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IMPRoving Cardiovascular RiSk Stratification Using T1 Mapping in General populatION Study Overview ================= Brief Summary ----------------- Magnetic properties of myocardial tissue change in the presence of disease. This is detectable in the change of rate of magnetic relaxation, and measurable by T1 and T2 mapping using cardiovascular magnetic resonance (CMR). These markers provide novel quantifiable imaging measures for myocardial tissue characterisation. Despite similar principles, the measurements differ considerably between different sequences, vendors and field strengths, yielding a necessity to establish robust sequence-specific normal ranges, diagnostic accuracy, relationships with clinical characteristics, cardiovascular risk factors, routine cardiac imaging parameters, and prognosis. A further unknown relates to separation between healthy myocardium and subclinical disease in subgroups of patients with suspected cardiac involvement. Examples include patients with possible inflammation, such as in patients with a recent COVID-19 infection or vaccination. Anticipated recruitment of a total of 3000 subjects, with 1500 subjects per field strength (1.5 and 3.0 Tesla). Official Title ----------------- IMPRoving Cardiovascular RiSk Stratification Using T1 Mapping in General populatION Conditions ----------------- Myocarditis, Heart Failure, Myocardial Fibrosis, Vascular Inflammation Intervention / Treatment ----------------- * Diagnostic Test: Cardiac Imaging Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Able to provide informed consent 18 years of age and over Absence of a valid clinical indication for CMR, and/or known or clinically relevant cardiac disease Exclusion Criteria: accepted contraindications for a contrast-enhanced CMR study (in line with MRI safety and SmPC for contrast agent) 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 | | --- | |Diagnostic Test: Cardiac Imaging|Subjects undergo CMR study with contrast agent (gadobutrol 0.1 mmol/kg; mapping, volumes, function, strain and LGE); transthoracic echocardiography and blood testing.| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | All-cause mortality | number of deaths | 1 year | | All-cause mortality | number of deaths | 5 years | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Heart Failure Outcome | Number of participants with events including death due to heart failure and and hospitalisation due to Heart Failure | 1 year and 5 years | | Cardiovascular Outcome | Number of participants with death due to myocardial infarction, heart failure, arrhythmia or vascular events (pulmonary embolism, aortic dissection, stroke) | 1 year and 5 years | | Arrhythmia Outcome | Number of participants with documented events including sudden cardiac death, appropriate ICD discharge, sustained VT | 1 year and 5 years | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Inflammation, Remodeling

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Study on the Etiology, Risk Factors and Pathogenesis of COPD Based on Clinical Bioinformatics Study Overview ================= Brief Summary ----------------- The risk factors and causes of chronic obstructive pulmonary disease（COPD）are not clear, so the prevalence of COPD is high and the prevention effect is not good. Because the pathogenesis of COPD is not completely elucidated, the diagnosis and classification of COPD are inaccurate which resulting in poor efficacy of treatment. Therefore, it is of great scientific and clinical significance to find out the risk factors and causes of COPD, to clarify its pathogenesis, to put forward the prevention and early intervention measures of COPD, to warn the occurrence of COPD, to predict the deterioration of the disease, to reduce the occurrence of COPD and to slow down the progress of COPD. The project establishes a cohort of COPD people，high-risk group and the healthy group. The project studys the risk factors, etiology and pathogenesis of COPD. The project studys the interaction between genetic factors and environmental factors on COPD and its effect on pathogenesis, progression and outcome of COPD. Detailed Description ----------------- The project establishes the data base and specimen bank for COPD.Then clinical bioinformatics technology is uesd to analyze the clinical information and epidemiological information. In the same time, Omics methods are used to study COPD-related genes and biomarkers . Finally, a multi-factor risk factor model for the occurrence and development of COPD is established by combining clinical information, epidemiological information and biomics results. Official Title ----------------- Study on the Etiology, Risk Factors and Pathogenesis ofCOPD Based on Clinical Bioinformatics Conditions ----------------- Chronic Obstructive Pulmonary Disease Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: ① Inclusion criteria for patients with COPD: Over 18 years of age. FEV1 / FVC< 70% was the diagnostic criterion for COPD after inhaling bronchodilators. ② Inclusion criteria for high-risk subjects: Over 18 years of age. Physical examination and routine laboratory tests were normal. Chest CT to exclude other pulmonary diseases. Lung function does not meet the diagnostic criteria for COPD. having one of the following risk factors: A. Smoking: current smokers, smoking index (number of years of smoking × number of cigarettes per day)≥ L. B. Biofuel exposure: Subjects frequently use charcoal, wood, and animal dung for home heating and cooking Or crops are defined as having a history of exposure to biofuels. C. Dust and chemical exposure: mining, quarrying, casting, grain dust, paint, chemicals and others (including non-return) In the above categories of self-reported) occupational dust or gas smoke exposure for more than 1 year. ③ Inclusion criteria of healthy control subjects: Over 18 years of age. Physical examination and routine laboratory tests were normal. Chest CT to exclude other pulmonary diseases. Lung function does not meet the diagnostic criteria for COPD. No risk factors (including smoking, biofuel exposure, dust or chemical exposure). Exclusion Criteria: History of other chronic lung diseases, such as bronchiectasis, pulmonary interstitial fibrosis, etc. History of acute lung disease within 3 months. History of malignant tumor. Pregnant and lactating women. 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 | | --- | --- | | COPD<br>Patients with chronic obstructive pulmonary disease | | | High Risk<br>People who do not suffer from COPD, but have high risk factor for COPD. | | | Health<br>People who do not suffer from COPD and do not have a high risk factor for COPD either. | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Risk factors and pathogenesis of of COPD | To establish a cohort of copd patients and high-risk population; To establish a multi-factor risk factor model for copd, and screen 5-10 risk factors related to the occurrence and development of COPD. | From date of participation in project until December 31, 2022 | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Clinical bioinformatics database for COPD | To find 1-2 susceptibility genes closely related to COPD through gene and epigenetic studies combined with clinical bioinformatics analysis and genomic research ; To find 3-5 biomarkers closely related to COPD through protein and metabolomics studies as well as clinical bioinformatics analysis. | From date of participation in project until December 31, 2022 | | Biological library of COPD | To verify the identified susceptibility genes and biomarkers in the existing COPD cohort, and then expand to be verified outside the cohort, to verify 5-7 related susceptibility genes and biomarkers; To further explore the pathogenesis of COPD by conducting preliminary mechanism studies on the discovered susceptibility genes and biomarkers combined with big data analysis; To build a unified copd data collection and sharing platform between local hospitals to achieve real-time monitoring of statistical analysis. | From date of participation in project until December 31, 2022 |

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Trial of Point-of-treatment Xpert MTB/RIF Assay Study Overview ================= Brief Summary ----------------- Xpert MTB/RIF assay is a novel automated molecular tool for the diagnosis of TB. Xpert can detect TB genetic material in sputum samples as well as test for genetic resistance to rifampicin providing results within 2 hours. Xpert received WHO endorsement in December 2010. There is limited data on the impact of Xpert on time-to-treatment and TB-related patient morbidity in primary care clinics. No studies have yet evaluated Xpert performed at the point-of-treatment (POT) i.e. in primary care clinic location. The investigators hypothesize that one sputum GeneXpert MTB/RIF assay performed at the POT will improve time-to-diagnosis, time-to-treatment and TB related patient morbidity for patients with suspected TB presenting to primary level TB clinics in high HIV prevalent settings. Detailed Description ----------------- Tuberculosis (TB) is one of the world's most important infectious causes of mortality and continues to kill 1.8 million people annually. Despite intensified standard measure of TB control, TB case detection rates are low, posing major hurdles for TB control. It is estimated that approximately 50% of patients with TB are still not diagnosed and treated appropriately. The problem is compounded by the increasing prevalence of multi drug resistant (MDR) and extensively drug resistant (XDR) TB and the close association between TB and HIV infection. Diagnostic tools introduced 100 years ago are still in routine use and increasingly inaccurate if the face of the HIV and TB syndemics. Consequently, many patients with active TB remain undiagnosed and continue to spread the disease within the community. Thus, missed or delayed diagnosis results in ongoing transmission, patient morbidity and mortality, and social and economic consequences. Currently, there is no available point-of-care, or even point-of-treatment test that allows early detection of active tuberculosis at the peripheral health clinic level. Lack of rapid, simple and accurate diagnostic tests at this level is a major hurdle in controlling the global burden of TB. A number of promising new TB diagnostics have shown initial promise but there remains an urgent need to assess their impact when used at the point-of-treatment in primary care level. In 2009, Cepheid released the Xpert® MTB/RIF Assay, which is the only system able to deliver answers directly from unprocessed samples by combining on-board preparation of the sample with real-time polymerase chain reaction (PCR) in less than 2 hours. Additionally, the Xpert® MTB/RIF Assay allows for simultaneous on-demand molecular testing for the detection of mycobacterium tuberculosis (M.tb) and rifampicin (frontline anti-TB drug) resistance. . The GeneXpert™ system consists of a GeneXpert instrument, personal computer and disposable fluidic cartridges. The system combines cartridge-based sample preparation with amplification and detection in a fully integrated and automated nucleic acid analysis instrument. Xpert has now been shown to be an accurate tool for the rapid diagnosis of tuberculosis in both smear-positive and smear-negative samples in both a multicentre evaluation and demonstration study with a sensitivity of approximately 70% in smear negative culture positive TB. Xpert testing in both these studies was performed at microscopy laboratories. In December 2010, on the basis of these results, Xpert was endorsed for TB diagnosis by the World Health Organisation (WHO) but is yet to be integrated into national tuberculosis control programmes. Limited data is available on the impacts of Xpert on patient important outcomes such as TB-related morbidity. No data is available about the feasibility and robustness of performing Xpert in primary care clinics at the POT using minimally trained nursing staff. The objective of this study will be to examine the feasibility and impact of a single point-of-treatment Gene Xpert MTB/RIF Assay performed by clinic staff compared to standard microscopy-centre based diagnostics. Special focus will be on the patient-related outcomes of time-to-treatment initiation, drop out rates and the mean difference in TB-morbidity scores in patients diagnosed with Xpert. The Xpert POT study will be a multicentre patient-level randomised controlled trial comparing a single sputum GeneXpert MTB/RIF Assay performed at point-of-treatment with same-day standard fluorescent smear microscopy for TB diagnosis at the primary level of care. A single liquid MGIT culture performed a regional laboratory will be used as the reference standard. Official Title ----------------- Multicentre Randomised Control Trial of Point-of-treatment (Clinic-based) Xpert MTB/RIF Assay Conditions ----------------- Tuberculosis Intervention / Treatment ----------------- * Procedure: Xpert MTB/RIF assay * Procedure: Smear microscopy Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Able and willing to give informed consent Ambulant patient presenting to TB clinic IF HIV negative requires 2 or more of the following: Cough ≥ 2 weeks loss of weight persistent fever ≥ 2 weeks and/or a single recorded temp > 38°C night sweats generalized fatigue hemoptysis or chest pain OR if HIV positive - any one of the following: current cough night sweats fever loss of weight Patient 18 years or above Exclusion Criteria: Inability to provide informed consent (e.g. mentally impaired) Unable to produce 2 sputa of ≥ 1ml TB treatment within the last 60 days Unable to potentially return for study follow-up at 2 and 6 months (i.e. leaving community) Patient not meeting inclusion criteria 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 Allocation: Randomized Intervention Model: Factorial Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Xpert MTB/RIF<br>Patients in this arm will receive 1 sputum Xpert MTB/RIF test (point-of-treatment) and 1 sputum sample for MGIT liquid TB culture (regional lab) | Procedure: Xpert MTB/RIF assay<br>* Automated nucleic-acid amplification test (fully integrated) test for TB<br>* Other names: Cepheid Xpert MTB/RIF assay;| | Active Comparator: Sputum smear microscopy<br>Patients in this study arm will receive 2 sputum samples for same-day smear microscopy and 1 of the sputum samples will have a MGIT Liquid culture (regional lab). | Procedure: Smear microscopy<br>* Smear microscopy involve sputum smear with either ziehl-neelsen or auramine-O staining of slides and light or fluorescence microscopy reading<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Difference in TB-related Morbidity | Time-specific (2 month) difference in morbidity between the Xpert MTB/RIF and smear microscopy study arms. Morbidity will be assessed using the TB Score and Karnosky performance scale | 2 months | | Difference in TB-related Morbidity | Time-specific (6 month) difference in morbidity between the Xpert MTB/RIF and smear microscopy study arms. Morbidity will be assessed using the TB Score and Karnosky performance scale | 6 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Time-to-diagnosis | Time from study enrollment to TB diagnosis in each study arm A diagnosis of TB will include: i) Smear microscopy: WHO classification for smear grading considered positive ii) Xpert MTB/RIF positive (mtb detected) iii) MGIT liquid culture positive | 6 months | | Drop-out and lost-to-follow up rates | Number of patients that are enrolled, randomized to a study arm, and then do not return to receive a positive test result, and Number of patients that are enrolled, randomized to a study arm, diagnosed with TB, and then are lost-to-follow up prior to completion of prescribed standard TB treatment | 1 year | | Feasibility of clinic-based performance of Xpert MTB/RIF assay performed by nursing staff without formal research training | Feasibility indicators for the performance of Xpert at POT will be recorded. These include indeterminate rates, turn-around-time, user appraisal and assessments and performance comparisons between laboratory and clinic-based Xpert MTB/RIF. | 6 months | | Individual patient-level cost analysis, cost-effectiveness evaluation and quality of health indices evaluation | Detailed documentation of patient and health system costs for TB diagnosis and treatment will be done at baseline, 2 month and 6 month time-points as well as quality of life health questionaires. | 1 year | | Time-to-treatment initiation | The time-to-treatment initiation for TB culture positive patients in each study arm will be compared Treatment commencement will be considered as the initiation of the first dose of anti-TB treatment at a registered DOTs facility | 6 months | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Tuberculosis, diagnosis, Xpert MTB/RIF, point-of-treatment, randomized controlled trial

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Comparison of Icg's Route of Administration During Laparoscopic Cholecystectomy Study Overview ================= Brief Summary ----------------- The aim of the trial is to compare the routes of administration of indocyanine green (ICG) during laparoscopic cholocystectomy. Detailed Description ----------------- Laparoscopic cholecystectomy is now the method of choice for the treatment of symptomatic and complicated gallstones. There are two major problems that can occur during and after a laparoscopic cholecystectomy. These are the remaining stones in the bile duct and the iatrogenic injuries of the bile ducts. Iatrogenic bile duct injuries are the most difficult complication of cholecystectomy and are a clinical entity that needs multifactorial treatment as it significantly increases morbidity, mortality and overall cost. Intraoperative cholangiography is used to prevent these complications. Intraoperative cholangiography is the traditional method of identifying bile duct anatomy during laparoscopic cholecystectomy. This method has the disadvantages that both the patient and the staff are exposed to radiation, while in order to perform it, catheterization of the cystic duct must be performed, which requires surgical procedures that increase the time of the operation, while in some cases it is not technically easy. Finally, with the intraoperative cholangiography, the injuries of the bile ducts are detected, after they have taken place, therefore it helps in their timely diagnosis but does not limit the frequency of their occurrence. Indocyanine green is a sterile, anionic, water-soluble but relatively hydrophobic tricarbocyanine molecule with a molecular weight of 751.4. It was developed in 1955 at Kodak Laboratories and in 1959 was approved for clinical use by the FDA. It has the property of fluorescing, after its administration, with a maximum absorption at 800 nm after exposure to infrared lighting. Its use offers an image of high clarity and sensitivity, target imaging, with parallel low acoustic emission. Indocyanine green has the following properties and advantages, which make it an important tool in the applications of medical sciences and studies. Following intravenous administration, it binds to plasma lipoproteins with minimal escape into the interstitial space. Extremely important for its clinical use is the complete excretion through the bile, as well as the non-production of metabolic products. It has low toxicity in the absence of ionization, which in combination with the short half-life of the substance, provides safety for the patient in its use and application in medical and biomedical sciences. It has low costs that in combination with its ease of use facilitates its application. No expensive equipment or large learning curve required. Also the possibility of recurrence with re-administration intraoperatively can offer a number of applications in laparoscopic surgery. It has a low rate of side effects and interactions with other drugs and preparations, a major allergic reaction has been reported in the literature. The first clinical applications of indocyanine green were to assess cardiac function, liver function in cirrhotic patients before hepatectomy, and to examine the retinal vessels. Its use in laparoscopic cholecystectomy, as already mentioned, is based on its ability to fluoresce when exposed to infrared light and in combination with the fact that when administered intravenously it is concentrated and excreted from the bile offers the possibility of intraoperative, fluorescent cholangiography that aims to identify the elements of the Callot triangle. This study aims to demonstrate that endocyanin green cholangiography is equivalent to or better than conventional cholangiography for the diagnosis of cholelithiasis and biliary injuries. It is therefore an important clinical application that will probably facilitate surgeons both in the prevention of biliary injuries and in the intraoperative diagnosis of cholelithiasis. Patients who will undergo laparoscopic cholecystectomy will be randomly divided into 3 (three) groups. The processing of the results will be done in the appropriate way and method. A total of 240 patients will be randomized into three groups of 80. In the first group (A) classical cholangiography will be performed. In group (B) will be performed intravenous fluorescent cholangiography with indocyanine green 6 (six) hours before the start of surgery. In the third group (C) will be performed intraoperative cholangiography with direct administration of indocyanine green to the gallbladder. Official Title ----------------- Comparison of Administration of Indocyanine Green (ICG) for Image-Guided Laparoscopic Cholocystectomy- A Randomized, Controlled, Prospective Trial Conditions ----------------- Laparoscopic; Cholecystectomy, Cholelithiasis; Bile Duct, Choledocholithiasis, Stone - Biliary, Post-Op Complication, Cholangiography, Indocyanine Green, Intraoperative Complications, Bile Duct Injury Intervention / Treatment ----------------- * Procedure: Indocyanine Green (ICG) administration Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: age older than 18 years old laparoscopic cholecystectomy elective surgery Exclusion Criteria: younger than 18 years old no consent to participate to the study history of allergic reaction to iodine products urgent or emergent cholecystectomy 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: Prevention Allocation: Randomized Intervention Model: Parallel Assignment Masking: Triple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Group A (standard cholangiography during surgery)<br>All patients will undergo laparoscopic cholecystectomy. In this group standard cholangiography will be performed during surgery. Standard cholangiography will be performed with selective catheterization of the cystic duct and infusion of a radiolucent substance (non-ionic low osmotic iodine). The category includes drugs such as iohexol, iopamidol, iopromide, ioversol, iobitriol, iomeprol and iodixanol. In our study we will use Xenetix (iobitriol) and perform cholangiography with C-ARM recording. | Procedure: Indocyanine Green (ICG) administration<br>* Patients will undergo laparoscopic cholecystectomy after they are randomly divided into 3 (three) groups. A total of 240 patients will be randomized into three groups of 80. In the first group (A) standard cholangiography will be performed. In group (B) intravenous fluorescent cholangiography with indocyanine green will be performed during surgery. ICG at a dose of 0.3 mg / mL / Kg 6 (six) hours prior to surgery will be administered. In the third group (C), intraoperative cholangiography will be performed with direct administration of indocyanine green at a dose of 0.03 mg / ml / Kg to the gallbladder.<br>* Other names: iodine solution administration;| | Active Comparator: Group B (cholangiography with iv administration of icg prior to surgery)<br>All patients will undergo laparoscopic cholecystectomy. In this group intravenous fluorescent cholangiography with indocyanine green will be given at a dose of 0.3 mg / mL / Kg 6 (six) hours before the start of surgery.The bile duct system will be recorded with a special camera (Karl Storz NIR / ICG). | Procedure: Indocyanine Green (ICG) administration<br>* Patients will undergo laparoscopic cholecystectomy after they are randomly divided into 3 (three) groups. A total of 240 patients will be randomized into three groups of 80. In the first group (A) standard cholangiography will be performed. In group (B) intravenous fluorescent cholangiography with indocyanine green will be performed during surgery. ICG at a dose of 0.3 mg / mL / Kg 6 (six) hours prior to surgery will be administered. In the third group (C), intraoperative cholangiography will be performed with direct administration of indocyanine green at a dose of 0.03 mg / ml / Kg to the gallbladder.<br>* Other names: iodine solution administration;| | Active Comparator: Group C (cholangiography with direct administration of icg to the bile duct system during surgery)<br>All patients will undergo laparoscopic cholecystectomy. In the third group intraoperative cholangiography will be performed with direct administration of indocyanine green at a dose of 0.03 mg / ml / Kg to the bile duct cyst. | Procedure: Indocyanine Green (ICG) administration<br>* Patients will undergo laparoscopic cholecystectomy after they are randomly divided into 3 (three) groups. A total of 240 patients will be randomized into three groups of 80. In the first group (A) standard cholangiography will be performed. In group (B) intravenous fluorescent cholangiography with indocyanine green will be performed during surgery. ICG at a dose of 0.3 mg / mL / Kg 6 (six) hours prior to surgery will be administered. In the third group (C), intraoperative cholangiography will be performed with direct administration of indocyanine green at a dose of 0.03 mg / ml / Kg to the gallbladder.<br>* Other names: iodine solution administration;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | successful imaging of biliary system | The anatomy of the extrahepatic bile ducts will be orally determined by the surgeon and the cases in which the oral description will coincide with the findings of cholangiography or not and where there were differences will be recorded. | intra-operatively | | operation duration | minutes | intra-operatively | | intra-operative complications (bleeding, bile duct leakage, bile duct injury) | presence or absence | intra-operatively | | applicability of the intra-operatively cholangiography | yes or no | intra-operatively | | presence of bile duct stones (choledocholithiasis) | yes or no | intra-operatively | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | gender | male or female | pre-operatively | | ASA score | number | pre-operatively | | age | years | pre-operatively | | body mass index | kg/m2 | pre-operatively | | indication for laparoscopic cholecystectomy | yes or no | pre-operatively | | SGOT | g/dL | 24 hours prior to surgery and 24 hours after the surgery | | SGPT | g/dL | 24 hours prior to surgery and 24 hours after the surgery | | ALP | g/dL | 24 hours prior to surgery and 24 hours after the surgery | | γ-GT | g/dL | 24 hours prior to surgery and 24 hours after the surgery | | total bilirubin | mg/dL | 24 hours prior to surgery and 24 hours after the surgery | | indirect bilirubin | mg/dL | 24 hours prior to surgery and 24 hours after the surgery | | direct bilirubin | mg/dL | 24 hours prior to surgery and 24 hours after the surgery | | PT | seconds | 24 hours prior to surgery and 24 hours after the surgery | | INR | number | 24 hours prior to surgery and 24 hours after the surgery | | aPTT | seconds | 24 hours prior to surgery and 24 hours after the surgery | | urea | mg/dL | 24 hours prior to surgery and 24 hours after the surgery | | creatinine | mg/dL | 24 hours prior to surgery and 24 hours after the surgery | | CRP | mg/L | 24 hours prior to surgery and 24 hours after the surgery | | WBC | mm3/L | 24 hours prior to surgery and 24 hours after the surgery | | ESR | mm | 24 hours prior to surgery and 24 hours after the surgery | | procalcitonin | mg/dL | 24 hours prior to surgery and 24 hours after the surgery | | TNF-a | pg/ml | 24 hours prior to surgery and 24 hours after the surgery | | IL-6 | pg/ml | 24 hours prior to surgery and 24 hours after the surgery |

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Safety, Tolerability, and Effect of TMC207 and Efavirenz in Healthy Volunteers Study Overview ================= Brief Summary ----------------- Common treatments for tuberculosis (TB) can interfere with certain antiretroviral (ARV) medications used to treat HIV. People whose immune systems are weakened by HIV infection are susceptible to TB, so it is important to find treatments for both that can be given in combination. This study will test the safety of combining a new medication for TB with an already approved HIV medication in healthy adults. Detailed Description ----------------- Tuberculosis (TB) is the second most deadly infectious disease after HIV. Multidrug-resistant TB (MDR-TB) has emerged as a worldwide epidemic, limiting treatment options. HIV infected people with suppressed immune systems are particularly susceptible to TB, and TB is the leading cause of death among people with HIV. Treating people infected with both HIV and TB is particularly problematic because rifamycins, the drug class usually used to treat TB, lower the effectiveness of certain anti-HIV medications. Studies of pharmacokinetics (PK), the interactions between drugs and body, are needed to determine which anti-TB and anti-HIV medications can be safely and effectively combined. This study will examine TMC207, a new anti-TB medication with the potential to shorten TB treatment time, combined with efavirenz (EFV), an antiretroviral (ARV) medication used in many first-line treatment regimens for HIV. The study will test PK and safety of this combination in healthy volunteers. Participation in this study will last 49 days. At entry, participants will complete basic assessments, including taking a medical history and completing a physical exam, an eye exam, an electrocardiogram (ECG) to measure heartbeat, a pregnancy test, and a blood test. Certain behaviors and substances will be prohibited during the study, including consuming grapefruit, alcohol, or caffeine (on PK visit days); taking nutritional supplements, over-the-counter herbal medicines, and certain medicines and drugs from other studies; and excessive smoking. Participants will also be asked to keep a medication diary to record all medications they take during the study. All participants will receive study medications on the same schedule: a single dose of TMC207 on Days 1 and 29, and daily dosing of EFV on Days 15 to 43. Participants will complete two PK visits, one from Days 1 to 3, and one from Days 28 to 31. During PK visits, participants will have their vital signs checked and undergo an ECG, and they may also complete a limited physical exam, give a medication history, and report on symptoms. They will have multiple blood samples taken via a catheter left in place for the 3-day visit. Blood samples will be taken before receiving TMC207; 1, 2, 3, 4, 5, 6, 8, and 12 hours after receiving TMC207; and again on the mornings of Days 2 and 3. Participants will complete six outpatient visits over the 11 days following each PK visit and one outpatient visit on Day 21, between PK visits. At outpatient visits participants will complete a blood draw and may complete a limited physical exam and medical history, record symptoms, and review their medication diaries. On Day 49 participants will complete their last study visit, repeating many of the assessments from baseline testing. In the case of side effects or abnormal blood tests, participants may be monitored longer for safety reasons. Official Title ----------------- A Phase I, Safety, Tolerability, and Pharmacokinetic Interaction Study of Single-Dose TMC207 and Efavirenz in Healthy Volunteers Conditions ----------------- Tuberculosis, HIV Intervention / Treatment ----------------- * Drug: Efavirenz (EFV) * Drug: TMC207 Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Females not of reproductive potential, defined as women who have been postmenopausal for at least 24 consecutive months or women who have undergone hysterectomy, bilateral oophorectomy, or bilateral tubal ligation Females who have been surgically sterilized and all males must agree to use contraceptives if participating in sexual activity that could lead to pregnancy while receiving the protocol-specified medications and for 4 weeks after stopping the medication Absence of HIV-1 infection, as documented by any licensed enzyme-linked immunosorbent assay (ELISA) test kit, within 21 days prior to study entry Estimated creatinine clearance of more than 50 ml/min, within 21 days prior to study entry, calculated by the Cockcroft-Gault method Laboratory test results obtained within 21 days prior to entry, including negative pregnancy test, negative hepatitis B and C tests, and certain blood values Exclusion Criteria: Use of any prescription medication known to inhibit or induce CYP3A metabolizing enzymes within 30 days prior to entry Planned use during the study, from day 0 through the last PK blood draw, of any of the following: prescription medication(s), herbal supplement(s), nutritional supplement(s), or over-the-counter medication(s). Multivitamins and acetaminophen, up to 650 mg every 6 hours as an analgesic, are permitted. Hospitalization for any reason, pharmacotherapy for serious illness, or use of any prescription medication(s) within 14 days prior to study entry Receipt of any investigational study drug within 21 days prior to study entry Known allergy, sensitivity, or hypersensitivity to EFV or TMC207 or components of their formulations, including cyclodextrin allergy Significant previous or active history of cardiovascular, renal, liver, hematologic, neurologic, gastrointestinal, psychiatric, endocrine, or immunologic disease(s), as determined by the site investigator. This is inclusive of chronic illnesses or gastrointestinal conditions that may affect drug absorption, etc. Additionally, any medical condition that, in the opinion of the site investigator, would interfere with the volunteer's ability to participate in the protocol will exclude participation. Active illicit drug use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements Suspicion of active tuberculosis (TB) by the site investigator Inability to abstain from alcoholic beverages, grapefruit, and grapefruit juice for the duration of the study For smokers, inability to smoke 5 cigarettes per day or less for the duration of the study Breastfeeding Electrocardiogram (ECG) showing first-degree or greater heart block or QT interval (QTc) greater than 440 ms within 21 days prior to study entry. First-degree heart block is defined as PR interval greater than 200 ms. 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 Intervention Model: Crossover Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: TMC207 alone and with EFV<br>Participants will receive single-dose TMC207 alone and then single-dose TMC207 with EFV. | Drug: Efavirenz (EFV)<br>* Oral dose of 600 mg daily, taken in the evening<br>* Other names: Sustiva;Drug: TMC207<br>* Single oral dose of 400 mg in the morning<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Area under curve (AUC) over 336 hours of TMC207, measured when dosed alone and when dosed together with efavirenz (EFV) 600 mg daily | | Measured at baseline and Days 1 to 15, 28, and 29 to 43 | | Signs or symptoms of toxicity ranked Grade 2 or higher, according to the DAIDS adverse event (AE) grading table | | Throughout study | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Maximum observed plasma or serum concentration (Cmax) and oral clearance (CL/F) of TMC207 and AUC, Cmax, and CL/F of the M2 metabolite of TMC207 when dosed alone and when dosed together with EFV 600 mg daily | | Measured at baseline and Days 1 to 15, 28, and 29 to 43 | | AUC over 24 hours, Cmax, Cmin, CL/F, and elimination half-life (T1/2) of EFV and host EFV metabolism genotype status (CYP2B6) obtained from whole blood samples taken at screening | | Measured at baseline and on Day 28 | | Correlation between AUC over 24 hours of EFV and AUC over 336 hours of TMC207 | | Measured at baseline and Days 1 to 15, 28, and 29 to 43 | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- ARV, Pharmacokinetics, TMC207, Efavirenz

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Bayer OA Knee Pain Pilot Study Overview ================= Brief Summary ----------------- The objective of this study is to investigate if MRI can be used to evaluated effect of knee artery embolization for knee osteoarthritis. Participants be evaluated in clinic, obtain a knee MRI, undergo embolization of the symptomatic knee, and follow up in clinic at 1, 6, and 12 months after embolization. A second MRI is obtained 6 months after embolization. Participants will keep a record of their pain level and treatment and answer questionnaires at each visit. In addition, this study aims to determine the effects of knee artery embolization on the amount of opioid (pain reliever drugs) needed to manage osteoarthritis-associated pain and change in quality of life. Official Title ----------------- Transcatheter Geniculate Arterial Embolization: Treatment and Monitoring of Response Conditions ----------------- Osteoarthritis, Knee Intervention / Treatment ----------------- * Diagnostic Test: dynamic contrast enhanced MRI * Procedure: geniculate artery embolization Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Age 25 to 90 Symptomatic osteoarthritis of one or both knees, with Kellgren-Lawrence grade 1-3 assessed by weight-bearing knee radiography, including post-traumatic osteoarthritis One or more months of non-surgical therapy for knee pain such as joint injections, oral NSAIDs, or opioid analgesia Subjects able to provide informed consent. As this is a study of pain, patients must be able to consent for themselves. Patients without contraindication to MRI imaging with gadolinium-based contrast. Exclusion Criteria: Anaphylaxis to gadolinium or iodinated contrast media Impaired renal function with GFR <30ml/min Severe atherosclerotic disease of the lower extremity precluding percutaneous angiographic access to the involved geniculate artery(ies) Active septic arthritis of the symptomatic knee within 2 months of screening Malignancy of the involved knee Rheumatoid Arthritis or Gout Prior knee surgery Hemarthrosis Females who are pregnant or plan to become pregnant during the study. All participants able to become pregnant will be administered a urine pregnancy test. Ages Eligible for Study ----------------- Minimum Age: 25 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 Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: GAE and MRI treatment arm<br>GAE is geniculate artery embolization. | Diagnostic Test: dynamic contrast enhanced MRI<br>* An MRI study of the knee will be done to check the degree of osteoarthritis and blood flow to the affected knee. This scan will take about 1-2 hour(s).<br>Procedure: geniculate artery embolization<br>* The physician will perform a diagnostic angiography, where they will take pictures of vessels near the knee that will be treated. Once the artery to be treated is identified, the doctor will guide a thin wire called a microwire, and a plastic tube called a microcatheter to the targeted artery, and more pictures of vessels at the knee will be taken. This picture will be used to see if there are any abnormal vessels at the knee, such as abnormal blood flow, abnormal vessel connections (between the veins and arteries), or new blood vessel growth. Once the targeted artery at the knee is confirmed, the doctor will inject enough particle embolic (Embozene) to slow or stop the blood flow in the geniculate artery. Once all vessels are treated, a final angiogram (pictures of blood vessels) will be performed to ensure that the blood flow has slowed.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in enhancement time intensity curves obtained from CE-MRI | To evaluate the effects of particle embolization on knee osteoarthritis progression using enhancement time intensity curves obtained from CE-MRI (Contrast Enhanced Magnetic Resonance Imaging) | change from baseline at 6 month post procedure | | Change in Whole-Organ Magnetic Resonance Scoring (WORMS) | To evaluate the effects of particle embolization on knee osteoarthritis progression using the WORMS scoring system. The higher the score, the worse the OA is. The scoring ranges from 0-332. | change from baseline at 6 month post procedure | | Change in Multicenter Osteoarthritis Study (MOST) grading system for synovitis | To evaluate the effects of particle embolization on knee osteoarthritis progression using the MOST grading system for synovitis. The higher the score, the worse the synovial inflammation is. The scoring ranges from 0-13. 0-4 normal or equivocal synovitis, 5-8 mild synovitis, 9-12 moderate synovitis, and 13 or greater is severe synovitis. | change from baseline at 6 month post procedure | | Number of participants with 50% reduction in pain scores | To determine the effects of geniculate artery embolization (GAE) on opioid requirements for managing OA associated pain. Assess pain using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Knee Injury and Osteoarthritis Outcome Score (KOOS). WOMAC is scored from 0-20 for pain, 0-8 for stiffness, and 0-68 for physical function. Higher scores indicate worse pain, stiffness, and function limitation. KOOS score is from 0-100, 0 being extreme problems and 100 being no problems. | change from baseline at 1 month post procedure | | Number of participants with 50% reduction in pain scores | To determine the effects of geniculate artery embolization (GAE) on opioid requirements for managing OA associated pain. Assess pain using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Knee Injury and Osteoarthritis Outcome Score (KOOS). WOMAC is scored from 0-20 for pain, 0-8 for stiffness, and 0-68 for physical function. Higher scores indicate worse pain, stiffness, and function limitation. KOOS score is from 0-100, 0 being extreme problems and 100 being no problems. | change from baseline at 6 month post procedure | | Number of participants with 50% reduction in pain scores | To determine the effects of geniculate artery embolization (GAE) on opioid requirements for managing OA associated pain. Assess pain using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Knee Injury and Osteoarthritis Outcome Score (KOOS). WOMAC is scored from 0-20 for pain, 0-8 for stiffness, and 0-68 for physical function. Higher scores indicate worse pain, stiffness, and function limitation. KOOS score is from 0-100, 0 being extreme problems and 100 being no problems. | change from baseline at 12 month post procedure | | Incidence of adverse events associated with GAE | The number of adverse events per participant | 1 month post procedure | | Incidence of adverse events associated with GAE | The number of adverse events per participant | 6 month post procedure | | Incidence of adverse events associated with GAE | The number of adverse events per participant | 12 month post procedure |

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Oxidative Stress in the Patient With Peroperative Analgesia by Intravenous Lidocaine Study Overview ================= Brief Summary ----------------- Depending on the anesthesiologist's habits, injection or not of a 1.5 mg/kg bolus of lidocaine at induction of anesthesia followed by a continuous infusion of 1.5 mg/kg/h. Additional blood sample at 3 different times without additional puncture compared to usual management: 1) during the placement of the venous line before induction (Reactive Oxygen Species), 2) 1h after the end of induction at the time of blood gas to adapt ventilation (Reactive Oxygen Species), 3) at 24h of the beginning of the intervention (Reactive Oxygen Species and antioxidant molecular profile). Detailed Description ----------------- Intraoperatively, depending on the habits of the anesthesiologist, lidocaine may be started after induction (bolus of 1.5 mg/kg then relay at 1.5 mg/kg/h until the end of the procedure) or not (control group). Three blood samples will be taken. The first one (T0) during the placement of the venous line before induction and the second one (T1) one hour after the end of induction when the blood gas on the arterial catheter is taken to adapt the ventilation. These samples will be taken by the nurse in charge of the patient during the procedure. The third sample (T24) will be taken 24 hours after the beginning of the operation, during the blood test (venous or arterial), by the nurse of the department where the patient will be hospitalized. These samples will allow the evaluation of the level of Reactive Oxygen Species (ROS) (T0, T1, T24 - 4ml dry tube) and the antioxidant molecular profile (T24 - same tube as for the evaluation of the ROS (Reactive Oxygen Species) level). The collection of patient data will stop at D1 after the sampling. The anesthesia protocol will be standardized, in accordance with the department's habits and respecting the recommendations of the French Society of Anaesthesia and Intensive Care (SFAR): patient monitoring (pulse oximeter, invasive arterial catheter, capnograph, curarimeter and sevoflurane concentration monitoring), pre-oxygenation, intravenous induction (propofol, sufentanil, atracurium or rocuronium - dose at the discretion of the anesthesiologist), and maintenance with sevoflurane Intraoperative analgesia will systematically include the injection of sufentanil as well as at the end of the surgery the administration of paracetamol (1g) and nefopam (20 mg) associated or not with an anti-inflammatory. After induction, a dose of 8 mg of dexamethasone will be administered to the patient for the prevention of postoperative nausea and vomiting. In the recovery room, morphine titration can be performed if Visual Analogue Scale (VAS)>3 (3mg/5min). The postoperative analgesia protocol will be left to the discretion of the anesthesiologist. The parameters collected will be the demographic characteristics (sex, age, weight, height), the terrain (ASA score), the results of the preoperative biological examination (blood ionogram, urea, creatinine, blood count, liver examination), the duration of anesthesia and the doses of drugs received intraoperatively. The parameters measured will be the level of Reactive Oxygen Species in the blood sub populations and the antioxidant molecular profile: Reactive Oxygen Species : Analysis will be performed by flow cytometry using DCFDA labeling after erythrocyte lysis. Leukocyte sub populations (lymphocytes, monocytes, polynuclears) will be identified by co-labeling with an anti-Cluster Differentiation 45 antibody (anti-CD45). Antioxidant molecular profile : Quantification of the expression of the 26 major antioxidant genes and their isoforms (antioxidogramTM; patent WO2012085188 A1) will be performed on whole blood after RNA extraction, retro transcription into deoxyribonucleic acid (cDNA) Official Title ----------------- Oxidative Stress in the Patient With Peroperative Analgesia by Intravenous Lidocaine Conditions ----------------- Oxidative Stress, Analgesia Intervention / Treatment ----------------- * Biological: Blood sample Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patients requiring urological or ear, nose & throat (ENT) surgery with arterial catheterisation ASA 1 to 3 ≥ 18 years Exclusion Criteria: Heart failure (NYHA ≥ 3) Liver failure (aspartate aminotransferase and/or alanine aminotransferase ≥ 2N) Chronic renal insufficiency (GFR ≤ 30 ml/min/1.73m2) Allergy or intolerance to lidocaine Epilepsy ASA 4 Objection to data processing 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 | | --- | --- | | With lidocaine<br>Patient with injection of a 1.5 mg/kg bolus of lidocaine at induction of anaesthesia | Biological: Blood sample<br>* Blood sample before induction, 1h after induction and 24h after the start of procedure<br>| | Without lidocaine<br>Patient without injection of a 1.5 mg/kg bolus of lidocaine at induction of anaesthesia | Biological: Blood sample<br>* Blood sample before induction, 1h after induction and 24h after the start of procedure<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Reactive Oxygen Species | Analysis will be performed by flow cytometry using DCFDA labelling after erythrocyte lysis. Leukocyte subpopulations (lymphocytes, monocytes, polynuclears) will be identified by co-labelling with an anti-CD45 | 1 hour after induction | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Reactive Oxygen Species | Analysis will be performed by flow cytometry using DCFDA labelling after erythrocyte lysis. Leukocyte subpopulations (lymphocytes, monocytes, polynuclears) will be identified by co-labelling with an anti-CD45 | 24 hours after the start of the procedure | | Molecular antioxidant profile | The quantification of the expression of the 26 main antioxidant genes and their isoforms (antioxydogramTM ; patent WO2012085188 A1) will be performed on whole blood after RNA extraction, retrotranscription in cDNA. | 24 hours after the start of the procedure |

