicted risk was greater than 20% was considered a high risk for major osteoporotic fracture, and when it was lower than 20%, it was considered a low risk of major osteoporotic fracture. | 6 months | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Postmenopause, Postmenopausal Osteoporosis, Hypovitaminosis D, Hyperparathyroidism, Risedronate, Osteopenia, Bone Mineral Density, Bone resorption

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Effect of Anesthetics on Oxygenation and Microcirculation During One-lung Ventilation Study Overview ================= Brief Summary ----------------- One-lung ventilation during thoracic surgery may affect systemic oxygenation and peripheral microcirculation by hypoxic pulmonary vasoconstriction. Both intravenous and inhalational anesthetics can be used during one-lung ventilation. However, there is still a controversy which anesthetic would be more appropriate during one-lung ventilation in the perspective of oxygenation and microcirculation. The investigators hypothesized that intravenous and inhalational anesthetics may affect oxygenation and microcirculation differently during one-lung ventilation. Detailed Description ----------------- Patients undergoing thoracic surgery including one-lung ventilation will be randomized to receive intravenous (propofol) or inhalational (desflurane) anesthetic. Systemic oxygenation can be evaluated by measuring partial pressure of oxygen in arterial blood analysis. Microcirculatory parameters can be obtained from vascular occlusion test. Among those parameters, recovery slope during vascular occlusion test is known to reflect recruitment of microvasculature in response to hypoxic or ischemic insult. In this study, we will compare arterial partial pressure of oxygen and recovery slope during one-lung ventilation between propofol and desflurane group. Official Title ----------------- Effect of Anesthetics on Oxygenation and Microcirculation During One-lung Ventilation Conditions ----------------- Mechanical Ventilation Complication Intervention / Treatment ----------------- * Drug: propofol * Drug: desflurane Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: undergoing thoracic surgery including one-lung ventilation Exclusion Criteria: refuse to enroll BMI over 30 kg/m(2) severe obstructive or restrictive lung disease preoperative supplemental oxygen, intubated, or mechanical ventilatory support preoperative arterial partial pressure of oxygen < 60 mmHg pregnancy history of coronary artery disease preoperative continuous infusion of vasopressor or inotropes cannot undergo vascular occlusion test: anatomical abnormality of both arms, severe peripheral vascular disease, presence of A-V fistula Ages Eligible for Study ----------------- Minimum Age: 20 Years Maximum Age: 90 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Triple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: propofol<br>Propofol is used as a maintenance anesthetic to patients in the propofol group. Intervention: propofol infusion by target-controlled infusion for maintaining anesthesia propofol (Fresofol MCT 2%) target effect site concentration: 4 5 mcg/ml, during general anesthesia | Drug: propofol<br>* Patients are randomized to receive intravenous anesthetic (propofol) or inhalational anesthetic (desflurane) as a maintenance anesthetic.<br>* Other names: propofol (Fresofol(R)2 MCT 2%, Fresenius Kabi);| | Experimental: desflurane<br>Desflurane is used as a maintenance anesthetic to patients in the desflurane group. Intervention: Desflurane administration for maintaining anesthesia desflurane (Suprane) inhalation as 6 8 vol% during general anesthesia | Drug: desflurane<br>* Patients are randomized to receive intravenous anesthetic (propofol) or inhalational anesthetic (desflurane) as a maintenance anesthetic.<br>* Other names: desflurane (Suprane(R), Baxter Healthcare);| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | arterial partial pressure of oxygen | Primary outcome is arterial partial pressure of oxygen 30 min after one-lung ventilation during thoracic surgery in propofol and desflurane groups. | 30 min after one-lung ventilation | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | recovery slope | Secondary outcome is recovery slope measured by vascular occlusion test 30 min after one-lung ventilation during thoracic surgery in propofol and desflurane groups. | 30 min after one-lung ventilation | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- oxygenation, microcirculation, one-lung ventilation, thoracic surgery