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A Study to Assess the Safety and Immune Response to Env-C DNA and Protein Vaccines in Kenya Study Overview ================= Brief Summary ----------------- This is a study of HIV vaccines. A vaccine is a medical product given to prevent certain diseases. The vaccine may educate the body to form a defensive response to try to prevent the disease from the beginning, or preventing it from taking hold of the body. This defensive response is called the immune response. The experimental vaccines in this study are Env-C Plasmid DNA and HIV Env gp145 C690 protein, given with different adjuvants. An adjuvant is a substance added to vaccines that can help make the vaccine more effective by improving the immune response, or by causing the immune response to last longer than it would without the adjuvant. The adjuvants are mixed with the vaccines and injected into muscle or placed on top of the skin. The HIV vaccines contain a piece of genetic material or a protein copied drom the HIV virus cover (Env), but they do not contain the virus itself. The vaccines cannot cause HIV infection or Acquired Immune Deficiency Syndrome (AIDS). The purpose of this study is to find out if the study vaccines with adjuvants cause side effects and are tolerable, whether humans respond (develop immune responses) to the vaccines, and how ling the effects of the study vaccines last. The study will also compare the effects of the study vaccines with adjuvants and adjuvant patch to those of placebo injections and placebo patch. The placebo will consist of saline (sterile saltwater) and will look like study vaccines, be given in the same way, but will have no active vaccine or adjuvant in it. A total of 126 participants will take part in the study and each will have up to 26 clinic visits and will be followed-up for a total of 108 weeks. Detailed Description ----------------- Antibodies are the most commonly recognized correlate of vaccine protection from infection; however the possible protective HIV antibody levels, which were induced by the modestly protective RV144 vaccine regimen with alum, rapidly decayed. Potentially, a novel, highly selective adjuvant combined with the correctly sequenced HIV antigen could slow antibody decay, increase antibody magnitude and induce antibodies of appropriate functional response. RV460 is an exploratory study that will assess the safety, tolerability, and immunogenicity of a vaccine regimen consisting of priming with an Env-C Plasmid DNA vaccine (with or without novel adjuvants) when given with or without adjuvanted HIV Env gp145 C.6980 protein vaccine and boosting with adjuvanted gp145 C.6980 protein with or without the gp120 DNA vaccine. The study will be carried out in Kericho, Kenya. 126 healthy adults will ben enrolled. Participants will be randomized into one of seven groups which have 15/3 vaccine/placebo recipients per group. Each participant will receive six injections (prim at week 0, 4, 12; boost at week 20, 32 and 56) and will be followed-up for a total of 108 weeks. Official Title ----------------- A Randomized, Double-Blind Phase 1 Trial to Evaluate the Safety and Immunogenicity of Priming With Env-C Plasmid DNA Vaccine Alone, With Different Adjuvants, or With an Adjuvanted HIV Env gp145 C.6980 Protein Vaccine and Boosting With the Adjuvanted HIV Env gp145 C.6980 Protein Vaccine With or Without the Env-C Plasmid DNA Vaccine in Healthy HIV Uninfected Adults in Kenya Conditions ----------------- HIV Infections Intervention / Treatment ----------------- * Biological: Env-C Plasmid DNA * Biological: HIV Env gp145 C.6980 protein * Drug: Rehydragel® * Biological: ALF43 * Biological: dmLT * Drug: Placebo (IM) * Drug: Placebo (TCl) Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Healthy, male and female participant aged 18 to 40 years and available for 26 months. Must be at low risk for HIV infection per investigator assessment and using the study risk assessment tool. Must be able to understand and complete the informed consent process. Must be capable of reading English or Kiswahili. Must agree to a home visit. Must complete a Test of Understanding (TOU) before enrollment. Must answer 9 out of 10 questions correctly with a maximum of three attempts. Must be in good general health without a clinically significant medical history. HIV-uninfected per diagnostic algorithm within 45 days of enrollment. Laboratory values: Hemoglobin 12.5-18.1 g/dL men 11.0-16.1 g/dL women White Cell Count 2.7-7.7 x 10³ cells/µL men 3.0-9.1 x 10³ cells/µL women Platelets: 125-370 10³ cells/µL men 125-444 10³ cells/µL women ALT and AST: ≤1.25 institutional upper limit of the reference range Creatinine: ≤1.25 institutional upper limit of the reference range Urinalysis: (dipstick) for blood and protein less than 1+ and negative glucose Female-Specific Criteria Negative urine pregnancy test for women at screening, the day of each vaccination, and before any invasive procedure. Already using and commits to continued use of an adequate birth control method for 45 days before to the first vaccination/placebo vaccination, and for at least 90 days after the final vaccine/placebo vaccination. Adequate birth control is defined as follows: Contraceptive medications delivered orally, intramuscularly, vaginally, or implanted, underneath the skin, surgical methods (hysterectomy or bilateral tubal ligation), condoms with spermicide, diaphragms, intrauterine device (IUD), vasectomy in a monogamous partner, or abstinence. Lymph Node Biopsy Inclusion Criteria Body mass index (BMI) <35 Platelets >150,000 International normalized ration (INR) <1.2 Verbal report of no NSAIDS/aspirin for 7 days prior. Negative pregnancy test for participants born female. Exclusion Criteria: A history of: Three or more sexual partners in the previous 24 weeks. Commercial sex work. Non-adherence to condom use in the absence of a long-term monogamous relationship. Intravenous drug use in the previous year. A sexually transmitted infection in the previous 24 weeks. Asplenia: any condition resulting in the absence of a functional spleen. Bleeding disorder diagnosed by a medical doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions). Breastfeeding or pregnant (positive pregnancy test) women or planning to become pregnant during the window between study enrollment and three months after the last vaccination visit. Any past, ongoing, or in remission history of treated or untreated autoimmune disease. Has known active Hepatitis B virus infection (or positive HBsAg). Has known active Hepatitis C infection. History of anaphylaxis or other serious adverse reaction to vaccines or allergies or reactions likely to be exacerbated by any component of the vaccine and placebo, including antibiotics or excipients. Absolute Neutrophil Count (ANC) <1.0 x 10³ cells/µL. Participant has received any of the following substances: Chronic use of therapies that may modify immune response, such as intravenous (IV) immune globulin and systemic corticosteroids (in doses of >20 mg/day prednisone equivalent for periods exceeding 10 days). The following exceptions are permitted and will not exclude study participation: Use of corticosteroid nasal spray for rhinitis; Topical corticosteroids for an acute uncomplicated dermatitis; or A short course (10 days or less, or a single injection) of corticosteroid for a non-chronic condition (based on investigator clinical judgment) at least 2 weeks before enrollment. Blood products within 120 days before HIV screening. Immunoglobulins within 30 days before HIV screening. Any experimental vaccine containing an adjuvant other than aluminum of an adjuvant not approved by the FDA or European Medicines Agency (EMA) as part of a licensed vaccine. CERVARIX vaccine against HPV (containing AS04) Receipt of any investigational HIV vaccine, investigational research agents or vaccine within 30 days before enrollment. Anti-tuberculosis prophylaxis or therapy during the past 90 days before enrollment. Any psychiatric, social condition, occupational reason, or other responsibility that, in the judgment of the investigator, is a contraindication to protocol compliance or impairs a participant's ability to give informed consent. Major psychiatric illness and or substance abuse problems during the past 12 months that, in the opinion of the investigator, would preclude participation. History of atopy or significant skin conditions. Study site employees who are involved in the protocol and or may have direct access to the study-related area. Lymph Node Biopsy Exclusion Criteria History of keloid formation. History of an inguinal hernia, inguinal canal cryptorchidism, varicocele, hydrocele. History of inguinal excisional lymph node biopsy. Final evaluation of eligibility is based on the medical judgment of the investigator. The Protocol Safety Review Team will also remain available to the investigator for consultation if desired. Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 40 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: Double Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Group 1: Vaccine or Placebo<br>3 doses of prime vaccination or placebo at weeks 0, 4, 12 followed by 3 doses of boost vaccination or placebo at weeks 20, 32, 56 | Biological: Env-C Plasmid DNA<br>* 2 mg per dose. Administered by intramuscular injection.<br>Biological: HIV Env gp145 C.6980 protein<br>* 100 µg per dose. Administered by intramuscular injection.<br>Drug: Rehydragel®<br>* Adjuvant. Aluminum hydroxide fluid gel. 500 µg per dose. Administered by intramuscular injection.<br>Drug: Placebo (IM)<br>* 0.9% sodium chloride (sterile saline). Administered by intramuscular injection.<br>| | Experimental: Group 2: Vaccine or Placebo<br>3 doses of prime vaccination or placebo at weeks 0, 4, 12 followed by 3 doses of boost vaccination or placebo at weeks 20, 32, 56 | Biological: Env-C Plasmid DNA<br>* 2 mg per dose. Administered by intramuscular injection.<br>Biological: HIV Env gp145 C.6980 protein<br>* 100 µg per dose. Administered by intramuscular injection.<br>Drug: Rehydragel®<br>* Adjuvant. Aluminum hydroxide fluid gel. 500 µg per dose. Administered by intramuscular injection.<br>Biological: ALF43<br>* Adjuvant. Army Liposome Formulation-43% Cholesterol. 200 µg per dose. Administered by intramuscular injection.<br>Drug: Placebo (IM)<br>* 0.9% sodium chloride (sterile saline). Administered by intramuscular injection.<br>| | Experimental: Group 3: Vaccine or Placebo<br>3 doses of prime vaccination or placebo at weeks 0, 4, 12 followed by 3 doses of boost vaccination or placebo at weeks 20, 32, 56 | Biological: Env-C Plasmid DNA<br>* 2 mg per dose. Administered by intramuscular injection.<br>Biological: HIV Env gp145 C.6980 protein<br>* 100 µg per dose. Administered by intramuscular injection.<br>Drug: Rehydragel®<br>* Adjuvant. Aluminum hydroxide fluid gel. 500 µg per dose. Administered by intramuscular injection.<br>Biological: dmLT<br>* Adjuvant. Recombinant double mutant Escherichia coli heat labile toxin. 50 µg per dose. Transcutaneous application (needle-free skin patch). 1 mL diluted dmLT added to gauze pad at site of injection.<br>Drug: Placebo (IM)<br>* 0.9% sodium chloride (sterile saline). Administered by intramuscular injection.<br>Drug: Placebo (TCl)<br>* Transcutaneous application (needle-free skin patch). 0.9% sodium chloride (sterile saline) added to gauze pad at site of injection.<br>| | Experimental: Group 4: Vaccine or Placebo<br>3 doses of prime vaccination or placebo at weeks 0, 4, 12 followed by 3 doses of boost vaccination or placebo at weeks 20, 32, 56 | Biological: Env-C Plasmid DNA<br>* 2 mg per dose. Administered by intramuscular injection.<br>Biological: HIV Env gp145 C.6980 protein<br>* 100 µg per dose. Administered by intramuscular injection.<br>Drug: Rehydragel®<br>* Adjuvant. Aluminum hydroxide fluid gel. 500 µg per dose. Administered by intramuscular injection.<br>Biological: ALF43<br>* Adjuvant. Army Liposome Formulation-43% Cholesterol. 200 µg per dose. Administered by intramuscular injection.<br>Biological: dmLT<br>* Adjuvant. Recombinant double mutant Escherichia coli heat labile toxin. 50 µg per dose. Transcutaneous application (needle-free skin patch). 1 mL diluted dmLT added to gauze pad at site of injection.<br>Drug: Placebo (IM)<br>* 0.9% sodium chloride (sterile saline). Administered by intramuscular injection.<br>Drug: Placebo (TCl)<br>* Transcutaneous application (needle-free skin patch). 0.9% sodium chloride (sterile saline) added to gauze pad at site of injection.<br>| | Experimental: Group 5: Vaccine or Placebo<br>3 doses of prime vaccination or placebo at weeks 0, 4, 12 followed by 3 doses of boost vaccination or placebo at weeks 20, 32, 56 | Biological: Env-C Plasmid DNA<br>* 2 mg per dose. Administered by intramuscular injection.<br>Biological: HIV Env gp145 C.6980 protein<br>* 100 µg per dose. Administered by intramuscular injection.<br>Drug: Rehydragel®<br>* Adjuvant. Aluminum hydroxide fluid gel. 500 µg per dose. Administered by intramuscular injection.<br>Biological: ALF43<br>* Adjuvant. Army Liposome Formulation-43% Cholesterol. 200 µg per dose. Administered by intramuscular injection.<br>Drug: Placebo (IM)<br>* 0.9% sodium chloride (sterile saline). Administered by intramuscular injection.<br>| | Experimental: Group 6: Vaccine or Placebo<br>3 doses of prime vaccination or placebo at weeks 0, 4, 12 followed by 3 doses of boost vaccination or placebo at weeks 20, 32, 56 | Biological: Env-C Plasmid DNA<br>* 2 mg per dose. Administered by intramuscular injection.<br>Biological: HIV Env gp145 C.6980 protein<br>* 100 µg per dose. Administered by intramuscular injection.<br>Drug: Rehydragel®<br>* Adjuvant. Aluminum hydroxide fluid gel. 500 µg per dose. Administered by intramuscular injection.<br>Biological: ALF43<br>* Adjuvant. Army Liposome Formulation-43% Cholesterol. 200 µg per dose. Administered by intramuscular injection.<br>Drug: Placebo (IM)<br>* 0.9% sodium chloride (sterile saline). Administered by intramuscular injection.<br>| | Experimental: Group 7: Vaccine or Placebo<br>3 doses of prime vaccination or placebo at weeks 0, 4, 12 followed by 3 doses of boost vaccination or placebo at weeks 20, 32, 56 | Biological: Env-C Plasmid DNA<br>* 2 mg per dose. Administered by intramuscular injection.<br>Biological: HIV Env gp145 C.6980 protein<br>* 100 µg per dose. Administered by intramuscular injection.<br>Drug: Rehydragel®<br>* Adjuvant. Aluminum hydroxide fluid gel. 500 µg per dose. Administered by intramuscular injection.<br>Biological: ALF43<br>* Adjuvant. Army Liposome Formulation-43% Cholesterol. 200 µg per dose. Administered by intramuscular injection.<br>Drug: Placebo (IM)<br>* 0.9% sodium chloride (sterile saline). Administered by intramuscular injection.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Number of solicited adverse events (AEs), related AEs and serious AEs (SAEs) | | Thru Week 105 | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Magnitude of plasma IgG binding antibodies in response to differing DNA priming regimens | Measured by binding antibody assays. | Thru Week 105 | | Durability of plasma IgG binding antibodies in response to differing DNA priming regimens | Measured by binding antibody assays. | Thru Week 105 | | Area under the curve (AUC) for plasma IgG binding antibodies in response to differing DNA priming regimens | Measured by binding antibody assays. | Thru Week 105 | | Magnitude of plasma IgG binding antibodies between groups with and without Rehydragel® after HIV Env gp145 C.6980 protein boosting | Measured by binding antibody assays. | Thru Week 105 | | Durability of plasma IgG binding antibodies between groups with and without Rehydragel® after HIV Env gp145 C.6980 protein boosting | Measured by binding antibody assays. | Thru Week 105 | | AUC for plasma IgG binding antibodies between groups with and without Rehydragel® after HIV Env gp145 C.6980 protein boosting | Measured by binding antibody assays. | Thru Week 105 | | Presence of plasma IgG binding antibodies | Functional antibodies assessed using rapid fluorometric Antibody-dependent Cell-Mediated Cytotoxicity (ADCC) Assay, Antibody-dependent Cell-mediated Phagocytosis (ADCP), Antibody-dependent Complement (ADC) activation assays, or other functional assays. Neutralizing antibodies assessed using cell line-based and PBMC assays with a panel of viruses from different HIV subtypes, including A, B, C, D, and other circulating recombinant forms (CRFs) such as AE and AG. | Thru Week 105 | | Presence of plasma IgA binding antibodies | Functional antibodies assessed using rapid fluorometric Antibody-dependent Cell-Mediated Cytotoxicity (ADCC) Assay, Antibody-dependent Cell-mediated Phagocytosis (ADCP), Antibody-dependent Complement (ADC) activation assays, or other functional assays. Neutralizing antibodies assessed using cell line-based and PBMC assays with a panel of viruses from different HIV subtypes, including A, B, C, D, and other circulating recombinant forms (CRFs) such as AE and AG. | Thru Week 105 | | Types of cell-mediated immune responses | Cryopreserved PBMC and lymph nodes will be stimulated with HIV-1-specific antigens and tested using standard (but not limited to) cellular immune assays which may include but are not limited to Intracellular cytokine Staining, ELISPOT, Lymphoproliferation assays, B-cell analysis, T-follicular helper cell and innate immune cell analysis. | Thru Week 105 | | Level of cell-mediated immune responses | Cryopreserved PBMC and lymph nodes will be stimulated with HIV-1-specific antigens and tested using standard (but not limited to) cellular immune assays which may include but are not limited to Intracellular cytokine Staining, ELISPOT, Lymphoproliferation assays, B-cell analysis, T-follicular helper cell and innate immune cell analysis. | Thru Week 105 | | Types of mucosal humoral responses | Including, but not limited to, plasma IgG and IgA binding antibodies to HIV Env proteins, IgG and IgA subclass, and functional assays. | Thru Week 104 |

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First in Human Study of ChAdOx1-HBV Study Overview ================= Brief Summary ----------------- This is a Phase 1, first in human study of ChAdOx1-HBV. The study will be conducted in 40 healthy participants and 12 participants with CHB and virally suppressed with oral antiviral medication. This will be an open-label, non randomised dose escalation study comparing the safety, tolerability and immunogenicity of 2 different doses of ChAdOx1 HBV vaccine. T cell responses in healthy participants who have received a prior two-dose series of AZD1222 will be compared with those who have received either the Pfizer COVID 19 vaccine or the Moderna mRNA COVID 19 vaccine. Detailed Description ----------------- This is a first in man human study of a therapeutic vaccine for chronic hepatitis B infection(ChAdOx1-1HBV). The vaccine will be given to participants in a dose escalation strategy (two doses). Five healthy participants will be administered the low dose first (cohort 1). Dose escalation will only be initiated in the next 5 healthy participants (cohort 2) following Safety Monitoring Committee (SMC) review. Six CHB participants will be administered the low dose (cohort 3) before the dose escalation is initiated in the remaining 6 CHB participants (cohort 4). Thirty healthy participants (15 who have received two doses of AZD1222 [cohort 5] and 15 who have received at least two prior doses of Pfizer/Moderna mRNA COVID 19 vaccine [cohort 6]) will be dosed in parallel with the high dose used in cohorts 2 and 4. Each participant will receive 1 dose of the vaccine (intramuscular injection). Participants (Volunteers & patients) in cohorts 1 to 4 will attend up to 9 study visits and cohorts 5 & 6 will attend up to 4 visits in total. The last visit will be 24 weeks after vaccination for cohorts 1 to 4 and 12 weeks for cohorts 5 & 6. Official Title ----------------- A Phase 1 Monotherapy Study to Evaluate the Safety, Tolerability & Immunogenicity of Vaccination With Candidate Chimpanzee Adenovirus-vectored HepB Virus Vaccine ChAdOx1 HBV in Healthy Participants & Participants With Chronic HepB Infection Conditions ----------------- Hepatitis B, Healthy Intervention / Treatment ----------------- * Biological: ChAdOx1-HBV Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Adult males or females aged ≥18 to ≤65 years at screening Body Mass Index ≤30 kg/m2 Able to provide informed consent indicating they understand the purpose of, and procedures required, for the study and are willing to participate If female, willing not to become pregnant up to 8 weeks after last dose of study vaccine, not breast feeding If female: Not pregnant, and one of the following: Of non-childbearing potential (i.e. women who have had a hysterectomy or tubal ligation or are post menopausal, as defined by no menses in ≥1 year) Sexual abstinence, only if the participant refrains from heterosexual intercourse during the entire study period and it is the usual lifestyle of the participant Of childbearing potential but agrees to practice highly effective contraception for 4 weeks prior to study vaccine and 8 weeks after study vaccine. Highly effective methods of contraception include one or more of the following: Male partner who is sterile (medically effective vasectomy) prior to the female participant's entry into the study and is the sole sexual partner for the female participant, Hormonal (oral, intravaginal, transdermal, implantable or injectable), An intrauterine hormone releasing system, An intrauterine device and Bilateral tubal occlusion Healthy participants (cohorts 1 and 2): Considered to be healthy with no current conditions that may significantly impair participant safety or influence study results, in the opinion of the Investigator Participants with well controlled CHB (cohorts 3 and 4): Documented evidence of chronic HBV infection (e.g. HBsAg positive ≥6 months with detectable HBsAg levels at screening) Receipt of only either entecavir or tenofovir for at least 12 months before screening Virally suppressed (HBV DNA <40 IU/mL for ≥6 months) HBsAg <4000IU/mL Participants with well controlled CHB (cohorts 3 and 4): 7. Documented evidence of chronic HBV infection (e.g. HBsAg positive ≥6 months with detectable HBsAg levels at screening) 8. Receipt of only either entecavir or tenofovir for at least 12 months before screening 9. Virally suppressed (HBV DNA <40 IU/mL for ≥6 months) 10. HBsAg <10000 IU/mL Healthy participants (cohort 5): 11. Considered to be healthy with no current conditions that may significantly impair participant safety or influence study results, in the opinion of the Investigator 12. Adult males or females aged ≥40 to ≤60 years at screening 13. Completed second dose of COVID-19 AZD1222 vaccine 10 to 18 weeks before enrolment Healthy participants (cohort 6): 14. Considered to be healthy with no current conditions that may significantly impair participant safety or influence study results, in the opinion of the Investigator 15. Adult males or females aged ≥40 to ≤60 years at screening 16. Received the latest dose of Completed of either Pfizer (Comirnaty®) or Moderna (Spikevax) mRNA COVID 19 vaccine 6 to 30 weeks before enrolment Exclusion Criteria: Presence of any significant acute or chronic, uncontrolled medical/ psychiatric illness Hepatitis C virus antibody positive. Human immunodeficiency virus antibody positive History or evidence of autoimmune disease or known immunodeficiency of any cause Prolonged therapy with immunomodulators (e.g. corticosteroids) or biologics (e.g. monoclonal antibodies, interferon) within 3 months of screening Receipt of immunoglobulin or other blood products within 3 months prior to screening Receipt of any investigational drug or vaccine within 3 months prior to screening Cohorts 1-4: Receipt of any adenoviral vaccine within 3 months prior to administration of ChAdOx1-HBV on Day 0, or plan to receive an adenoviral-based vaccine within 3 months after Day 0 Cohorts 5 and 6: Receipt of any adenoviral vaccine (other than AZD1222 per inclusion criterion 13) within 3 months prior to administration of ChAdOx1-HBV on Day 0, or plan to receive an adenoviral-based vaccine within 3 months after Day 0 Receipt of any live vaccines within 30 days prior to screening Receipt of any inactivated vaccines within 14 days prior to screening History of allergic disease or reactions likely to be exacerbated by any component of the vaccine Any history of anaphylaxis in reaction to vaccination Malignancy within 5 years prior to screening with the exception of specific cancers that are cured by surgical resection (e.g. except basal cell skin carcinoma of the skin and cervical carcinoma). Participants under evaluation for possible malignancy are not eligible Current alcohol or substance abuse judged by the Investigator to potentially interfere with participant safety and compliance Significant cardiac disease or unstable uncontrolled cardiac disease Any laboratory test at screening which is abnormal and which is deemed by the Investigator to be clinically significant Any other finding that, in the opinion of the Investigator, deems the participant unsuitable for the study Additionally, for healthy participants (cohorts 1, 2, 5 and 6) HBsAg positive Additionally, for participants with well controlled CHB (cohorts 3 and 4) Co infection with hepatitis delta Documented cirrhosis or advanced fibrosis indicated by a liver biopsy within 6 months prior to screening. In the absence of an appropriate liver biopsy, either 1 of the following: Screening Fibroscan with a result >9 kPa within ≤6 months of screening or Screening FibroTest >0.48 and aspartate aminotransferase (AST) to platelet ratio index of >1 In the event of discordant results between non-invasive methods, the Fibroscan result will take precedence. Alanine transaminase (ALT) >3 × upper limit of normal, international normalised ratio (INR) >1.5 unless the participant was stable on an anticoagulant regimen affecting INR, albumin <35 g/L, total bilirubin >2 mg/dL, platelet count <100,000/mL A history of liver decompensation (e.g. ascites, encephalopathy or variceal haemorrhage) Prior or current hepatocellular carcinoma Chronic liver disease of a non HBV aetiology Any herbal supplements and or other medicines with potential liver toxicity within the previous 3 months prior to enrolment into this study 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: Sequential Assignment Interventional Model Description: The participants will be recruited in 6 cohorts as follows - Cohort 1 - Healthy Volunteers - Low dose Vaccine - 5 participants Cohort 2 - Healthy Volunteers - High dose Vaccine - 5 participants Cohort 3 - Participants with Chronic Hepatitis B infection - Low dose - 6 participants Cohort 4 - Participants with Chronic Hepatitis B infection - High dose - 6 participants Cohort 5 - Healthy Volunteers who have completed 2 doses of COVID-19 AZD1222 vaccine Cohort 6 - Healthy Volunteers who have completed 2 doses of either Pfizer or Moderna mRNA COVID 19 vaccine Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Healthy Volunteers with low dose vaccination<br>5 Healthy Volunteers receiving low dose vaccination | Biological: ChAdOx1-HBV<br>* chimpanzee adenovirus-vectored hepatitis B virus vaccine<br>| | Experimental: Healthy Volunteers with high dose vaccination<br>5 Healthy Volunteers receiving high dose vaccination | Biological: ChAdOx1-HBV<br>* chimpanzee adenovirus-vectored hepatitis B virus vaccine<br>| | Experimental: Chronic Hepatitis B participants with low dose vaccination<br>6 participants with Chronic Hepatitis B infection receiving low dose vaccination | Biological: ChAdOx1-HBV<br>* chimpanzee adenovirus-vectored hepatitis B virus vaccine<br>| | Experimental: Chronic Hepatitis B participants with high dose vaccination<br>6 participants with Chronic Hepatitis B infection receiving high dose vaccination | Biological: ChAdOx1-HBV<br>* chimpanzee adenovirus-vectored hepatitis B virus vaccine<br>| | Experimental: Healthy Volunteers who have had COVID-19 AZD1222 vaccine<br>15 participants who have had 2 doses of COVID-19 AZD1222 vaccine | Biological: ChAdOx1-HBV<br>* chimpanzee adenovirus-vectored hepatitis B virus vaccine<br>| | Experimental: Healthy Volunteers who have had Pfizer/Moderna mRNA COVID 19 vaccine<br>15 participants who have had Pfizer/Moderna mRNA COVID 19 vaccine | Biological: ChAdOx1-HBV<br>* chimpanzee adenovirus-vectored hepatitis B virus vaccine<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Adverse events | Adverse events and/or adverse events leading to study discontinuation | From screening up to day 7 for solicited AE's, unsolicited events through study completion (on average 6 months) | | Serious adverse events | Serious adverse events related to the study vaccine | from day 0 to up to 6 months | | Grade ≥3 local and systemic reactions | Local reactogenicity - pain, induration, warmth, erythema at the vaccination site Systemic: feverishness, chills, myalgia, fatigue, headache, nausea, arthralgia, malaise | from day 0 to day 3 |

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Initiating Ketamine in Acutely Suicidal Patients in the Emergency Department Study Overview ================= Brief Summary ----------------- Current treatment for acutely suicidal patients are limited to hospitalization, psychotherapy, electro-convulsant therapy, or a combination of the aforementioned. However, this has added to the national boarding problem. Long term pharmacologic treatment for suicidal behaviors and mood stabilization has been studied in specific populations. In these populations, the decreases in suicidal ideation results from stabilization of the underlying psychiatric illness. Ketamine is most commonly used as an anesthetic with analgesic properties. It has been used off-label for pain management, procedural sedation, status epilepticus, and treatment resistant depression. It has been safely administered intravenously and well tolerated for chronic Post Traumatic Stress Disorder. It increases norepinephrine, dopamine, and serotonin through adrenergic neuron stimulation and prevention of catecholamine uptake. There is a strong corollary between stress and the development of depression and suicidal behaviors. It is proposed that the use of low dose intravenous ketamine may have benefit on the suicidal ideation of patients presenting to the Emergency Department. Detailed Description ----------------- There is a strong corollary between stress and the development of depression and suicidal behaviors. The neurobiological mediators of stress are primarily controlled by the noradrenergic and corticotropin-releasing factor (CRF) median eminence systems. Furthermore, stress directly and indirectly, through the Hypothalamic Pituitary Axis, activates the Locus Coeruleus (LC), which is the primary producer of NE in the central nervous system (CNS). Directly, glutaminergic neurons send excitatory signals to the LC via interaction with N-Methyl-D-Aspartate (NMDA) receptors NMDA antagonists, such as ketamine, can dampen the glutaminergic system, which has been implicated during states of depression and low moods. The neurobiological commonality between multiple psychiatric disorders and depression, suicide, and attempted suicide is a decrease in serotonergic activity. It has been shown that patients who died of suicide, have decreased serotonin transporter in the ventromedial prefrontal cortex and anterior cingulate, which are areas that control decision making or willful action. The prefrontal cortex is important for inhibitory behavioral control. A potential treatment modality of ketamine, is that it produces activation of this region.35 The anterior cingulate cortex has been shown to be associated with impulsive aggression compared to control. Clinical studies have shown that low CSF 5-HIAA, metabolite in serotonin system, has been implicated and positively correlated to aggression scores and impulsivity. This is interesting because, suicides in the military are thought to have an impulsivity component, triggered by one or more major life stressors. Another region associated with suicide is the infralimbic cortex. A recent study, based on neuroimaging techniques, demonstrated that glucose metabolism in this region was associated with SI at baseline, and decreases in SI was observed after ketamine infusion. This is the same region target by deep brain stimulation, for depression treatment. Additionally, the infralimbic cortex has been implicated in behavioral flexibility. Implicating that ketamine's anti-suicidal properties may stem from its ability to promoting cognitive flexibility. Most likely due to its ability to increase brain-derived neurotrophic factor (BDNF), which is a major contributor to neuronal plasticity. BDNF also plays key roles in synaptic and long-term potentiation, which may counteract the decreased levels in Mood Disorder (MDD) patients. Furthermore, ketamine infusion has been shown to change sleep slow wave activity. This biomarker is functionally related to increased synaptic strengthening and cortical synchronization. These factors, combined, may be implicated in not only ketamine's antidepressant effects and counteraction of decreased synaptic plasticity seen mood disorders, but also its ability to have week long lasting effects. This information leads us to hypothesize that treatment of acutely suicidal patients with ketamine would: 1) decrease suicidal ideationto a clinically significant degree, and 2) the effect of ketamine will be seen for as long as one-week post administration. To the best of our knowledge, this study does not duplicate any ongoing work. Instead, it would strengthen power to past studies and current work. There are four clinical trials investigating ketamine's effect on SI. One has an unknown status. There are two that are investigating ketamine in relationship to psychiatric standard of care, whereas this study is investigating its effects against a saline placebo. Finally, the last clinical trial is investigating the Neurobiology of Suicide. Their phase 2 component, which utilizes a similar protocol, uses ketamine as a tool to identify potential biomarkers for suicide. Furthermore, this study differs from Janssen Research & Development's clinical trial in administration route and study design. Their study focuses on using ketamine through intranasal administration. Their primary outcomes are the long-term safety and efficacy, and the design of their study is an open label multicenter trial. This research does not duplicate any prior work. To date, there is only one study, from Iran, that evaluates the effectiveness of ketamine in high risk patients, or those that present as acutely suicidal to the ED. This was a single blinded trial that utilized 0.2mg/kg infused over one minute. The study indicated significant decrease in their measurement outcomes. However, they concluded that ketamine is not a good choice for treatment because it did not meet their cut off values. Their results might have been influenced by the rapid infusion over one minute, which differs from our study as well as the vast majority of the literature. We believe the slower 40-minute infusion is necessary for optimal results, as the larger dosage has produced more clinically meaningful results in prior studies, and the slower infusion produced less negative side effects. They chose the minimal dose shown to diminish SI41 200 ng/ml (0.2 mg/kg), which provokes lateral nystagmus.35 This protocol utilizes a higher dose, 0.5 mg/kg, which is the ED50 for narcosis. Our study is medically relevant because dosage effects on SI have not been studied. Comparison of our studies may address questions regarding the optimal dose and infusion rate. The BSSI will measure the severity of SI. It is based on the interviewer rated version of the original Scale for Suicidal Ideation (SSI), which is one of the few document suicide assessment tools with predictive validity for suicide completion. The internal reliability, test and retest validity, as well as invariance over time has been demonstrated for the BSS. Furthermore, the first five items of the BSSI are a common clinical screening for the presence of suicidal thoughts. For these reasons, the BSSI was chosen as our primary outcomes measure. Two studies have indicated that the cut off between high and low risk is a BSS ≥ 2. A recent investigation has determined BSSI ≥ 6 is predictive of future suicide attempts. These two values will serve in our analysis. The Montgomery- Åsberg Depression Rating Scale (MADRS) is a widely known 10 item clinician administered measure of depression severity. Since it's development in the late 1970s, it has become more popular than the gold standard, Hamilton rating scale for Depression (HAM-D). It is considered to be more sensitive to change, just as effective, and simpler to use clinically. However, the reliability depends on good interrater agreement. Difficulties in clinical trial to show signal detection for known effective drugs have implicated clinician administered measurement as a possible source of error. To avoid poor interrater reliability, rater bias, and variable interview quality, this trial will utilize the self-administered version of the MADRS-S. This has 9 items and a total score ranging from 0 to 27.50 The scoring of MADRS-S has shown to be similar to that of physician scoring. The emotional pain of the suicidal patient requires empathetic care that may not always be possible with the time pressures, volume, and pragmatic nature of the ED environment. A pharmacologic intervention with rapid effects to decrease SI would play a vital role in improving the standard of care for this vulnerable population. Official Title ----------------- Initiating Ketamine in Acutely Suicidal Patients in the Emergency Department Conditions ----------------- Suicide, Suicide Threat, Depression Severe Intervention / Treatment ----------------- * Drug: Ketamine Hydrochloride * Drug: Normal saline Participation Criteria ================= Eligibility Criteria ----------------- Subject Inclusion and Selection Criteria Patient demographics will consist of Active, Reserve, or retired military personnel or their dependents. Subjects must meet the following inclusion criteria: Adult (18 to 89 years old) Present with active SI Deemed to being admitted to inpatient psychiatric unit Subject Exclusion Criteria: Age < 18 years old or > 89 years old Currently presenting with psychosis as determined by mental health consultant Have a history of Cognitive disorder that would impair understanding of consent Have a personal/family history of Schizophrenia Currently pregnant or nursing Serious and unstable medical condition/problems Inability to medically clear Non-English Speakers Civilian Humanitarians Have previously enrolled in this study Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 89 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: Single Group Assignment Interventional Model Description: Experimental versus Placebo Masking: Quadruple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Experimental-Ketamine<br>single dose IV Ketamine (Ketalar) 0.5mg/kg in 100ml Normal Saline infused over 40 minutes | Drug: Ketamine Hydrochloride<br>* Experimental Procedure Baseline evaluation of suicidal severity (BSSI) & degree of depressive symptoms (MADRS-S) will be evaluated through self-administered questionnaires. The experimental and placebo arms will receive a single dose of IV ketamine, 0.5 mg/kg in 100 cc NS or 100 cc of NS infused over 40 minutes. Post ketamine re-evaluation of outcome measures at four and twenty-four hours will determine clinical effectiveness of ketamine intervention Inspection of admission and transfer time provides time measurement for LOS. This secondary measure is needed to determine efficiency of intervention. Post ketamine re-evaluation of outcome measure at one-week post infusion will elucidate ketamine's durability of effect.<br>* Other names: Experimental Arm;| | Placebo Comparator: Placebo-Saline<br>100ml Normal Saline infused over 40 minutes | Drug: Normal saline<br>* Experimental Procedure Baseline evaluation of suicidal severity (BSSI) & degree of depressive symptoms (MADRS-S) will be evaluated through self-administered questionnaires. The placebo arms will receive a single dose of 100 cc of NS infused over 40 minutes. Post Placebo infusion re-evaluation of outcome measures at four and twenty-four hours Inspection of admission and transfer time provides time measurement for LOS. This secondary measure is needed to determine efficiency of intervention. Post Normal Saline re-evaluation of outcome measure at one-week post infusion.<br>* Other names: Placebo Comparator;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Suicidal Severity-clinical efficacy | completion of BSSI to evaluate suicidal severity. | 4 hour+/1 after infusion completion, performed for placebo and drug arms | | Suicidal Severity-clinical efficacy | completion of BSSI to evaluate suicidal severity. | 24-36 hours after infusion completion, performed for placebo and drug arms | | Suicidal Severity-duration of efficacy | completion of BSSI to evaluate suicidal severity. | 1week+/-1 day after infusion completion, performed for placebo and drug arms | | Depression symptoms-clinical efficacy | completion of MADRS-S to evaluate depression symptoms. | 4 hours +/-1 after infusion completion, performed for placebo and drug arms | | Depression symptoms-clinical efficacy | completion of MADRS-S to evaluate depression symptoms. | 24-46 hours after infusion completion, performed for placebo and drug arms | | Depression symptoms-duration of efficacy | completion of MADRS-S to evaluate depression symptoms. | 1 week +/-1 day after infusion completion, performed for placebo and drug arms | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Length of Stay | inspection of admission and transfer or discharge date | performed on medical record review at 1 week | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- ketamine

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Enduring Happiness and Continued Self-Enhancement (ENHANCE) 2.0 Study Overview ================= Brief Summary ----------------- The study is designed to compare the efficacy of two programs intended to improve happiness and well-being among healthy, community adults between the ages of 25 and 75 years. Participants will complete either an in-person program (ENHANCE) or a mindfulness-based stress reduction (MBSR) self-help program over 3-months. The ENHANCE program will include 12-weekly sessions based on researched principles of happiness. Alternatively, the MBSR self-help guide will teach ways to replace stress-promoting habits. Participants will be asked to complete a series of measures at three points of the study: at the start of the study, the end of the study, and 3-months following the study. Detailed Description ----------------- In 2011, the United Nations defined happiness as a fundamental human goal and invited Member States to pursue measures that enhance the happiness of their citizens. The majority of people across the globe agree that happiness is an important goal. In accordance with this global goal to be happy, the psychological literature abounds with interventions to combat problems that may prevent people from being happy-from obesity to depression and physical pain. However, happiness is not simply the absence of problems. Yet, interventions to help people attain and maintain higher levels of happiness are rare. Accordingly, in a previous study, the investigators designed and evaluated the efficacy of a theoretically-grounded, evidence-based randomized controlled trial for enhancing happiness and well-being. In the present study, it is the goal to assess the efficacy of modifications made to the original program, and compare the program to a self-help comparison group. All participants in the study will complete weekly questionnaires, as well as the same battery of online assessments at baseline, the end of the study, and 3-months following the study. The investigators will be examining if changes seen from baseline to the end of the interventions are maintained through a maintenance intervention in both arms for 3 months following the primary intervention. It is expect that participants actively completing the in-person ENHANCE program will report greater increase in their overall levels of happiness/well-being at the end of the 12-week program compared to participants in the MBSR self-help group. It is predicted that there will be a downstream effect on happiness for all participants' mental and physical health, cognitive function, social relationships, and other positive outcomes, but that this effect will be greater for participants in the active in-person ENHANCE group. The insights gained from this research could be used in future intervention research towards promoting health, achievement, citizenship, and better relationships. Official Title ----------------- Enduring Happiness and Continued Self-Enhancement (ENHANCE) 2.0: A Well-Being Program Conditions ----------------- Well-being Intervention / Treatment ----------------- * Behavioral: ENHANCE group * Behavioral: MBSR group Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: All participants in the study will include males and females between the ages of 25 and 75 years. Participants of all racial and ethnic backgrounds will be eligible to participate. Participants of all religious and spiritual orientations will be eligible to participate. Exclusion Criteria: Participants will be screened for major psychological disorders, such as anxiety and depression using the Patient Health Questionnaire-9 (PHQ-9. Participants who are screened with a major mental illness (such as severe depression as determined by a cut-off score of 15 or greater on the PHQ-9) will be advised that this study is not designed as a treatment for mental illness (including severe depression), and will be given a list of the appropriate mental health services offered in their community (e.g., Kelowna Mental Health and Substance Use Services). Ages Eligible for Study ----------------- Minimum Age: 25 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: Other Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: ENHANCE group<br>The ENHANCE group is comprised of 12 weekly session to be completed in-person and delivered by trained group facilitators. | Behavioral: ENHANCE group<br>* The ENHANCE program includes an initial 3-month treatment of 12 weekly sessions (including an introductory session, a final session, and 10 content sessions) followed by a 3-month maintenance phase intervention with bi-weekly sessions. Over the course of the program, participants will learn about 10 evidenced-based principles of happiness and how these principles can be applied effectively in their lives. At the final session, participants will receive feedback outlining the happiness principles and activities that fit them best, and will then be asked to work on creating a plan for integrating those principles into their daily lives.<br>| | Active Comparator: MBSR group<br>The MBSR group will complete a self-help workbook entitled, A Mindfulness-Based Stress Reduction Workbook over a 12 week period. | Behavioral: MBSR group<br>* The MBSR program is based on the self-help workbook entitled, A Mindfulness-Based Stress Reduction Workbook. This workbook is authored by Drs. Bob Stahl and Elisha Goldstein - who are both certified MBSR trainers. The workbook is written to help everyday people learn how to replace stress-promoting habits with mindfully-based ones to improve overall well-being. The workbook begins by providing a thorough introduction to the basic tenets of mindfulness, and improving well-being through the use of mindfulness-based skills. The workbook outlines, in detail, several skills-based exercises for practicing mindfulness across different aspects of a person's life. The MBSR group will be provided with a recommended weekly schedule for the initial 3-month treatment and a list of additional resources to be completed over the 3-month maintenance phase.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change from Baseline Satisfaction With Life | Satisfaction With Life Scale | Baseline, 3, 6 months | | Change from Baseline in Positive Affect | Scale of Positive and Negative Experience: SPANE | Baseline, 3, 6 months | | Change from Baseline in Negative Affect | Scale of Positive and Negative Experience: SPANE | Baseline, 3, 6 months | | Change from Baseline in Meaning in Life | Meaning in Life Questionnaire | Baseline, 3, 6 months | | Change from Baseline in Thriving | Comprehensive Inventory of Thriving | Baseline, 3, 6 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change from Baseline in Physical Activity | Step count captured from Fitbits | Baseline, 3, 6 months | | Change from Baseline in Perceived Social Support | The Social Provisions Scale | Baseline, 3, 6 months | | Change from Baseline in Relationship Satisfaction | The Revised Dyadic Adjustment Scale | Baseline, 3, 6 months | | Change from Baseline to attention, concentration, reaction time, memory, processing speed, executive functioning and decision-making | Automated Neuropsychological Assessment Metrics (ANAM) | Baseline, 3, 6 months | | Change from Baseline in Implicit Theories of Well-Being | | Baseline, 3, 6 months | | Change from baseline to Empathy | The Toronto Empathy Questionnaire | Baseline, 3, 6 months | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Well-being, Comparative Clinical Trial, Positive Psychology Intervention, Mindfulness Based Stress Reduction (MBSR), Group Therapy, Happiness, Bibliotherapy

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Quetiapine in Patients With Bipolar and Alcohol Abuse/Dependence Study Overview ================= Brief Summary ----------------- The abuse of alcohol is especially common in people with bipolar disorder. However, very little is known about the pharmacotherapy of people with both bipolar disorder and alcohol abuse/dependence. The purpose of this study is to determine if alcohol use and cravings are decreased with quetiapine add-on therapy compared to placebo and to determine if quetiapine add-on therapy is associated with greater improvement in mood, impulsivity, functioning and decreased alcohol use than placebo. Detailed Description ----------------- Experimental: After obtaining informed consent, 100 patients with bipolar I, or II disorders and alcohol abuse/dependence confirmed by a structured clinical interview (SCID) will be enrolled. from referral sources in the community we have developed over the past 3 years. A medical history and physical examination, including an eye exam with an ophthalmoscope, will also be performed at baseline to rule out serious medical illnesses and cataracts. Baseline labs including a liver panel and CBC will be obtained. Women of child-bearing potential will be given a urine pregnancy test. Baseline measures of psychiatric symptoms will be assessed with the HRSD, YMRS, and Barratt Impulsiveness Scale. Alcohol cravings will be assessed with the Obsessive Compulsive Drinking Scale (OCDS). Alcohol use including number of drinks/2 weeks, days used in the past two weeks, and days of heavy use will be obtained as will a urine drug/alcohol screen. Alcohol use and cravings will also be recorded throughout the study. Side-effects will be assessed with a general side effects scale, the Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale (SAS), and Barnes Akathesia Rating Scale (BARS). GGT levels will also be repeated at weeks 6 and 12. The subjects will be randomized and receive quetiapine or identical appearing placebo add-on therapy in a double-blind fashion for 12 weeks. Subjects will return every two weeks for reevaluation with the above outcome measures and for upward titration of study drug. All subjects will be given the option of receiving open-label quetiapine for an additional 4 weeks (with continuing assessment of mood and alcohol use/cravings every 2 weeks) at the end of the study or discontinuing medication. Official Title ----------------- A Randomized, Double-Blind, Placebo-Controlled Add-On Trial of Quetiapine in Patients With Bipolar Disorder and Alcohol Abuse/ Dependence. Conditions ----------------- Bipolar Disorder, Alcohol Abuse/Dependence Intervention / Treatment ----------------- * Drug: Quetiapine Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Bipolar I or II Ages 18-70 Exclusion Criteria: Life threatening medical condition causing participation in the study hazardous Alcohol abuse within the past 2 weeks History of cataracts or likely cataracts on baseline eye exam History of hepatic cirrhosis or AST or ALT more than three times normal limit Current active suicidal or homicidal ideation History of allergic reaction, poor response or intolerable side effects to quetiapine Antipsychotic use within 7 days of beginning quetiapine therapy Mental retardation, dementia or other severe cognitive impairment 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 Masking: Quadruple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Quetiapine<br>Quetiapine | Drug: Quetiapine<br> <br> | | Placebo Comparator: Placebo<br>Inactive ingredient matching the active medication in appearance | Drug: Quetiapine<br> <br> | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Number of Standard Drinks | | Weekly |

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Determination of HCC With Octanoate Breath Test vs. MRI Diagnosis Study Overview ================= Brief Summary ----------------- An Octanoate breath test will be used to assess the presence of Hepatocellular Carcinoma in subjects with risk. The gold standard will be MRI. Detailed Description ----------------- Informed consent will be obtained from all patients prior to enrollment. The trial will be conducted in compliance with this protocol, with GCP standards, and the applicable regulatory requirements. This study will be cross-sectional, where patients will be enrolled on a walk in basis. Once one arm is completed the other one will be enriched in order to obtain at least 50 positive and at least 50 negative HCC subjects as defined by MRI. All patients will undergo AFP and US if they do not have results within the past three months. If the patient undergoes liver FNA, the biopsy results will be evaluated for the presence of HCC. For all patients, a case report form will be completed. All patients will undergo a physical examination, and their medical history/concomitant medications, weight, height and age will be recorded. Furthermore, recent (past 3 months) blood test results, if available, may be recorded. If relevant (woman of child bearing age), a pregnancy test will be performed to rule out pregnancy when performing the breath test. All MRI negative patients with low OBT results will undergo additional MRI within 6 to 12 months post OBT to rule out HCC occurrence. If available, all additional MRI/CT/US results will be recorded within the patient's CRF. Official Title ----------------- Evaluation of the Capability of the ¹³C-Octanoate Breath Test (OBT) Measurement to Differentiate Between Presence and Absence of HCC Determined by MRI in Patients With Chronic Liver Disease Conditions ----------------- Hepatocellular Carcinoma (HCC) Intervention / Treatment ----------------- * Device: ¹³C-Octanoate Breath Test Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Any patients with chronic liver disease at risk for HCC. Age ≥ 18 years. Patient has an MRI result (positive or negative for HCC) up to 3 months prior to recruitment or will be scheduled for an MRI during the trial period. Patient is naïve to HCC treatment (RFA or TACE or Oral HCC treatments) since last MRI. Exclusion Criteria: Any patients with chronic liver disease at risk for HCC. Age ≥ 18 years. Patient has an MRI result (positive or negative for HCC) up to 3 months prior to recruitment or will be scheduled for an MRI during the trial period. Patient is naïve to HCC treatment (RFA or TACE or Oral HCC treatments) since last MRI. Patients currently receiving total parenteral nutrition if they have contraindications to oral drugs. Women who are pregnant or breast feeding. Patient taking drugs that can interfere with octanoate metabolism or can also cause NAFLD independent of the metabolic syndrome, including: corticosteroids, amiodarone, tetracycline, valproic acid, methotrexate, stavudine, zidovudine. Patient, based on the opinion of the investigator, should not be enrolled into this study. Patient unable or unwilling to sign informed consent. Patients that are participating in other clinical trials evaluating experimental treatments or procedures 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 Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: Single Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: HCC positive<br>Breath testing utilizing 13C is a safe, non-invasive means for measuring a certain pathway's metabolic rate. 13C is a stable, non-radioactive isotope which can be incorporated into a specific location within a test substrate so it would be released when the compound is metabolized by the liver. Hepatic metabolism of the compound is assessed by measuring the ratio of 13CO2/12CO2 in exhaled breath. | Device: ¹³C-Octanoate Breath Test<br>* Octanoate Breath Test to be performed on subjects with suspected HCC<br>* Other names: Sodium caprylate;| | Experimental: HCC negative<br>Breath testing utilizing 13C is a safe, non-invasive means for measuring a certain pathway's metabolic rate. 13C is a stable, non-radioactive isotope which can be incorporated into a specific location within a test substrate so it would be released when the compound is metabolized by the liver. Hepatic metabolism of the compound is assessed by measuring the ratio of 13CO2/12CO2 in exhaled breath. | Device: ¹³C-Octanoate Breath Test<br>* Octanoate Breath Test to be performed on subjects with suspected HCC<br>* Other names: Sodium caprylate;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | 13CO2/12CO2 ratio | | 60 minutes |

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Augmenting Zyprexa With Naltrexone to Ameliorate Metabolic Side-Effects Study Overview ================= Brief Summary ----------------- The main purpose of this study is to determine whether the opioid antagonist naltrexone is helpful in ameliorating the weight gain and other adverse metabolic side effects experienced by schizophrenic patients taking the second generation antipsychotic (SGA) Zyprexa. Schizophrenics may have an altered/enhanced endogenous opioidergic drive, and because of this, normally painful stimuli will be sensed as less painful in schizophrenics vs. healthy controls. A secondary hypothesis for this study is that naltrexone augmentation of Zyprexa will normalize subjective pain ratings. Our tertiary objective is to examine the safety and tolerability of naltrexone in Zyprexa-treated patients with schizophrenia. Detailed Description ----------------- Zyprexa is one of the most commonly prescribed second generation antipsychotic drugs (SGAs), but its (and other SGA's) side effects contribute to the development of obesity and to the Metabolic Syndrome. Both conditions, which are more prevalent even in unmedicated schizophrenic patients, are associated with increased cardiovascular morbidity and mortality. The mechanisms of these side effects are likely to be multifactorial and to involve peripheral and central factors alike. The present proposal asks a fundamental question: How the endogenous opioidergic systems are involved in Zyprexa-induced obesity and in related metabolic disturbances. We further hypothesize that if the excess of central opioid activity creates metabolic problems for patients, it is reasonable to expect amelioration of the symptoms through blockade of opioid receptors. The proposed project is designed to test this hypothesis by complimenting clinical psychopharmacology with pain medicine research and functional magnetic resonance imaging (fMRI) to empirically measure clinical outcomes of Zyprexa pharmacotherapy augmentation with the opioid receptor antagonist, naltrexone. Our objectives and hypotheses are as follows: to determine the effects of naltrexone on weight gain, metabolic (e.g., cholesterol, lipids, insulin, leptin and glucose levels), anthropometric and nutritional characteristics in Zyprexa treated schizophrenic patients, to examine the effects of naltrexone on subjective pain ratings, and to investigate the safety and tolerability of naltrexone in Zyprexa-treated schizophrenic patients. Official Title ----------------- Augmenting Zyprexa With Naltrexone: Normalization of the Weight Gain Side Effect and the CNS Reward and Sensory Function Conditions ----------------- Schizophrenia, Psychotic Disorders Intervention / Treatment ----------------- * Drug: naltrexone * Drug: placebo Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Meeting DSM-IV-TR criteria for schizophrenia/schizoaffective disorder, confirmed by clinical interview with PI and SCID-I. On a stable dose of Zyprexa (i.e., greater than or equal to 10mg/day and less than or equal to 30mg/day) for at least 2 months; patients on typical antipsychotics or in a medications-free state will be also included and used for baseline comparison. Sufficient clinical stability (i.e., BPRS psychotic symptoms score of less than 19; BPRS anxiety/depression symptoms score of less than 15). Participation approved by the treating psychiatrist. BMI greater than or equal to 30kg/m^2 or BMI greater than or equal to 27kg/m^2 plus one symptom of the Metabolic Syndrome (i.e., fasting blood sugar greater than 125mg/dL, hypertension or dyslipidemia). Sufficient social stability following study admission, such as having safe, reliable living quarters, telephone access and at least one living relative or significant other willing to assist the subject following discharge from the study and to assist the staff if necessary to locate the subject subsequently. English speaking and reading ability sufficient to comprehend consent without assistance. Good physical health, no history of significant medical, surgical, or neurological illness, including any history of head trauma. Right-handedness Able to cooperate and comply with study procedures. Exclusion Criteria: DSM-IV-TR diagnosis of current drug/alcohol dependence. Any lifetime history of dementia, bipolar disorder, major depression, other psychotic disorder, past or current drug/alcohol dependence, past or current eating disorder. Potentially confounding neurological condition (e.g., seizure disorder, head trauma accompanied by loss of consciousness greater than ten minutes or amnesia, brain surgery, multiple sclerosis, Parkinson's disease), or potentially confounding medical condition (e.g., diabetes mellitus or other endocrinopathy, chronic obstructive pulmonary disease, congestive heart failure, hepatitis, hepatic failure or cirrhosis, AIDS, pacemaker, kidney problems, hypokalemia, edema, and allergy to glucose). Allergy or hypersensitivity to naltrexone Abnormal laboratory, ECG or EEG results, elevated serum aminotransferases. Use within the previous month of any potentially confounding medications such as opioid agonists (e.g., morphine or codeine) or drugs with prominent orexigenic/anorexigenic effects (e.g., anticholinergics), insulin, oral hypoglycemics, amphetamines, opioid analgesics, anti-depressants including tricyclics, MAO inhibitors or mirtazapine, as determined by history and/or urine toxicology screen. Patient is pregnant or planning on becoming pregnant. Any cognitive impairment that precludes informed consent. Any chronic pain condition and/or any condition that may require opioid treatment in the course of the study. Dangerousness: any suicidal, assaultive or homicidal risks Ages Eligible for Study ----------------- Minimum Age: 21 Years Maximum Age: 55 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: Double Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: 1<br>taking naltrexone | Drug: naltrexone<br>* 50mg naltrexone, 1 tablet a day for 12 weeks.<br>| | Placebo Comparator: 2<br>taking placebo | Drug: placebo<br>* lactose placebo, 1 capsule every day for 12 weeks<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Weight and Body Mass Index | | 12 weeks | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Subjective pain ratings, fMRI activations in the a priori selected ROIs, waist, waist/hip ratio, fasting blood glucose, LDL cholesterol, HDL cholesterol, triglycerides, fat body mass, insulin, leptin, and food intake | | 12 weeks | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Zyprexa, naltrexone, schizophrenia, Metabolic Syndrome, pain

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A Safety, Tolerability, Efficacy and Exposure Study of XEN801 Topical Gel Study Overview ================= Brief Summary ----------------- Phase 1/2 study enrolling up to 60 healthy volunteers in Phase 1 followed by approximately 150 subjects with acne vulgaris in Phase 2. Detailed Description ----------------- Phase 1/2 study enrolling up to 60 healthy volunteers followed by approximately 150 subjects with acne vulgaris. Data from Phase 1 stage will be reviewed before progressing to Phase 2. Phase 1 is an open label study to determine safety, tolerability of XPF-005 topical gel and exposure of XEN801 (active ingredient). Up to 5 cohorts of 12 healthy volunteers will each receive different dose volumes of XPF-005 gel or Placebo gel on their face and back for 14 or 21 days. Safety assessments are completed and PK samples are collected at study visits. Phase 2 is a randomized, double-blind, vehicle-controlled, parallel-group study to determine safety, tolerability, efficacy of XPF-005 topical gel and exposure of XEN801 (active ingredient). Approximately 150 subjects with acne vulgaris will apply XPF-005 or matching placebo gel on their face for 12 weeks. Safety and efficacy assessments are completed and PK samples are collected at study visits. Safety assessments include local skin tolerability assessments, vital signs, physical examination, 12-lead ECG, safety laboratory blood and urine and adverse event reporting. Efficacy assessments include acne lesion counts and Investigator's Global Assessment (IGA). Official Title ----------------- A Phase 1 and 2 Randomized, Double-Blind, Vehicle-Controlled, Parallel-Group Study to Evaluate the Safety, Tolerability, Efficacy, and Exposure of up to 12 Weeks of XPF-005 Treatment in Healthy Volunteers and Subjects With Acne Vulgaris Conditions ----------------- Acne Vulgaris Intervention / Treatment ----------------- * Drug: XPF-005 * Drug: Placebo Participation Criteria ================= Eligibility Criteria ----------------- Key Inclusion Criteria: Aged between 18 and 50, inclusive Male or female, agree to comply with contraceptive requirements Signed Informed Consent Form Clinical diagnosis of facial acne vulgaris defined as: 25 to 75 inflammatory lesions, 20 to 120 non-inflammatory lesions, and an IGA score of ≥3 Agree to refrain from using any topical acne treatments on the face or any oral acne treatments. Topical acne treatment that do not have significant or measurable systemic absorption are permitted for treatment of the back, shoulders, and chest only Key Exclusion Criteria: Known sensitivity to any topical or dermal product, including alcohol Female who is breast feeding, pregnant, or planning to become pregnant Any skin condition of the face other than acne vulgaris Two or more active nodular lesions Excessive facial hair that would interfere with the evaluation of safety or with the diagnosis or assessment of acne vulgaris Use of tanning beds/booths, or excessive sun exposure Use of over-the-counter topical medications for treatment of acne vulgaris on the face within 14 days of baseline Use of systemic corticosteroids, antibiotics, anti-acne drugs, anti-inflammatory drugs (NSAIDs are permitted) or prescription topical retinoid use on the face within 28 days prior the baseline Initiation of hormonal therapy or dose change to hormonal therapy within 12 weeks prior to baseline. Use of androgen receptor blockers (eg, spironolactone, flutamide) within 12 weeks prior to baseline Use of oral retinoid (eg, isotretinoin, alitretinoin) within 12 months prior to baseline and vitamin A supplements >10,000 units/day within 6 months prior to baseline Facial procedures (eg, microdermabrasion, chemical or laser peel) within 8 weeks prior to baseline Photodynamic therapy within 12 weeks prior to baseline Any other reason that would make the subject, in the opinion of the Investigator or Sponsor, unsuitable for the study Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum 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 Masking: Quadruple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: XPF-005<br>Active treatment: XPF-005 Gel | Drug: XPF-005<br>* Comparison of active treatment XPF-005 topical gel against Placebo (XPF-005 Vehicle Gel) applied to face for acne vulgaris.<br>| | Placebo Comparator: Vehicle gel<br>Placebo: XPF-005 Vehicle Gel | Drug: Placebo<br> <br> | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change from Baseline in acne lesion count | | Week 12 | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change from Baseline in acne lesion count | | Week 4 and 8 | | Change from Baseline in Investigator Global Assessment (IGA) | | Week 4, 8 and 12 |

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Phase-I Study of Radiolabeled DFH-12 (PulmoBind) for Molecular Imaging of the Pulmonary Circulation Study Overview ================= Brief Summary ----------------- Pulmonary hypertension (PH) can be the result of various clinical conditions. It may be idiopathic or associated with various cardiovascular and lung disorders. Currently there is no test that can non-invasively detect abnormalities of the pulmonary circulation. There is a growing need for a non-invasive method to detect PH. There currently exists only ne agent approved in Canada for clinical imaging of the pulmonary circulation, 99mTc-labeled macroaggregates. This agent is exclusively used for the diagnosis of physical defects of the circulation due to pulmonary embolus. This agent is larger than small pulmonary vessels, limiting its sensitivity to detect small vascular defects, as well as potential infectious risks since albumin macroaggregates are derived from human albumin. There is need then for new lung tracers that could provide a greater safety profile while enabling functional as well as anatomical imaging of the pulmonary circulation. DFH-12 (PulmoBind) is a peptide derived from human adrenomedullin (hAMI-52). Hence the development of this novel AM derivative, PulmoBind, for molecular imaging of the pulmonary circulation. PulmoBind is labeled with 99mTc, the most commonly used imaging isotope in nuclear medicine. Official Title ----------------- Phase-I Study of Radiolabeled DFH-12 (PulmoBind) for Molecular Imaging of the Pulmonary Circulation Conditions ----------------- Pulmonary Disease, Pulmonary Hypertension Intervention / Treatment ----------------- * Radiation: 99mTC-PulmoBind Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: male or female greater than 18 years of age. Female subjects must be post-menopausal (defined as two years after menstrual cycle) within normal range for the following: BP systolic 100-140 mmHg and diastolic 50-90 mmHg; HR 60-100 beats per minute; oral temperature less than 37.6 degrees Centigrade; respiratory rate 12-20 breaths per minute; normal lung function tests; normal echocardiogram including estimation of pulmonary artery systolic pressure; normal chest x-ray; Normal electrocardiogram Exclusion Criteria: any known chronic or acute medical condition with or without the need for chronic pharmacologic therapy or any condition that may interfere with normal biodistribution of DFH-12. Includes but not limited to: lung parenchymal or lung vascular diseases such as chronic obstructive pulmonary disease, bronchitis, lung cancer, pleural effusion, emphysema, asthma, pulmonary fibrosis, occupational lung disease, pulmonary hypertension (primary or secondary), systemic hypertension, diabetes, cancer, kidney disease, liver disease, heart failure or previous myocardial infarction, coronary artery disease, peripheral vascular disease or inflammatory disease; subjects requiring chronic administration of any substance for a medical condition, active smoking or history of smoking for more than one year in the past 10 years, known self-reported alcoholism (active or abstinent); unable to tolerate study procedures ex.(venipuncture, movement restrictions during imaging); previous nuclear study since one week (to avoid cross-contamination) Ages Eligible for Study ----------------- Minimum 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: Diagnostic Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: DFH-12 PulmoBind<br>DFH-12 PulmoBind - 3 doses of; 5mCi for 5 subjects, 10mCifor 5 subjects and 15mCi for 10 subject | Radiation: 99mTC-PulmoBind<br>* DFH-12 (PulmoBind) is a peptide derived from human adrenomedullin (hAMI-52). Adrenomedullin (AM) is a 52-amino acid peptide produced by many tissues in the body, including the vascular endothelium. 3 radiolabeled doses of PulmoBind will be used in this study (5mCi, 10mCi and 15mCi) 5 healthy subjects per dose for the 5 mci and the 10 mci groups but 10 subjects will be used for the 15 mci group.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | To determine optimal dose of PulmoBind to be administered for lung imaging in humans | To determine the optimal dose of Pulmobind by evaluating the safety and efficacy in three groups of subjects with 3 different doses of study drug; 5mCi, 10mCi, and 15 mCi.For safety evaluation we will provide pharmacokinetic and biodistribution data following injections of the 3 doses mentioned. Vital signs, hematology and biochemistry will also be captured for each of the doses up to 24 and 48 hours after injections of PulmoBind. Furthermore local and systemic reactions 24 hours and 48 hours after injections of PulmoBind will also be captured. | 48 hours |

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The Influence of Plaquenil/Hydroxychloroquine (HCQ) on Insulin Secretion Study Overview ================= Brief Summary ----------------- Antimalarials such as hydroxychloroquine (HCQ), are among the oldest prescribed drugs still used in clinical practice. Relatively inexpensive and well tolerated, these drugs have been recognized to be effective in autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Interestingly, there is growing evidence of their beneficial impact on cardiovascular risk, particularly diabetes. HCQ therapy can improve balance in patients with unbalanced diabetes. This drug therapy may be a new therapeutic approach for diabetes. There is need for a better understanding of the mechanisms responsible for the improvement of the metabolic response to drug treatment. The investigators hypothesize that treatment with a drug improves the function of the beta cell and its ability to secrete insulin in response to glucose. The investigators will examine the impact of short-term therapy for HCQ in beta cell function in healthy volunteers and in patients with type 2 diabetes. Conditions ----------------- Diabetes Type Two Intervention / Treatment ----------------- * Drug: Hydroxychloroquine Participation Criteria ================= Eligibility Criteria ----------------- Two groups will participate in this study: Healthy volunteers and Diabetes patients A. Healthy volunteers Inclusion Criteria: Age: 18-40 Without acute disease at the day of the experiment. Signed informed consent Exclusion Criteria: Malignancy Steroids or NSAID on a daily basis B. Diabetes patients Inclusion Criteria: Age: 20-60 Diabetes type two Untreated or on metformin treatment Exclusion Criteria: Hypoglycemic medications Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 60 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: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Healthy volunteers<br> | Drug: Hydroxychloroquine<br>* 200 MG Plaquenil three times a day<br>* Other names: Plaquenil;| | Experimental: Diabetes patients<br> | Drug: Hydroxychloroquine<br>* 200 MG Plaquenil three times a day<br>* Other names: Plaquenil;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | glucose level | | the change in glucose level between baseline and after three hours |

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Long Acting FSH Plus Antagonist Versus Daily FSH Plus Antagonist Versus Short Agonist Protocol in Poor Responders Undergoing IVF Study Overview ================= Brief Summary ----------------- Despite the progression in assisted reproductive technology (ART), poor ovarian response to controlled ovarian stimulation remains a challenge for clinicians and a source of distress for patients. Multiple strategies have been tried to overcome these obstacles. The increase of the gonadotropin administration have been associated with a very low pregnancy rate. The introduction of GnRH agonist protocol, which takes advantage of the initial rise in endogenous gonadotropins that follows the agonist administration in the early follicular phase and subsequently prevents a premature LH surge, with fewer cycle cancellations, have improved cycle parameters and increased pregnancy rate. Recently, GnRH antagonists were introduced in ART treatment. They are effective in preventing a premature LH surge and allow for a more natural recruitment of follicles in the follicular phase in a non suppressed ovary. However, the randomized studies comparing the efficacy of these two regimens reported conflicting and nonsignificant results. Moreover, more recently adjuvant therapies for COH such as growth hormone therapy or pyridostigmine, oral L-arginine, and transdermal testosterone failed to improve IVF outcomes. Recently, the new treatment option with corifollitropin alfa, able to keep the circulating FSH level above the threshold necessary to support multi-follicular growth for an entire week, in a GnRH antagonist protocol seems to have a potential beneficial effect in poor responders. The aim of this study is to compare long-acting FSH/GnRH antagonist with daily FSH/GnRH antagonist with short GnRH agonist protocol on IVF outcome in poor responder patients . Official Title ----------------- Long Acting FSH Plus GnRH Antagonist Versus Daily FSH Plus GnRH Antagonist Versus Short Agonist Regimens in Poor Responder Patients Undergoing IVF: a Randomized Study. Conditions ----------------- Female Infertility, Poor Responder Intervention / Treatment ----------------- * Drug: Long acting FSH and GnRH antagonist * Drug: Daily FSH and GnRH antagonist * Drug: Triptorelin and recombinant FSH Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: women with at least two of the following criteria: I) age > 40 years old; II) basal follicular stimulation hormone (FSH) > 12 mIU/ml; III) three or fewer oocytes retrieved in the previous IVF cycle; IV) low estradiol levels on the day of human chorionic gonadotropin (hCG) administration (< 1500 pmol/ml). Exclusion Criteria: body mass index > 30 biochemical and ultrasound evidence of polycystic ovary syndrome stage III-IV endometriosis inflammatory or autoimmune disorders metabolic disease infertility medications (gonadotropins, clomiphene citrate) within the past two months Ages Eligible for Study ----------------- Minimum Age: 25 Years Maximum Age: 44 Years Sexes Eligible for Study ----------------- Female 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: Long acting FSH and GnrH antagonist<br>Woman in long acting FSH and GnRH antagonist arm receive an initial dose of 150 mcg Corifollitropin alfa on second day of the menstrual cycle followed by a fixed daily dose of 0.25 mg of GnRH antagonist on day 7 of the cycle onwards. On the ninth day of the cycle, a daily fixed dose of 300 IU of recombinant FSH will be administered until the day of ovulation triggering. | Drug: Long acting FSH and GnRH antagonist<br>* Woman in long acting FSH and GnRH antagonist arm receive an initial dose of 150 mcg Corifollitropin alfa on second day of the menstrual cycle followed by a fixed daily dose of 0.25 mg of GnRH antagonist on day 7 of the cycle onwards. On the ninth day of the cycle, a daily fixed dose of 300 IU of recombinant FSH will be administered until the day of ovulation triggering.<br>| | Experimental: daily FSH and GnRH antagonist<br>Woman in daily FSH and GnRH antagonist arm receive a fixed dose of 300 IU of recombinantFSH starting 3 day of the menstrual cycle followed by a fixed daily dose of 0.25 mg of GnRH antagonist on day 7 of the cycle onwards until the day of ovulation triggering. | Drug: Daily FSH and GnRH antagonist<br>* Woman in daily FSH and GnRH antagonist arm receive a fixed dose of 300 IU of recombinantFSH starting 3 day of the menstrual cycle followed by a fixed daily dose of 0.25 mg of GnRH antagonist on day 7 of the cycle onwards until the day of ovulation triggering.<br>| | Experimental: Triptorelin and recombinant FSH<br>Women in triptorelin and recombinant FSH arm receive a fixed dose of 0.05 mg of triprorelin from the 1 day of the menstrual cycle followed by a fixed dose of 300 IU of recombinant FSH starting 3 day until the day of HCG administration. | Drug: Triptorelin and recombinant FSH<br>* Women in Triptorelin and recombinant FSH arm receive a fixed dose of 0.05 mg of Triprorelin from the 1 day of the menstrual cycle followed by a fixed dose of 300 IU of recombinant FSH starting 3 day untill the day of HCG administration.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Clinical pregnancy rate | | Time Frame: until 12th gestational week | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Implantation rate | | Time Frame: until 12th gestational week | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Poor responders, IVF, GnRH agonist, GnRH antagonist, recombinant FSH

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Dialysate Temperature in Peritoneal Dialysis Study Overview ================= Brief Summary ----------------- Patients on continuous ambulatory peritoneal dialysis (PD) are encouraged to warm dialysate to 37°C before peritoneal infusion; main international PD guidelines do not provide specific recommendation, and patients generally warm dialysate batches partially or do not warm them at all. Warming of dialysate is a time-consuming procedure, not free from potential risks (i.e. degradation of glucose), and should be justified by a clear clinical benefit. The investigators designed a single blind randomized controlled trial where PD patients were randomized to receive a peritoneal equilibration test either with dialysate at a controlled temperature of 37°C (intervention group) or with dialysate warmed with conventional methods (control group). Primary end-point was a higher peritoneal creatinine clearance in patients in the intervention group. Detailed Description ----------------- Peritoneal dialysis (PD) currently represents the main choice for home renal replacement treatment for patients with end stage renal disease. One of the limitations of PD technique is represented by the difficulty in achieving target dialytic clearances and PD adequacy for some patients, especially with increasing PD vintage. A potentially relevant issue in PD clearances is the effect of dialysate temperature on depuration. Indeed, it is common for clinicians to advise patients in Continuous Ambulatory Peritoneal Dialysis (CAPD) to warm the dialysate before infusion into the peritoneal cavity, with different methods (microwave oven, warming cabin, warming pad). Nevertheless, main international PD guidelines do not provide specific recommendations on this topic. Only guidelines from the British Columbia Renal Agency (Canada) dedicate a specific chapter to the temperature of dialysate, recommending its warming to 37°C before peritoneal infusion, mainly in order to avoid an uncomfortable lowering of body temperature. On the other hand, warming of PD batches could lead to hot spots formation inside the batch, especially with microwaves, and to degradation of glucose leading to the formation of toxic glucose degradation products (GDPs). Also, notable differences in room temperature exist according to geographical latitude and year season, and there are no clear and detailed reports in the literature regarding intolerable effects of the infusion of dialysate at room temperature. It must be acknowledged that it is common practice for patients to warm dialysate batches only partially or not to warm them at all. Moreover, warming pads that are most commonly used by CAPD patients do not effectively warm the dialysate up to 37°C. In the Peritoneal Dialysis Unit at Azienda Ospedaliero-Universitaria di Modena, it was recently observed that average dialysate temperature at infusion was 31.1°C, even if the pad was calibrated to 37°C [unpublished data]. With respect to the effects on toxins clearances through the peritoneal membrane, a higher dialysate temperature could theoretically favor vasodilation of peritoneal membrane microcirculation, potentially increasing the passage of substances. Severe microcirculatory dysfunction has been reported in PD patients and any intervention designed to ameliorate microcirculatory flow at peritoneal level could be beneficial. Surprisingly, reports regarding the effects of dialysate temperature on peritoneal clearances in PD in humans are surprisingly scarce. In 1967 Gross et al reported an increase in the exchange of substances between peritoneal fluid and blood upon warming of the PD fluid to 37°C (compared to 20°C) in a patient treated with intermittent peritoneal dialysis; the increase in urea clearance with the 37°C solution was 35% on average. In contrast, Indraprasit et al did not encounter differences in peritoneal creatinine clearance utilizing dialysate at room temperature (27-31°C) and warmed at 37°C in a group of 18 patients in PD. Confirmation of the effects of dialysate temperature on peritoneal clearances would be of great interest in order to maximize the depurative potential of PD and to justify patients' effort to warm the batches. In order to determine the real effects of dialysate temperature on peritoneal clearances and transport characteristics, abdominal discomfort and vital signs, the investigators designed a randomized controlled trial comparing two strategies of peritoneal dialysate warming. Study design and participants PD patients, both in CAPD and automated PD, in regular follow-up at the Nephrology Unit of the University Hospital of Modena, were randomized to receive a single dialysis exchange, either with dialysate at a controlled temperature of 37°C (intervention group) or with dialysate at warmed with conventional methods at uncontrolled temperature (control group). Randomization was generated through the use of the Random Allocation software11. Primary end-point of our study was peritoneal creatinine clearance. Secondary end-points were: peritoneal urea clearance, creatinine and urea mass transfer area coefficient (MTAC), abdominal discomfort, blood pressure and body temperature. A power analysis was performed while designing the study using the few data available in the literature; setting the alpha-error level at 0.05 for a 2-tailed t-test with a statistical power of 95% (beta-error 0.05) the estimated sample needed was 14 patients (7 per group). Official Title ----------------- Influence of Dialysate Temperature on Peritoneal Creatinine Clearance in Patients in Peritoneal Dialysis Conditions ----------------- Peritoneal Dialysis Complication Intervention / Treatment ----------------- * Drug: peritoneal dialysate at 37°C temperature Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: age > 18 years ability to give informed consent peritoneal dialysis (PD) treatment PD vintage of more than 3 months absence of signs of active acute systemic or localized infections at least four weeks apart from the trial Exclusion Criteria: pregnancy 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: Randomized Intervention Model: Parallel Assignment Masking: Single Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Intervention group<br>Patients received Peritoneal Equilibration Test (PET). In the intervention group, dialysate was warmed in a specific microwave oven calibrated to 37°C and infusion temperature was confirmed to be 37°C before infusion | Drug: peritoneal dialysate at 37°C temperature<br>* during a PET test, patients received peritoneal dialysate warmed at 37°C before infusion<br>| | No Intervention: Control group<br>Patients received Peritoneal Equilibration Test (PET). In the control group, current practice was used (batch warming with a pad calibrated to 37°C) and dialysate temperature was measured just before infusion. | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | peritoneal creatinine clearance | Peritoneal clearance of creatinine was calculated with the following formula: Cx = [Dx] x dialysate volume / [Px] / 240 where Cx represents clearance of creatinine expressed in ml/min, [Dx] represents the concentration of creatinine in dialysate at the end of the exchange (4 hours) expressed in mg/dl, dialysate volume represents the total volume drained at the end of the exchange (4 hours), [Px] represents the concentration of creatinine in plasma after 2 hours from the beginning of the exchange expressed in mg/dl and 240 represents minutes contained in the 4 hours of the exchange. | 4 hours - Peritoneal equilibration test | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | peritoneal urea clearance | Peritoneal clearance of urea was calculated with the following formula: Cx = [Dx] x dialysate volume / [Px] / 240 where Cx represents clearance of urea expressed in ml/min, [Dx] represents the concentration of urea in dialysate at the end of the exchange (4 hours) expressed in mg/dl, dialysate volume represents the total volume drained at the end of the exchange (4 hours), [Px] represents the concentration of urea in plasma after 2 hours from the beginning of the exchange expressed in mg/dl and 240 represents minutes contained in the 4 hours of the exchange. | 4 hours - Peritoneal equilibration test | | creatinine and urea mass transfer area coefficient | Mass transfer area coefficients (MTAC) for creatinine and urea were calculated with the RenalSoft software (converted from the PD Adequest software) from Baxter Healthcare, Deerfield, IL, U.S.A. Correction for plasmatic water concentration was not added, since the main purpose was to compare MTACs from the intervention and control group and not to obtain absolute data. | 4 hours - Peritoneal equilibration test | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- peritoneal dialysis, dialysate temperature, peritoneal creatinine clearance