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Dexmedetomidine Versus Hyalase Treatment of Carpal Tunnel Syndrome Study Overview ================= Brief Summary ----------------- Carpal tunnel syndrome (CTS) is a common peripheral entrapment neuropathy, this study aims to investigate if, and to what extent hydro-dissection hyalase and saline versus dexmedetomidine upon the median nerve could offer symptoms and clinical improvement Detailed Description ----------------- Carpal tunnel syndrome (CTS) is the most common compression syndrome the upper extremities. Its problem has a high prevalence ranged estimated prevalence of 3.8% in the general population, 3 and 7.8% in the working population. It occurs at any age, especially in individuals in their 40s to 60s, and the male: female ratio is reported to be 3:7. A lot of treatment modalities have been tried to improve the condition, starting from local anesthetic injection, steroid, and up to surgical decompression of the nerves. Official Title ----------------- Dexmedetomidine Versus Hyalase Local Injection for Pain Alleviation in Patients With Carpal Tunnel Syndrome; A Randomized Clinical Trial Conditions ----------------- Carpal Tunnel Syndrome, Pain, Chronic Intervention / Treatment ----------------- * Drug: Dexmedetomidine * Drug: Hyalase Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: adult patients complaining of carpal tunnel syndrome of 3 month duration or more diagnosed axonal neuropathy using electrodiagnosis , nerve conduction study Exclusion Criteria: • patient refusal infection at the site of intervention local anesthetic allergy Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 60 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Dexmeditomidine group<br>injection of 1 microgram/kg dexmedetomidine + 10 cc saline injection nearby median nerve as hydrodissection | Drug: Dexmedetomidine<br>* injection of 1 microgram/kg dexmeditomidine + 10 cc saline injection nearby median nerve as hydrodissection<br>| | Active Comparator: Hyalase<br>injection of Hyalase + 10 cc saline injection nearby median nerve as hydro-dissection | Drug: Hyalase<br>* injection of Hyalase + 10 cc saline injection nearby median nerve as hydro-dissection<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Pain alleviation | pain alleviation improvement of pain measured by visual analog scale , no pain the scale equal zero , and worst pain the scale equal 10 | 6 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Median nerve cross sectional area | Changes in ultrasound imaging change of cross sectional area in cubic mellimeter | 6 months |

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Pharmacokinetics of Oral Capsule in Healthy Japanese vs. Caucasian Subjects Study Overview ================= Brief Summary ----------------- This is a single and multiple dose, parallel group study to assess safety and pharmacokinetics of oral HTL0018318 in healthy Japanese and Caucasian subjects. Detailed Description ----------------- This is a single and multiple dose, parallel group study to assess safety and pharmacokinetics of oral HTL0018318 in healthy Japanese and Caucasian subjects. The study will be conducted in two parts: (A) single doses of HTL0018318 in healthy, adult, male Caucasian and Japanese subjects; (B) multiple doses of HTL0018318 in healthy, adult, male Caucasian and Japanese subjects. Official Title ----------------- A Two-part, Single and Multiple Dose, Parallel Group Study to Assess Safety and Pharmacokinetics of Oral HTL0018318 in Healthy Japanese and Caucasian Subjects Conditions ----------------- Safety Issues, Pharmacokinetics Intervention / Treatment ----------------- * Drug: HTL0018318 * Drug: Placebo oral capsule Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Male subjects, either Caucasian or Japanese aged ≥20 and ≤40 years. Japanese subjects must have lived outside of Japan for ≤ 5 years in total and be first generation Japanese, defined as born in Japan and having 4 biologic grandparents who are ethnic Japanese. The Caucasian subjects should be distinguished especially by very light to brown skin pigmentation and straight to wavy or curly hair, and should be indigenous to Europe, northern Africa and western Asia. Therefore, the study may include Caucasian subjects from North America, New Zealand, Australia and South Africa. Subjects must have a body mass index (BMI) between 18.0-25.0 kg/m² inclusive. Male subjects, if heterosexually active and with a female partner of childbearing potential or a pregnant or breastfeeding partner, must agree to use barrier contraception (male condom) for the treatment period and for at least 3 months after the end of the systemic exposure of the study drug. Satisfactory medical assessment with no clinically significant or relevant abnormalities. Able to perform spirometry/peak flow with a satisfactory technique at screening. Ability to provide written, personally signed, and dated informed consent to participate in the study, in accordance with the International Council of Harmonization Good Clinical Practice (GCP) Guideline E6. An understanding, ability, and willingness to fully comply with study procedures and restrictions Exclusion Criteria: Any history of any condition associated with cognitive impairment, including but not limited to schizophrenia and dementia. History of epilepsy or seizures of any kind at any time. Current or relevant history of any physical or psychiatric illness that may require treatment or make the subject unlikely to fully comply with the requirements of the study or complete the study, or any condition that presents undue risk from the investigational product or study procedures. The history or presence of any of the following cardiac conditions: known structural cardiac abnormalities; family history of long QT syndrome; cardiac syncope or recurrent, idiopathic syncope; exercise related clinically significant cardiac events. Presence or history of drug or alcohol abuse in the last 5 years, or the inability to refrain from alcohol use from 48 hours before screening, dosing and each scheduled visit until the end of the study. Use of tobacco in any form (e.g., smoking or chewing) or other nicotine-containing products in any form (e.g., gum, patch, electronic cigarettes) within 3 months prior to the planned first day of dosing. Use of prescription medications within 14 days or 10 half-lives (whichever is longer) prior to Day 1 of the dosing period, or any over-the-counter (OTC) medication (including multivitamin, herbal, or homeopathic preparations, excluding hormonal contraception, hormone-replacement therapy, and/or an occasional dose of acetaminophen) within 7 days prior to Day 1 of the dosing period. History of significant allergic reaction (anaphylaxis, angioedema) to any product (food, pharmaceutical, etc). Has donated or lost 400 mL blood or more within the last 16 weeks preceding the first day of dosing. Ages Eligible for Study ----------------- Minimum Age: 20 Years Maximum Age: 40 Years Sexes Eligible for Study ----------------- Male Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Triple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: HTL0018318 Low dose, Part A.<br>Part A. 1 single dose on day 1. Discharged on day 4 of Period 1 (following 10 day washout). | Drug: HTL0018318<br>* Part A single dose Part B five doses<br>| | Active Comparator: HTL0018318 High dose, Part A<br>1 single dose on day 1. Discharged on day 4 of period 2 (following 10 day washout). | Drug: HTL0018318<br>* Part A single dose Part B five doses<br>| | Active Comparator: HTL0018318 Low dose, Part B<br>1 dose daily for 5 days (5 active doses total). Discharged on day 8 of period 1. | Drug: HTL0018318<br>* Part A single dose Part B five doses<br>| | Placebo Comparator: Placebo oral capsule, Part B<br>1 dose daily for 5 days (5 active doses total). Discharged on day 8 of period 1. | Drug: Placebo oral capsule<br>* Part B only<br>* Other names: placebo, placebo - cap;| | Active Comparator: HTL0018318 High dose, Part B.<br>1 dose daily for 5 days (5 active doses total). Discharged on day 8 of period 2. | Drug: HTL0018318<br>* Part A single dose Part B five doses<br>| | Placebo Comparator: Placebo oral capsule, Part B.<br>1 dose daily for 5 days (5 active doses total). Discharged on day 8 of period 2. | Drug: Placebo oral capsule<br>* Part B only<br>* Other names: placebo, placebo - cap;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Cmax | Comparison of pharmacokinetics in plasma | Baseline to 72 hours | | Tmax | Comparison of pharmacokinetics in plasma | Baseline to 72 hours | | Area under the curve | Comparison of pharmacokinetics in plasma | Baseline to 72 hours | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Delay in absorption (Tlag) | Pharmacokinetics in plasma | Baseline to 72 hours | | Rate of elimination | Pharmacokinetics in plasma | Baseline to 72 hours | | Half life (t1/2) | Pharmacokinetics in plasma | Baseline to 72 hours | | Amount excreted in urine | Pharmacokinetics in urine | Baseline to 72 hours | | Fraction of dose eliminated unchanged in urine (fe/F) | Pharmacokinetics in urine | Baseline to 72 hours | | Treatment emergent adverse events (TEAEs) | Safety and tolerability | Up to 14 day post dose | | Number of participants with abnormal physical exam results | Safety and tolerability | Up to 14 day post dose | | Heart Rate | Safety and tolerability | Up to 14 day post dose | | Number of participants with abnormal laboratory values | Safety and tolerability | Up to 14 day post dose | | ECG | Safety and tolerability | Up to 14 day post dose | | Blood pressure | Safety and tolerability | Up to 14 day post dose |