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A Study of Bortezomib, Lenalidomide and Dexamethasone (VRd) Followed by Cilta-cel, a CAR-T Therapy Directed Against BCMA Versus VRd Followed by Lenalidomide and Dexamethasone (Rd) Therapy in Participants With Newly Diagnosed Multiple Myeloma for Whom ASCT is Not Planned as Initial Therapy Study Overview ================= Brief Summary ----------------- The purpose of this study is to compare the efficacy of Bortezomib, Lenalidomide and Dexamethasone (VRd) induction followed by a single administration of ciltacabtagene autoleucel (cilta-cel) versus VRd induction followed by Lenalidomide and Dexamethasone (Rd) maintenance in newly diagnosed multiple myeloma participants for whom ASCT is not planned as initial therapy in terms of Progression Free Survival (PFS). Detailed Description ----------------- Multiple myeloma (MM) is a malignant plasma cell disorder characterized by the production of monoclonal immunoglobulin (Ig) proteins or protein fragments (M proteins) that have lost their function. JNJ-68284528 (ciltacabtagene autoleucel [cilta-cel]) is an autologous chimeric antigen receptor T cell (CAR-T) therapy that targets B-cell maturation antigen (BCMA), a molecule expressed on the surface of mature B lymphocytes and malignant plasma cells. The primary hypothesis of this study is that in participants with newly diagnosed MM, treatment with VRd induction followed by a single administration of cilta-cel will significantly improve progression free survival compared to Bortezomib, Lenalidomide and Dexamethasone (VRd) induction followed by Rd maintenance. The study will screen participants with newly diagnosed MM who are not planned to receive autologous stem cell transplant (ASCT) as initial therapy. This study will be conducted in 4 phases: Screening (up to 28 days), Pre-randomization Treatment, Treatment, and Follow-up. Assessments like patient-reported outcome(s) (PROs), electrocardiogram (ECG), vital signs and pharmacokinetics will be performed during the study. Safety evaluations will include review of adverse events, laboratory test results, vital sign measurements, physical examination findings, assessment of cardiac function, Immune-Effector Cell-Associated Encephalopathy (ICE) and handwriting assessments (only for Arm B) and Eastern Cooperative Oncology Group (ECOG) performance status. Safety data will be periodically reviewed by an Independent Data Monitoring Committee (IDMC). The duration of the study is approximately 12 years 5 months. Official Title ----------------- A Phase 3 Randomized Study Comparing Bortezomib, Lenalidomide and Dexamethasone (VRd) Followed by Ciltacabtagene Autoleucel, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against BCMA Versus Bortezomib, Lenalidomide, and Dexamethasone (VRd) Followed by Lenalidomide and Dexamethasone (Rd) Therapy in Participants With Newly Diagnosed Multiple Myeloma for Whom Hematopoietic Stem Cell Transplant is Not Planned as Initial Therapy Conditions ----------------- Multiple Myeloma Intervention / Treatment ----------------- * Drug: Bortezomib * Drug: Dexamethasone * Drug: Lenalidomide * Drug: Cilta-cel * Drug: Cyclophosphamide * Drug: Fludarabine Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Documented diagnosis of multiple myeloma (MM) according to International Myeloma Working Group (IMWG) diagnostic criteria Measurable disease at screening as defined by any of the following: Serum monoclonal paraprotein (M-protein) level greater than or equal to (>=)1.0 gram per deciliter (g/dL) or urine M-protein level >=200 milligram (mg)/24 hours; or Light chain MM in whom only measurable disease is by serum free light chain (FLC) levels: Serum immunoglobin (Ig) free light chain >=10 milligrams per deciliter (mg/dL) and abnormal serum Ig kappa/lambda FLC ratio Eastern Cooperative Oncology Group Performance Status grade of 0 or 1 Not considered for high-dose chemotherapy with Autologous Stem Cell Transplant (ASCT) due to: Ineligible due to advanced age; or Ineligible due to presence of comorbid condition(s) likely to have a negative impact on tolerability of high-dose chemotherapy with ASCT; or Deferral of high-dose chemotherapy with ASCT as initial treatment A woman of childbearing potential (WOCBP) must have 2 negative highly sensitive serum or urine pregnancy tests (beta-human chorionic gonadotropin) prior to starting Bortezomib, Lenalidomide and Dexamethasone (VRd) and must agree to further testing during the study. Clinical laboratory values meeting the following criteria during the screening phase: hemoglobin greater than or equal to (>=) 8.0 g/dL (>=5 millimoles per liter [mmol/L]), recombinant human erythropoietin use is permitted; platelets >=75 *10^9/L; absolute lymphocyte count >=0.3 *10^9/L; absolute neutrophil count (ANC) >=1.0 ×10^9/L (prior growth factor support is permitted but must be without support in the 7 days prior to the laboratory test); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to (<=) 3.0 * upper limit of normal (ULN); estimated glomerular filtration rate >=40 milliliter per minute/1.73 meter square (mL/min/1.73 m^2) based upon modified diet in renal disease formula (MDRD-4) calculation or a 24-hour urine collection; total bilirubin <=2.0 * ULN; except in participants with congenital hyperbilirubinemia, such as Gilbert syndrome (in which case direct bilirubin <=2.0 * ULN is required) Exclusion Criteria: Frailty index of >=2 according to Myeloma Geriatric Assessment score Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5 Known active, or prior history of central nervous system (CNS) involvement or clinical signs of meningeal involvement of MM Stroke or seizure within 6 months of signing Informed Consent Form (ICF) Seropositive for human immunodeficiency virus (HIV) Vaccinated with live, attenuated vaccine within 4 weeks prior to first dose of VRd Participant must not require continuous supplemental oxygen Hepatitis B infection Hepatitis C infection Prior treatment with chimeric antigen receptor T (CAR-T) therapy directed at any target Any therapy that is targeted to B-cell maturation antigen (BCMA) 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: VRd+Rd (Standard Therapy)<br>Participants will receive bortezomib, lenalidomide, and dexamethasone (VRd) regimen for 6 cycles before randomization. Following randomization, participants in Arm A will receive 2 more cycles of VRd. In VRd treatment, participants will receive bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8 and 11 of each cycle (Cycles 1 to 8), oral lenalidomide 25 mg on Days 1 to 14 of each cycle (Cycles 1 to 8) and oral dexamethasone 20 mg on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each cycle (Cycles 1 to 8). Each cycle will consist of 21 days. After 8 cycles of VRd, treatment will continue with lenalidomide and dexamethasone (Rd) maintenance therapy. In Rd treatment, participants will receive oral lenalidomide 25 mg on Days 1 to 21 of each cycle and oral dexamethasone 40 mg on Days 1, 8, 15, and 22 of each cycle. Each cycle will consist of 28 days. Participants will continue to receive Rd until confirmed progressive disease or unacceptable toxicity. | Drug: Bortezomib<br>* Bortezomib will be administered SC.<br>Drug: Dexamethasone<br>* Dexamethasone will be administered orally.<br>Drug: Lenalidomide<br>* Lenalidomide will be administered orally.<br>| | Experimental: Arm B: VRd+Ciltacabtagene Autoleucel (Cilta-cel)<br>Participants will receive VRd regimen for 6 cycles before randomization. Following randomization, participants in Arm B will undergo apheresis and receive two more cycles of VRd as bridging therapy. In VRd treatment, participants will receive bortezomib 1.3 mg/m^2 SC on Days 1, 4, 8 and 11 of each cycle for Cycles 1 to 8; oral lenalidomide 25 mg on days 1 to 14 of each cycle for Cycles 1 to 8 and oral dexamethasone 20 mg on days 1, 2, 4, 5, 8, 9, 11 and 12 of each cycle for Cycles 1 to 8. Each cycle will consist of 21 days. After 8 cycles of VRd, participants will receive a conditioning regimen (cyclophosphamide 300 mg/m^2 intravenous [IV] and fludarabine 30 mg/m^2 IV daily for 3 days) and Cilta-cel infusion 0.75*10^6 chimeric antigen receptor (CAR)-positive viable T cells/kilogram (kg). | Drug: Bortezomib<br>* Bortezomib will be administered SC.<br>Drug: Dexamethasone<br>* Dexamethasone will be administered orally.<br>Drug: Lenalidomide<br>* Lenalidomide will be administered orally.<br>Drug: Cilta-cel<br>* Cilta-cel infusion will be administered.<br>* Other names: JNJ-68284528;Drug: Cyclophosphamide<br>* Cyclophosphamide will be administered intravenously.<br>Drug: Fludarabine<br>* Fludarabine will be administered intravenously.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Progression Free Survival (PFS) | Progression-free survival is defined as the time from the date of randomization to the date of first documented Progressive Disease (PD), as defined in the International Myeloma Working Group (IMWG) criteria, or death due to any cause, whichever occurs first. | Up to 4 years and 5 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Sustained Minimal Residual Disease (MRD) Negative CR | Sustained MRD negative complete response (CR) as determined by next generation sequencing (NGS) with sensitivity of 10^-5, and defined by MRD negative CR plus at least 12 months durability of the MRD negative CR status. | Up to 12 years and 5 months | | MRD Negative CR at 9 Months | MRD negative CR rate at 9 months is defined as the percentage of participants who achieve MRD negative CR status at 9±3 months after the randomization date. | 9 months | | Overall MRD Negative CR | Overall MRD negative is defined as the percentage of participants who achieve MRD negativity at any time after the date of randomization before initiation of subsequent therapy. | Up to 12 years and 5 months | | Overall Survival (OS) | Overall survival is measured from the date of randomization to the date of the participant's death. | Up to 12 years and 5 months | | Complete Response or Better | CR or better is defined as percentage of participants who achieve a CR response or Stringent Complete Response (sCR) response according to the IMWG criteria. | Up to 12 years and 5 months | | Time to Subsequent Anti-myeloma Therapy | Time to subsequent anti-myeloma therapy is defined as the time from randomization to the start of subsequent anti-myeloma therapy. | Up to 12 years and 5 months | | Progression Free Survival on Next-line Therapy (PFS2) | PFS2 is defined as the time interval between the date of randomization and date of event, which is defined as PD as assessed by investigator that starts after the next line of subsequent therapy, or death from any cause, whichever occurs first. | Up to 12 years and 5 months | | Number of Participants with Adverse Events (AEs), Abnormalities in Laboratory Parameters, 12-Lead Electrocardiogram (ECG), Physical Examination, and Vital Signs | Number of participants with AEs, abnormalities in laboratory parameters (complete blood count [CBC] with differential, coagulation, chimeric antigen receptor T cell [CAR-T] chemistry, full metabolic panel etc.), 12-lead ECG, physical examination, and vital signs will be reported. | Up to 12 years and 5 months | | Arm B: Systemic Cytokine Concentrations | Serum or plasma proteomic profiling of cytokines (such as interleukin [IL] 6, IL-15, and IL 10) concentrations will be measured for biomarker assessment. | Up to Day 112 | | Arm B: Levels of Chimeric Antigen Receptor T cell (CAR-T) Cell Activation Markers | CAR-T cell activation markers including, but not limited to, CD4+, CD8+, CD25+, central memory, effector memory cells will be reported. An evaluation of cell populations may be performed by flow cytometry, cytometry by time of flight (CyTOF), single cell RNA sequencing (scRNAseq) or similar technologies and be correlated with response. | Up to 12 years and 5 months | | Arm B: Levels of Soluble B-cell Maturation Antigen (BCMA) | Levels of soluble BCMA will be reported. | Up to 1 year | | Arm B: Levels of Cilta-cel Expansion (proliferation), and Persistence | Levels of cilta-cel expansion (proliferation), and persistence via monitoring CAR-T positive cell counts and CAR transgene level will be reported. | Up to 12 years and 5 months | | Arm B: Number of Participants with Anti-cilta-cel Antibodies | Number of participants with anti-cilta-cel antibodies will be reported. | Up to 12 years and 5 months | | Arm B: Number of Participants with Presence of Replication Competent Lentivirus | Number of participants with presence of replication competent lentivirus will be reported. | Up to 12 years and 5 months | | Change from Baseline in Health-Related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC-QLQ-C30) Scale Score | The EORTC QLQ-C30 includes 30 items in 5 functional scales (physical, role, emotional, cognitive, and social), 1 global health status scale, 3 symptom scales (pain, fatigue, nausea/vomiting), and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The responses are reported using a verbal rating scale. The item and scale scores are transformed to a 0 to 100 scale. A higher score represents greater HRQoL, better functioning, and more (worse) symptoms. | Baseline up to 12 years and 5 months | | Change from Baseline in Health-Related Quality of Life as Assessed by MySIm-Q Scale Score | The MySIm-Q is a disease-specific PRO assessment complementary to the EORTC-QLQ-C30. It includes 17 items with recall period of 7 days and responses are reported on a 5-point verbal rating scale. Item responses are scored from 0 to 4. Higher scores indicate greater severity/impact. | Baseline up to 12 years and 5 months | | Change from Baseline in Health-Related Quality of Life as Assessed by European Quality of Life - 5 Dimensions-5 Levels (EQ-5D-5L) Scale Score | The EQ-5D-5L is a generic measure of health status. The EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each of the 5 dimensions is divided into 5 levels of perceived problems, where Level 1: no problem, Level 2: slight problems, Level 3: moderate problems, Level 4: severe problems and Level 5: extreme problems, plus a visual analog scale rating health today with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). | Baseline up to 12 years and 5 months | | Change from Baseline in Health-Related Quality of Life as Assessed by Patient Global Impression of Symptom Severity (PGIS) Scale Score | The PGIS uses 2 items to assess the participant's perception of the severity of their disease symptoms and impact using a 5-point verbal rating scale. Score ranges from 1 (None) to 5 (Very Severe). | Baseline up to 12 years and 5 months | | Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Items | The National Cancer Institute's PRO-CTCAE is an item library of common adverse events experienced by people with cancer that are appropriate for self-reporting. Each symptom selected for inclusion can be rated by up to 3 attributes characterizing the presence/frequency, severity, and/or interference that ranges from 0 to 4 with higher scores indicating higher frequency or greater severity/impact. | Up to 161 days | | Time to Worsening of Symptoms, Functioning and Overall Well-being | Time to worsening is measured as the interval from the date of randomization to the start date of worsening in MySIm-Q symptom, impact, or total scores. | Up to 12 year and 5 months | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Newly Diagnosed Multiple Myeloma, Cellular Therapy, CAR-T Therapy, BCMA CAR-T

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Neuroprotective Effects of Xenon Treatment in Patients With Cerebral Infarction Study Overview ================= Brief Summary ----------------- In the Russian Federation, ischemic cerebral infarction is recorded annually in more than 450,000 people. It is the second most common cause of death after coronary heart disease. The 30-day mortality rate after an ischemic cerebral infarction is more than 25%, and during the following year about half of the patients die. To date, all candidate neuroprotective drugs tested in various clinical trials have demonstrated insufficient efficacy . Therefore, the development of new approaches to the treatment of severe brain injuries of various etiologies is one of the most important tasks of critical condition medicine. Brain damage due to stroke triggers a number of pathophysiological reactions, which are based on the accumulation of glutamate with the development of excitotoxicity. The effect of glutamate on NMDA receptors is one of the main factors of neurodegenerative disorders. Xenon is an anesthetic whose neuroprotective properties have been shown in many experimental studies. Хenon inhalation after ischemia and reperfusion suppresses ischemic brain damage and tPA-induced cerebral hemorrhages, and damage to the blood-brain barrier. The most interesting is a randomized controlled trial performed by R. Laitio et al. (2016), in which the use of xenon in combination with hypothermia in clinical practice was studied for the first time. In patients who have undergone community-acquired cardiac arrest, xenon inhalation at a concentration of 40 vol.% within 24 hours in combination with hypothermia, led to less damage to the white matter of the brain than with patients using hypothermia alone. The 6-month mortality rate was 27% in the xenon and hypothermia group and 35% in the hypothermia group. It is important to note that today, despite a large pool of convincing preclinical studies proving the neuroprotective properties of xenon, there is not a single clinical study of its use in ischemic stroke. Therefore, the research objectives is to determine whether the strategy of using xenon-oxygen mixture inhalation is better than oxygen-air mixture inhalation with respect to the change in scores on the NIHSS, Rankin and Glasgow coma scales on day 7, the duration of stay in the ICU and the frequency of nosocomial pneumonia. Detailed Description ----------------- In the Russian Federation, ischemic cerebral infarction is recorded annually in more than 450,000 people. It is the second most common cause of death after coronary heart disease. The 30-day mortality rate after an ischemic cerebral infarction is more than 25%, and during the following year about half of the patients die, which is more than 200,000 people. The consequences of stroke belong to the first place among the causes of primary disability. No more than 15% of those who have suffered a stroke return to work or fully perform their previous household duties, and the rest, due to disability, need lifelong medical and social rehabilitation. To date, all candidate neuroprotective drugs tested in various clinical trials have demonstrated insufficient efficacy . Therefore, the development of new approaches to the treatment of severe brain injuries of various etiologies is one of the most important tasks of critical condition medicine. Brain damage due to stroke triggers a number of pathophysiological reactions, which are based on the accumulation of glutamate with the development of excitotoxicity. The effect of glutamate on NMDA receptors is one of the main factors of neurodegenerative disorders. Xenon is an anesthetic whose neuroprotective properties have been shown in many experimental studies. However, the clinical part is still presented rather modestly. After it was discovered that xenon is an inhibitor of NMDA receptors, it was shown that xenon can protect neuronal cell cultures from damage caused by NMDA, glutamate, or oxygen-glucose deprivation. It has been experimentally established that xenon is an inhibitor of tissue plasminogen activator (tPA) and dose-dependent inhibits tPA-induced thrombolysis; xenon inhalation after ischemia and reperfusion suppresses ischemic brain damage and tPA-induced cerebral hemorrhages, and damage to the blood-brain barrier. Exposure to xenon after transient ischemia in rats leads to a decrease in the volume of infarction, depending on the concentration, exposure time and improvement of neurological function 7 days after ischemia. To date, a role has been discovered in the implementation of molecular mechanisms of xenon neuroprotection of double-pore potassium channels (TREK-1), which provide a basic ion current that weakens neuronal excitability, thereby protecting neurons from damage. The role of adenosine triphosphate (ATP)-sensitive potassium channels of the plasmalemma in the realization of the protective properties of xenon is also discussed in the scientific literature. It was shown that under in vitro conditions in the culture of neurons, xenon protected them from damage caused by glucose and oxygen deprivation by activating ATP-sensitive potassium channels in the plasmalemma. There is evidence of the effect of xenon inhalation on the phosphorylation of glycogen synthase-3ß, a key enzyme of the anti-apoptotic neuronal cascade, and an increase in the pool of enzymes involved in the antioxidant protection of the brain. An experimental study showed a distinct anti-inflammatory effect of this anesthetic, which consisted in an increase in the ability of neutrophils to spontaneous apoptosis and a decrease in the expression of adhesion molecules CD11b and CD66b on their surface after modeling an inflammatory reaction. Also, the anti-inflammatory properties of xenon were shown when modeling traumatic brain injury in vivo, when its exposure for 60 minutes caused a significant decrease in the expression of pro-inflammatory genes NF-kB1 and NF-kB2, responsible for the synthesis of cytokines and other molecules involved in inflammation. Considering that the inflammatory reaction that forms in the first hours of ischemic brain damage largely determines the severity of its further course, such an effect on neutrophils can reduce the severity of damage to nervous tissue. The most interesting is a randomized controlled trial performed by R. Laitio et al. (2016), in which the use of xenon in combination with hypothermia in clinical practice was studied for the first time. In patients who have undergone community-acquired cardiac arrest, xenon inhalation at a concentration of 40 vol.% within 24 hours in combination with hypothermia, led to less damage to the white matter of the brain than with patients using hypothermia alone. The 6-month mortality rate was 27% in the xenon and hypothermia group and 35% in the hypothermia group. However, the study was not powerful enough. It is important to note that today, despite a large pool of convincing preclinical studies proving the neuroprotective properties of xenon, there is not a single clinical study of its use in ischemic stroke. Therefore, the research objectives is to determine whether the strategy of using xenon-oxygen mixture inhalation is better than oxygen-air mixture inhalation with respect to the change in scores on the NIHSS, Rankin and Glasgow coma scales on day 7, the duration of stay in the ICU and the frequency of nosocomial pneumonia. Official Title ----------------- Neuroprotective Effects of Xenon Treatment in Patients With Cerebral Infarction: Randomized Single-blinded Placebo-controlled Trial Conditions ----------------- Ischemic Stroke Intervention / Treatment ----------------- * Drug: Xenon * Drug: Oxygen 30 % Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Age > 18; Ischemic stroke with a NIHSS score at the time of hospitalization from 5 to 15 points Score on the Glasgow coma scale ≥ 13 points Assessment of the patient no later than 8 hours after the appearance of the first signs of ONMC Signed voluntary informed consent to participate in the study. Exclusion Criteria: Myocardial infarction in the previous 6 months Body mass index > 35 kg/m2 Class of chronic kidney disease ≥ 3b NYHA class ≥ 3 Decompensated insulin-dependent diabetes mellitus The need for inotropic and/or vasopressor support The presence of thrombolysis associated with an actual ischemic stroke Documented pneumonia within 3 months before 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: Double Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Xenon<br> | Drug: Xenon<br>* Xenon is injected into the body by inhalation in the form of xenon-oxygen mixtures, in which the concentration of xenon is 30%, and oxygen is 30%. Xenon inhalation is carried out for 30 min daily for 3 days.<br>| | Placebo Comparator: Oxygen<br> | Drug: Oxygen 30 %<br>* Oxygen-air mixture is injected into the body by inhalation. The oxygen concentration is 30%. Inhalation of oxygen-air mixture is carried out for 30 min daily for 3 days<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | National Institutes of Health Stroke Scale | Change of scores on the National Institutes of Health Stroke Scale. Minimal score equal 0. Maximal score equal 42. Less score means better outcome. | 7 day | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Rankin scale | Change in Rankin scale scores Minimal score equal 0. Maximal score equal 5. Less score means better outcome. | day 7 | | Glasgow coma scale | Change of points on the Glasgow coma scale Minimal score equal 0. Maximal score equal 15. Less score means worse outcome. | day 7 | | Duration of stay in the intensive care unit | day of the intensive care unit discharge - day of the randomization | 28 days | | Nosocomial pneumonia | The incidence of nosocomial pneumonia | 28 days | | Mortality | All cause mortality | 28 days | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Xenon, Ischemic stroke, Organ protection, Critical care

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Cilengitide in Treating Children With Refractory Primary Brain Tumors Study Overview ================= Brief Summary ----------------- This phase I trial is studying the side effects and best dose of cilengitide in treating children with recurrent, progressive, or refractory primary CNS tumors. Cilengitide may slow the growth of brain cancer cells by stopping blood flow to the tumor. Detailed Description ----------------- PRIMARY OBJECTIVES: I. To describe the acute and dose-limiting toxicities (DLT) and define the maximum tolerated dose (MTD) of cilengitide (EMD 121974) when administered to children and adolescents with refractory primary brain tumors. SECONDARY OBJECTIVES: I. To obtain preliminary evidence of biologic activity by determining alterations in tissue perfusion, tumor blood flow and metabolic activity using MR perfusion, PET and MRS and correlating these findings with changes in tumor size by volumetric MRI. II. To characterize inter- and intra-patient variability in the pharmacokinetics of cilengitide and to estimate cilengitide renal clearance in this patient population. III. To characterize the pharmacogenetic polymorphisms in drug transporters (e.g., MRP4, BCRP) and relate to cilengitide disposition. IV. To evaluate changes in circulating endothelial cells (CECs) and circulating endothelial precursors (CEPs) in patients treated with cilengitide, and to investigate the correlation between changes in CECs and CEPs, plasma, serum and urine angiogenic protein levels such as VEGF, and clinical outcome. V. To obtain preliminary information about the efficacy of cilengitide in this patient population. OUTLINE: This is a dose-escalation, multicenter study. Patients receive cilengitide (EMD 121974) IV over 1 hour twice weekly. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of cilengitide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 25% of patients are expected to experience dose-limiting toxicity. Once the MTD is determined, 6 additional patients are accrued and treated at that dose level for a total of 12 patients at the MTD. Patients receiving treatment are followed weekly for the first three months then monthly for one year or 13 courses of treatment. Patients discontinuing treatment will be followed for resolution of all adverse events occurring while on treatment and/or within 30 days of the last administration of study drug. Patients will be followed for the shortest of 1) three months after the last protocol based treatment, or 2) the date other therapy is initiated. Official Title ----------------- Phase I Study of Cilengitide (EMD 121974) in Children With Refractory Brain Tumors Conditions ----------------- Childhood Central Nervous System Germ Cell Tumor, Childhood Choroid Plexus Tumor, Childhood Craniopharyngioma, Childhood Ependymoblastoma, Childhood Grade I Meningioma, Childhood Grade II Meningioma, Childhood Grade III Meningioma, Childhood High-grade Cerebellar Astrocytoma, Childhood High-grade Cerebral Astrocytoma, Childhood Infratentorial Ependymoma, Childhood Low-grade Cerebellar Astrocytoma, Childhood Low-grade Cerebral Astrocytoma, Childhood Medulloepithelioma, Childhood Mixed Glioma, Childhood Oligodendroglioma, Childhood Supratentorial Ependymoma, Recurrent Childhood Brain Stem Glioma, Recurrent Childhood Brain Tumor, Recurrent Childhood Cerebellar Astrocytoma, Recurrent Childhood Cerebral Astrocytoma, Recurrent Childhood Ependymoma, Recurrent Childhood Medulloblastoma, Recurrent Childhood Pineoblastoma, Recurrent Childhood Subependymal Giant Cell Astrocytoma, Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor, Recurrent Childhood Visual Pathway and Hypothalamic Glioma Intervention / Treatment ----------------- * Drug: cilengitide * Other: laboratory biomarker analysis Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patients with histological diagnosis of primary CNS tumor and evidence that the tumor is recurrent or progressive and refractory to standard therapy, including histologically benign CNS tumors (e.g. low-grade glioma); clinical and radiographic evidence of a brain stem or optic pathway glioma is required in the absence of histologic diagnosis Karnofsky or Modified Lansky Score ≥ 50% Patients with neurological deficits should have deficits that are stable for ≥ 1 week prior to study entry Chemotherapy: Patients with evidence of recovery from prior therapy; no investigational agent, including biologic agent, within two (2) weeks of study entry; at least six (6) weeks from nitrosourea agent to study entry; at least four (4) weeks from any myelosuppressive therapy to study entry Bone Marrow Transplant: Greater than six (6) months prior to study entry XRT: At least six (6) weeks from prior radiation therapy to study entry; greater than three (3) months from prior craniospinal irradiation (> 24 Gy) or total body irradiation to study entry; greater than two (2) weeks from local palliative irradiation to study entry Anti-convulsants: Patients will be eligible for this study even if they are receiving anti-convulsants Growth factors: Off all colony forming growth factor(s) > one (1) week prior to study entry (G-CSF, GM-CSF, erythropoietin) Corticosteroids: Patients receiving corticosteroids must be receiving a stable dose for ≥ one (1) week prior to study entry ANC > 1,000/μl Platelets > 100,000/μl (transfusion independent) Hemoglobin > 8.0 g/dl (may be transfused) Patients with bone marrow involvement may be eligible Creatinine < 1.5 times normal range for age GFR > 70 ml/min/1.73m^2 Total bilirubin ≤ upper limit of normal for age SGPT (ALT) and SGOT (AST) < 2.5 times upper limit of normal Cilengitide was teratogenic when tested in animals; as such, female patients of childbearing potential must have a negative serum or urine pregnancy test prior to study entry; female patients must avoid breast feeding while on study Patients of childbearing potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study Signed informed consent according to institutional guidelines must be obtained prior to patient registration Exclusion Criteria: Patient must not be receiving any other anticancer or experimental drug therapy, with the exception of corticosteroids Patient must have no uncontrolled infection Patient has no overt renal, hepatic, cardiac or pulmonary disease Ages Eligible for Study ----------------- 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: Treatment (cilengitide)<br>Patients receive cilengitide (EMD 121974) IV over 1 hour twice weekly. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of cilengitide until the MTD is determined. The MTD is defined as the dose at which 25% of patients are expected to experience dose-limiting toxicity. Once the MTD is determined, 6 additional patients are accrued and treated at that dose level for a total of 12 patients at the MTD. | Drug: cilengitide<br>* Given IV<br>* Other names: EMD 121974;Other: laboratory biomarker analysis<br>* Correlative studies<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | MTD of cilengitide | | 4 weeks | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Response | Reported and recorded descriptively. | Up to 3 months |

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A Multi-Site Clinical Evaluation of the ARIES Norovirus Assay Study Overview ================= Brief Summary ----------------- The ARIES Norovirus Assay is a real-time PCR based qualitative in vitro diagnostic test for the direct detection of Norovirus GI/GII RNA from stool specimens obtained from symptomatic patients. The purpose of this study is to establish the diagnostic accuracy of ARIES Norovirus Assay. Detailed Description ----------------- The ARIES Norovirus Assay is a real-time polymerase chain reaction (PCR) based qualitative in vitro diagnostic test for the direct detection of Norovirus GI/GII RNA from stool specimens obtained from symptomatic patients. The objective is to establish the diagnostic accuracy of the ARIES Norovirus assay through a multi-site, method comparison on prospectively collected leftover, stool specimens. Diagnostic accuracy will be expressed in terms of clinical sensitivity (or positive agreement) and specificity (or negative agreement) Official Title ----------------- A Multi-Site Clinical Evaluation of the ARIES Norovirus Assay in Patients With Signs and Symptoms of Acute Gastroenteritis Conditions ----------------- Acute Gastroenteritis Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: The specimen is from a patient with symptoms of acute gastroenteritis. The specimen is from a male or female subject who was either hospitalized, admitted to a hospital emergency department or visiting an outpatient clinic. The subject's specimen is an unpreserved, unformed (liquid or soft) stool submitted for testing at the site. Exclusion Criteria: The specimen is from an individual with known and documented non-infectious conditions such as ulcerative colitis, irritable bowel syndrome and/or Crohn's disease The specimen was not properly collected, transported, processed or stored according to the instructions provided by the sponsor. 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 | | --- | --- | --- | | Diagnostic accuracy will be expressed in terms of clinical sensitivity (or positive agreement) and specificity (or negative agreement). | Accuracy determinations (diagnostic sensitivity and specificity, positive and negative agreement) were based on the fraction of comparator positive (or negative) results which were also positive (or negative) by ARIES Norovirus Assay. | Within the first year of sample collection |

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Efficacy and Safety of ab Interno Trabeculectomy With the Kahook Dual Blade Study Overview ================= Brief Summary ----------------- The Kahook Dual Blade is a single-use device specially designed to create a clean cut in the trabecular meshwork. This ablation in the trabecular meshwork allows a better outflow of the aqueous humor, thus reducing the intraocular pressure (IOP), theoretically beyond the IOP reduction achieved by other minimally invasive glaucoma surgery (MIGS) devices. Studies already published showed good results in terms of the reduction of the number of glaucoma medications and the reduction in the IOP, but not a single study has been performed prospectively comparing the efficacy of the technique, not even with the cataract surgery. Detailed Description ----------------- This new device, the Kahook Dual Blade, has been specially designed to create a gentle cut compared to other cutting-devices that also remove the trabecular meshwork. Preclinical investigation showed no harm in the surrounding tissues. Only two prospective studies have been published, showing good results in terms of IOP reduction and a significant cut-off in the glaucoma medications. However, to better assess the real effect, a prospective comparison with cataract surgery or any other trabecular technique should be performed. We also aimed to determine the safety of the procedure. Study design A prospective, randomized controlled, interventional study was conducted to determine the efficacy and safety of the Kahook Dual Blade. Patients with cataract and open-angle glaucoma or ocular hypertension (OHT) were included. Subjects Patients were consecutively recruited from the Department of Glaucoma. Eligible patients were asked to participate if cataract surgery was indicated due to best-corrected visual acuity (BCVA) bellow 0.5 (in decimal scale), and moderate IOP reduction and a cut-off of the glaucoma medications was also aimed. Patients included in the study had been previously diagnosed with primary open-angle (POAG), pseudoexfoliative glaucoma (PSX) or OHT, and mild-to-moderate glaucoma according to the Hodapp-Parrish-Anderson classification, preoperative IOP ≤ 24 mmHg on at least one hypotensive medication, and coexistence of cataract without narrowing the angle (visible scleral spur at least in 2 quadrants). Both eyes from the same patient could be eligible if they both met the inclusion criteria. Subjects who did not fulfill the inclusion criteria were excluded: patients with other glaucoma subtypes (elevated episcleral venous pressure, orbital occupancy, Sturge-Weber syndrome or any type of angle-closure glaucoma). Patients who underwent any intraocular surgery in the previous six months, including any laser or surgical intervention for glaucoma, or patients with any ophthalmic diseases that may interfere with tests were excluded. Severe or end-stage glaucoma or those with an indication of filtering or glaucoma drainage implant surgeries due to a high IOP with the maximum tolerated medication or glaucoma progression were also exclude. All subjects were thoroughly examined before clinical intervention. This included a medical history review, slit-lamp examination, IOP determination with hand-held applanation tonometer, gonioscopy, dilated fundus examination, endothelial cell count (ECC) including cell and size automated detection with specular microscopy (EM-3000, Tomey Corporation, Nagoya, Japan), simulated keratometry (simK) determined by topography (Pentacam®, Oculus, Wetzlar, Germany), and standard automated perimetry (VF) (G1-Tendency Oriented Perimeter, Octopus® 1-2-3, Haag-Streit, USA). Assignation and surgical technique For safety reasons, patients did not discontinue any topical hypotensive medications before surgery. A randomized, controlled study was designed. Eyes were randomly assigned to each treatment group (www.random.org). If both eyes of the same patient were eligible to participate in the study, they could be allocated in different treatment groups due to randomization. All surgeries were performed by two experienced glaucoma surgeons. Standard cataract surgery with phacoemulsification using a 1.8 mm clear corneal incision (CCI) and intraocular lens (IOL) capsular bag placement was performed under topical anesthesia and 1% intracameral lidocaine. The surgeons were blinded to randomization until the end of the cataract surgery. At this point, if the patient was assigned to the treatment group the surgeon instilled acetylcholine 1% to reduce the pupillary size and facilitate visualization of the angle structures. To help maintain width, the anterior chamber was filled with a viscoelastic agent. Since the ab interno trabeculectomy is performed in the nasal quadrant, the surgeons then situated temporal, the patient's head was rotated 45 degrees in the opposite direction of the surgical site, and the microscope was tilted 30 to 45 degrees towards the surgeon. To guarantee better access to the nasal area of the angle, a 1.8 mm keratome was employed to widen the paracentesis. Further details of the surgical technique are described elsewhere. Postoperative medications and follow-up Hypotensive medication was not administered intra- or post-operatively unless an IOP spike was detected. Postoperative topical treatment included a fixed combination of antibiotic plus steroid (tobramycin 0.3% and dexamethasone 0.1%) six times a day for seven days; this was tapered over the next four weeks. Visits were undertaken at 1 day, 1 week, 1 month, 2 months, 3 months, 6 months, and 12 months. During follow-up, results of the slit-lamp examination, applanation tonometer IOP, and the number of medications were recorded at all visits. The VF and the ECC were also re-tested at 6 and 12 months. All the postoperative visits were conducted by the same examiner (NVA). Topical glaucoma medication was re-introduced if the target IOP according to the severity of the visual field was not achieved, o a higher than preoperative IOP was found. Outcome measures - Data analysis Data obtained from each group were evaluated to determine the efficacy and safety of both interventions. The primary study outcomes were IOP and the number of glaucoma treatments. VF, ECC, BCVA and simK were secondary outcomes used to define the safety of both procedures. Success was defined as an IOP reduction of ≥ 20% from baseline; this cut-off was based on that reported in other glaucoma surgeries and is used for evaluation of this trabecular technique. The Saphiro-Wilk test was used to assess the sample distribution. Independent and dependent sample t-tests, when possible, were used to compare the results between groups and over time for each group. As both eyes of the same patient could be included in any of the treatment groups, generalized estimating equations (GEE) for repeated measures (IOP and number of medications) were also performed. A random-effect logistic regression was employed to analyse baseline characteristics associated with the success endpoint (IOP reduction of ≥20% from baseline). Statistical significance was set at a two-sided p-value ≤ 0.05. Statistical analyses were performed using Stata® version 14.1 (StataCorp, College Station, Texas, USA). Official Title ----------------- Efficacy and Safety of the ab Interno Trabeculectomy With Kahook Dual Blade Combined With Cataract Surgery Versus Cataract Surgery Alone: a Prospective, Single-center, Randomized Study Conditions ----------------- Glaucoma, Open-Angle, Ocular Hypertension, Eye Diseases, Hypertension, Intraocular Pressure, Cataract Intervention / Treatment ----------------- * Procedure: Ab interno trabeculectomy * Procedure: Cataract Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Participants aged 18 - 85 years Full comprehension and signing of the informed consent Preoperative intraocular pressure below 24 mmHg and at least one glaucoma medication Previous diagnose of open-angle glaucoma or ocular hypertension, including pseudoexfoliative glaucoma or pigment dispersion syndrome Mild to moderate glaucoma, according to the Hodapp-Parrish-Anderson classification Exclusion Criteria: Not signing of the informed consent Not being able to attend to all the follow-up visits Young females during pregnancy or lactation Any other form of glaucoma not previously mentioned Glaucoma secondary to elevated episcleral venous pressure Preoperative best-corrected visual acuity lower than 0.1 Clear lens extraction Severe or end-stage glaucoma Previous glaucoma surgery, cataract surgery or retinal surgery Patients taking anticoagulant medication that could not be discontinued during the perioperative period Oral anhydrase carbonic inhibitors Severe or uncontrolled systemic disease Ages Eligible for Study ----------------- Minimum Age: 18 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: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Interventional Model Description: One group received combined surgery, while the other cataract surgery alone Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Combined surgery<br>Participants intervened of combined ab interno trabeculectomy and cataract surgery at the same time | Procedure: Ab interno trabeculectomy<br>* Ab interno trabeculectomy performed after pupil contraction and 90 degrees ablation of the nasal trabecular meshwork<br>Procedure: Cataract<br>* Cataract surgery with minimal clear cornea incision and phacoemulsification<br>| | Active Comparator: Cataract surgery<br>Participants intervened of cataract surgery alone | Procedure: Cataract<br>* Cataract surgery with minimal clear cornea incision and phacoemulsification<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Evolution during follow up of the intraocular pressure | in mmHg | Up to 12 months | | Reduction in number of glaucoma medications | Difference between number of glaucoma medications before and after the treatment | Up to 12 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Increase in visual acuity | Best corrected visual acuity in decimal scale | Up to 12 months | | Rate of reduction in endothelial cell count | Number of cells, cells/mm^2 | Up to 12 months | | Increase of corneal astigmatism | simulated keratometry, in diopters | Up to 12 months | | Rate of visual field progression | mean deviation, in decibels | Up to 12 months | | Proportion of patients achieving the success endpoint | Achieving a 20 percent reduction from basal intraocular pressure | Up to 12 months | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Glaucoma, Ocular hypertension, Glaucoma, Open-Angle, Ab interno trabeculectomy, Phacoemulsification, Combined surgery, Minimally Invasive Glaucoma Surgery

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Impact of Forced Expiration On Pleural Drainage Duration (KPDP) Study Overview ================= Brief Summary ----------------- Following thoracic surgery, pleural effusion in pleural cavity requires post-operative drainage. Pleural effusion is responsible for pulmonary congestion, atelectasis, hypoventilation, lower efficacy of diaphragmatic curse, lower pulmonary reexpansion and vicious attitude. These complications could be avoided by respiratory physiotherapy. Forced expiration technic in ipsilateral decubitus is one of these technics but has never been proved better than other technics regarding its efficiency. The aim of the study is to compare the impact of such a technic on post operative thoracic drainage after pulmonary, pleural or mediastinal pediatric surgery. Detailed Description ----------------- Following thoracic surgery, pleural effusion in pleural cavity requires post-operative drainage, most often for few days (2 to 5 days) until fluid quantity is lower than 50 mL / 24h. Pleural effusion may cause pulmonary congestion, atelectasis, hypoventilation, lower efficacy of diaphragmatic curse, lower pulmonary reexpansion and vicious attitude. Respiratory physiotherapy in such situations has different aims : pulmonary decongestion and reexpansion, aid for drainage and pleural fluid reduction, avoiding complications and preventing vicious attitudes. These aims are learned in Physiotherapy formation institutes. The forced expiration technic in ipsilateral decubitus is justified by pleural physiology and is used after pediatric surgery without any scientific evidence regarding his efficacy Using pulmonary physiotherapy after pulmonary, mediastinal or pleural surgery for children is not systematic and depends on prescriber without any professional recommendation. Actually no scientific evidence regarding technical or postural indicates improvement of effusion drainage. It seems to be necessary to validate efficiency of such a technic and evaluate its consequences on post-operative pain. Furthermore, this pleural drainage impacts directly the duration of hospitalization and paramedical workload Official Title ----------------- Impact of Ipsilateral Decubitus Forced Expiration On Duration of Pleural Drainage After Pulmonary Surgery in Children : Randomized Trial Conditions ----------------- Pulmonary Malformations, Child Intervention / Treatment ----------------- * Procedure: Forced expiration Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Children 0-4 years In front have a mediastinum or lung surgery (lung segmentectomy or lobectomy or non anatomical lung resection) with pleural drainage, regardless of the type drain Whose parents or the holder of parental authority have signed a consent Whose parents or the holder of parental authority are affiliated to a social security scheme Exclusion Criteria: chest trauma Oncology (chest tumors, lung metastases) Drained Pleuropneumopathies Spine Surgery Heart surgery Surgery for pectus excavatum Route of anterior surgical approach sternotomy chest kind Patients intubated and / or ventilated Patients with preoperative sepsis Ages Eligible for Study ----------------- Minimum Age: 1 Day Maximum Age: 48 Weeks 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: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: forced expiration<br>2 daily sessions of forced expiration on ipsilateral decubitus from day 1 after surgery until chest tube removal | Procedure: Forced expiration<br>* Amongst chest physiotherapy technics, forced expiration is one of the passive procedures used in pediatrics. The patient is positioned on ipsilateral decubitus and the physiotherapist is behind the patient, placing one hand on the patient abdomen and the other on the patient lateral chest. During expiration, the abdominal hand apply a pressure directed posteriorly and superiorly for the patient. Simultaneously, the thoracic hand apply a pressure posteriorly and inferiorly for the patient. The session's duration is 15 minutes after what the physiotherapist replace the patient in dorsal decubitus.Two sessions a day will be performed<br>| | No Intervention: control<br>No session of forced expiration | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | assessment of pleural drainage duration | During the post-operative period until chest tube removal amount of pleural liquid drained is daily assessed. | 3 days | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | assessment of total amount of pleural liquid drained | Calculating cumulative volume of liquid provided by the drain (until it reaches 50 cc or less during the last day) during the post-operative period until chest tube removal | 3 days | | Assessment of pain | Pain scale score (EVENDOL 0 to 15) | 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 5, 48 | | patient's respiratory parameters | level of oxygen dependency (L/min) during the post-operative period until chest tube removal | 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 | | paramedical workload | Paramedical workload assessed by the time consumption (Hours) due to drainage tube | 3 days | | Oxygen blood saturation | Oxygen blood saturation (%) during the post-operative period until chest tube removal | 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- chest physiotherapy, post operative period, forced expiration, pleural drainage duration

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The Effect of Electroacustimulation on Postoperative Nausea, Vomiting and Pain in Outpatient Plastic Surgery Patients Study Overview ================= Brief Summary ----------------- Introduction: Current rates of postoperative nausea and vomiting (PONV) experienced by outpatient surgery patients are as high as 20-30%. Electroacustimulation (EAS) therapy has been demonstrated to be effective in controlling these symptoms, but trials identifying their efficacy in the outpatient surgery population are lacking. This study integrates conventional pharmacotherapy with alternative medicine in prevention of PONV. Materials and Methods: One hundred twenty two patients undergoing surgery procedures at an outpatient surgery center were randomized to two treatment arms. The first arm was standardized pharmacologic PONV prevention typical for patients undergoing outpatient surgery, while the second arm employed the use of ReliefBand, an FDA-approved electroacustimulation (EAS) device with pharmacologic treatment to relieve symptoms of PONV and pain. EAS is a derivative of acupuncture therapy that uses a small electrical current to stimulate acupuncture points on the human body and is thought to relieve nausea, vomiting and pain. Outcomes measured were post-op questionnaires evaluating pain and nausea symptoms, emetic events, the need for rescue medications and the time to discharge. Official Title ----------------- The Effect of Electroacustimulation on Postoperative Nausea, Vomiting and Pain in Outpatient Plastic Surgery Patients: A Prospective, Randomized, Blinded Clinical Trial Conditions ----------------- Postoperative Nausea and Vomiting Intervention / Treatment ----------------- * Device: Electroacustimulation Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: undergoing surgery at the University of Wisconsin outpatient surgery center Exclusion Criteria: pregnancy currently experiencing menstrual symptoms cardiac pacemaker previous experience with acupuncture therapy pharmacologic treatment for nausea or vomiting in the 24 hours prior to surgery 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: Prevention Allocation: Randomized Intervention Model: Parallel Assignment Masking: Single Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Electroacustimulation<br>Received electroacustimulation at the wrist using a small, battery-powered electroacustimulation device. | Device: Electroacustimulation<br>* Electroacustimulation (EAS) is a derivative form of acupuncture therapy where a small current of electricity instead of a needle is used to stimulate an acupoint on the human body in an effort to create therapeutic effects.<br>* Other names: ReliefBand (Aeromedix, Jackson, WY);| | Sham Comparator: Control<br>Received a device that was not turned on. | Device: Electroacustimulation<br>* Electroacustimulation (EAS) is a derivative form of acupuncture therapy where a small current of electricity instead of a needle is used to stimulate an acupoint on the human body in an effort to create therapeutic effects.<br>* Other names: ReliefBand (Aeromedix, Jackson, WY);| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Post-operative Nausea Scores | Nausea is scored on a scale of 1-10 where 1 is least nauseated and 10 is severely nauseated. Nausea scores will be collected 30, 60, and 120 minutes after surgery. | 24 hours | | Incidence of Post-operative Emetic Events | | 24 hours | | Number of Participants With Post-operative Need for Rescue Medications | | 24 hours | | Time to Participant Discharge | | 24 hours | | Phone Survey of Nausea / Vomiting Symptoms 24 Hours Post-op | Phone survey of nausea/vomiting symptoms was administered on postoperative day 1. The survey consists of 8 questions, including: 1) a query about whether or not participant has experienced nausea since returning home; 2) rate nausea severity on a scale of 1-10 (where 10 is the most severe); 3) a query about satisfaction of nausea control; 4) a question asking if they would use the same post-op nausea treatment again; 5) a query about what activities the participant has been unable to do since surgery; 6) whether or not the participant has taken prescription medicine for treatment of nausea since returning home; 7) whether or not participant has taken prescription medicine for treatment of pain since returning home; and 8) if yes for 6-7, which medications. | 24 hours post-op | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Postoperative Pain Scores | Participants will evaluate their postoperative pain score on a scale of 1-10 where 1 is the least pain and 10 is the most severe pain. Pain scores will be evaluated at 30, 60, and 120 minutes postop. | 24 hours | | Number of Participants Who Took Pain Medicine in the First 24 Hours Post-op | Phone survey of post-op pain medication usage was administered on postoperative day 1. | 24 hours post-op |

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A Study of LY3526318 in Healthy Participants Study Overview ================= Brief Summary ----------------- The main purpose of this study is to learn more about the safety and side effects of LY3526318 when given by mouth to healthy participants. The study will have two parts. Each participant will enroll in only one part. For each participant, Part A will last up to 28 days and Part B will last up to 51 days, including screening and follow-up. Official Title ----------------- A Safety, Tolerability, Pharmacokinetic, and Pilot Food Effect Study of Single- and Multiple-Ascending Doses of LY3526318 in Healthy Participants Conditions ----------------- Healthy Intervention / Treatment ----------------- * Drug: LY3526318 * Drug: Placebo Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Part A Cohorts: - Healthy male participants (including self-reported surgically sterile males) must agree to the following: When engaging in sex with Women of Child-Bearing Potential (WOCBP) both the male participant and his female partner must use highly effective contraception consisting of 2 forms of birth control (1 of which must be a male barrier method such as a latex or polyurethane condom) from start of dosing throughout the clinical study period, and for 90 days after the final study drug administration Nonsurgically sterile male participants must not donate sperm at any time from start of dosing until 90 days beyond the administration of study drug All Part A and Part B Cohorts: Female participants must be nonpregnant and not lactating, or of nonchildbearing potential (either surgically sterilized [e.g. tubal occlusion, hysterectomy, bilateral salpingectomy] or physiologically incapable of becoming pregnant, or postmenopausal with amenorrhea for at least 12 consecutive months). Healthy female participants of child-bearing potential who have a fertile male sexual partner must be willing and able to practice effective contraception from admission to 30 days after the final visit. Sexually active participants must use a combination of 2 of the following methods of contraception, including at least 1 so-called 'barrier' method: Hormonal contraceptive (oral, transdermal patches, vaginal or injectable) Intrauterine device with or without hormones Condom ('barrier' method) Diaphragm or cervical cap Sexual abstinence Have a body mass index 18 to 32 kilograms per square meter (kg/m²) Exclusion Criteria: Are currently enrolled in a clinical study involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study Have a history or presence of medical illness including, but not limited to, any cardiovascular, hepatic, respiratory, hematological, endocrine, psychiatric or neurological disease, convulsions, or any clinically significant laboratory abnormality In the opinion of the investigator are considered to be a danger to themselves Have an abnormality in the 12-lead electrocardiogram (ECG) Have a history of clinically significant multiple or severe drug allergies or severe post treatment hypersensitivity reactions Have donated blood of more than 500 milliliter (mL) within the previous month Are unwilling to stop alcohol and caffeinated beverage consumption and smoking/use of tobacco while resident in the CRU Have an average weekly alcohol intake that exceeds 21 units per week (1 unit = 12 ounces (oz) or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits Have an abnormal blood pressure Participants with a history of drug abuse Have received treatment with biologic agents (such as monoclonal antibodies, including marketed drugs) within 3 months or 5 half-lives (whichever is longer) Are unwilling to comply with the required dietary restrictions 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: Sequential Assignment Masking: Double Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: LY3526318 - Part A<br>LY3526318 administered orally once. | Drug: LY3526318<br>* Administered orally<br>| | Placebo Comparator: Placebo - Part A<br>Placebo administered orally once. | Drug: Placebo<br>* Administered orally<br>| | Experimental: LY3526318 - Part B<br>LY3526318 administered once orally on consecutive days. | Drug: LY3526318<br>* Administered orally<br>| | Placebo Comparator: Placebo - Part B<br>Placebo administered once orally on consecutive days. | Drug: Placebo<br>* Administered orally<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module | Baseline through Study Completion (Part A: Day 38; Part B: Day 51) | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of LY3526318 | PK: AUC of LY3526318 | Part A: Predose on Day 1 through Day 3; Part B: Predose on Day 1 through Day 15 | | PK: Maximum Observed Drug Concentration (Cmax) of LY3526318 | PK: Cmax of LY3526318 | Part A: Predose on Day 1 through Day 3; Part B: Predose on Day 1 through Day 15 | | PK: Time to Cmax (Tmax) of LY3526318 | PK: Tmax of LY3526318 | Part A: Predose on Day 1 through Day 3; Part B: Predose on Day 1 through Day 15 |

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Home Management of Malaria and Pneumonia Study Overview ================= Brief Summary ----------------- A well-implemented community-based program of early and appropriate treatment of fevers/malaria episodes and pneumonia,will improve child survival as measured by a reduction of the less than five mortality rate. Detailed Description ----------------- An integrated approach of home and community management of malaria and pneumonia may increase the proportion of children receiving prompt treatment; improve child survival as measured by a reduction of the under five mortality rate. To test this hypothesis, a cluster randomised controlled trial will be performed, involving children less than 5 years of age, in Burkina Faso using a community-based supplying community health workers (CHWs), a core group of mothers (KOLs) with Coartem and cotrimoxazole specially packed in age-specific blisters containing a full course of treatment. The study will be carried out in 111 clusters of a rural district in Burkina Faso where malaria and pneumonia are two major mortality causes in under five mortality. Official Title ----------------- Home and Community Management of Fevers/Malaria and Pneumonia in Children Under-five: a Cluster Randomised Controlled Trial of an Integrated Approach in a Rural District of Burkina Faso Conditions ----------------- Malaria, Pneumonia Intervention / Treatment ----------------- * Other: home/community case management Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: living in one of the study cluster (villages) no story of allergy to any of the study drugs history of fever or body temperature >= 38.5°C Exclusion Criteria: signs of severity/complications like impaired consciousness, convulsions, fast breathing etc Ages Eligible for Study ----------------- Minimum Age: 6 Months Maximum Age: 59 Months 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 | | --- | --- | | No Intervention: nothing at home level<br>No intervention at community level. The study drugs (arthemeter/Lumefantrine and Cotrimoxazole) available at the health facility drug stores level and prescribed exclusively to sick children attending to the health facility for care seeking. No Community Heath Worker /Key Opinion leader (CHWs/KOLs) selected in those clusters | | | Experimental: Home management of malaria<br>At the community level, the Community health workers/ keay opinion leader (HWs/KOLs) trained and equipped to provide the antimalarial drug (arthemeter/Lumefantrine ) to any child with fever (hot body) without any other signs of complications like impaired consciousness, convulsions, etc | Other: home/community case management<br> <br> | | Experimental: Home management of malaria and pneumonia<br>At the community level, the Community health workers/ key opinion leader (HWs/KOLs) trained and equipped to provide the antimalarial drug (arthemeter/Lumefantrine ) or antibiotic (Cotrimoxazole) to any child with fever (hot body) without any other signs of complications like impaired consciousness, convulsions, etc. The treatment decision making for the CHWs/KOLs based on the algorithm | Other: home/community case management<br> <br> | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Number of death in children aged 6 to 59 months | annual crude mortality rate in children aged 0 to 6 months in the different study arms | 12 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | - specific mortality preceded by acute febrile illness of children aged 6 to 59 months - severe malaria cases at community level | | 12 months | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Impact of home management of malaria and pneumonia on child mortality, home management of malaria and pneumonia

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Screening Strategy for Asymptomatic Sexually Transmitted Infections (STI) in a Cohort of HIV Outpatients Men Who Have Sex With Men (DRIVER) Study Overview ================= Brief Summary ----------------- Comparison of two screening strategies of asymptomatic sexually transmitted infections : routine screening versus screening as reported by the risks taken by the patient, in a cohort of HIV outpatients men who have sex with men. The aim of this study will be create and validate a simple tool for clinicians. A digital tool will be developed will allowed empowerment of HIV-positive men who have sex with men. Detailed Description ----------------- Main objectives are : create and validate a risk score for STIs (DRIVER score) in a population of HIV-positive men who have sex with men (MSM). determine the prevalence of asymptomatic STIs in a population of HIV-positive MSM Secondary objectives are : compare 2 screening strategies regarding STIs in HIV-positive MSM (systematic screening vs screening according to self-declared risk factors) conduct a cost-efficiency analysis of both strategies evaluate patients' knowledge of STIs develop a DRIVER digital tool that will be made available to patients on websites, mobile apps… Position of the problem : Over the past 15 years, a resurgence of symptomatic STIs has been observed at both at the global and at the local (French) level. This has been true for gonorrhea since 2008, for syphilis since 2000 and for lymphogranuloma venereum since 2003. The epidemiology of asymptomatic STIs has not been studied as thoroughly but asymptomatic carriage of Neisseria gonorrhoeae and Chlamydia trachomatis as well as latent syphilis account for at least half of cases declared in the past few years. The population of HIV-positive MSM is the demographic category with the highest rates of STIs. In addition, risky sexual attitudes are on the rise in the MSM population in general (in 2010, the French RESIST Network reported that condom use during anal penetrations between males had dropped from 49% in 2008 to 37% in 2010). Screening practices are currently center- and healthcare-provider dependant. Study will allow a comparison of screening practices thanks to a score that will be built, validated and made available to clinicians and patients. Type of study : Prospective, non randomized, multicentric and cross-sectional Timeline : Study duration : 18 months Beginning of study : March 2015 Official Title ----------------- Asymptomatic Sexually Transmitted Infections (STI) : Comparison of Two Screening Strategies Routine Screening Versus Screening as Reported by the Risks Taken by the Patient, in a Cohort of HIV Outpatients Men Who Have Sex With Men Conditions ----------------- HIV Intervention / Treatment ----------------- * Other: creation of a STIs score risk * Other: validation of a STIs score risk Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: HIV positive outpatients Men who have sex with men Speaking, literate french Having a french health insurance or an equivalent Asymptomatic for a STI the appointment day Exclusion Criteria: Men who never had sex with men Protected adults (adults under guardianship) Have a STI symptom ( anal discharge, urethritis, proctitis, chancre, rush) Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 75 Years Sexes Eligible for Study ----------------- Male Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Primary Purpose: Screening Allocation: Non-Randomized Intervention Model: Factorial Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Other: First period<br>creation of a STIs score risk pharyngeal swab+urinary collection+blood specimens+rectal Chlamydia trachomatis l Neisseria gonorrhoeae (CT/GC) testing | Other: creation of a STIs score risk<br>* 4 questionnaires 3 screening test ( syphilis, chlamydia, gonorrhea)<br>* Other names: First period;| | Other: Second period<br>validation of a STIs score risk pharyngeal swab+urinary collection+blood specimens+rectal Chlamydia trachomatis l Neisseria gonorrhoeae (CT/GC) testing | Other: validation of a STIs score risk<br>* DRIVER questionnaire (DRIVER STI score risk) 3 screening test ( syphilis, chlamydia, gonorrhea)<br>* Other names: Second period;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Sexually Transmitted Infections risk score in men HIV positive | Construction of a STI risk score | 6 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | cost-efficacy of a targeted screening versus universal screening | conduct a cost-efficiency analysis of both strategies | 12 months | | patients' knowledge of STIs evaluated by a Sexually Transmitted Disease Knowledge Questionnaire (STD-KQ) | patients' knowledge of STIs will be evaluate | 3 months | | prevalence of asymptomatic STIs in a population of HIV-positive MSM | | 6 months | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- HIV-positive MSM (men who have sex with men), asymptomatic sexually transmitted infections, screening

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A Phase II, Open-Label Study Evaluating the Effect Of GW786034 In Subjects With Ovarian Cancer Study Overview ================= Brief Summary ----------------- This study was designed to find out how effective and safe GW786034, is in the treatment of epithelial ovarian, fallopian tube, or primary peritoneal cancer that has not responded to standard treatment. Official Title ----------------- This Study is a Non-randomized, Open-label, Multi-center Phase II Study of GW786034 to Evaluate the Administration of Oral GW786034 in Subjects With Ovarian Cancer. Conditions ----------------- Peritoneal Cancer, Ovarian Cancer, Neoplasms, Ovarian, Fallopian Tube Cancer Intervention / Treatment ----------------- * Drug: GW786034 Participation Criteria ================= Eligibility Criteria ----------------- Inclusion criteria: Confirmed diagnosis of epithelial ovarian, fallopian tube or primary peritoneal carcinoma. Has received one prior platinum-based chemotherapy regimen(cisplatin,carboplatin, or oxaliplatin). Has psychological, familial, sociological or geographical condition that does not permit compliance with the protocol. Is on a specifically prohibited medication or requires these medications during treatment with GW786034. Exclusion criteria: Has had any surgery, chemotherapy, hormonal therapy, biologic, immunotherapy, or radiotherapy with in the last 28 days and has not recovered from such prior therapy. Poorly controlled hypertension(systolic 140mmHg or higher or Diastolic 90mmHg or higher). Currently taking warfarin. Low molecular weight heparin and low-dose warfarin(1mg per day)is permitted. Ages Eligible for Study ----------------- Minimum Age: 21 Years Sexes Eligible for Study ----------------- Female 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: Pazopanib<br>800 mg GW786034 administered orally on a daily basis. | Drug: GW786034<br>* 800 mg GW786034 administered orally on a daily basis.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Best Biochemical Response (Cancer Antigen [CA-125]) | Defined using modified Gynecologic Cancer Intergroup (GCIG) criteria: 50% response=≥50% decrease from baseline CA-125 (higher of 2 pretreatment CA-125 assessments) then confirmed after 21 days. 50% CA-125 response was normalized (CA-125 >21U/mL) or non-normalized (CA-125≤1U/mL). Progressive disease (PD) =CA-125 increase ≥100% from nadir (nadir >21U/mL) or ≥42U/mL (nadir ≤21U/mL); nadir was lowest CA-125. PD was confirmed after 21 days; otherwise=unconfirmed PD. Stable disease=scenarios that do not meet 50% response or PD. CA-125 response rate was defined as % of participants with 50% response. | Baseline to response (up to 3 years) | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Time to Biochemical Response (CA-125) | Time to biochemical response was calculated as the date pazopanib was first dosed to the date CA-125 was first reduced by 50% or greater. The reduction in CA-125 of 50% or greater was to be confirmed by a repeat measurement (no earlier than 21 days after initial evaluation documenting decrement). This was calculated for all participants with confirmed CA-125 50% reduction. | Baseline to response (up to 3 years) | | Duration of Biochemical Response (CA-125) | Calculated as the date of confirmed first 50% or greater reduction in CA-125 to date of documented progression by clinical, radiographic, or biochemical criteria, whichever occurred earliest. This was calculated for all participants with confirmed CA-125 50% reduction. | Baseline to response (up to 3 years) | | CA-125 Doubling Time Prior to and During Treatment With Pazopanib | CA-125 doubling time is defined as the time for CA-125 to double from baseline value. This measure was not reported, as no participants had a post-baseline CA-125 that was double the baseline value. Therefore, the data did not warrant a report. | Baseline to doubling of CA-125 (up to 3 years) | | Overall Response and Stable Disease (SD) | Overall response and stable disease (SD) are based on biochemical, radiographic, and clinical assessments according to the modified criteria of Gynecologic Cancer Intergroup (GCIG) (see primary outcome). Response is presented as the percentage of participants with the given response. | Baseline to response (up to 3 years) | | Median Progression-free Survival (PFS) | Progression-free survival analysis was performed on all participants and then stratified by CA-125 response status (having confirmed 50% reduction or not). PFS was defined as the time from the date of the first dose of study drug to the date of documented and confirmed progression by clinical, radiographic, or biochemical criteria, whichever occurred earliest, or to date of death due to any causes. | Date of the first dose of study drug to the date of documented and confirmed progression by clinical, radiographic, or biochemical criteria, whichever occurred earliest, or to date of death due to any causes (up to 2 years) | | Overall Tumor Response | Overall tumor response following daily administration of pazopanib was defined using radiographic assessments based on Response Evaluation Criteria for Solid Tumors (RECIST) criteria for subjects with measurable disease at baseline. | Baseline to response (up to 3 years) | | Number of Participants With the Indicated Maximum Shift From Baseline (BL) in Diastolic Blood Pressure | Summary of shifts in diastolic blood pressure from baseline to the maximum change in the study. mmHg, millimeters of mercury. | Baseline to response (up to 3 years) | | Number of Participants With the Indicated Maximum Shift From Baseline (BL) in Systolic Blood Pressure | Summary of shifts in systolic blood pressure from baseline to the maximum change in the study. mmHg, millimeters of mercury. | Baseline to response (up to 3 years) | | Number of Participants With the Indicated Maximum Shift From Baseline (BL) in Heart Rate | Summary of shifts in heart rate from baseline to the maximum change in the study. bpm, beats per minute. | Baseline to response (up to 3 years) | | Mean Change From Baseline to Response in Albumin | Change from baseline is calculated as the value at the time of response minus the value at Baseline. | Baseline to response (up to 3 years) | | Mean Change From Baseline to Response in Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Change from baseline is calculated as the value at the time of response minus the value at Baseline. | Baseline to response (up to 3 years) | | Mean Change From Baseline to Response in Amylase and Lipase | Change from baseline is calculated as the value at the time of response minus the value at Baseline. | Baseline to response (up to 3 years) | | Mean Change From Baseline to Response in Total Bilirubin and Creatinine | Change from baseline is calculated as the value at the time of response minus the value at Baseline. | Baseline to response (up to 3 years) | | Mean Change From Baseline to Response in Calcium, Glucose, Potassium, Sodium, and Urea | Change from baseline is calculated as the value at the time of response minus the value at Baseline. | Baseline to response (up to 3 years) | | Mean Change From Baseline to Response in Thyroxine | Change from baseline is calculated as the value at the time of response minus the value at Baseline. | Baseline to response (up to 3 years) | | Mean Change From Baseline to Response in Thyroid Stimulating Hormone | Change from baseline is calculated as the value at the time of response minus the value at Baseline. | Baseline to response (up to 3 years) | | Mean Change From Baseline to Response in Hemoglobin and Hematocrit | Change from baseline is calculated as the value at the time of response minus the value at Baseline. | Baseline to response (up to 3 years) | | Mean Change From Baseline to Response in Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | Change from baseline is calculated as the value at the time of response minus the value at Baseline. | Baseline to response (up to 3 years) | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Pazopanib, Fallopian tube cancer, Ovarian epithelial cancer, Peritoneal cancer

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Randomised Study Comparing Discharge 3 Days After Surgery to Home Within 24 Hours After Laparoscopic Hysterectomy. Study Overview ================= Brief Summary ----------------- Hysterectomy is one of the most performed surgery in gynecologic surgery. Actually, 70 000 hysterectomies are performed each year in France. Laparoscopic surgery is in progression. The percentage of hysterectomies performed laparoscopically is increasing. The advantage of laparoscopy include fewer infections, less operative pain, faster recovery time and shorter hospital stay. In France, the average of hospital stay after laparoscopic hysterectomy reduced to 3-4 days. The study hypothesis is that a shorter postoperative stay does not decrease the quality of life of the patients. This study will compare the evolution of quality of life (with a questionnaire concerning measuring health related quality of life the Euroqol EQ-5D) of patients discharged after 3 days hospital stay to patients discharged the first day after a laparoscopic hysterectomy. Official Title ----------------- Randomised Study Comparing Discharge 3 Days After Surgery to Home Within 24 Hours After Laparoscopic Hysterectomy. Conditions ----------------- Women Who Undergo a Laparoscopic Hysterectomy for Benign Disease. Intervention / Treatment ----------------- * Other: shorter hospitalization stay * Other: questionnaires Participation Criteria ================= Eligibility Criteria ----------------- Inclusion criteria: age between 35 and 70. affiliation to a social security system signed informed consent form disponibility of an responsible and valid accompanying person during 48 hours home situation, less than one hour to go to an adapted structure of care access to a phone Exclusion criteria: comorbidity which will automatically increase the period of hospital stay contraindication in laparoscopy difficulty to understand the protocol no social security cover Ages Eligible for Study ----------------- Minimum Age: 35 Years Maximum Age: 70 Years Sexes Eligible for Study ----------------- Female Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Design Details Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Other: A group : Conventional hospitalization<br>Patients discharged after 3 days hospital stay after laparoscopic hysterectomy | Other: questionnaires<br> <br> | | Experimental: B group : shorter stay<br>Patients going home within 24 hours discharged the first day after laparoscopic hysterectomy. | Other: shorter hospitalization stay<br> <br> Other: questionnaires<br> <br> | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Quality of life assessed by the Euroqol EQ-5D | Measure of quality of life with a questionnaire concerning health related quality of life (the Euroqol EQ-5D).The patients will complete the questionnaire at up to 30th days after the laparoscopic hysterectomy. | up to 30th days after the laparoscopic hysterectomy. | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Quality of life with assessed by the short SF-36 score (the 36 items Short Form Health Survey). in pre-operative time and 30 days after the hysterectomy. | | In pre-operative time and 30 days after the hysterectomy. | | Patient satisfaction | | Patient satisfaction assessed one month after intervention | | Evaluation of pain by Visual Analog Scale for Pain and by analgesic drugs consumption | | the day of intervention, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days and 30 days after intervention | | Anxiety assessment by the State trait anxiety inventory forme Y-A | | before intervention, the firt day, the second day, the third day after intervention, one week after intervention and one month after intervention. | | Patient recovery and discharge after intervention assessed by Post-Anaesthetic Discharge Scoring System (PADSS score). | | 8 hours after laparoscopic surgery | | Comparison between a hospital stay of 3-4 days after laparoscopic hysterectomy costs and hospital stay of 1day after laparoscopic hysterectomy costs from the day of intervention until one month after intervention. | The assessment will take into account any case of rehospitalization | each day from the date of intervention untill one month after intervention. | | Perioperative morbidity | | from intervention untill one month after intervention | | Number of rehospitalization | | one month after intervention |

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Phase Ib/II Study Evaluating Orteronel (Without Prednisone) Combined With Itraconazole In Men With Castration-Resistant Prostate Cancer (CRPC) Study Overview ================= Brief Summary ----------------- This research is being done to test the safety and anti-cancer activity of the combination of an investigational drug called orteronel, with a drug called itraconazole in the treatment of castration-resistant prostate cancer. Orteronel is an investigational drug known as a 17,20-lyase enzyme inhibitor, meaning that it blocks the formation of male sex hormones. Itraconazole is approved by the Food and Drug Administration (FDA) for the treatment of various fungal infections such as fingernail/toenail infections and other more serious fungal infections. While it has shown evidence of activity against prostate cancer in prior studies, it is not approved for use in cancer. The FDA is allowing the use of orteronel and itraconazole in this research study. In addition to its antifungal properties, itraconazole was discovered to function to block angiogenesis (blood vessel formation to tumors) to block a cellular pathway thought to be important in prostate cancer known as the Hedgehog pathway. Investigators hypothesize that blocking male sex hormone production with orteronel will increase reliance on the Hedgehog pathway in prostate cancer cells which can then be blocked with itraconazole and that the combination of these two drugs will be more effective than either alone. Detailed Description ----------------- Hedgehog (Hh) pathway signaling may be important in prostate cancer progression and this pathway is upregulated in the castration-resistant state. More potent (maximal) castration achievable by CYP17 inhibition, using orteronel, may further upregulate Hh pathway activation. Itraconazole administered at high doses (600 mg/day) may function as a modest Hh inhibitor. In a pilot phase II trial, investigators have shown that single-agent high-dose itraconazole produced PSA reductions in 29% of men with metastatic castration-resistant prostate cancer (CRPC), reduced circulating tumor cell counts in 62% of patients with unfavorable baseline counts, and prolonged progression-free survival compared to historical data. Moreover, clinical responses to itraconazole appeared to correlate with Hh pathway suppression, as measured by GLI1 mRNA analysis from serial skin biopsies. Investigators propose to evaluate the potent CYP17/lyase inhibitor, orteronel, in combination with itraconazole at escalating dose levels (100 mg BID, 200 mg BID, 300 mg BID) in men with non-metastatic or metastatic CRPC by conducting an open-label phase Ib/II trial. Importantly, unlike the related compound, ketoconazole, itraconazole very rarely results in adrenal suppression. Side effects previously seen at the highest dose of itraconazole (600 mg/day) were mild and included nausea, rash, diarrhea, vomiting, hypokalemia, edema, headache, hypertension, fever, pruritis, and abnormal liver function tests. Of note, orteronel will be given without concurrent prednisone in this trial. This is because the combination of itraconazole and corticosteroids can lead to Cushing's syndrome (hypercortisolism) by impairing corticosteroid metabolism through CYP3A4. Therefore, this study provides an opportunity to evaluate a steroid-free orteronel combination regimen. If this combination is safe and tolerable, subsequent studies would aim to compare the clinical efficacy of orteronel-itraconazole versus orteronel alone using a randomized phase II trial design. Official Title ----------------- Phase Ib/II Study Evaluating Orteronel (Without Prednisone) Combined With Itraconazole In Men With Castration-Resistant Prostate Cancer (CRPC) Conditions ----------------- Prostate Cancer, Castration-resistant Prostate Cancer Intervention / Treatment ----------------- * Drug: Itraconazole * Drug: Orteronel Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: > 18 years of age must provide written consent must agree to use contraception has a diagnosis of castrate resistant prostate cancer normal clinical lab values ALT and AST must be ≤ 2.5 x the upper limit of normal (ULN). Total bilirubin must be ≤ 1.5 x ULN. Estimated creatinine clearance using the Cockcroft-Gault formula must be > 40 mL/minute Absolute neutrophil count (ANC) must be ≥ 1500/uL Platelet count must be ≥ 100,000/uL has stable medical conditions (including absence of acute exacerbations of chronic illnesses, serious infections or major surgery within 4 weeks before first dose of drug castrate level of testosterone (< 50ng/dL) screening calculated ejection fraction of > 50% by ECHO. Exclusion Criteria: received prior therapy with orteronel, ketoconazole, aminoglutethimide, or abiraterone. Prior enzalutamide treatment is permitted. prior use of docetaxel for CRPC symptomatic metastatic disease with signs of rapid progression per investigator's clinical judgment or hepatic metastases currently receiving corticosteroids concurrent use of acid-lowering drugs (histamine antagonists, proton pump inhibitors) known hypersensitivity to compounds related to orteronel, orteronel excipients, itraconazole or related compounds including other azole antifungals concurrent administration of other drugs that significantly interact with CYP450 3A4 isoenzyme known brain metastases treatment with any investigational products within one month before the first dose of study drug diagnosis of or treatment for another systemic malignancy within 2 years before the first dose of study drug, or previously diagnosed with another malignancy and have any evidence of residual disease history of myocardial infarction, unstable symptomatic ischemic heart disease, ongoing arrhythmias of Grade >2 (NCI CTCAE version 4.0, effective dates 14 June 2010), thromboembolic events (e.g. deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), or any other cardiac condition (e.g. pericardial effusion, restrictive has New York Heart Association (NYHA) Class III or IV heart failure uncontrolled hypertension despite appropriate medical therapy (systolic blood pressure >160 mm Hg or diastolic blood pressure >90 mmHg) at 2 separate measurements no more than 60 minutes apart during the Screening visit). has known gastrointestinal (GI) disease or GI procedure that could interfere with the GI absorption or tolerance of orteronel, including difficulty swallowing tablets likely unable to comply with the protocol or cooperate fully with the investigator and site personnel Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- Male 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 | Intervention/Treatment | | --- | |Drug: Itraconazole|100 mg 200 mg 300 mg| |Drug: Orteronel|300 mg| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Maximum Tolerated Dose | This is a dose escalation phase I trial where 3 subjects will be enrolled at each dose level. If no dose limiting toxicities (DLTs) are seen at a dose level, the study moves to the next dose level. If 1 DLT is seen, 3 additional subjects must be enrolled at the current dose level. If 2-3 DLTs are seen, we will stop accrual to that particular dose level, and the previous dose level becomes the maximum tolerated dose. | 12 months after study initiation | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Grade and severity of adverse events | To determine the safety and tolerability of the combination regimen: orteronel + itraconazole. The grade and severity of adverse events will be assessed using CTCAE v4.0 | up to 25 months | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- metastatic disease, non-metastatic disease, prostate cancer, castration-resistant prostate cancer

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Donor Umbilical Cord Blood Transplant By Injection Into the Bone Marrow in Treating Patients With Hematologic Cancer Study Overview ================= Brief Summary ----------------- Rationale: Giving chemotherapy and total-body irradiation before a donor umbilical cord blood transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from the donor's umbilical cord blood are injected into the patient's bone marrow they may help make stem cells, red blood cells, white blood cells, and platelets. Purpose: This phase I/II trial is studying the side effects of donor umbilical cord blood transplant when given directly into the bone marrow and to see how well it works in treating patients with hematologic cancer. Detailed Description ----------------- Objectives: Primary Determine the safety, in terms of infusional toxicity, of myeloablative unrelated donor double-unit umbilical cord blood (UCB) transplantation via intra-bone marrow injection (IBMI) in patients with advanced or high-risk hematologic malignancy. Determine whether treatment with this regimen improves the time to neutrophil engraftment (compared to historical controls) in these patients. Secondary Determine the incidence of sustained donor engraftment in patients treated with this regimen. Determine the relative contribution of each UCB unit to initial and sustained donor engraftment in these patients. Determine the incidence of grade II-IV and grade III-IV acute graft-vs-host disease (GVHD) and chronic GVHD in patients treated with this regimen. Determine the incidence of day 100 and 180 transplant-related mortality in patients treated with this regimen. Determine the probability of survival at 100 days and 1 year post-transplantation in these patients. Outline: This is a nonrandomized study. Patients receive a myeloablative conditioning regimen. Patients also receive immunosuppression, growth factor, and supportive care as in protocol MT2005-10 (NCT00309842). Patients receive 2 units of donor umbilical cord blood (UCB) by intra-bone marrow injection (IBMI) over 10 minutes each on day 0. If the IBMI procedure is not possible, then the UCB units are given intravenously (IV.) After completion of study therapy, patients are followed periodically for 5 years. Projected Accrual: A total of 36 patients will be accrued for this study. Official Title ----------------- A Phase I/II Study of Double Unit Umbilical Cord Blood (UCB) Transplantation Utilizing Graft Administration Via Intra-Bone Marrow Injection (Companion Protocol to MT2000-25) Conditions ----------------- Myeloproliferative Disorders, Leukemia, Lymphoma, Myelodysplastic Syndromes Intervention / Treatment ----------------- * Procedure: umbilical cord blood transplantation Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Acute myeloid leukemia (AML): high risk CR1 Acute lymphocytic leukemia (ALL): high risk CR1 [t(9;22), t (1:19), t(4;11) or other MLL rearrangements] or > 1 cycle to obtain CR; CR2+. All patients must be in CR as defined by hematological recovery, AND <5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%. Chronic myelogenous leukemia (CML) excluding refractory blast crisis. To be eligible in first chronic phase (CP1) patient must have failed or be intolerant to imatinib mesylate. Myelodysplasia (MDS) IPSS Int-2 or High risk (i.e. RAEB, RAEBt) or refractory anemia with severe pancytopenia or high risk cytogenetics. Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma or follicular lymphoma that have progressed after at least two prior therapies. Patients with bulky disease (nodal mass greater than 5 cm). Lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia are eligible after initial therapy in CR1+ or PR1+. Large cell NHL > CR2/> PR2. Patients in CR2/PR2 with initial short remission (<6 months) are eligible. Lymphoblastic lymphoma. Multiple myeloma beyond PR2. Karnofsky performance status (PS) 90-100% (adults) Lansky PS 50-100% (children) Acceptable organ function Exclusion Criteria: Active infection at time of transplantation History of HIV infection Pregnant or breast feeding. Chemotherapy refractory large cell and high grade NHL (ie progressive disease after > 2 salvage regimens) Extensive prior therapy including > 12 months alkylator therapy or > 6 months alkylator therapy with extensive radiation. Diffuse myelofibrosis of BM (bone marrow) (any severity) regardless of primary diagnosis (focal fibrosis acceptable provided it involves < 20% of BM volume). History of pelvic irradiation. Ages Eligible for Study ----------------- Minimum Age: 12 Years Maximum Age: 45 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: Transplant Patients<br>Patients receiving umbilical cord blood transplantation. | Procedure: umbilical cord blood transplantation<br>* The graft will be given by slow injection into each posterior iliac crest.<br>* Other names: UCBT;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Median Number of Days to Neutrophil Engraftment | Number of days to neutrophil recovery observed in recipients of two umbilical cord blood units (UCB)administered i.v. Neutrophil recovery is defined as first of 3 consecutive days with ANC (absolute neutrophil count) greater than or equal to 500/ul. | Daily through Day 60 post transplant | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Number of Patients Achieving Neutrophil Recovery | Number of patients with sustained neutrophil recovery with chimerism (evidence of engraftment of both cord blood transplants) at 6 months. | 6 months | | Number of Patients With Evidence of Engraftment. | Number of patients who received both cord blood units and achieved sustained donor engraftment | 1 year | | Number of Patients With Acute Graft-versus-host Disease (GVHD) | Number of patients who exhibited grade II-IV acute GVHD at 100 days post umbilical cord blood transplant. | 100 days post transplant | | Number of Patients With Transplant-related Mortality (TRM) | Number of patients who were deceased at days 100 and 180 from any cause other than relapse. | Day 100 and Day 180 | | Number of Patients Surviving at Day 100 and 1 Year. | Overall survival of patients-Number of patients who were alive at Day 100 and 1 year post transplant. | Day 100 and 1 year | | Number of Patients With Grade III-IV Acute Graft-versus-host Disease (GVHD) | Number of umbilical cord blood transplant patients developing severe GVHD at 100 days post transplant. | 100 days post transplant | | Number of Patients With Chronic Graft-versus-host Disease (GVHD). | Number of umbilical cord blood transplant patients with limited and extensive chronic GVHD. | 1 year post transplant | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- mantle cell lymphoma, adult acute myeloid leukemia in remission, adult acute myeloid leukemia, childhood acute myeloid leukemia in remission, secondary acute myeloid leukemia, accelerated phase chronic myelogenous leukemia, childhood chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, relapsing chronic myelogenous leukemia, refractory anemia with excess blasts, de novo myelodysplastic syndromes, myelodysplastic syndromes, adult diffuse large cell lymphoma, adult diffuse mixed cell lymphoma, adult diffuse small cleaved cell lymphoma, adult lymphoblastic lymphoma, grade 3 follicular lymphoma, childhood large cell lymphoma, childhood lymphoblastic lymphoma, adult acute lymphoblastic leukemia, acute lymphoblastic leukemia, refractory anemia, refractory cytopenia, childhood acute myeloid leukemia, adult immunoblastic large cell lymphoma, blastic phase chronic myelogenous leukemia, chronic eosinophilic leukemia, chronic neutrophilic leukemia, childhood small noncleaved cell lymphoma, childhood myelodysplastic syndromes

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A Study on the Safety and Effectiveness of IBI318 Combined With Conventional TACE (cTACE) as a Perioperative Treatment for Potentially Resected Hepatocellular Carcinoma Study Overview ================= Brief Summary ----------------- The purpose of this phase Ib study is to assess the safety, tolerability and effectiveness of IBI318 in combination with conventional TACE (cTACE) in patients with potentially resected hepatocellular carcinoma. Official Title ----------------- A Phase Ib Study to Evaluate the Safety and Efficacy of IBI318 Combined With Conventional TACE (cTACE) as a Perioperative Treatment for Potentially Resected Hepatocellular Carcinoma Conditions ----------------- Hepatocellular Carcinoma Intervention / Treatment ----------------- * Drug: IBI318 * Procedure: cTACE * Drug: placebo Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Aged ≥ 18 years and ≤ 75 years at the time of consent. Hepatocellular carcinoma confirmed by histology/cytology. Lesions with measurable disease at baseline by mRECIST. Barcelona Clinic Liver Cancer stage A or B for hepatocellular carcinoma exceeding Milan criteria. Child-Pugh: <=6 Adequate organ and bone marrow function. Exclusion Criteria: With fibrous lamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma components in tumor tissues. Having previously received standard systemic therapy, ablative therapy, interventional therapy and surgical treatment for hepatocellular carcinoma. Potential liver transplant candidates Have a history of hepatic encephalopathy or have a history of liver transplantation. With clinical symptoms requires drainage of pleural effusion, ascites or pericardial effusion. 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: Quadruple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: IBI318 combined with conventional TACE (cTACE)<br> | Drug: IBI318<br>* before surgery IBI318 intravenous injection Q2W,after surgery IBI318 intravenous injection Q4W<br>Procedure: cTACE<br>* conventional transarterial chemoembolization<br>| | Placebo Comparator: Placebo combined with conventional TACE (cTACE)<br> | Procedure: cTACE<br>* conventional transarterial chemoembolization<br>Drug: placebo<br>* before surgery placebo intravenous injection Q2W,after surgery placebo intravenous injection Q4W<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Number of participants experiencing clinical and laboratory adverse events (AEs) | | Up to 90 days post last dose | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | The percentage of subjects with pathological Complete Response (pCR) after liver resection | | 3 years | | The percentage of subjects with major pathological response (MPR) after liver resection | | 3 years | | The percentage of subjects with R0 resection | | 3 years | | Objective response rate (ORR) in two arms based on mRECIST by investigator | | 3 years | | Disease-free survival (DFS) in two arms based on mRECIST by investigator | | 3 years | | Overall survival (OS) in two arms | | 3 years |

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Appetite Regulation by Human Chemosignals From Tears and Plasma Study Overview ================= Brief Summary ----------------- Obesity is closely related to metabolic diseases and its prevalence is sharply increasing. However, there is no safe and effective treatment for obesity so far, the investigators need a breakthrough idea to curtail the constant threat of obesity. It has been recently demonstrated that emotional tears of women can modify sexual responses, one of basic instincts, in men. As appetite and food intake is another basic instinct, chemosignals from tears and plasma may modify appetite and eating behavior in humans. Conditions ----------------- Obesity Intervention / Treatment ----------------- * Biological: Sniffing emotional tears * Biological: Sniffing trickled saline * Biological: Sniffing fasting plasma * Biological: Sniffing postprandial plasma Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Woman: Negative for HIV, Syphilis (VDRL), and Hepatitis B and C Man: Has a body mass index (BMI) of 18.5 kg/m2 to 27 kg/m2, inclusive. Exclusion Criteria: Woman: Has eyelids inflammation, conjunctivitis, keratitis, lacrimal duct obstruction. Has skin diseases around eyes. Man: Has diabetes mellitus or dyslipidemia on medication. Received gastrointestinal surgery except appendectomy and hemorrhoidectomy. Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 35 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Design Details Allocation: Randomized Intervention Model: Crossover Assignment Masking: Double Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Tears<br>Emotional tears of female volunteers while watching sad video clips | Biological: Sniffing emotional tears<br>* A band-aid soaked 100μl of emotional tears will be applied just below nostrils.<br>* Other names: Emotional tears;| | Placebo Comparator: Saline<br>Saline collected after being trickled down women's skin below eyes like tears | Biological: Sniffing trickled saline<br>* A band-aid soaked 100μl of trickled saline will be applied just below nostrils.<br>* Other names: Trickled saline;| | Placebo Comparator: Fasting<br>Their own overnight fasting plasma of male volunteers | Biological: Sniffing fasting plasma<br>* A band-aid soaked 100μl of own fasting plasma will be applied just below nostrils.<br>* Other names: Fasting plasma;| | Experimental: Prandial<br>Their own postprandial plasma of male volunteers | Biological: Sniffing postprandial plasma<br>* A band-aid soaked 100μl of own postprandial plasma will be applied just below nostrils.<br>* Other names: Postprandial plasma;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | The degree of appetite by visual analogue scale (VAS) and the amount of food intake by standard test meals in male volunteers while sniffing tears, trickled saline (control), and postprandial and fasting plasma in random order. | | Visual analogue scale (VAS) will be rated 10 minutes after initial sniffing of tears/plasma just before eating standard test meals. The amount of food intake will be measured by weighing the meals before and after eating. | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Appetite regulating hormones(ghrelin, GLP-1, PYY), glucose, testosterone. Determination of tears, tickled saline, and plasma. | | Blood samples for measuring appetite regulating hormones, glucose, testosterone will be collected at -10, 0, and 60 min. | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Emotional tears, Postprandial plasma, Chemosignal, Obesity, Appetite, Food intake

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Intratumoral Budding (ITB) in Preoperative Biopsies of Colon and Rectal Cancer Study Overview ================= Brief Summary ----------------- All the preoperative biopsies of patients suffering colorectal cancer (CRC) will be immunohistochemically stained with a pancytokeratin marker to detect Tumor buds. then, the intratumoral buds (ITB) in the densest Region of Tumor buds, namely the hot spot will be counted. Subsequently, the probability of N stage (lymphnodes), M stage (metastases) and disease free survival (DFS) will be calculated based on an existing logistic Regression model already developed by our previous retrospective work. Additionally, a Standardisation of ITB using a well- established Software will develop an algorithm which will help to eliminate inter- observer variability of Tumor budding Counts. Official Title ----------------- Assessment of Intratumoral Budding (ITB) in Preoperative Biopsies of Colon and Rectal Cancer Patients: a Prospective Observational Study Conditions ----------------- CRC Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patients with newly diagnosed stages I and IV colorectal cancer (CRC) Age ≥ 18 years Written Informed Consent Exclusion Criteria: No consent < 18 years Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Study Plan ================= How is the study designed? ----------------- What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | correlation of ITB based calculated N stage with real N stage in CRC - patients | | 24 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | correlation of ITB based calculated DFS with real DFS in CRC - patients | | 24 months |

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Mobile Education for Emergency Ultrasound Study Overview ================= Brief Summary ----------------- The investigators aim to investigate the feasibility of using mobile application platform for sonographic education. Junior physicians at the National Taiwan University Hospital will be enrolled in this study. To design and develop a secure mobile application platform (consisting of mobile device and a cloud-based server) for interactive teaching, remote social-based consultation and discussion. The information exchange through the platform carries images and simulated cases. This pioneer study can provide experience of mobile sonographic education and contribute to current medical education. Moreover, it can improve decision-making process and quality of care, and could lessen crowdedness at emergency departments. Furthermore, the integrated platform can be used in other educational programs in the future. Detailed Description ----------------- As usual, it takes time for junior emergency physicians to have good diagnostic accuracy through traditional sonographic education. Applying the technology built in this project, junior emergency physicians will be provided with intelligent learning programs anywhere and anytime. Junior physicians at the National Taiwan University Hospital will be enrolled in this study. Official Title ----------------- Mobile Education for Emergency Ultrasound Conditions ----------------- Educational Problems Intervention / Treatment ----------------- * Other: educational platform Participation Criteria ================= Eligibility Criteria ----------------- Inclusion criteria: The junior physicians of the department of emergency medicine of the National Taiwan University Hospital. Exclusion criteria: The junior physicians of the department of emergency medicine of the National Taiwan University Hospital, refused to enter the study. Ages Eligible for Study ----------------- Minimum Age: 20 Years Maximum Age: 50 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 | | --- | --- | | use of the educational platform<br>Before the hand-on practice and assessements, the participants use the platform for learning. | Other: educational platform<br>* The platform would be opened before they entered the study.<br>| | without use of the educational platform<br>Before the hand-on practice and assessements, the participants did not use the platform for learning. | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | assessment for ultrasound scanning | use 5-point Likert scale (1 to 5 scores) | one week | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- emergency medicine ,emergency ultrasound