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The Influence of Acute Myocardial Infarction Checklist on the Door-to-Balloon Time Study Overview ================= Brief Summary ----------------- This study was designed to investigate the influence of the acute myocardial infarction checklist on the door-to-balloon time in patients suffering from acute STEMI at Far Eastern Memorial Hospital Official Title ----------------- The Influence of Acute Myocardial Infarction Checklist on the Door-to-Balloon Time in Patients Suffering From Acute ST-Elevation Myocardial Infarction Conditions ----------------- Myocardial Infarction Intervention / Treatment ----------------- * Other: acute myocardial infarction checklist Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: all patients who presented to the emergency department of Far Eastern Memorial Hospital within 12 hours of the onset of ischemic chest pain patients with diagnostic criteria of acute ST-elevation myocardial infarction on electrocardiogram, e.g. at least 0.1 mV in two or more contiguous electrocardiographic leads or a new onset of bundle branch block patients were preparing for emergency cardiac catheterization Exclusion Criteria: patients who did not fulfill the diagnostic criteria of acute myocardial infarction on electrocardiogram patients who were not eligible for cardiac catheterization patients who refused cardiac catheterization patients who suffered from acute myocardial infarction after admission to ward or intensive care unit for any reason patients who had an ambiguous diagnosis that the decision of emergency cardiac catheterization was made after admission to ward or intensive care unit Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | intervention group<br>patients presented with acute ST-elevation myocardial infarction and received emergency cardiac catheterization between March 1, 2007 and Oct. 31, 2007 | Other: acute myocardial infarction checklist<br>* For every patient fulfilling the criteria of enrollment, an acute myocardial infarction checklist was incorporated into the patient's medical records at emergency department immediately after a diagnosis of acute ST-elevation myocardial infarction was made. All the time sequences concerning different managements at different locations were recorded by nurses and/or physicians as instructions on the checklist.<br>| | control group<br>patients presented with acute ST-elevation myocardial infarction and received emergency cardiac catheterization between April 1, 2006 and Feb. 28, 2007 | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | median door-to-balloon time | | at cath. lab | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | in-hospital mortality | | at hospital discharge | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- myocardial infarction, catheterization, angioplasty, door-to-balloon time

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