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Acute Effects of Oral Ketone Ester on Cardiac Function in Patients With COVID-19 Study Overview ================= Brief Summary ----------------- Based on Chinese studies, cardiac injury occurs in 20-30% of hospitalized patients and contributes to 40% of deaths. There are many possible mechanisms of cardiac injury in COVID-19 patients and increased myocardial oxygen demand and decreased myocardial oxygen supply are likely contributors to increased risk of myocardial infarction and heart failure. Interventions reducing the risk of cardiac injury are needed. Ketone bodies, such as 3-hydroxybutyrate and acetoacetate, can maintain ATP production in the heart and brain during starvation. It has been suggested that ketone bodies are more efficient substrates of energy metabolism than glucose, with a lower oxygen consumption per ATP-molecule produced. In addition, the reduction in hospitalizations due to heart failure observed in type 2 diabetes patients treated with sodium-glucose cotransporter 2 inhibitors, is suggested to be partly attributable to increased levels of 3-hydroxybutyrate. Infusion with 3-hydroxybutyrate reaching a plasma level of approximately 3 mM had acute beneficial hemodynamic effects in patients with heart failure and in healthy controls in a study by Nielsen et al. Improved haemodynamics and reduced systemic oxygen consumption might be of great benefit in patients with COVID-19. The primary endpoint is left ventricular ejection fraction. Secondary endpoints are conventional echocardiography parameters, peripheral blood oxygen saturation, venous blood oxygen saturation and urine creatinine clearance. The study population are twelve previously hospitalized patients with COVID-19 The study design is a randomized placebo-controlled double-blinded crossed-over acute intervention study. Official Title ----------------- Acute Effects of Oral Ketone Ester on Cardiac Function in Patients With COVID-19 Conditions ----------------- COVID-19 Intervention / Treatment ----------------- * Dietary Supplement: D-beta-hydroxybutyrate-(R)-1,3 butanediol monoester * Dietary Supplement: Placebo Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: - Patients previously hospitalized at hospitals of greater Copenhagen and the Zealand region with a laboratory confirmed diagnosis of COVID-19 > 18 years of age. Exclusion Criteria: Persons not able to cooperate Persons unable to understand and sign informed consent Diagnosis with chronic obstructive pulmonary disease Diagnosis with asthma Active treatment with sodium-glucose transporter 2 inhibitors eGFR < 15 ml/min/1.73m2 insulin-dependent diabetes 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 Interventional Model Description: Randomized placebo-controlled double-blinded crossed-over acute intervention study. Masking: Triple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: D-beta-hydroxybutyrate-(R)-1,3 butanediol monoester<br> | Dietary Supplement: D-beta-hydroxybutyrate-(R)-1,3 butanediol monoester<br>* The intervention is D-beta-hydroxybutyrate-(R)-1,3 butanediol monoester and will be bought commercially. As an example: One bottle of KetoneAid KE4 PRO with 60 ml contains 30 g D-beta-hydroxybutyrate-(R)-1,3 butanediol monoester. For more information please refer to: https://shop.ketoneaid.com/collections/all/products/ke4-pro. Placebo will be a taste-matched water solution provided by the company. The placebo solution and the active solution will be prepared in identic bottles and investigators will be blinded.<br>| | Placebo Comparator: Placebo<br> | Dietary Supplement: Placebo<br>* Taste-matched water<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Left Ventricular ejection fraction | Echocardiography | 1 hour | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Global longitudinal strain | Echocardiography | 1 hour | | Cardiac output | Echocardiography | 1 hour | | Peripheral blood oxygen saturation | Pulse oximetry | 5 minutes | | Venous blood oxygen saturation | blood gas analysis | 5 minutes | | Urine creatinine clearance | Urine will be collected during the two cross-over sessions and urine creatinine will be measured on these two volumes. Creatinine clearance in ml/min/1.73m2 will then be estimated and compared with plasma creatinine for estimating kidney function. | 12 hours |

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Mass Balance of Oral [14C]TPN171H in Healthy Male Subjects Study Overview ================= Brief Summary ----------------- This study is objective to evaluate the in vivo absorption, excretion and biotransformation pathways of [14C]-TPN171H in Chinese male healthy volunteers, and to reveal the overall pharmacokinetic characteristics of TPN171H in human body, so as to provide basis for rational use of the drug. Detailed Description ----------------- This will be an open-label, single-center study to evaluate the mass-balance and pharmacokinetics of TPN171H in approximately 6 healthy male subjects receiving a single oral 10 mg dose of TPN171H containing approximately 100 microcuries of [14C]-TPN171H. Subjects will be checked in to the research unit from approximately 24 hours prior to dosing and remain in house until greater than 80% of the administered radioactivity is collected from bodily excreta or until less than 1% of the administered radioactivity is recovered from excreta in two consecutive time intervals, and blood sample radioactivity concentration at two consecutive time points less than 3 times the plasma background value. This study will investigate the main biotransformation and elimination pathways of TPN171H in the human body and will seek to identify compound's major metabolites. Official Title ----------------- A Phase I Study of the Mass Balance of a Single Oral Administration of [14C]TPN171H in Healthy Male Subjects Conditions ----------------- Healthy Male Subjects Intervention / Treatment ----------------- * Drug: [14C]TPN171H Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Healthy male subjects between the ages of 19 and 55 years,with normal bowel movements (1 2 times a day); Body Mass Index of 19 to 26 kg/m2; Body weight no less than 50 kg; Physical examination, vital signs examination, laboratory examination (blood routine, urine routine, blood biochemistry, thyroid function, stool routine and occult blood, etc.), 12 lead ECG, B-ultrasound, chest X-ray and fundus examination results were normal or abnormal without clinical significance; The male subjects with fertility had no child rearing plan or sperm donation plan with their sexual partners during the trial and within one year after taking the drug, and could take reliable contraceptive measures; Fully understand the purpose and requirements of this trial, voluntarily participate in the clinical trial and sign the written informed consent, and can complete the whole trial process according to the test requirements. Exclusion Criteria: People with allergies or allergic diseases, or known allergies to test preparations, any of their ingredients, and related preparations; There are clear diseases of the central nervous system, cardiovascular system, digestive system (including those with severe fatty liver in B-ultrasound examination), respiratory system, urinary system, blood system, metabolic disorders, etc. and require medical intervention or other unsuitable clinical trials Those with tested diseases (such as history of mental illness, etc.); those with a history of orthostatic hypotension; Blurred vision or a history of the following ocular diseases: nonvascular anterior ischemic optic neuropathy (NAION), abnormal color vision, hereditary retinal degeneration (such as retinitis pigmentosa), macular degeneration; Any drug that inhibits or induces liver drug-metabolizing enzymes (inducers-barbiturates, carbamazepine, phenytoin, rifampicin, dexamethasone, rifabutin, rifapentine) has been used within 30 days before administration ; Inhibitors-SSRI antidepressants, cimetidine, diltiazem, macrolides, verapamil, imidazole antifungals, sedatives and hypnotics, fluoroquinolones, antihistamines, etc.); Those who have taken any prescription drugs, over-the-counter drugs, Chinese herbal medicines or health care products within 2 weeks before administration; or those who have participated in other drug clinical trials and received trial drugs within 3 months before administration; Those who have a history of drug dependence (including a history of drug use) within 2 years before administration; or urine drug abuse screening (morphine, tetrahydrocannabinol acid, methamphetamine, dimethylene oxyamphetamine) , Ketamine and cocaine) positive; Those who smoke more than 10 cigarettes per day and do not agree to avoid using any tobacco products during the trial period; Positive results of alcohol breath test, or current/previous alcoholics (drinking more than 21 standard units per week. 1 standard unit contains 14 g of alcohol, such as 360 mL of beer or 45 mL of 40% spirits or 150 mL wine); People who have consumed excessive amounts of grapefruit juice, tea, coffee and/or caffeinated beverages for a long time (more than 8 cups a day, 1 cup equal to 250 mL); Those who are positive for hepatitis B surface antigen (HBsAg), HCV antibody, syphilis antibody and HIV antibody; Blood loss or blood donation of 400 mL or more within 3 months before administration; Those who have been vaccinated within 6 months before administration; A history of fainting needles or fainting blood; Hemorrhoids or perianal diseases with regular/current stools; habitual constipation or diarrhea, irritable bowel syndrome, inflammatory bowel disease; Workers who need to be exposed to radioactive conditions for a long time; or have significant radioactive exposure more than 2 chest/abdominal CT, or more than 3 other types of X-ray examinations) within 1 year before administration or participated in radiopharmaceutical labeling Experimenter The investigator believes that there are other factors that are not suitable for participating in this trial. Ages Eligible for Study ----------------- Minimum Age: 18 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: Basic Science Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: [14C]TPN171H<br> | Drug: [14C]TPN171H<br>* A single 10 mg oral dose of [14C]TPN171H containing approximately 100 microcurie of [14C]-TPN171H.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Cmax - maximum observed plasma concentration | | From time zero up to 336 hours post-dose following oral administration of [14C]TPN171H | | Tmax - time at which Cmax occurs | | From time zero up to 336 hours post-dose following oral administration of [14C]TPN171H | | AUC0 t - area under the plasma concentration time curve from time zero to the last measurable concentration | | From time zero up to 336 hours post-dose following oral administration of [14C]TPN171H | | AUC0-∞ - area under the plasma concentration-time curve from time zero to infinity | | From time zero up to 336 hours post-dose following oral administration of [14C]TPN171H | | Total radioactivity in urine and faeces | | From time zero up to 336 hours post-dose following oral administration of [14C]TPN171H | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Mass balance, TPN171H, Simmerafil

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Dose Finding Study for Continuous Spinal Anaesthesia Study Overview ================= Brief Summary ----------------- Fixation of fractured neck of femur is a common Orthopedic surgery. Anaesthesia can be challenging in some cases like in haemodynamical unstable patients. The investigators have evidence of minimum effective local anaesthetic dose (MLAD) in hip replacement surgery but MLAD to achieve surgical anaesthesia for operative fixation of FNF is still unknown. A step-up/step-down methodology was used successfully in regional anaesthesia and also in other areas of anaesthesia. In pregnant ladies in whom spinal anaesthesia is performed on the side, significant correlation exist between the vertebral length measured from cervical 7 to the iliac creast and MLAD. The investigators aim it was to determine the MLAD of hyperbaric 0.5% bupivacaine required for Continuous spinal anaesthesia for the operative fixation of FNF. Detailed Description ----------------- Fractured neck of femur (FNF) is a common cause of admission to hospital in elderly patients and requires operative fixation. Spinal anaesthesia (SA) is one of the options, since 1899 when Bier described first administration this technique went through many changes. Spinal anaesthesia has the definitive advantage that profound nerve block can be produced in a large part of the body by the relatively simple injection of a small amount of local anaesthetic. Although in some cases single shot SA is contraindicated or can have severe haemodynamic side effects. In elderly patients undergoing hip fracture repair, continuous spinal anaesthesia (CSA) provides fewer episodes of hypotension and severe hypotension compared with a single intrathecal injection of 7.5 mg bupivacaine. We have evidence of minimum effective local anaesthetic dose (MLAD) in hip replacement surgery but MLAD to achieve surgical anaesthesia for operative fixation of FNF is still unknown. It would however be beneficial for those patients who are haemodinamicaly unstable. A step-up/step-down methodology was used successfully in regional anaesthesia and also in other areas of anaesthesia. In pregnant ladies in whom spinal anaesthesia is performed on the side, significant correlation exist between the vertebral length measured from cervical 7 to the iliac creast and MLAD. We propose to study the MLAD for continuous spinal anaesthesia (CSA) for the operative fixation of FNF. Objectives: We would like to determine the MLAD of hyperbaric 0.5% bupivacaine required for CSA for the operative fixation of FNF. After ethical approval and having obtained appropriate consent we will start recruitment to the study. Patients will receive no premedication prior to their arrival to the operating room. All patients will receive oxygen (35% oxgen Venturi facemask) during the procedure, including the first postoperative hours. Standard monitoring including continuous electrocardiogram, noninvasive automated arterial blood pressure and pulse oximetry will be applied. Patients will receive ultrasound guided femoral nerve block, 15 ml of 2% lignocaine before being turned to the lateral position for lumbar puncture. After antiseptic preparation of the area, lumbar puncture will be performed by an experienced senior anesthesiologist. Subarachnoid puncture will be performed with a 18-gauge Tuohy needle at the L4-5 or L3-4 interspace using a midline approach. Three cm of a 22-gauge catheter will be introduced cephalad through the needle. The initial dose is arbitrarily chosen as 1 ml of 0.5 % isobaric bupivacaine on the basis of clinical experience, the local anaesthetic will be injected through the catheter over 5-10 s. After completion of injection the patients remain in the lateral position for 5 min and then will be returned to the supine position. Successive injections of 0.2 ml of 0.5 % isobaric bupivacaine will be performed every 15 min until a satisfactory sensory level is obtained (T12). Using a step-up/step-down model, the dose used for following patients will be determined by the outcome of the preceding intrathecal block. In the case of failure of the initial dose when there is a need to administer extra dose of local anaesthetic after 15 minutes, the initial dose will be increased by 0.1 ml. Conversely, spinal success will result in a reduction in dose by 0.1 ml. Noninvasive automated blood pressure and heart rate measurements will be recorded before the spinal anesthesia (baseline) and every three minutes after the end of local anesthetic injection till the end of surgery. Hypotension is defined as a decrease of more than 20% from the baseline systolic arterial blood pressure (SAP). Severe hypotension is defined as a decrease in SAP more than 30% of baseline value. Hypotension will be treated with IV boluses of ephedrine 6 mg if the heart rate is below 60/minutes or phenylephrine 100 microgramm if the heart rate is above 60/minutes. In case of failure or insufficient block, general anesthesia will be performed. A blinded observer will be assessing the dermatome level of sensory blockade with an ice-cold test (ethyl-chloride spray) bilaterally after injection of the local anesthetic. Block assessment will be performed at 15min intervals up to 45 min after completion of the initial intrathecal injection. The modified Bromage scale (0 - non-motor block; 1 hip flexion with extended leg blocked, 2-knee flexion blocked, 3-complete motor block) will be used for degree of motor block bilaterally. Sensory function will be scored as being present or absent. Surgical anesthesia is defined as a with absent appreciation of cold sensation. The time interval at which surgical anesthesia is achieved will be noted. Total spinal anaesthesia failure is defined as absence of surgical anesthesia at 45 min. The number of hypotensive episodes, total vasopressor administered, and the iv. fluid infused will be recorded. Catheters in the CSA group were removed after the surgery. All patients will be receiving 1 g of intravenous paracetamol and 75 mg of diclofenac sodium during surgery. Postoperative analgesia will consist of 1 g of oral paracetamol every 6 hours and 75 mg of diclofenac sodium twice daily for 72 h after surgery. Oxycodone 5 mg will be prescribed for rescue analgesia after spinal anaesthesia regression. Study-stopping Rules Based on previous non-probability sequential dosing, up-and-down dose finding studies with similar binary outcomes. We are estimating that a minimum of five independent negative positive up-and-down deflections are required to calculate MLAD. Official Title ----------------- Determination of the Minimum Local Anaesthetic Needed for Operative Fixation of Fractured Neck of Femur With Continuous Spinal Anaesthesia Conditions ----------------- Femoral Fracture Intervention / Treatment ----------------- * Procedure: Continuous spinal anaesthesia Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Above 60 years ASA I to III patients Exclusion Criteria: Patient refusal Outside Age Range Coagulation disorders Head injury or other associated injuries Loss of consciousness and signs of acute coronary syndrome Mini-Mental Score < 25 Allergy to bupivacaine, lignocaine Skin lesions/infection at site of injection Sepsis Ages Eligible for Study ----------------- Minimum Age: 60 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: Continuous spinal anaesthesia<br> | Procedure: Continuous spinal anaesthesia<br>* Standard monitoring including continuous electrocardiogram, noninvasive automated arterial blood pressure and pulse oximetry will be applied. Subarachnoid puncture will be performed with a 18-gauge Tuohy needle at the L4-5 or L3-4 interspace using a midline approach. Three cm of a 22-gauge catheter will be introduced cephalad through the needle. The initial dose is arbitrarily chosen as 1 ml of 0.5 % isobaric bupivacaine on the basis of clinical experience, the local anaesthetic will be injected through the catheter over 5-10 s. After completion of injection the patients remain in the lateral position for 5 min and then will be returned to the supine position. Successive injections of 0.2 ml of 0.5 % isobaric bupivacaine will be performed every 15 min until a satisfactory sensory level is obtained (T12).<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | MLAD of 0.5 % bupivacaine for operative fixation of fractured neck of femur patients | Subarachnoid puncture will be performed with a 18-gauge Tuohy needle at the L4-5 or L3-4 interspace using a midline approach. Three cm of a 22-gauge catheter will be introduced cephalad through the needle. The initial dose is arbitrarily chosen as 1 ml of 0.5 % isobaric bupivacaine on the basis of clinical experience, the local anaesthetic will be injected through the catheter over 5-10 s. | In every 15 minutes after performing spinal anaesthesia the spinal block will be assessed | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | MLAD/ vertebral length | | In every 15 minutes after performing spinal anaesthesia the spinal block will be assessed | | Pain experienced by the patients in the operating theatre. | | In every 15 minutes after performing spinal anaesthesia the spinal block will be assessed | | Patient satisfaction after surgery regarding pain relief. | | In every 15 minutes after performing spinal anaesthesia the spinal block will be assessed | | Difference (if any) in effect on haemodynamic variables (i.e. heart rate and blood pressure). | | After performing spinal anaesthesia the blood pressure will be measured in every three minutes, ECG and pulse oximetry will me recorded continuously | | Side effects of medication | | After performing spinal anaesthesia the blood pressure will be measured in every three minutes, ECG and pulse oximetry will me recorded continuously |

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Effect of Dynamic Taping on Landing Biomechanical Characteristics in Volleyball and Basketball Players With Symptoms of Patellar Tendinopathy Study Overview ================= Brief Summary ----------------- Patellar tendinopathy (PT) is an overuse injury associated with loading activities, and popular among basketball and volleyball players. Although altered biomechanical characteristics during landing has been suggested as one of the risk factors for the development of PT, previous evidence failed to show the link between the sagittal plane biomechanics of the hip and knee joint and PT; and little was known about the frontal and horizontal plane biomechanics in athletes with PT. While other factors such as motor control or muscle activation also have not been explored fully. The purpose of this study is to compare hip motor control and biomechanical characteristics of the hip and knee joint during landing in athletes with and without symptomatic PT. Detailed Description ----------------- Background: Patellar tendinopathy is an overuse injury associated with loading activities, and it is thought to be caused by repetitive force applied to the patellar tendon. Patellar tendinopathy is popular among basketball and volleyball players, particularly in men. Although altered biomechanical characteristics during landing has been suggested as one of the risk factors for the development of patellar tendinopathy, previous evidence failed to show the link between the sagittal plane biomechanics of the hip and knee joint and patellar tendinopathy; and little was known about the frontal and horizontal plane biomechanics in athletes with patellar tendinopathy. Among those factors contributing to the biomechanical characteristics, hip and quadriceps strength were shown linked with the presence of patellar tendinopathy, while other factors such as motor control or muscle activation have not been explored fully. The purpose of this study is to compare hip motor control and biomechanical characteristics of the hip and knee joint during landing in athletes with and without symptomatic patellar tendinopathy. The investigators hypothesize that the athletes with symptomatic patellar tendinopathy have poorer motor control and different landing biomechanics as compared with asymptomatic athletes. Method: the investigators plan to recruit seventeen symptomatic patellar tendinopathy athletes for the experimental group, using demographic data (sex, age, height, weight, exercise type) of experimental group to match seventeen non-symptomatic athletes as control group. The assessment included hip motor control in various directions, and measurement of kinetics, kinematics and muscle activation during the step-down task, drop vertical jump and countermovement jump using the computer-aided video motion analysis system (Vicon) and the surface EMG (Delsys). The group difference will be tested using Mann-Whitney U test for the score of motor control test battery, and MANOVA for the biomechanical characteristics. The significant level was set at 0.05. Official Title ----------------- Effect of Dynamic Taping on Landing Biomechanical Characteristics in Volleyball and Basketball Players With Symptoms of Patellar Tendinopathy Conditions ----------------- Biomechanical Phenomena Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: at the age of 18 to 40 years old volleyball and basketball players have more than 2 years training experience over 90 minutes of training time per week symptomatic group: having patellar tendon pain during loading task last for 3 months VISA-P questionnaire score ≦80 asymptomatic group: without any lower extremity pain in past 3 months VISA-P questionnaire score >80 Exclusion Criteria: volleyball and basketball players joined the school team or professional level unbearable pain occurred at the patellar tendon when conducting landing tasks with a history of patellar tendon pain before there are currently other acute injuries to the lower extremity lower extremity has undergone surgery or fracture in the past with a history of rheumatoid arthritis, systematic and neurological diseases Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 40 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 | | --- | --- | | symptomatic group<br>Individuals with patellar tendon pain last for 3 months Individuals age between 18-40 years old Victorian Institute of Sport Assessment (VISA) Questionnaire score ≦80 | | | asymptomatic group<br>Individuals without any lower extremity pain in past 3 months Individuals age between 18-40 years old Victorian Institute of Sport Assessment (VISA) Questionnaire score >80 | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | lower extremities joint angle | hip joint flexion, extension, abduction, adduction, internal rotation, external rotation angle, knee joint flexion, extension angle | Immediately during the experiment | | lower extremities joint angular velocity | hip joint flexion, extension, abduction, adduction, internal rotation, external rotation angle, knee joint flexion, extension angle divided by time | Immediately during the experiment | | lower extremities joint angular acceleration | lower extremities joint angular velocity divided by time | Immediately during the experiment | | ground reaction force | anterior, posterior, medial, lateral, vertical ground reaction force | Immediately during the experiment | | lower extremities joint force | calculate the reaction force between segments | Immediately during the experiment | | lower extremities joint moment | calculate the reaction moment between segments | Immediately during the experiment | | lower extremities joint power | calculate the reaction moment between segments | Immediately during the experiment | | time to peak ground reaction force | time period from initial contact to peak vertical ground reaction force | Immediately during the experiment | | loading rate of ground reaction force | peak vertical ground reaction force divided by time to peak ground reaction force | Immediately during the experiment | | net joint work | integral of joint power over time | Immediately during the experiment | | patellar tendon force | knee joint moment divided by moment arm | Immediately during the experiment | | Lower extremity muscles activation during landing task | The investigator will place surface electromyography (sEMG)(Delsys, USA) on subjects' bilateral gluteus maximum, gluteus medius, semitendinosus, biceps femoris, vastus medialis, vastus lateralis muscles to record muscles activities. | Immediately during the experiment | | Hip joint motor control | The investigator will ask subject to do the hip flexion, hip internal rotation, hip abduction/external rotation and hip adduction control task. | pre-experiment | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Lower extremities joint angle | Measuring bilateral ankle dorsiflexion range of motion by the physical therapist with goniometer. | pre-experiment | | Lower extremities muscle force | The hip extensor, external rotator, abductor, knee extensor, flexor muscle force measured by the physical therapist with a hand-held dynamometer | pre-experiment | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- patellar tendinopathy, volleyball, basketball, landing, biomechanics, EMG, muscle activation, kinetics, kinematics

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A Retrospective Cohort Study to Develop Markers for TB Severity and Treatment Progress Study Overview ================= Brief Summary ----------------- The objective of this study is to compare how accurately the Xpert MTB/RIF assay Ct value at diagnosis and the AI-based tuberculosis activity score predict the treatment outcome of rifampin-susceptible pulmonary tuberculosis patients. As a retrospective observational study, data from patients diagnosed with rifampin susceptible pulmonary tuberculosis through the Xpert MTB/RIF assay performed on sputum in 2019 at the participating institutions will be analyzed (up to 900 people). Official Title ----------------- A Retrospective Cohort Study to Develop Markers for TB Severity and Treatment Progress Conditions ----------------- Pulmonary Tuberculoses, Tuberculosis, Pulmonary Intervention / Treatment ----------------- * Other: Medical records review Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patients diagnosed with rifampin-susceptible pulmonary tuberculosis by Xpert MTB/RIF assay with sputum samples between January 1, 2019 and December 31, 2019 Exclusion Criteria: None Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Intervention/Treatment | | --- | |Other: Medical records review|The clinical characteristics at the time of diagnosis of rifampin-susceptible pulmonary tuberculosis patients, the Xpert MTB/RIF assay Ct value, the tuberculosis activity score based on AI of the chest image, and treatment results will be collected retrospectively through medical records.| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Negative culture conversion until 8 weeks after initiation of treatment | Conversion from positive tuberculosis culture to negative tuberculosis culture | Within 8 weeks of initiating treatment | | Time to negative culture conversion | Time (days) to conversion from positive tuberculosis culture to negative tuberculosis culture | Within 6 months of initiating treatment | | Treatment outcome including 1) Cure 2) Treatment completion 3) Treatment failure 4) Death 5) Loss of follow-up 6) Unknown | Cure: confirmed negative culture conversion plus negative culture results from at least one sputum on the month of treatment completion Treatment completion: confirmed negative culture conversion at least once during treatment Treatment failure: positive culture results after 4 months of treatment Death: death during treatment Loss of follow-up: loss of follow-up during treatment Unknown | Within 2 years of initiating treatment |

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Factors in Learning And Plasticity: Macular Degeneration Study Overview ================= Brief Summary ----------------- A greater understanding of plasticity after central vision loss can inform new therapies for treating low vision and has the potential to benefit millions of individuals suffering from low vision. The treatment of low vision is particularly relevant to the mission of the NEI to support research on visual disorders, mechanisms of visual function, and preservation of sight. The comparison of different training and outcome factors is in line with the NIMH RDOC framework and studies in an aging population are consistent with the mission of the NIA. Detailed Description ----------------- Research on perceptual learning (PL) has been dominated by studies that seek to isolate and improve individual visual processes. However, an important translational outcome of PL research is to address the needs of patients with vision loss, who seek to improve performance on daily tasks such as reading, navigation, and face recognition. These more ecological cases of behavioral change and cortical plasticity, which are inherently complex and integrative, have revealed significant gaps in a more holistic understanding of how multiple visual processes and their associated brain systems jointly contribute to durable and generalizable PL. To address these gaps, here the investigators study simulated and natural central vision loss. The investigators focus on macular degeneration (MD), one of the most common causes of vision loss (projected to affect 248 million people worldwide by 2040), which results from damage to photoreceptors in the macula that disrupts central vision. Such central vision loss is a superb lens through which study to how ecologically relevant changes in the use of vision relate to changing brain activity and connectivity because it represents a massive alteration in visual experience requiring reliance on peripheral vision for daily tasks. With the use of eye-trackers and gaze-contingent displays that induce central scotomas, central vision loss can be simulated in normally seeing individuals, who then develop peripheral looking patterns that resemble compensatory vision strategies seen in MD patients. Ideal use of peripheral vision requires improvement in multiple vision domains, three of the most important being: early visual processing (e.g., visual sensitivity), mid-level visual processing (e.g., spatial integration), and attention and eye-movements. To date, no study has systematically investigated these three domains of PL and their neural underpinnings. The proposed research plan rests on rigorous prior work showing that PL influences multiple brain structures and functions related to these three domains. The investigators propose a novel approach of systematically measuring how different training regimes related to the three domains influence a broad range of psychophysical and ecological behaviors (Aim 1), how these changes arise from plasticity in brain structure and function (Aim 2), and how PL after simulated central vision loss compares to PL in MD (Aim 3). This work is significant and innovative as it will be the first integrated study of PL characterizing multiple trainable factors and their impact on diverse behavioral outcomes and on cutting-edge assessments of neural representations and dynamics. It is also the first study to directly compare PL in MD patients with PL in a controlled model system of central visual field loss with simulated scotomas, which if validated will allow the use of this model system to interrogate MD in larger samples of healthy individuals. The investigators will also share a unique dataset that will help the field to understand behavioral and neural plasticity after central vision loss and individual differences in responsiveness to training. Finally, this work will illuminate basic mechanisms of brain plasticity after sensory loss that may generalize to other forms of rehabilitation after peripheral or central damage. Official Title ----------------- Characterization of Multiple Factors in Training and Plasticity in Central Vision Loss: Macular Degeneration Conditions ----------------- Central Visual Impairment, Macular Degeneration Intervention / Treatment ----------------- * Behavioral: Training visual sensitivity * Behavioral: Combination training Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Aged 18-89 Severely impaired vision in both eyes (20/100 or worse) diagnosis of Macular Degeneration by an Ophthalmologist Light sensitivity in the macular retina that is at least 10 dB units worse than in peripheral regions, as demonstrated by a scanning laser ophthalmoscope (MAIA) Medical record review indicating this level of disease severity has been present for at least 2 years Reside within 50 miles of study site Exclusion Criteria: Pacemaker or any ferromagnetic metal implanted in their body Metal of any type implanted in their head (limited dental work is acceptable) Claustrophobia Being hearing-impaired Weight over 300 pounds Maximum body girth over 60 inches Previous serious head injury Presence of hallucinations or delusions Excessive old, or colorful tattoos, especially near the head Pregnancy Braces/permanent retainer Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 89 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: Single Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Training visual sensitivity<br>A standard Perceptual Learning approach to train early visual processes of discriminating the orientation of Gabor patches presented at threshold- level contrast. Preliminary data, using this method, in normally seeing and MD participants show both feasibility and preliminary evidence that this training gives rise to improvements in acuity. | Behavioral: Training visual sensitivity<br>* Investigators adopt a standard PL approach to train early visual processes of discriminating the orientation of Gabor patches presented at threshold contrast. Across training blocks, Gabors will range in spatial frequency, where contrast is adapted with a 3/1 staircase. Whenever a specific contrast threshold is reached, spatial frequency will increase by 2 cycles per degree and contrast will be reset. Preliminary data from this method in normally seeing and MD participants show both feasibility and tentative evidence that this training gives rise to improvements in acuity.<br>| | Experimental: Combination training<br>In combination training, investigators test the extent to which a combined training gives rise to the joint benefits of each training individually, or integrative benefits potentially surpassing benefits of the individual training alone. The visual sensitivity task will alternate across blocks with the spatial integration task, using the timing of targets and location switches from spatial attention training. | Behavioral: Combination training<br>* Daily tasks involve a combination of being sensitive to basic visual features, being able to integrate these features, and directing attention and eye movements to better evaluate the information of potential interest. To address this integrative nature of real-world vision, this condition combines elements of training visual sensitivity, spatial integration, and spatial attention.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change from Baseline Radial Bias from the Crowding Task after completion of Training at approximately 7 weeks | The ratio of the crowding threshold along the axis connected to the fovea vs. along the orthogonal axis. | Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average | | Change from Baseline Saccadic Precision after Completion of Training at approximately 7 weeks | Consistency across trials in placement of the first saccade calculated by the distribution across trials (bivariate contour ellipse area) of the landing point of the first fixation of each trial. | Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average | | Change from Baseline Fixation Stability after Completion of Training at approximately 7 weeks | Normalizing fixations in the PRL to the first fixation to that region and calculating the distribution of all fixation locations in this normalized space (measured as a bivariate contour ellipse area). | Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- plasticity, central vision loss, perceptual learning

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Outcome Following Phacoemulsification Versus Small Incision Cataract Surgery (SICS) Study Overview ================= Brief Summary ----------------- Hypothesis : Phacoemulsification is superior to SICS with regards to: Immediate unaided high and low contrast visual performance Its impact on quality of life. Detailed Description ----------------- Phacoemulsification procedure Infiniti Vision System with Software 2.03 or higher, OZil handpiece (HP) Anaesthesia: topical Incision: temporal clear corneal 2.2 mm single plane CCC and hydrodissection, sculpting and division using step by step chop in situ and lateral separation, I/A. Single-piece AcrySof IOL (SN60WF) in the bag SICS procedure Anaesthesia: peribulbar Incision: superior scleral tunnel 6.5 to 7 mm CCC and hydrodissection Nuclear expression: blumenthal technique using anterior chamber maintainer, manual cortical clean-up Single-piece PMMA (MZ60BD) in the bag Official Title ----------------- Comparison of Phacoemulsification Versus Manual Small Incision Cataract Surgery (SICS) : A Randomized Control Trial Conditions ----------------- Visual Outcomes, Quality of Life Intervention / Treatment ----------------- * Procedure: phacoemulsification and SICS * Procedure: manual small incision surgery * Procedure: phacoemulsification Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Prospective subjects should be diagnosed with senile cataract. Subject must require extraction of cataract in one eye followed by implantation of an AcrySof (SN60WF) or PMMA (MZ60BD) posterior chamber intraocular lens. Pupil dilation equal or greater to 7 mm after mydriasis. Patients undergoing cataract surgery for the first eye. Visual prognosis equal or greater to 6/12. Exclusion Criteria: Patients with history of ocular pathology, glaucoma, uveitis, high myopia, PEX, or corneal pathology. Patients with traumatic, subluxated and posterior polar cataract. Patients who had previously ocular surgery in the past 6 months prior to the screening visit. Patients with diabetic retinopathy. Patients who are not suitable for follow-up visits. Patients with Fuchs' Dystrophy, Macular Degeneration, Ocular Surface Disease that will interfere with normal recovery. Any patients with significant intra-operative complications will be removed from the overall analysis of the results. All patient data should still be recorded, even if from the excluded patient group. Ages Eligible for Study ----------------- Minimum Age: 50 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: Triple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: manual small incision cataract surgery<br>surgical intervention by small incision cataract surgery | Procedure: manual small incision surgery<br> <br> * Other names: exrtracapsular cataract surgery;| | Other: phacoemulsification<br>surgical intervention by phacoemulsification | Procedure: phacoemulsification and SICS<br>* SICS with rigid IOL implantation Phaco with foldable IOL implantation<br>* Other names: Manual SICS;Procedure: phacoemulsification<br>* cataract surgery<br>* Other names: extracapsualr cataract surgery;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | immediate unaided and aided visual acuity | | immediate and mid term (12 months) | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Assessment of unaided and aided low contrast sensitivity | | 3 and 12 months | | Intra-operative complications immediate post-operative day corneal edema anterior chamber inflammation | | day 1, 1 week | | To assess improvement in quality of life | | 3 and 12 months | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- phacoemulsification, manual small incision cataract surgery, visual acuity, contrast sensitivity, quality of vision

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Vanderbilt Childhood Obesity Registry Study Overview ================= Brief Summary ----------------- In order to better understand early onset obesity and to identify patients in interested in future research studies, including clinical trials, we aim to develop a registry for patients with early onset obesity. Detailed Description ----------------- Obesity is an epidemic effecting the pediatric population. Currently, 17% of children are classified as obese and 32% as overweight. Many of these children develop complications including type 2 diabetes, dyslipidemia, hypertension and hepatic steatosis. Obesity is a global epidemic that lacks effective treatment options. Obesity has many underlying causes including genetic predisposition and environmental factors. Understanding the genetic basis of obesity may allow for more precisely targeted interventions including specific dietary plans and pharmacologic treatments. The most common cause of genetic obesity is haploinsufficiency of the melanocortin-4 receptor (MC4R). In obese adult cohorts, the prevalence of pathogenic MC4R mutations is 1-2%. Commercial testing is available for many obesity syndromes, but the cost is high and charges are not always covered by insurance. Clinicians have little motivation to test patients for MC4R mutations as no treatments are available and it is not clear if genetic testing results change patient behavior. This particular lab and other groups are working to develop novel pharmacologic treatments for obesity syndromes, such as MC4R deficiency. In order to better understand early onset obesity and to identify patients in interested in future research studies, including clinical trials, the investigators aim to develop a registry for patients with early onset obesity. Official Title ----------------- Vanderbilt Childhood Obesity Registry Conditions ----------------- Childhood Onset Obesity, Pediatric Obesity, Childhood Obesity Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: BMI >97th percentile for age and gender before 6 years old Able to give written, informed consent/assent Exclusion Criteria: Diagnosis of Prader-Willi syndrome Use of exogenous steroids or other medications known to cause abnormal weight gain Cushing's syndrome, untreated growth hormone deficiency or untreated hypothyroidism as an etiology for the obesity Hypothalamic obesity (obesity due to a brain tumor, head trauma or other brain lesion) Currently pregnant Ages Eligible for Study ----------------- Minimum Age: 2 Years Maximum Age: 100 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 genetic mutations in DNA analysis | | 5 years |

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Efficacy of PENNSAID® for Pain Management in the Emergency Department Study Overview ================= Brief Summary ----------------- The primary objective of this study is to compare the pain relieving effect and speed of onset of PENNSAID to that of standard oral diclofenac under double blind conditions using a growth curve approach to pain measurement. The investigators will test the hypothesis that PENNSAID will provide more rapid pain relief than oral diclofenac during the ED visit. The secondary goal of the proposed work is to discover and model the onset and course of pain relief during the emergency department (ED) visit. Official Title ----------------- Efficacy of PENNSAID® for Pain Management in the Emergency Department Conditions ----------------- Pain, Ankle Sprain Intervention / Treatment ----------------- * Drug: PENNSAID * Drug: Diclofenac hydroxyethylpyrrolidine Participation Criteria ================= Eligibility Criteria ----------------- Inclusion: -We will include ED patients presenting with an acutely painful ankle sprain for which NSAIDs constitute standard of care pain management. The following will be excluded: Those with lacerations, bites, burns any head trauma pregnant anyone with a pre-existing chronic pain condition inflammatory intestinal disorders such as Crohn's disease or ulcerative colitis anyone regularly using another NSAID or anti-coagulation medication anyone who has experienced asthma after NSAID use compromised cognitive abilities a significant co-morbidity that will compromise participation had joint replacements known hypersensitivity to diclofenac or allergic responses to NSAIDs as a class active stomach and/or duodenal ulceration or gastrointestinal bleeding anyone admitted with severe active bleeding recent heart surgery severe liver or renal insufficiency prisoner mentally disabled patients wards of the state cognitive or decisional impairment 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: Pennsaid<br>Active Pennsaid and oral placebo | Drug: PENNSAID<br>* active treatment with PENNSAID and oral placebo. Subjects will apply 40 drops of Pennsaid to the affected ankle joint once, and will take a single placebo pill.<br>| | Active Comparator: Oral Diclofenac<br>Oral diclofenac and placebo lotion (2.3% DMSO solution) | Drug: Diclofenac hydroxyethylpyrrolidine<br>* active treatment oral Diclofenac and PENNSAID placebo. Patients will take a single 50mg dose of oral diclofenac and will apply 40 drops of placebo lotion (2.3% DMSO) to the affected ankle once.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in pain score | Compare the pain relieving effect and speed of onset of PENNSAID to that of standard oral diclofenac. | Measure at 5 minute intervals for the duration of the ER visit | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | pain trajectory model | The secondary goal of the proposed work is to discover and model the onset and course of pain relief during the ED visit | nine months | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- pain management

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EAT-DUTA AndroCoV Trial Study Overview ================= Brief Summary ----------------- During the continuing SARS-CoV-2 (COVID-19) pandemic, several studies have reported a significant difference in the rate of severe cases between adult females and adult males (42% vs 58%). Among children under the age of 14, the rate of severe cases was reported to be extremely low. To explain this difference, several theories have been proposed including cigarette smoking and lifestyle habits. However, no theory fits both the gender difference in severe cases as well as reduced risk in pre-pubescent children. Our past research on male androgenetic alopecia (AGA) has led us to investigate an association between androgens and COVID-19 pathogenesis. In normal subjects, androgen expression demonstrates significant variation between men and women as well as between adults and pre-pubescent children. SARS-CoV-2 primarily infects type II pneumocytes in the human lung. SARS-CoV-2 enters pneumocytes, by anchoring to the ACE2 cell surface receptor. Prior to receptor binding, viral spike proteins undergo proteolytic priming by the transmembrane protease, serine 2 (TMPRSS2). TMPRSS2 inhibition or knock down reduces ability of SARS-CoV-1 (a related virus to SARS-CoV-2) to infect cells in vitro. Additionally, TMPRSS2 also facilitates entry of influenza A and influenza B into primary human airway cells and type II pneumocytes. The human TMPRSS2 gene has a 15 bp androgen response element and in humans, androgens are the only known transcription promoters for the TMPRSS2 gene. In a study of androgen-stimulated prostate cancer cells (LNCaP), TMPRSS2 mRNA expression increase was mediated by the androgen receptor.10 Further, the ACE2 receptor, also critical for SARS-CoV-2 viral infectivity, is affected by male sex hormones with higher activity found in males. Androgenetic alopecia (AGA), often referred to as male pattern hair loss, is the most common form of hair loss among men. The development of androgenetic alopecia is androgen mediated and is dependent on genetic variants found in the androgen receptor gene located on the X chromosome. We hypothesized that men with AGA would be more prone to severe COVID-19 disease. We conducted a preliminary observational study of hospitalized COVID-19 patients at two Spanish tertiary hospitals between March 23-April 6, 2020 to test this theory. In total, 41 Caucasian males admitted to the hospitals with a diagnosis of bilateral SARS-CoV-2 pneumonia were analyzed. The mean age of patients was 58 years (range 23-79). Among them, 29 (71%) were diagnosed with AGA (16 (39%) were classified as severe AGA (Hamilton IV or above)) and 12 (29%) did not present clinical signs of AGA. The diagnosis of AGA was performed clinically by a dermatologist. The precise prevalence of AGA among otherwise healthy Spanish Caucasian males is unknown; however, based on published literature, the expected prevalence of a similar age-matched Caucasian population is approximately 31-53%. Further, according to the European Center for Disease Control and Prevention (https://www.ecdc.europa.eu/sites/default/files/documents/covid-19-rapid-risk-assessment-coronavirus-disease-2019-eighth-update-8-april-2020.pdf): Of the confirmed cases in China, 3.8% (1 716/44 672) were healthcare workers. Of those, 14.8% were severely or critically ill and 5% of the severe cases died. Latest figures reported from Italy show that 9% of COVID-19 cases are healthcare workers, with Lombardy region reporting up to 20% of cases in healthcare workers. In Spain, the latest COVID-19 situation overview from the Ministry of Health reports that 26% of COVID-19 cases are in healthcare workers. In a Dutch study, healthcare workers were tested voluntarily for COVID-19 and 6% tested positive. In a report on 30 cases in healthcare workers in China, all cases had a history of direct contact (distance within 1 metre) with COVID-19 patients, with an average number of 12 contacts, and the average cumulative contact time being two hours (1.5, 2.7). In the Dutch study, only 3% of the healthcare workers reported being exposed to hospital patients with COVID-19 prior onset of symptoms and 63% had worked while asymptomatic. Based on the scientific rationale combined with this preliminary observation, we propose to test an anti-androgen as a treatment for patients recently diagnosed with COVID-19. This study is intended to explore the possible protective role of anti-androgens in SARS-CoV-2 infection, including reduction of virological duration and disease severity. Official Title ----------------- Early Antiandrogen Treatment (EAT) With Dutasteride for COVID-19 (EAT-DUTA AndroCoV Trial) Conditions ----------------- Covid19 Intervention / Treatment ----------------- * Drug: Dutasteride 0.5 mg * Drug: Azithromycin * Drug: Nitazoxanide * Drug: Placebo Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Male ≥18 years old Laboratory confirmed positive SARS-CoV-2 rtPCR test within 7 days prior to randomization Clinical status on the COVID-19 Ordinal Scale (defined in Section 5.1) of 1 to 3 Subject (or legally authorized representative) gives written informed consent prior to performing any study procedures Subject (or legally authorized representative) agree that subject will not participate in another COVID-19 trial while participating in this study Exclusion Criteria: Subject enrolled in a study to investigate a treatment for COVID-19 Require oxygen use, hospitalization or mechanical ventilation Tachycardia (HR > 150 bpm) or hypotension (BP < 90/60 mmHg) Patients who are allergic to the investigational product or similar drugs (or any excipients); Subjects with QTcF > 450 ms Subjects with uncontrolled medical conditions that could compromise participation in the study - uncontrolled hypertension (BP > 220/120 mmHg), uncontrolled hypothyroidism (TSH > 10 iU/L), uncontrolled diabetes mellitus (HbA1c > 12%) Alanine Transaminase (ALT) or Aspartate Transaminase (AST) > 5 times the upper limit of normal. Estimated glomerular filtration rate (eGFR) < 30 ml/min or requiring dialysis Subject (or legally authorized representative) not willing or unable to provide informed consent Not willing to provide informed consent Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- Male 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: Dutasteride<br>Dutasteride 0.5mg/day q.d. for 30 days or until COVID-19 remission (defined as full remission of symptoms plus viral clearance through rtPCR-SARS-CoV-2) | Drug: Dutasteride 0.5 mg<br>* Use of dutasteride 0.5mg/day q.d. for 30 days or until COVID-19 remission, in recently diagnosed COVID-19 subjects.<br>Drug: Azithromycin<br>* Azithromycin 500mg/day for 05 days<br>Drug: Nitazoxanide<br>* 500mg twice daily for 06 days<br>| | Placebo Comparator: Placebo<br>Placebo q.d. for 30 days or until COVID-19 remission (defined as full remission of symptoms plus viral clearance through rtPCR-SARS-CoV-2) | Drug: Azithromycin<br>* Azithromycin 500mg/day for 05 days<br>Drug: Nitazoxanide<br>* 500mg twice daily for 06 days<br>Drug: Placebo<br>* Use of placebo q.d. for 30 days or until COVID-19 remission, in recently diagnosed COVID-19 subjects.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Positivity rate of rtPCR-SARS-CoV-2 (qualitative analysis) | Treatment efficacy of dutasteride relative to placebo arm as assessed by viral load measured by positivity rate (% of positive, detected rtSARS-CoV-2) | Day 7 | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | World Health Organization (WHO) Clinical Progression Scale [0 to 10; 0 = uninfected; 10 = death] | Treatment efficacy of dutasteride relative to placebo arm as assessed by World Health Organization (WHO) Clinical Progression Scale [0 to 10; 0 = uninfected; 10 = death] | Day 14 | | World Health Organization (WHO) COVID=19 Ordinal Scale for Clinical Improvement [1 to 8; 1 = not hospitalized, no limitation on activities; 8 = death] | Treatment efficacy of dutasteride relative to placebo arm as assessed by World Health Organization (WHO) COVID=19 Ordinal Scale for Clinical Improvement [1 to 8; 1 = not hospitalized, no limitation on activities; 8 = death] | Day 7 | | Time-to-recovery | Recovery is defined as the first day on which the subject satisfies category one from the COVID ordinal scale (defined in Section 5.1): (1) Not hospitalized, no limitations on activities. [Parameter: Number of days until achieve Category 1 of the World Health Organization (WHO) COVID=19 Ordinal Scale for Clinical Improvement [1 to 8; 1 = not hospitalized, no limitation on activities; 8 = death] | Day 28 | | SARS-CoV-2 viral load | Treatment efficacy dutasteride relative to placebo arm as assessed by viral load measured by rtPCR-SARS-CoV-2 (CTs) | Day 5 | | Duration of fatigue | Treatment efficacy of dutasteride relative to placebo arm as assessed by duration of fatigue (days) | Day 14 | | Duration of anosmia | Treatment efficacy of dutasteride relative to placebo arm as assessed by duration of anosmia (days) | Day 14 | | Overall duration of clinical manifestations | Treatment efficacy of dutasteride relative to placebo arm as assessed by duration of overall symptoms (days) | Day 14 | | Proportion of subjects needing additional drugs or interventions | Defined as the number of subjects who have required additional drugs (glucocorticoids, anticoagulants, etc) or interventions allocated to each arm divided by the number of subjects randomized to that specific arm (%). Treatment efficacy dutasteride relative to placebo arm as assessed by the proportion of subjects needing additional drugs or interventions in each arm. (%) | Day 28 | | Proportion of subjects needing oxygen use | Defined as the number of subjects who have required oxygen use allocated to each arm divided by the number of subjects randomized to that specific arm (%). Treatment efficacy of dutasteride relative to placebo arm as assessed by the proportion of subjects needing oxygen use in each arm. (%) | Day 28 | | Proportion of subjects needing high-flow oxygen therapy or non-invasive ventilation | Defined as the number of subjects who have required high-flow oxygen use or non-invasive mechanical ventilation allocated to each arm divided by the number of subjects randomized to that specific arm (%). Treatment efficacy of dutasteride relative to placebo arm as assessed by the proportion of subjects needing high-flow oxygen use or non-invasive mechanical ventilation in each arm. | Day 28 | | Proportion of hospitalizations | Defined as the number of hospitalizations in each arm divided by the number of subjects randomized to that specific arm (%). Treatment efficacy of dutasteride relative to placebo arm as assessed by the proportion of hospitalizations in each arm. | Day 28 | | Proportion of mechanical ventilation use | Defined as the number of subjects that needed mechanical ventilation in each arm divided by the number of subjects randomized to that specific arm (%). Treatment efficacy of dutasteride relative to placebo arm as assessed by the number of mechanical ventilation use in each arm divided by the number of subjects randomized to that specific arm. | Day 28 | | Proportion of vasopressors use | Defined as the number of subjects that needed vasopressors use in each arm divided by the number of subjects randomized to that specific arm (%).Treatment efficacy of dutasteride relative to placebo arm as assessed by the number of subjects needing use of pressors in each arm divided by the number of subjects randomized to that specific arm. | Day 28 | | Proportion of deaths | Treatment efficacy of dutasteride relative to placebo arm as assessed by the number of subjects who have died in each arm divided by the numbers of subjects randomized to the treatment arm (%). | Day 60 | | Duration of new oxygen use | Treatment efficacy of dutasteride relative to placebo arm as assessed by the duration of new oxygen use measured in days among subjects that did not require oxygen upon randomization and required oxygen use after the beginning of treatment, in each arm (days) | Day 28 | | Duration of hospitalization | Treatment efficacy of dutasteride relative to placebo arm as assessed by the duration of hospitalization measured in days among subjects that required hospitalization, in each arm (days) | Day 28 | | Duration of mechanical ventilation | Treatment efficacy of dutasteride relative to placebo arm as assessed by the duration of mechanical ventilation measured in days among subjects that required mechanical ventilation, in each arm (days) | Day 28 | | Proportion of increased ultrasensitive C-reactive protein (usCRP) (defined as usRCP > 7 mg/L) | Treatment efficacy of dutasteride relative to placebo arm as assessed by the number of subjects presenting increased ultrasensitive C-reactive protein (usCRP) at Day 1, divided by the number of subjects randomized to that specific arm (%). | Day 1 | | Proportion of increased ultrasensitive C-reactive protein (usCRP) (defined as usRCP > 7 mg/L) | Treatment efficacy of dutasteride relative to placebo arm as assessed by the number of subjects presenting increased ultrasensitive C-reactive protein (usCRP) at Day 3, divided by the number of subjects randomized to that specific arm (%). | Day 3 | | Proportion of increased ultrasensitive C-reactive protein (usCRP) (defined as usRCP > 7 mg/L) | Treatment efficacy of dutasteride relative to placebo arm as assessed by the number of subjects presenting increased ultrasensitive C-reactive protein (usCRP) at Day 7, divided by the number of subjects randomized to that specific arm (%). | Day 7 | | Proportion of decrease in erythrocyte sedimentation rate (ESR) (defined as ESR decrease > 50% compared to baseline (Day 0)) | Treatment efficacy of dutasteride relative to placebo arm as assessed by the number of subjects presenting ESR decrease > 50% at Day 1, divided by the number of subjects randomized to that specific arm (%). | Day 1 | | Proportion of decrease in erythrocyte sedimentation rate (ESR) (defined as ESR decrease > 50% compared to baseline (Day 0)) | Treatment efficacy of dutasteride relative to placebo arm as assessed by the number of subjects presenting ESR decrease > 50% at Day 3, divided by the number of subjects randomized to that specific arm (%). | Day 3 | | Proportion of decrease in erythrocyte sedimentation rate (ESR) (defined as ESR decrease > 50% compared to baseline (Day 0)) | Treatment efficacy of dutasteride relative to placebo arm as assessed by the number of subjects presenting ESR decrease > 50% at Day 7, divided by the number of subjects randomized to that specific arm (%). | Day 7 | | Proportion of increase in eosinophils (defined as eosinophils increase > 50% compared to baseline (Day 0)) | Treatment efficacy of dutasteride relative to placebo arm as assessed by the number of subjects presenting eosinophils increase > 50% at Day 1, divided by the number of subjects randomized to that specific arm (%). | Day 1 | | Proportion of increase in eosinophils (defined as eosinophils increase > 50% compared to baseline (Day 0)) | Treatment efficacy of dutasteride relative to placebo arm as assessed by the number of subjects presenting eosinophils increase > 50% at Day 3, divided by the number of subjects randomized to that specific arm (%). | Day 3 | | Proportion of increase in eosinophils (defined as eosinophils increase > 50% compared to baseline (Day 0)) | Treatment efficacy of dutasteride relative to placebo arm as assessed by the number of subjects presenting eosinophils increase > 50% at Day 7, divided by the number of subjects randomized to that specific arm (%). | Day 7 | | Proportion of increased d-dimer (defined as d-dimer > 500 mg/dL) | Treatment efficacy of dutasteride relative to placebo arm as assessed by the number of subjects presenting increased d-dimer protein (usCRP) at Day 7, divided by the number of subjects randomized to that specific arm (%). | Day 7 | | Variation in oxygen saturation compared to baseline (Day 0) | Treatment efficacy of dutasteride relative to placebo arm as assessed by the mean variation of oxygen saturation of subjects randomized to that specific arm (%) at Day 1 compared to baseline (Day 0). | Day 1 | | Variation in oxygen saturation compared to baseline (Day 0) | Treatment efficacy of dutasteride relative to placebo arm as assessed by the mean variation of oxygen saturation of subjects randomized to that specific arm (%) at Day 3 compared to baseline (Day 0). | Day 3 | | Variation in oxygen saturation compared to baseline (Day 0) | Treatment efficacy of dutasteride relative to placebo arm as assessed by the mean variation of oxygen saturation of subjects randomized to that specific arm (%) at Day 5 compared to baseline (Day 0). | Day 5 | | Variation in oxygen saturation compared to baseline (Day 0) | Treatment efficacy of dutasteride relative to placebo arm as assessed by the mean variation of oxygen saturation of subjects randomized to that specific arm (%) at Day 7 compared to baseline (Day 0). | Day 7 | | Disease duration | Treatment efficacy of dutasteride relative to placebo arm as assessed by duration of symptoms, complications, or any other COVID-related clinical or biochemical sign of disease (days) | Day 30 | | Change in viral load from baseline to Day 5 | Treatment efficacy of dutasteride relative to placebo arm as assessed by change in viral load from baseline to Day 5 measured by rtPCR-SARS-CoV-2 (CTs) | Day 5 | | Proportion of post-COVID mental symptoms | Treatment efficacy of dutasteride relative to placebo arm as assessed by the number of subjects persisting with mental symptoms after COVID-19 resolution in each arm divided by the number of subjects randomized to that specific arm (%) at Day 30. | Day 30 | | Proportion of post-COVID physical symptoms | Treatment efficacy of dutasteride relative to placebo arm as assessed by the number of subjects persisting with physical symptoms after COVID-19 resolution in each arm divided by the number of subjects randomized to that specific arm (%) at Day 30. | Day 30 | | Proportion of post-COVID overall symptoms | Treatment efficacy of dutasteride relative to placebo arm as assessed by the number of subjects persisting with any symptoms after COVID-19 resolution in each arm divided by the number of subjects randomized to that specific arm (%) at Day 30. | Day 30 | | Proportion of post-COVID mental symptoms | Treatment efficacy of dutasteride relative to placebo arm as assessed by the number of subjects persisting with mental symptoms after COVID-19 resolution in each arm divided by the number of subjects randomized to that specific arm (%) at Day 60. | Day 60 | | Proportion of post-COVID physical symptoms | Treatment efficacy of dutasteride relative to placebo arm as assessed by the number of subjects persisting with physical symptoms after COVID-19 resolution in each arm divided by the number of subjects randomized to that specific arm (%) at Day 60. | Day 60 | | Proportion of post-COVID overall symptoms | Treatment efficacy of dutasteride relative to placebo arm as assessed by the number of subjects persisting with any symptoms after COVID-19 resolution in each arm divided by the number of subjects randomized to that specific arm (%) at Day 60. | Day 60 | | Proportion of post-COVID mental symptoms | Treatment efficacy of dutasteride relative to placebo arm as assessed by the number of subjects persisting with mental symptoms after COVID-19 resolution in each arm divided by the number of subjects randomized to that specific arm (%) at Day 90. | Day 90 | | Proportion of post-COVID physical symptoms | Treatment efficacy of dutasteride relative to placebo arm as assessed by the number of subjects persisting with physical symptoms after COVID-19 resolution in each arm divided by the number of subjects randomized to that specific arm (%) at Day 90. | Day 90 | | Proportion of post-COVID overall symptoms | Treatment efficacy of dutasteride relative to placebo arm as assessed by the number of subjects persisting with any symptoms after COVID-19 resolution in each arm divided by the number of subjects randomized to that specific arm (%) at Day 90. | Day 90 | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- SARS-CoV-2, Dutasteride

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Study of Open Label Losartan in COVID-19 Study Overview ================= Brief Summary ----------------- This is an open label, phase 1 clinical trial to evaluate the safety of losartan in respiratory failure due to COVID-19. Briefly, 50 patients with COVID-19 and respiratory failure who meet eligibility criteria and agree to participation in the study will be placed on losartan 25 mg daily on study day 0. If parameters are met the dose of losartan will be increased to 50 mg once daily on study day 3. Participants will continue losartan until they experience resolution of respiratory failure (normal oxygen levels on room air), are discharged from the hospital, meet stoppage criteria (detailed below) or complete 14 days of therapy. Patients and/or surrogate decision maker who do not give consent to treatment will be asked to allow collection of data from their medical record for use as a control group. We will also collect medical information relating to safety criteria on historical controls treated at the University of Kansas Hospital in the 30 days prior to the study start date (3/25/2020) and during the study period. Detailed Description ----------------- This is an open label, phase 1 clinical trial to evaluate the safety of losartan in respiratory failure due to COVID-19. Clinical Trial setup: Detailed inclusion and exclusion criteria are listed below. Briefly, 50 patients with COVID-19 and respiratory failure who meet criteria and agree to participation in the study will be placed on losartan 25 mg daily on study day 0. If parameters are met the dose of losartan will be increased to 50 mg once daily on study day 3. Participants will continue losartan until they experience resolution of respiratory failure (normal oxygen levels on room air), are discharged from the hospital, meet stoppage criteria (detailed below) or complete 14 days of therapy. Patients and/or surrogate decision maker who do not give consent to treatment will be asked to allow collection of data from their medical record for use as a control group. Stoppage criteria for losartan Hyperkalemia (persistent values >5.5 mM recorded on at least 2 readings). Worsening renal function (Cockcroft-Gault <30 mL/min/1.73 m2) or urinary output <20 mL/h. Skin rashes, palpitations or other moderate or severe adverse events (interference with usual daily activities) without clear explanation should warrant immediate cessation of treatment and notification of study personnel. Development of sustained hypotension defined as SBP <90 mmHg, DBP <60 mmHg recorded on at least two readings 30 min apart or use of norepinephrine >0.1 µg/kg/min. Any change in monitor lab parameters deemed significant and potentially related to study drug by the Investigator. Official Title ----------------- An Open Label Phase 1 Trial of Losartan for Worsening Respiratory Illness in COVID-19 Conditions ----------------- COVID-19 Intervention / Treatment ----------------- * Drug: Losartan Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Age >18 years admitted to the University of Kansas Health System. Confirmation of infection with SARS-CoV-2 by PCR testing. Hypoxic respiratory failure Requiring mechanical ventilation or oxygen OR a SpO2 ≤94% on room air or a PaO2/FiO2 (P/F) ratio <300 OR tachypnea (respiratory rate ≥24 breaths/min). Criteria to be met within 48 hours prior to Day 0. Other concomitant medications such as antivirals and hydroxychloroquine are allowed. Participants prescribed standard of care (SOC) losartan (25mg QD) within 48 hours of consenting may be considered for enrollment if eligibility criteria are met based on EMR data assessment, i.e. no other ARB or ACE prior to SOC medication administration. If participant is eligible and signs consent form, investigational losartan 25mg QD will be ordered to replace SOC prescription on the following scheduled dose. Exclusion Criteria: Pregnancy. Respiratory failure due to a process other than COVID-19. Intolerance to ARBs. Previous treatment with an ARB or ACE inhibitor (see exception in inclusion criteria). Current chronic use of medication with known interactions with losartan including NSAIDs (intermittent prior use is acceptable), potassium supplementation aliskiren. Blood pressure less than 90 mm Hg systolic or 60 mm Hg diastolic recorded on at least two readings 30 min apart. Need for vasopressors, unless norepinephrine ≤0.1 µg/kg/min Hyperkalemia (serum K+ >5.5 mM). Known cardiac failure (left ventricular ejection fraction ≤35%), renal insufficiency (Cockcroft-Gault <30 mL/min/1.73 m2 or urinary output <20 mL/h), hepatic failure (LFTs > 5x normal upper limit). Known renal artery stenosis. Neurological, psychiatric, endocrine or neoplastic diseases that are judged to interfere with participation in the study. On another interventional trial (including one for COVID-19) that excludes participation. 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: 50 patients with COVID-19 and respiratory failure who meet criteria and agree to participation in the study will be placed on losartan 25 mg once daily on study day 0. If parameters are met the dose of losartan will be increased to 50 mg once daily on study day 3. Patients and/or surrogate decision maker who do not give consent to treatment will be asked to allow collection of data from their medical record for use as a control group.We will also collect medical information relating to safety criteria on historical controls treated at the University of Kansas Hospital in the 30 days prior to the study start date (3/25/2020) and during the study period. Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Open Label Losartan<br>50 patients with COVID-19 and respiratory failure who meet criteria and agree to participation in the study will be placed on losartan 25 mg once daily on study day 0. If parameters are met the dose of losartan will be increased to 50 mg once daily on study day 3. Participants will continue losartan until they experience resolution of respiratory failure (normal oxygen levels on room air), are discharged from the hospital, meet stoppage criteria or complete 14 days of therapy. | Drug: Losartan<br>* 25 mg QD from day 0 to day 3. Dose escalation to 50 mg QD until study completion<br>* Other names: Cozaar;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Number of participants with treatment-related adverse events as assessed by protocol definition of AE | Safety will be reported based on Protocol defined AEs. For the purpose of this protocol, an AE will be defined as as any untoward medical occurrence in a subject during the study listed under DMSB - Anticipated Adverse Events and Grading Scale section of this protocol as well as safety monitoring data listed on protocol table 1 as well as stoppage criteria for losartan. The event does not necessarily have a causal relationship with the treatment. AEs will be collected for both study groups, treatment and control from the time the ICF is signed until the subject completes study participation. | 14 days of losartan treatment | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Number of days on supplemental oxygen in respiratory failure due to COVID-19 | Number of days on supplemental oxygen in respiratory failure due to COVID-19 | 14 days of losartan treatment | | Incidence of mechanical ventilation use | Incidence of mechanical ventilation use | 14 days of losartan treatment | | Days on mechanical ventilation | Days on mechanical ventilation | 14 days of losartan treatment | | Incidence of non-invasive positive pressure ventilation or heated high flow nasal cannula use | Incidence of non-invasive positive pressure ventilation or heated high flow nasal cannula use | 14 days of losartan treatment | | Days on non-invasive positive pressure ventilation or high flow nasal cannula | Days on non-invasive positive pressure ventilation or high flow nasal cannula | 14 days of losartan treatment | | Incidence of transfer to ICU from non-ICU hospital bed | Incidence of transfer to ICU from non-ICU hospital bed | 14 days of losartan treatment | | ICU length of stay (days) | ICU length of stay (days) | 14 days of losartan treatment | | 30-day mortality rate | 30-day mortality rate | 30 days after diagnosis of COVID-19 | | Hospital length of stay (days) | Hospital length of stay (days) | 14 days of losartan treatment | | Cumulative incidence of severe adverse events | Cumulative incidence of severe adverse events | 14 days of losartan treatment | | Cumulative incidence of adverse events | Cumulative incidence of adverse events | 14 days of losartan treatment | | Change from baseline in oxygenation | Change from baseline in oxygenation | 14 days of losartan treatment | | Incidence of medications with possible antiviral activity (hydroxychloroquine, lopinavir/ritonavir, ribavirin or remdesivir) or adjunctive therapy use (e.g., tocilizumab) | Incidence of medications with possible antiviral activity (hydroxychloroquine, lopinavir/ritonavir, ribavirin or remdesivir) or adjunctive therapy use (e.g., tocilizumab) | 14 days of losartan treatment | | Incidence (and length in days) of extracorporeal membrane oxygenation use | Incidence (and length in days) of extracorporeal membrane oxygenation use | 14 days of losartan treatment | | Incidence (and length in days) of renal replacement therapy use | Incidence (and length in days) of renal replacement therapy use | 14 days of losartan treatment | | Intolerance of high dose (50mg) losartan after tolerating 25mg | Intolerance of high dose (50mg) losartan after tolerating 25mg | 14 days of losartan treatment | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- COVID-19, losartan, respiratory failure, SARS-CoV-2

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Phase III Comparative Study(Open-Label) of MRA for Rheumatoid Arthritis(RA) Study Overview ================= Brief Summary ----------------- To evaluate clinical efficacy and tolerability of MRA, patients with RA are randomized to receive either MRA or conventional DMARDs. Official Title ----------------- An Open-Label, Phase III Study to Evaluate the Efficacy and Safety of MRA in Patients With RA Conditions ----------------- Rheumatoid Arthritis Intervention / Treatment ----------------- * Drug: MRA (Tocilizumab) * Other: current treatment Participation Criteria ================= Eligibility Criteria ----------------- Inclusion criteria Diagnosed as having RA, on the basis of the criteria stipulated by the American Conference on Rheumatism (ACR) in 1987. With RA that has continued for at least 6 months but less than 5 years, with the date of first appearance being taken as the date of RA diagnosis. Active RA despite at least one DMARD or immunosuppressant. Active disease is defined as having at least 6 tender and 6 swollen joints among 49 and 46 joints stipulated by the Japanese Rheumatism Foundation's Drug Evaluation Committee and ESR at least 30 mm/hr and CRP not less than 2.0mg/dL. Exclusion criteria Shown to have class-IV Steinbrocker's functional activity in an evaluation carried out within 4 weeks before administration of the study drug. Treated with drugs that delay joint destruction (infliximab, etanercept, leflunomide, etc.) within 3 months before administration of the study drug. The oral corticosteroid dose (prednisolone equivalent of up to 10 mg/day)has not been fixed 2 weeks before administration of the study drug. Subjected to any of the following within 4 weeks before administration of the study drug: (i) Change in dosage of currently administered DMARDs and/or immunosuppressive agents. (ii) Plasma exchange method. (iii) Surgical treatment (operations, etc.). Ages Eligible for Study ----------------- Minimum Age: 20 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: 1<br> | Drug: MRA (Tocilizumab)<br>* 8mg /kg /4week for 52 weeks<br>| | Other: 2<br>continue current treatment | Other: current treatment<br>* continue current treatment<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in the erosion score, as determined by the modified Sharp method. | | week 52 | | Frequency and severity of adverse events and adverse drug reactions | | throughout study | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in the erosion score | | week 28 | | Changes in the joint space narrowing score and total Sharp score | | week 28, 52 |

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Conception of an ICF Core Set for Systemic Sclerosis Study Overview ================= Brief Summary ----------------- The purpose of this study is to create and validate an ICF core Set for Systemic sclerosis Detailed Description ----------------- In 2002 was published WHO's International Classification of Functioning, Disability and Health (ICF). ICF defines disability as the negative aspects of the interaction between an individual (with a health condition) and that individual's contextual factors (personal and environmental factors). Interactions are specified in five domains, classified from body, individual and societal perspectives by means of two lists: a list of body functions and structure, and a list of domains of activity and participation. Since an individual's functioning and disability occurs in a context, the ICF also includes a list of environmental factors. ICF core sets, which are short lists of ICF categories relevant for specific conditions, serve as practical tools for clinical practice and allow standardisation of data for health information and research. Core sets have already been developed and validated for several musculoskeletal diseases, such as low back pain, osteoarthritis, or osteoporosis, but not yet for systemic sclerosis. Official Title ----------------- Conception of an ICF Core Set for Systemic Sclerosis Conditions ----------------- Systemic Sclerosis Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Male or female aged 18 and older Diagnosis of ScS made according to ACR and/or Leroy et Medsger criteria Patient giving his informed consent to participate in the study Exclusion Criteria: Severe chronic disease associated with ScS : stroke, multiple sclerosis, Parkinson's disease,… Cognitive or behavioral disorders making assessment impossible Inability to speak and write French 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 | | --- | --- | --- | | Validation of an ICF core Set for Systemic sclerosis | Submit the list of items to a cohort of 100 patients and experts. | Between the 13th and 24th month | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Translation of concepts identified such as items ICF (linking). | Translation of extracted data and set up the core set | Between the 10th and 12th month | | Creation of a database from a qualitative survey | This database will be elaborated considering information from a qualitative survey of 100 patients, a consultation with experts and a review of the literature | During the first 9 months | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- ICF, Core sets, Systemic sclerosis, Function, Evaluation

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Combined Application of Remote and Intra-Coronary Ischemic Conditioning in Acute Myocardial Infarction Study Overview ================= Brief Summary ----------------- Infarct size is a major determinant of prognosis after AMI. Evidence indicates that the combination of intracoronary ischemic conditioning (ICIC) and remote ischemic conditioning (RIC) can significantly reduce infarct size in STEMI patients. Whether the combination of these two interventions may improve clinical outcome after STEMI remains unknown. The objective of the present study is to determine whether combination of ICIC and RIC can improve STEMI patients clinical outcome at 6 months. Official Title ----------------- Combined Application of Remote and Intra-Coronary Ischemic Conditioning in Acute Myocardial Infarction: A Multicenter, Randomized, Controlled Clinical Trial (CARIOCA Study) Conditions ----------------- Myocardial Infarction, Acute Intervention / Treatment ----------------- * Device: Remote ischemic conditioning and intracoronary ischemic conditioning * Device: Patients with no remote ischemic conditioning and no intracoronary ischemic conditioning Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: All (male and female) patients, aged over 18, Presenting within 12 hours of the onset of chest pain, For whom the clinical decision was made to treat with percutaneous coronary intervention (PCI), ST segment elevation ≥ 0.2 mV in two contiguous ECG leads, Written informed consent obtained or oral informed consent certified by a third party. Non inclusion Criteria: Patients with cardiogenic shock, Patients with uncontrolled (treated or untreated) hypertension (> 180/110 mmHg), Patients with loss of consciousness or confused, Patients without health coverage, Patient with any legal protection measure, Female patients currently pregnant (oral diagnosis) or women of childbearing age who were not using contraception. Exclusion Criteria: Patients with main occlusion localized on : LAD: distal or ostial segment, Non dominant RCA / CX: mid or distal segment, Dominant RCA / CX: distal segment, Any other arteries apart LAD/CX/RCA; Patients with evidence of coronary collaterals to the risk region (Rentrop score ≥ 2); Patients with an opened (TIMI > 1) culprit coronary artery on initial admission coronary angiography or a failed PCI (final TIMI=0). 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 | | --- | --- | | Experimental: RIC+ ICIC +<br>Patients with remote ischemic conditioning and intracoronary ischemic conditioning | Device: Remote ischemic conditioning and intracoronary ischemic conditioning<br>* RIC: Four cycles of [5 min brachial cuff inflation at 200 mmHg followed by 5 min of cuff deflation] started as soon as possible prior to PCI reperfusion. At least one full cycle (inflation + deflation) has to be completed before PCI reperfusion. ICIC: Four cycles of [1 min balloon inflation followed by 1 min balloon deflation] started as soon as possible after reopening of the culprit coronary artery (maximum within 3 minutes after reflow). The balloon will be placed carefully above the culprit lesion so as to minimize potential micro-embolization.<br>| | Other: RCI - ICIC -<br>Control group with no remote ischemic conditioning and no intracoronary ischemic conditioning | Device: Patients with no remote ischemic conditioning and no intracoronary ischemic conditioning<br>* Brachial cuff is positioned during 40 minutes but not inflated. No intracoronary balloon inflation.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Combined incidence of [all-cause mortality; worsening of heart failure during initial hospitalization or re-hospitalization for heart failure at 6 months after MI, large infarct defined as CK peak at 6 hours > 4500 UI/L] | | 6 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Cardiovascular death at 6 months. | | 6 months | | Worsening of heart failure | Worsening of heart failure during initial hospitalization or re-hospitalization for heart failure at 6 months. | 6 months | | Time to first event [all-cause mortality; worsening of heart failure during initial hospitalization or re-hospitalization for heart failure] | | 6 months | | Major Adverse Cardiac Events (MACE) | MACE at 6 months: [all-cause mortality; worsening of heart failure during initial hospitalization or re-hospitalization for heart failure; malignant ventricular arrhythmias; recurrent infarction; unstable angina; unplanned revascularization; stroke]. | 6 months | | Renal failure | Renal failure (+25% increase in serum creatinine at 6 months versus baseline). | 6 months | | Peak of creatine kinase | | 4-6 hours post-PCI | | creatine kinase | | 5 days | | Measure hsCRP | | 5 days | | Rate of CRP | | 5 days | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- ST-elevation myocardial infarction

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Low Dose Naltrexone to Improve Physical Health in Patients With Vasculitis Study Overview ================= Brief Summary ----------------- Naltrexone is an FDA approved drug (for alcoholism) that has found widespread use off-label to treat pain and improve quality of life at much lower doses than are used for the approved indication. There are a few scientific studies in three conditions (fibromyalgia, Crohn's disease, and multiple sclerosis) that suggest that this drug has benefit and is safe. However, considering the extent of use in other conditions, and uncertainty about the mechanism of action study is needed in a diverse set of diseases, including vasculitis. The purpose of this clinical trial is to determine if low dose naltrexone is effective in improving health-related quality of life (HRQoL) among patients with vasculitis. Although it is a pilot study, a placebo-controlled component is used because of the prominent placebo group effect seen in studies with self-reported subjective outcomes. Detailed Description ----------------- This is a multi-center, randomized, double-blind, cross-over, placebo-controlled trial to evaluate the efficacy of low-dose naltrexone (LDN) 4.5 mg nightly in improving self-reported physical health in patients with vasculitis. At study enrollment, each patient will be randomized to receive either LDN for 6 weeks followed by oral placebo for 6 weeks, or placebo for 6 weeks followed by LDN for 6 weeks. The primary outcome measure and some secondary outcome measures are patient-reported and will be recorded every 3 weeks, or every 6 weeks Official Title ----------------- Low Dose Naltrexone to Improve Physical Health in Patients With Vasculitis Conditions ----------------- Eosinophilic Granulomatosis With Polyangiitis (EGPA), Churg-Strauss Syndrome (CSS), Giant Cell Arteritis, Granulomatosis With Polyangiitis, Microscopic Polyangiitis, Polyarteritis Nodosa, Takayasu Arteritis Intervention / Treatment ----------------- * Drug: Naltrexone Hydrochloride * Other: Placebo Comparator Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patients must meet all of the following criteria in order to be eligible for enrollment: 1. Criteria for diagnosis of giant cell arteritis (GCA), Takayasu's arteritis (TAK), polyarteritis nodosa (PAN), granulomatosis with polyangiitis (GPA, Wegener's), microscopic polyangiitis (MPA), or eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss), as used for the VCRC longitudinal studies a. Giant cell arteritis: According to the American College of Rheumatology (ACR) criteria for classification of GCA, meeting at least 2 of the following 5 remaining criteria at the time of diagnosis of GCA: Age of disease onset >50 years (required) i. New onset or new type of localized pain in the head ii. Temporal artery abnormality (i.e. temporal artery tenderness to palpation or decreased pulsation, unrelated to arteriosclerosis of cervical arteries) iii. ESR of >40 mm in the first hour by Westergren method iv. Temporal artery biopsy showing vasculitis characterized by a predominance of mononuclear cell infiltration or granulomatous inflammation, usually with multinucleated giant cells v. Large Vessel Vasculitis (LVV) by angiogram or biopsy not explained by something else b. Takayasu's arteritis: According to an adaption of the American College of Rheumatology criteria, meeting at least 2 of the following 5 remaining criteria at the time of inclusion of TAK: Arteriogram abnormalities compatible with TAK (includes conventional dye angiography or MR angiography or CT angiography) (required) i. Age at disease onset ≤50 years ii. Claudication of extremities iii. Decreased brachial artery pulse (one or both arteries) iv. Blood pressure difference of >10mm Hg between the arms v. Bruit over subclavian arteritis or aorta c. Polyarteritis nodosa: An adaption of the America College of Rheumatology criteria will be used for the diagnosis of PAN. At the time of inclusion, one major and one minor criteria or two major criteria or isolated cutaneous PAN must be met. i. Major criteria (not explained by other causes): Arteriographic abnormality Presence of granulocyte or mixed leukocyte infiltrate in an arterial wall on biopsy Mononeuropathy or polyneuropathy ii. Minor criteria (not explained by other causes) 1. Weight loss > 4 kg 2. Livedo reticularis, cutaneous ulcerations, or skin nodules 3. Testicular pain or tenderness 4. Myalgias 5. Diastolic blood pressure >90mm Hg 6. Elevated BUN or serum creatinine levels 7. Ischemic abdominal pain iii. Isolated cutaneous polyarteritis nodosa Biopsy-proven cutaneous PAN d. Granulomatosis with polyangiitis: Participants can be enrolled if two of the five modified American College of Rheumatology criteria are met: i. Nasal or oral inflammation: painful or painless oral ulcers or purulent or blood nasal discharge ii. Abnormal chest radiograph: nodules, fixed infiltrates, or cavities iii. Urinary sediment: microhematuria or red cell casts iv. Granulomatous inflammation on biopsy: granulomatous inflammation within the wall of an artery or in the perivascular area v. ANCA positivity by enzyme immunoassay for either PR3- or MPO-ANCA e. Microscopic polyangiitis: The following Chapel Hill Consensus Conference Definitions for MPA need to be met: i. Necrotizing vasculitis with few or no immune deposits affects small vessel (i.e., capillaries, venules, or arterioles) ii. Necrotizing arteritis involving small and medium-sized arteritis may be present iii. Necrotizing glomerulonephritis is very common iv. Pulmonary capillaritis often occurs f. Eosinophilic granulomatosis with polyangiitis: An adaptation of the American College of Rheumatology criteria will be used for the diagnosis of EGPA. At the time of inclusion, four of the six items must have documented evidence: i. Asthma ii. Peak peripheral blood eosinophilia of >10% of total WBC iii. Peripheral neuropathy attributable to vasculitis iv. Transient pulmonary infiltrates on chest imaging studies v. Paranasal sinus abnormalities or nasal polyposis vi. Eosinophilic inflammation on tissue biopsy If patients have 4 of the above 6 criteria but lack clear-cut documentation of small vessel vasculitis, they are also eligible for enrollment. Baseline normalized score on PROMIS Global Physical Health of 40 or lower. Vasculitis in remission or very low disease activity, as defined by Physician Global Assessment 0-1 for at least 12 weeks Stable immunosuppressive therapy (including prednisone) related to vasculitis for at least 12 weeks No change in medications in the past 12 weeks made with the expectation of improving pain, fatigue, or mood No plan to change medication or a non-pharmacologic treatment regimen likely to affect pain, fatigue, mood, or vasculitis activity during the next 12 weeks Age of 18 years or older Willingness and ability to comply with treatment and follow-up procedures, including receipt of weekly phone calls from the study coordinator Willingness and ability to provide informed consent - Exclusion Criteria: Change in any medication related to control of vasculitis, pain, fatigue, or mood within the past 12 weeks (medications taken as needed must be in a stable pattern per the patient's estimation) Use of another investigational agent as part of a clinical trial within 30 days of enrollment Current use of any opioid agonist including tramadol or suboxone Change in vasculitis activity in the past 12 weeks, as defined by a change in Physician Global Assessment greater than 1 Baseline normalized score more than 40 on PROMIS Global Physical Health New major medical problem or surgery in past 12 weeks Pregnancy or breastfeeding Inability to provide informed consent or comply with study procedures Schizophrenia or bipolar disorder Poorly controlled depression or anxiety, as defined by a score of ≥ 20 on PHQ-9 Liver cirrhosis Significant kidney disease, defined as glomerular filtration rate <30ml/min 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: Quadruple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Naltrexone Hydrochloride<br>Naltrexone hydrochloride for oral use, 4.5 mg per capsule, taken once a day for 6 weeks. | Other: Placebo Comparator<br>* A placebo tablet which matches the drug will be taken daily for 6 weeks.<br>| | Placebo Comparator: Placebo Comparator<br>Placebo to match naltrexone for oral use to be taken once a day for 6 weeks. | Drug: Naltrexone Hydrochloride<br>* Naltrexone Hydrochloride will be taken daily (dose 4.5 mg) for six weeks<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | PROMIS Global Physical Health | Questionnaire about improved health related quality of life to a greater extent than placebo. | Week 12. | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | PROMIS Global Physical Health | Questionnaire about improved health related quality of life to a greater extent than placebo. | 9 weeks | | SF-36 (physical component subscore) | Health related quality of life measured by a questionnaire. | 12 weeks | | PROMIS Questionnaires | Questions will ask about anxiety, depression, and sleep disturbance on the PROMIS short form, PROMIS Global Mental Health, and on PROMIS-CAT will ask about physical function, fatigue, satisfaction with social roles, and pain interference, as well in the pain intensity item. | 12 weeks | | Clinical Global Impression of Severity (CGI-S) | 7-point scale of patients' self-reporting of severity during the study. | 12 weeks | | Clinical Global Impression of Improvement (CGI-I) | 7-point scale of patients' self-reporting of severity during the study. | 12 weeks |

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Study of Monalizumab and Cetuximab in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Study Overview ================= Brief Summary ----------------- The objective of this study is to evaluate in a 3 +3 design, the safety of escalating doses of Monalizumab given IV in combination with cetuximab in patients who have received prior systemic regimen(s) for recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN). Cohorts expansion will evaluate antitumor activity of monalizumab and cetuximab with or without anti-PD(L)1 Official Title ----------------- Phase 1b/2 Trial of IPH2201 And Cetuximab in Patients With Human Papillomavirus (HPV) (+) and HPV (-) Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Conditions ----------------- Head and Neck Neoplasms Intervention / Treatment ----------------- * Biological: Monalizumab * Biological: Cetuximab * Biological: Anti-PD(L)1 Participation Criteria ================= Eligibility Criteria ----------------- Main Inclusion Criteria: Age ≥ 18 years Histologically or cytologically-confirmed, HPV (+) or HPV (-) squamous cell carcinoma of the nasopharynx (WHO Type 1), oropharynx, hypopharynx, larynx (supraglottis, glottis, subglottis) or oral cavity. Recurrent or metastatic disease, documented by imaging (CT scan, MRI, X-ray) and/or physical examination with measurable disease as per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 For phase II cohorts: Cohort #1: Patients who received a maximum of two prior systemic regimens for recurrent and/or metastatic disease and not amenable to further therapy with curative intent Cohort #2: Patients with R/M SCCHN not amenable to therapy of curative intent, who have received a maximum of two prior systemic regimens in the R/M setting and who have received prior PD-(L)1 blockers Cohort #3: Patients with R/M SCCHN who have not received prior systemic regimens in the R/M setting and who have not received prior PD-(L)1 inhibitors Main Exclusion Criteria: For phase II cohort #1 and cohort #2: Patients who received more than 2 prior systemic regimens for recurrent and/or metastatic disease (no restriction in the phase Ib part of the trial). For phase II cohort #1 and cohort #2: Patients who received cetuximab or another inhibitor of epidermal growth factor receptor are excluded from the phase II of the trial, except if cetuximab was given as part of a primary treatment approach, with no progressive disease for at least 4 months following the end of prior cetuximab treatment. 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: Sequential Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Dose escalation<br>Dose escalation of monalizumab in combination with cetuximab | Biological: Monalizumab<br> <br> * Other names: IPH2201;Biological: Cetuximab<br> <br> | | Experimental: Expansion cohort 1<br>monalizumab + cetuximab expansion cohort | Biological: Monalizumab<br> <br> * Other names: IPH2201;Biological: Cetuximab<br> <br> | | Experimental: Expansion cohort 2<br>monalizumab + cetuximab expansion cohort in patients with prior exposure to PD-(L)1 blockers | Biological: Monalizumab<br> <br> * Other names: IPH2201;Biological: Cetuximab<br> <br> | | Experimental: Expansion cohort 3<br>monalizumab + cetuximab + anti-PD(L)1 | Biological: Monalizumab<br> <br> * Other names: IPH2201;Biological: Cetuximab<br> <br> Biological: Anti-PD(L)1<br> <br> | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Occurrence of Dose Limiting Toxicities (DLT) in the dose escalation part of the study | To assess the occurrence of Drug Limited Toxicities (DLTs) | within 4 weeks after first administration | | Objective Response Rate for expansion cohorts | rate of patients in complete or partial response according to RECIST 1.1. | up to 12 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Objective Response Rate for dose escalation part of the study | rate of patients in complete or partial response according to RECIST 1.1 | up to 12 months | | Duration of Response for expansion cohorts | Duration of complete and partial response | From confirmed response until disease progression, up to 12 months | | Progression Free Survival for expansion cohorts | time between the start of treatment and the first documented progression or death | Until disease progression or death, up to 2 years | | Overall Survival for expansion cohorts | time between the start of treatment and death | Until death, up to 2 years |

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Online Mindfulness-based Tic Reduction (Phase Two) Study Overview ================= Brief Summary ----------------- Tourette Syndrome (TS) and Persistent Tic Disorder (PTD) are chronic and potentially disabling neurobiological conditions. Although a range of pharmacological and psychosocial treatments exists, a significant number of individuals either do not respond to the current treatments or find them unacceptable. Thus, it is essential that researchers continue to develop and test novel treatment approaches. In this randomized controlled trial the investigators will compare two different online group-based interventions for tics: a mindfulness-based program (Mindfulness-based Intervention for Tics (MBIT), and a psychoeducational and supportive therapy program (Tic Information and Coping Strategies (TICS)). The purpose of this study is to determine which intervention is more helpful for adults with a tic disorder. Official Title ----------------- Online Mindfulness-based Tic Reduction: Development and Testing (Phase Two) Conditions ----------------- Tourette Syndrome, Persistent Tic Disorder Intervention / Treatment ----------------- * Behavioral: Mindfulness-based Intervention for Tics * Behavioral: Tic Information and Coping Strategies Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: be 18 years of age or older, possess a primary diagnosis of Tourette Syndrome or Persistent Tic Disorder, be fluent in English reside in the United States, either not be taking any tic suppressant medication or other psychotropic medication or be at a stable dose for 8 weeks prior to the baseline assessment and throughout the study Exclusion Criteria: be receiving concurrent psychotherapy for the duration of the study have prior extensive experience with mindfulness and/or meditation and have another medical or psychological condition that would prevent the individual from fully engaging in the study or require a higher level of care (e.g., suicidality). 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: Randomized Controlled Trial Masking: Single Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Mindfulness-based Intervention for Tics<br>8-week group-based mindfulness-based program | Behavioral: Mindfulness-based Intervention for Tics<br>* Psychological intervention that focuses on cultivating awareness of urges to tic and developing a different relationship to those urges through meditation and other mindfulness practices.<br>| | Active Comparator: Tic Information and Coping Strategies<br>8-week group-based educational and supportive therapy program | Behavioral: Tic Information and Coping Strategies<br>* Psychological Intervention that focuses on learning more about tics, practicing a range of strategies for coping with tics (e.g., relaxation, effective communication), and discussing challenges commonly experienced by individuals with tics.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in Yale Global Tic Severity Scale (YGTSS) Total Tic Severity Score | Clinician-rated measure of tic severity | Screening, Week 0, Week 9, Week 13, Week 35 | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Clinical Global Impressions Scale | | Weeks 0, 9, 13, 35 | | Adult Tic Questionnaire | | Weeks 0, 9, 13, 35 | | Yale-Brown Obsessive Compulsive Scale | | Weeks 0, 9, 13, 35 | | Attention-Deficit Hyperactivity Rating Scale | | Weeks 0, 9, 13, 35 | | Depression Anxiety Stress Scale | | Weeks 0, 9, 13, 35 | | Premonitory Urge to Tic Scale | | Weeks 0, 9, 13, 35 | | Tic Rating Form | | Weeks 1-8 | | Problem Rating Form | | Weeks 1-8 | | Patient Health Questionnaire-9 | | Weeks 0, 9, 13, 35 | | Work and Social Adjustment Survey | | Weeks 0, 9, 13, 35 | | Five Facet Mindfulness Questionnaire | | Weeks 0, 4, 8, 9, 13, 35 | | Credibility and Expectancy Questionnaire | | Week 3 | | Patient Satisfaction Questionnaire | | Week 9 | | Self Compassion Scale | | Weeks 0, 9, 13, 35 | | Affective Reactivity Index | | Weeks 0, 9, 13, 35 | | Brief Irritability Test | | Weeks 0, 9, 13, 35 | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Tourette Syndrome, Tic Disorder, Online, Adults, Mindfulness, Therapy

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Study of Major Cardiovascular Events in Patients With Nonvalvular Atrial Fibrillation Treated With Rivaroxaban Study Overview ================= Brief Summary ----------------- Evaluation of the performance of the 2MACE index in a population of nonvalvular atrial fibrillation (NVAF) patients treated with rivaroxaban in Spain Official Title ----------------- Study of Risk Factors of Major Cardiovascular Events in Patients With Nonvalvular Atrial Fibrillation Treated With a Direct Oral Anticoagulant (Rivaroxaban) Conditions ----------------- Atrial Fibrillation Intervention / Treatment ----------------- * Drug: Rivaroxaban (Xarelto, BAY59-7939) Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Adult patients aged 18 years or older. Patients with diagnosis of NVAF. Patients treated with rivaroxaban from at least six months prior to the study inclusion. Patients who have been given appropriate information about the study objectives and procedures and who have given their written informed consent. Exclusion Criteria: Patients participating in an investigational program with interventions outside of routine clinical practice. Patients who initiate treatment with rivaroxaban after the start of the study inclusion period. Prosthetic heart valves or the presence of any severe valvulopathies. Patients with severe cognitive impairment. Patients with chronic infections (HIV infection, hepatitis C virus, hepatitis B virus) or systemic autoimmune diseases. Patients with active cancer. Patients with liver insufficiency (eg. cirrhosis). 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 | | --- | --- | | Rivaroxaban<br>Non-valvular atrial fibrillation (NVAF) patients treated with rivaroxaban for at least 6 months prior to the study inclusion | Drug: Rivaroxaban (Xarelto, BAY59-7939)<br>* As prescribed by the treating physician<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | 2MACE score | MACE: Major adverse cardiovascular events. 2MACE: History of Myocardial infarction/ Cardiac revascularization and Metabolic Syndrome, Age >75 years, Congestive heart failure (ejection fraction <40%), Thrombo-Embolism | At baseline | | Occurrence of MACE to evaluate the performance of the 2MACE index | Percentage of patients with MACE including fatal/nonfatal myocardial infarction, cardiac revascularization and cardiovascular death | At 2 years and 6 months or early termination | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Incorporation of additional risk factors to the 2MACE index or replacing some of the existing ones | Risk factors to the 2MACE index (e.g. body mass index, smoking, drugs use, estimated glomerular filtration rate, structural cardio-pathology) | At baseline | | Occurrence of major cardiovascular events (fatal/nonfatal myocardial infarction, cardiac revascularization and cardiovascular death) | | At baseline, at 1 year, at 2 years, at 2 years and 6 months or early termination | | Occurrence of stroke | | At baseline, at 1 year, at 2 years, at 2 years and 6 months or early termination | | Occurrence of transient ischemic attack (TIA) | | At baseline, at 1 year, at 2 years, at 2 years and 6 months or early termination | | Occurrence of systemic embolism | | At baseline, at 1 year, at 2 years, at 2 years and 6 months or early termination | | Thromboembolic risk based on the CHADS2 score | CHADS2: Cardiac Failure, Hypertension, Age, Diabetes, Stroke | At baseline | | Thromboembolic risk based on the CHA2DS2-VASC | CHA2DS2-VASc:Cardiac failure, Hypertension, Age ≥75, Diabetes, Stroke -Vascular disease, Age and Sex category | At baseline | | Number of MACEs occurring during the study | | At 1 year, at 2 years, at 2 years and 6 months or early termination | | Patients' profile | Baseline patients' profile defined by: sociodemographic data, anthropometric data, previous relevant medical history, cardiac medical history distinct to atrial fibrillation, comorbidities (renal failure, left ventricular dysfunction, hypertension, thyroid dysfunction, liver failure, alcoholism) | At baseline | | Number of cases (frequency) of metabolism syndrome at enrollment with/without the occurrence of myocardial infarction or coronary revascularization | | At baseline |

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Pilot Safety Study of Injectable SIS for Critical Limb Ischemia Study Overview ================= Brief Summary ----------------- This study is intended to collect safety and effectiveness data on the Cook Injectable Small Intestinal Submucosa (SIS) Official Title ----------------- Pilot Safety Study of Injectable Small Intestine Submucosa (SIS) for Critical Limb Ischemia Conditions ----------------- Critical Limb Ischemia, Peripheral Arterial Disease, Peripheral Vascular Disease Intervention / Treatment ----------------- * Device: Injectable SIS Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Diagnosis of critical limb ischemia Rutherford 4-5 or Leriche-Fontaine IIIB Patient unable to be treated by endovascular or surgical means Exclusion Criteria: Patient's age is <21 Patient is pregnant or breast-feeding (or is planning to become pregnant within the next year) Patient has had a previous surgery, within 30 days of the study procedure Patient has any planned surgical or interventional procedure within 30 days after the study procedure Patient has a life expectancy less than 1 year Patient has a known allergy to pigs or pig products, or has a religious or cultural objection to the use of pig tissue Additional restrictions as specified in the Clinical Investigation Plan 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 Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Treatment<br>Injectable SIS | Device: Injectable SIS<br>* Injectable SIS<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Frequency and types of adverse events after treatment with the Cook Injectable SIS | | 180 days | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- critical limb ischemia, wound healing, amputation

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Relaxation and Exercise In Lymphoma Patients Study Overview ================= Brief Summary ----------------- This study will aim to compare the effects of an Exercise programme and a Relaxation Intervention in lymphoma patients in remission post-chemotherapy on quality of life, cardiovascular fitness, exercise tolerance, muscle strength, psychological status, social well-being and biological markers. Subjects will be recruited from a specialist lymphoma clinic in South West London and randomly allocated to an exercise or a relaxation home programme. The study aims to determine the more effective intervention of the two in relation to the outcome measures. The investigators anticipate that the interventions will result in less adverse events and improved quality of life and physical fitness, and subjects will require less medication, less counseling and cancer nurse specialist care, leading to leading to a reduction in hospital and surgery attendances. Detailed Description ----------------- Significant improvements have been made in the survival rates in cancer patients. Due to factors such as screening and earlier detection of cancer and advances in treatment, cancer today is a curable disease for many. However, cancer survivors are at a significantly increased risk of morbidity and adverse effects due to treatment exposures. Commonly reported consequences of cancer treatment include fatigue, pain, depression, anxiety, reduced performance status and decreased quality of life Hence cancer today is considered more as a chronic illness, and there is increasing research being carried out on cancer survivorship and recommendations for survivorship care pathways to include interventions to enhance both physical and psychosocial functioning in cancer survivors. Previous studies have demonstrated that both exercise and interventions such as relaxation have a positive effect on both physical and psychosocial complaints of cancer survivors. These interventions are carried out in different ways, have different requirements and perceptions of the two can also be very different. No trial to date has been carried out comparing the effects of these interventions on the quality of life in cancer survivors. Furthermore, majority of the above research has been carried out on the most prevalent cancers including breast cancer, prostate cancer and colorectal cancer, and several authors have called for future research to focus on other understudied survivor groups, including haematologic cancer sites. This study aims to compare the effect of exercise and relaxation interventions on quality of life in lymphoma survivors. The aim of the present study is to compare the effects of an Exercise Intervention Program with a Relaxation Intervention in a sample of lymphoma patients in remission post-chemotherapy. Eligible subjects will be randomised to one of two arms - either an exercise or a relaxation arm. Both arms comprise of a home programme of their intervention (either exercise or relaxation) for half an hour, carried out three times a week. Subjects are assessed using the primary and secondary outcome measures at baseline, midway (6 weeks) and at the end of the intervention (12 weeks). It is hypothesised that a 12 week training programme of both exercise and relaxation would improve the quality of life of lymphoma survivors, however the exercise programme would result in a significantly greater improvement than relaxation. The null hypothesis would state that there would be no significant difference between exercise or relaxation groups following a 12 week training programme in lymphoma survivors. The aims of the study are as follows: Primary aim To compare the effectiveness of Exercise with Relaxation in the improvement of overall wellbeing and quality of life using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30). Secondary aims To determine whether these interventions result in: Improved cardio-respiratory fitness (resting HR and BP) and pulmonary function (spirometry) Improved fitness and exercise tolerance using the 6 Minute Walk Test Improved emotional and functional confidence as measured by the Health related quality of life questionnaire Functional Assessment of Cancer Therapy Lymphoma version (FACT-Lym) Decreased anxiety and depression levels using the Hospital Anxiety and Depression Scale (HADS) Changes in haematology (haemoglobin, immunoglobulins, white count) and biochemical (serum albumin, corrected calcium, creatinine) parameters Compare the results of the above outcome measures between the two interventions Analyse subject perceptions of interventions in focus groups Official Title ----------------- A Comparison of Exercise Training With Relaxation Intervention in Lymphoma Patients Post-chemotherapy. Conditions ----------------- Lymphoma, Quality of Life Intervention / Treatment ----------------- * Behavioral: Exercise * Behavioral: Relaxation Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patients with histologically confirmed lymphoma in remission post-chemotherapy Age 18 years or older Ability to give informed consent Good Performance status (ECOG 0-2) Clinically able to carry out exercise training programme on a regular basis Exclusion Criteria: Patients with progressive disease Poor performance status (ECOG status 3 or more) Abnormal resting ECG unexplained by further cardiological investigations Pregnancy Difficulty breathing at rest Persistent cough, fever or illness Cognitive impairment sufficient to limit ability to perform quality of life questionnaires or understand instructions 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: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Exercise Intervention<br>Subjects allocated to the Exercise arm will aim to undertake a personal prescribed home exercise programme for half an hour three times a week. Exercises will be progressed at 6 weeks as subjects progress. All exercise sessions will be documented in the logbooks provided. Outcome measures will be assessed at baseline, mid-way (6 weeks) and at the end of intervention (12 weeks). | Behavioral: Exercise<br>* The Exercise intervention will consist of aerobic activity followed by upper and lower limb resistance training using Therabands and some core exercises.<br>* Other names: Exercise Training;| | Experimental: Relaxation Intervention<br>Subjects allocated to the Relaxation arm will aim to undertake a guided relaxation programme on a CD for half an hour three times a week. All relaxation sessions will be documented in the logbooks provided. Outcome measures will be assessed at baseline, mid-way (6 weeks) and at the end of intervention (12 weeks). | Behavioral: Relaxation<br>* The Relaxation intervention will consist of a chair-based program incorporating breathing exercises, meditation, visualisation and progressive muscle relaxation.<br>* Other names: Mindfulness;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) | The EORTC-QLQ-C30 is a self-administered questionnaire which assesses aspects of function, symptoms, and global health and QOL in samples of cancer patients. It has been demonstrated to be a valid and reliable tool in the literature, takes approximately eleven minutes to complete and most subjects require no assistance. | Baseline, 6 weeks and 12 weeks | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in Six Minute Walk Test distance and Heart Rate | The Six Minute Walk Test (6MWT) is a valid and reliable tool used in a variety of clinical settings, and validated for use with cancer patients. The patient is read out a set of standardised instructions to walk around a measured distance continuously as fast as they can for six minutes. Following this, the distance covered is measured and recorded, as well as their Heart Rate, Saturations, Rate of Perceived Exertion and Dyspnoea (using Borg scales) are recorded. This test gives an indication of general fitness and overall function. | Baseline, 6 weeks and 12 weeks | | Change in Grip Strength | Grip strength will be determined using hand-held dynamometry following a set of standardised guidelines. This is a common method that is used extensively to assess general strength characteristics. | Baseline, 6 weeks and 12 weeks | | Change in Spirometry values | Measures of pulmonary capacity and function including Forced Vital Capacity (FVC), Forced Expiratory Volume in one second (FEV1), Forced Expiratory Ratio (FER) and Peak Expiratory Flow (PEF) will be taken via microspirometry. | Baseline, 6 weeks and 12 weeks | | Change in FACT-Lym Questionnaire | The Functional Assessment of Chronic Illness questionnaires, have been validated in studies of cancer management and are designed to encompass the whole range of psychosocial factors. Here, the lymphoma-specific (FACT-Lym) self-administered questionaire will be used. | Baseline, 6 weeks and 12 weeks | | Change in Hospital Anxiety and Depression Scale | The Hospital Anxiety and Depression Scale (HADS) is a valid tool for the identification of psychiatric complications of cancer such as depression, anxiety or distress in cancer settings. It is a self-administered questionnaire. | Baseline, 6 weeks and 12 weeks | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- cancer survivorship, exercise, relaxation, mindfulness

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Efficacy, Safety and Tolerability of a Novel Malathion Formulation in Patients 2 Years and Older With Head Lice Study Overview ================= Brief Summary ----------------- In this study, Malathion Gel 0.5% will be compared to Nix (permethrin 1%) as a treatment for head lice in patients 2 years of age and older. Malathion Gel 0.5% is a new formulation of an established head lice treatment. The new formulation has been evaluated in 2 previous studies of patients 2 years of age and older. Detailed Description ----------------- This is a Phase III, multi-center, investigator-blinded, two-arm, randomized, parallel group study, evaluating the safety and efficacy of a Malathion Gel, 0.5% formulation, manufactured by Taro. The objective is to show superiority of the novel product to an active control, Nix® Crème Rinse, manufactured by Insight Pharmaceuticals. Official Title ----------------- A Multi-Center Phase III Study to Evaluate Malathion Gel 0.5% Formulation, for the Control of Head Lice in Pediatric Subjects and Adult Subjects With Pediculosis Capitis Conditions ----------------- Pediculosis Intervention / Treatment ----------------- * Drug: Malathion gel 0.5% * Drug: Permethrin 1% rinse (Nix Crème) Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Confirmed active head lice infestation Exclusion Criteria: Allergy to pediculicides or hair care products Scalp conditions other than head lice Previous head lice treatment within the past 4 weeks Current antibiotic treatment Ages Eligible for Study ----------------- Minimum Age: 2 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: Malathion Gel<br>Malathion gel 0.5% 30 minute application | Drug: Malathion gel 0.5%<br>* Malathion gel 0.5% applied to scalp for 30 minutes. May be repeated in 1 week if head lice are still present.<br>| | Active Comparator: Nix Crème Rinse<br>Nix Crème Rinse applied to scalp for 10 minutes | Drug: Permethrin 1% rinse (Nix Crème)<br>* Permethrin 1% shampooed into scalp for 10 minutes. May be repeated in 1 week if head head lice are still present.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Proportion of Index Subjects Free of Any Lice 14 Days After Their Last Treatment in the Modified ITT (LOCF) | The primary efficacy variable was the proportion of index subjects who were considered a Treatment Success 14 days after their last treatment (Day 14 visit if only treated on Day 1, Day 21 visit if treated on Day 1 and Day 7) Treatment Success in the Efficacy ITT (LOCF) index subjects: 150 from 403 randomized (the youngest subject in the household that met the index case criteria (having nits and at least 3 live lice)) | 3 weeks | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Proportion of Subjects Who Were Considered a Treatment Success 14 Days After Their First Treatment in the Modified ITT (LOCF). | The secondary efficacy variable was the proportion of subjects who were considered a Treatment Success 14 days after their first treatment. Treatment Success in the Efficacy ITT (LOCF) | 3 weeks | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Head Lice

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Ultrasound Guided Anterior Quadratus Lumborum Block Study Overview ================= Brief Summary ----------------- Percutaneous nephrolithotomy (PNL) is frequently used today for renal stones. percutaneous nephrolithotomy (PNL) procedure has become the treatment of choice for many patients with symptomatic renal stones . Patients undergoing PNL suffer from acute postoperative pain, despite a multimodal analgesic regime. This is a randomised controlled trial efficacy of the anterior Quadratus Lumborum Block (QLB) in terms of analgesic efficacy in patients who undergo percutaneous nephrolithotomy. Detailed Description ----------------- Many analgesic procedures such as NSAID, opioid and regional anesthesia procedures are used as a part of multimodal analgesia for postoperative Percutaneous nephrolithotomy pain. In this study we will use the ultrasound -guided anterior Quadratus Lumborum Block . Local anesthesic will be injected between quadratus lumborum muscle and psoas muscle with ultrasound.Analgesic effect of this block will be detected by using morphine consumption and visual analogue scale . Official Title ----------------- Ultrasound Guided Anterior Quadratus Lumborum Block for Postoperative Pain After Percutaneous Nephrolithotomy: Randomized Controlled Trial Conditions ----------------- Postoperative Pain, Ultrasound Intervention / Treatment ----------------- * Drug: Morphine Sulfate * Procedure: Group P * Procedure: Group A Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patients who were in the American Society of Anesthesiologists (ASA) I-III class and underwent elective Percutaneous nephrolithotomy Exclusion Criteria: Previous history of opioid use preoperatively, Allergy to local anesthetics, The presence of any systemic infection, Ages Eligible for Study ----------------- Minimum Age: 20 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 Interventional Model Description: prospective,randomized,single blind Masking: Double Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Group A<br>Group A:Ultrasound guided unilateral anterior Quadratus Lumborum block with 20 ml %0.25 bupivacaine+PCA (morphine) | Drug: Morphine Sulfate<br>* patient-controlled analgesia (PCA) morphine<br>* Other names: Morphine;Procedure: Group A<br>* Group A:Ultrasound guided unilateral anterior Quadratus Lumborum block with 20 ml %0.25 Bupivacaine<br>* Other names: Bupivacaine;| | Sham Comparator: Group P<br>Group P:PCA (morphine) | Drug: Morphine Sulfate<br>* patient-controlled analgesia (PCA) morphine<br>* Other names: Morphine;Procedure: Group P<br>* Group P:patient-controlled analgesia (PCA) morphine<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Visual Analog Scale | Visual Analog Scale was used for pain.Pain intensity was measured using 0-10 cm visual analogue scale (VAS). (0= no pain, 10=intolerable pain) | Postoperative 24 hours | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | morphine consumption | morphine consumption | Postoperative 24 hours | | side effect profile | side effect profile (Nausea and vomiting scale,Hypotension,Ramsay Sedation Scale) Nausea and vomiting scale (nausea-vomiting scale (NVS): 1. No nausea is present, 2. Mild nausea is present. 3. Severe nausea is present. 4. Vomiting is present) In case of a NVS score of >3, an anti-emetic drug was administered. Hypotension Ramsay Sedation Scale (Ramsay Sedation Scale (RSS) : 1. Anxiety, agitation are present; 2. Cooperated, awake; 3. Sedatized, response to commands; 4. Sleepy, immediately awoken by auditory stimulus or glabella tap; 5. Sleepy, deep response to auditory stimulus or glabella tap and 6. Sleepy, no response to auditory stimulus or glabella tap ) | Postoperative 24 hours | | additional analgesic use | additional analgesic use | Postoperative 24 hours | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- quadratus lumborum block, pain, ultrasound, percutaneous nephrolithotomy

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Efficacy, Safety, and Tolerability of Cenicriviroc (CVC) in Combination With Truvada or Sustiva Plus Truvada in HIV 1-infected, Antiretroviral Treatment-naïve, Adult Patients Infected With Only CCR5-tropic Virus Study Overview ================= Brief Summary ----------------- This is a randomized, double-blind, double-dummy, 48-week, comparative study. Approximately 150 HIV-infected, treatment-naïve patients with CCR5-tropic virus will be stratified by HIV-1 RNA: ≥100,000 copies/mL versus <100,000 copies/mL and will be randomized 2:2:1 to receive: Arm A: CVC 100 mg (2 tablets, 50 mg each) QD + CVC matching placebo (2 tablets) QD + EFV matching placebo (1 tablet) QHS + FTC/TDF (1 tablet) QD. Arm B: CVC 200 mg (4 tablets, 50 mg each) QD + EFV matching placebo (1 tablet) QHS + FTC/TDF (1 tablet) QD. Arm C: CVC matching placebo (4 tablets) QD + EFV 600 mg (1 tablet) QHS + FTC/TDF (1 tablet) QD. Doses of both CVC/placebo and EFV/ placebo will be administered as double-blinded study drug. FTC/TDF will be administered as open-label study drug in a fixed-dose combination formulation (Truvada). CVC/placebo should be taken following breakfast; EFV should be taken on an empty stomach at bedtime. HIV-1 RNA levels and CD4+ and CD8+ cell counts, percentages, and ratios will be measured at every visit. Samples for viral tropism and resistance testing in case of virologic failure will be collected at Screening and each on-treatment visit. Biomarkers associated with inflammation and immune activation will be measured at Baseline (predose) and each study visit thereafter, with flow cytometry obtained at weeks 4, 12, 24, 48, and 52. Fasting metabolic indicators of glucose control (glucose and insulin for HOMA-IR, HbA1c) and fasting lipid profiles (HDL, LDL, total cholesterol, and triglycerides) will be measured at Baseline (predose) and Weeks 4, 12, 24, 48, and 52. Waist-to-hip ratios will be measured at Baseline and Weeks 24 and 48. Plasma samples will be collected and stored for possible future studies at Baseline (predose) and every visit thereafter. Official Title ----------------- A Phase 2b Randomized, Double-Blind, Double-Dummy Trial of 100 or 200 mg Once-Daily Doses of Cenicriviroc (CVC, TBR 652) or Once-Daily EFV, Each With Open-Label FTC/TDF, in HIV 1-Infected, Antiretroviral Treatment-Naïve, Adult Patients With Only CCR5-Tropic Virus Conditions ----------------- HIV-1 Infection Intervention / Treatment ----------------- * Drug: Cenicriviroc 100 mg * Drug: Cenicriviroc 200 mg + Truvada * Drug: Sustiva + Truvada Participation Criteria ================= Eligibility Criteria ----------------- Selected Inclusion Criteria: Adult male and female, HIV-1-infected patients 18 years old and older. Body mass index (BMI) 18 to < 35 kg/m2. Antiretroviral treatment-naïve. Treatment-naïve is defined as: No prior nonnucleoside reverse transcriptase inhibitor, other than in women who received a single dose of perinatal nevirapine who have no K103 viral mutation. No prior CCR5 antagonist therapy. No more than 10 days of any other prior antiretroviral therapy. HIV-1 CCR5-tropic-only virus. Plasma HIV-1 RNA level >/=1,000 copies/mL at first Screening. CD4 cell count >/=250 cells/mm3 at first Screening. Selected Exclusion Criteria: Presence of CXCR4- or dual/mixed-tropic HIV-1 virus. Presence of primary resistance mutations or phenotypic resistance to TDF, FTC, or EFV and/or mutations associated with multidrug nucleoside/nucleotide resistance. An active CDC category C disease (except cutaneous Kaposi's sarcoma not requiring systemic therapy during the trial). Any historical CD4 count < 200 cells/mm3. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value Grade > 2 or total bilirubin greater than the upper limit of normal (ULN). History of HIV-2, hepatitis B and/or C, cirrhosis of the liver, or any known active or chronic liver disease. Hepatitis B vaccinated patients are eligible. 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: Quadruple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: CVC 100 mg + Truvada<br> | Drug: Cenicriviroc 100 mg<br>* 100 mg CVC plus Truvada<br>| | Experimental: CVC 200 mg + Truvada<br> | Drug: Cenicriviroc 200 mg + Truvada<br>* 200 mg CVC plus Truvada<br>| | Active Comparator: Sustiva + Truvada<br> | Drug: Sustiva + Truvada<br>* Sustiva plus Truvada<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | To determine the percentage of patients who achieve HIV-1 RNA levels below 50 copies/mL at Week 24 | | 24 weeks | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- HIV-1 Infection, CCR5-tropic, Anti-retroviral naive

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Safety and Immunogenicity of Vi-CRM197 Vaccine Against S. Typhi in Children, Older Infants and Infants Study Overview ================= Brief Summary ----------------- This phase 2 trial is aimed to obtain information on the safety and immunogenicity of the Vi-CRM197 in children and infants from various age groups in the Philippines where Typhoid Fever is highly endemic and an efficacious vaccine against this disease is very much needed. Official Title ----------------- A Phase 2, Randomized, Controlled, Observer Blind, Single Center Study of the Safety, Reactogenicity and Immunogenicity of the NVGH Glycoconjugate Vaccine Against S. Typhi in Children, Older Infants and Infants Conditions ----------------- Typhoid Fever Intervention / Treatment ----------------- * Biological: Vi-CRM197 vaccine * Biological: Pneumococcal conjugate vaccine * Biological: Vi Polysaccharide (PS) vaccine Participation Criteria ================= Eligibility Criteria ----------------- Inclusion criteria: Subjects belonging to 3 age groups will be enrolled into the trial: children (24 to 59 months of age at enrollment), older infants (9 to 12 months of age at enrollment) and infants (6 weeks of age at enrolment). Written informed consent will be obtained by the parents/ guardians before enrollment into the trial. Infants who have been vaccinated with BCG and HBV at birth and OPV at any time since birth can be enrolled into the trial, while infants who have received DTwP+HBV+Hib due at 6 weeks of age as per local EPI schedule cannot be enrolled into the trial. Ages Eligible for Study ----------------- Minimum Age: 6 Weeks Maximum Age: 59 Months 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: Quadruple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Vi-CRM, Older infants<br>Older Infants (9 to 12 months) receiving 2 doses of NVGH Vi-CRM197 vaccine | Biological: Vi-CRM197 vaccine<br> <br> | | Active Comparator: PNC13, Older infants<br>Older infants (9 to 12 months) receiving 2 doses of Pneumococcal conjugate vaccine | Biological: Pneumococcal conjugate vaccine<br> <br> * Other names: Prevenar 13;| | Experimental: Vi-CRM, Infants<br>Infants (6 to 8 weeks) receiving 3 doses of NVGH Vi-CRM197 vaccine | Biological: Vi-CRM197 vaccine<br> <br> | | Active Comparator: PNC13, Infants<br>Infants (6 to 8 weeks) receiving 3 doses of Pneumococcal conjugate vaccine | Biological: Pneumococcal conjugate vaccine<br> <br> * Other names: Prevenar 13;| | Experimental: Vi-CRM, Children<br>Children (24 to 59 months) receiving 2 doses of NVGH Vi-CRM197 vaccine | Biological: Vi-CRM197 vaccine<br> <br> | | Active Comparator: Vi-PS, Children<br>Children (24 to 59 months) receiving 1 dose of licensed Vi Polysaccharide vaccine and 1 dose of Pneumococcal conjugate vaccine | Biological: Pneumococcal conjugate vaccine<br> <br> * Other names: Prevenar 13;Biological: Vi Polysaccharide (PS) vaccine<br> <br> * Other names: Typherix;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Percentage of Subjects With at Least 4-fold Increase in Anti-Vi Enzyme-linked Immunosorbent Assay (ELISA) Titer | | At 28 days after last vaccination as compared to baseline | | Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titer | | At 6 months after last vaccination as compared to baseline | | Anti-Vi ELISA Geometric Mean Concentration (GMC) | | At 28 days after last vaccination | | Anti-Vi ELISA GMC | | At 6 months after last vaccination | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Number of Participants With Any Solicited Local and Systemic Reaction, After Any Vaccination | Solicited local reactions were: erythema, induration, pain/tenderness. Solicited systemic reactions were; lethargy, irritability, vomiting, diarrhoea, loss of appetite (and persistent crying in the older infants and infants age group) | During the 7-day follow-up period after vaccination |

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Adoptive Cord Blood Immunotherapy for EBV, CMV, BKV and Adenovirus Reactivation/Infection or Prophylaxis Study Overview ================= Brief Summary ----------------- This Phase I-II dose-finding trial to determine the optimal dose of intravenous (IV) injection dose of donor-derived cytotoxic T lymphocytes (CTLs) specific for CMV, EBV, BKV and Adenovirus. A maximum of 36 patients will be treated in up to 18 cohorts each of size 2, with the first cohort treated at the lowest dose level 1, all successive doses chosen by the EffTox method, and no untried dose level skipped when escalating. The scientific goal of the trial is to determine an optimal IV-CTL cell dose level among the three doses 1.0x107cells/m2, 2 x107cells/m2 and 5x107cells/m2., hereafter dose levels 1, 2, 3. Dose-finding will be done using the sequentially adaptive EffTox trade-off-based design of Thall et al. Detailed Description ----------------- This Phase I-II dose-finding trial to determine the optimal dose of intravenous (IV) injection dose of donor-derived cytotoxic T lymphocytes (CTLs) specific for CMV, EBV, BKV and Adenovirus. A maximum of 36 patients will be treated in up to 18 cohorts each of size 2, with the first cohort treated at the lowest dose level 1, all successive doses chosen by the EffTox method, and no untried dose level skipped when escalating. The scientific goal of the trial is to determine an optimal IV-CTL cell dose level among the three doses 1.0x107cells/m2, 2 x107cells/m2 and 5x107cells/m2., hereafter dose levels 1, 2, 3. Dose-finding will be done using the sequentially adaptive EffTox trade-off-based design of Thall et al. To implement the design's model using the latest EffTox version 4.0.12 program, doses will coded numerically to be 1, 2, 3. CMV/AdV /EBV/BKV specific T cells will be thawed and given or thawed and diluted into a total volume of 10 mL of Plasmalyte A by slow intravenous injection over 1-2 minutes. This is a traditional Phase I dose escalation study of a single infusion of CMV/AdV/EBV/BKV-specific CTLs to patients at risk for CMV and EBV reactivation and Adenoviral and BK virus infection after umbilical cord blood transplantation. Three dose levels will be explored. The lowest dose level will be 1x107cells/m2 and the highest will be 5x107/m2. There will be 2-6 patients at each dose level (depending on toxicity) following the scheme below. The decision on whether it is safe to escalate to next dose level or not will be made after at least two patients in each dose level have finished their 45-days toxicity follow up. If the first two patients have not finished their 45 days follow-up, up to 2 additional incoming patients can be enrolled at the current dose level. In addition, we will give the option of administering 2 additional doses (at the same dose level), 28 days after the first infusion of the same dose, in subjects who have a partial response after one dose or who have received other therapy that may affect the persistence or function of the infused CTL in vivo. If there are no toxicities and immunological efficacy is not seen at any dose, then the doses will be further escalated after additional local and federal approval. Dose Levels and Dosing Schedule Dose Level CTL Dose Given from Day +30 post SCT 1x107/m2 2.0x107/m2 5x107/m2 Escalation of Multi-virus-specific CTL infusions CMV/AdV/EBV/BKV CTL will be given from day +30 either as prophylaxis or treatment for CMV, EBV, BK and/or adenovirus infection. If the patient has viral reactivation or evidence of CMV/EBV/AdV/BKV disease (e.g. pneumonitis, gastroenteritis and/or retinitis or Post Transplant Lymphoproliferative Disorder (PTLD) or hemorrhagic cystitis the CTL can be given with concurrent antiviral pharmacotherapy. A dose escalation scheme utilizing cohorts of two patients will be used Each cohort of 2 patients will be treated and observed for 45 days for toxicity, dose escalation, and GvHD. The algorithm described in Section 9 will be used to determine the dose for each cohort. If 1x107CTL/m2 results in unacceptable toxicity or efficacy, the study will be closed to accrual. The Optimal Dose of Infused CMV/AdV/EBV/BKV-Specific CTL After all patients in the trial have been evaluated, the optimal dose of infused CMV/AdV/EBV-specific CTL will be determined by the algorithm using the sequentially adaptive EffTox trade-off-based design of Thall et al. Official Title ----------------- Adoptive Cord Blood ImmunotHerapy Using Expanded Cord Blood T Cells for EBV, CMV, BKV and Adenovirus Reactivation/Infection or ProphylaxiS Conditions ----------------- Viral Infection Intervention / Treatment ----------------- * Biological: CMV/AdV /EBV/BKV specific T cells Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Inclusion Criteria at the Time of Procurement Pediatric and adult patients (there are no lower and upper age limits for patients) with malignant or nonmalignant diseases who are candidates for transplant. Patients must have a CB unit (or units) matched with the patient at 4, 5, or 6/6 HLA class I (serological) and II (molecular) antigens. The unit selected for CTL expansion must be either: be cryopreserved in two fractions, with a minimum of 2.5x107 total nucleated cells (TNC) per kg pre-thaw in the fraction which will be used for the primary transplant. The remaining fraction will be used to generate the CTLs to give at day 30 or beyond as described below. OR be cryopreserved with a cell dose that totals > 3x10e7 TNC per kg pre thaw. On thaw, 20% of the total volume will be used for CTL manufacture to give at day 30 or beyond and the remaining 80% will be used for the primary transplant. For recipients of double CBT, if possible both CB units should be cryopreserved in two fractions and T-cells will be made from both units if possible. Inclusion Criteria at the Time of CTL Infusion Recipients of at least one unmanipulated cord blood unit as described above (i.e. from a HLA matched or mismatched unrelated donor) transplant at risk for or with CMV/Adenoviral/BKV and/or EBV infection or reactivation. Lansky/Karnofsky scores ≥60 Absolute neutrophil count (ANC) greater than 500/u No evidence of GVHD > Grade II at time of enrollment Life expectancy > 30 days Absence of severe renal disease (Creatinine < 3x normal for age) Absence of severe hepatic disease. Direct bilirubin must be < 3 mg/dl and AST < 5x upper limit of normal Patient must be at least 30 days post transplant to be eligible to receive CTL Written informed consent and/or signed assent line from patient, parent or guardian Exclusion Criteria: Exclusion Criteria at the Time of Procurement Pregnant or lactating Patients with active central nervous system disease Patients with Karnofsky performance status <70% Patients with grade 3 or 4 or primary myelofibrosis Patients with suitable related donors Exclusion Criteria at the Time of CTL Infusion Pregnant or lactating Patient on Fi02 of >60% Unable to wean steroids to ≤0.5 mg/kg/day prednisone or equivalent Patients with Grade 3 hyperbilirubinemia Patients with other uncontrolled infections (except CMV and/or adenovirus and/or EBVemia and/or BK viruria/viremia). For bacterial infections, patients must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to enrollment. For fungal infections patients must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection for 1 week prior to enrollment. Progressing infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection. Patients with less than 50% donor chimerism in either peripheral blood or bone marrow or patients with relapse of original disease Patients who have received investigational (IND) product within 28 days of screening for CTL infusion under this study 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: CMV/AdV /EBV/BKV specific T cells<br>CMV/AdV /EBV/BKV specific T cells will be thawed and transferred to a syringe given by slow intravenous injection over 1-2 minutes. Three dose levels will be explored. The lowest dose level will be 1x107cells/m2 and the highest will be 5x107/m2. | Biological: CMV/AdV /EBV/BKV specific T cells<br>* Each cohort of 2 patients will be treated and observed for 45 days for toxicity, dose escalation, and GvHD. The algorithm of sequentially adaptive EffTox trade-off-based design of Thall et al will be used to determine the dose for each cohort. If 1x107CTL/m2 results in unacceptable toxicity or efficacy, the study will be closed to accrual.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Number of participants with investigational product-related adverse events as assessed by CTCAE v4.03 | The study will determine the optimal dose of intravenous injection of donor-derived cytotoxic T lymphocytes (CTLs) specific for CMV, EBV, Adenovirus and BK virus( BKV) given to patients with or at risk for CMV, EBV, BK virus and adenovirus infection after cord blood transplant. The safety will be assessed by investigational product-related adverse events as per CTCAE v4.03. | 45 days for toxicity | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Impact of CMV/AdV /EBV/BKV specific T cells will be measured by existence of cells in the system. | To evaluate the impact of CTLs on CMV/AdV /EBV/BKV -specific T-lymphocyte immune reconstitution. The impact will be evaluated by the number of months/years of cell survival. | 12 months |

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Seasonal Influenza DNA Vaccine & Seasonal Influenza Trivalent Inactivated Vaccine (TIV) in Children & Adolescents Study Overview ================= Brief Summary ----------------- This is a Phase I, dose escalation study in healthy adolescents and children (6-17 years) to evaluate the safety, tolerability, and immunogenicity of a prime-boost regimen of the 2012/2013 seasonal influenza DNA vaccine (HA DNA) followed by licensed 2012/2013 TIV vaccine. The comparator groups will receive licensed 2012/2013 TIV as prime and boost. The hypothesis is that the 2012/2013 HA DNA prime-TIV boost regimen will be safe and result in a broader and more durable immune response than is observed in age-matched comparator TIV-TIV groups. Detailed Description ----------------- Vaccines are an effective way to prevent influenza infection. Each year the World Health Organization (WHO) and the U.S FDA recommend the influenza strains to include in the seasonal influenza vaccines. The licensed seasonal influenza vaccines are directed against 3 influenza virus strains: an influenza A H1N1, an influenza A H3N2, and an influenza B. The currently approved vaccines depend upon labor-intensive methods that limit manufacturing speed and capacity. Influenza vaccines that can be more rapidly produced and that induce stronger, broader and more persistent immune responses are a recognized public health need. In this protocol we will evaluate an investigational seasonal influenza (HA DNA) vaccine in healthy adolescents and children (6-17 years). Some participants will receive HA DNA vaccine prime followed by licensed trivalent influenza vaccine (TIV) boost 18 weeks later. Other participants will receive two TIV injections 18 weeks apart. The results will be compared. The HA DNA vaccine and TIV are both directed at the 3 influenza strains selected for the 2012/2013 vaccines. Prior studies in adults of avian and seasonal influenza DNA vaccines have been completed. The DNA vaccinations were assessed as safe and well tolerated in adults. The immune response to avian influenza is augmented by DNA vaccine priming compared to two vaccinations with the inactivated avian influenza (H5N1)vaccine when the prime-boost interval is 12-24 weeks, but not when the prime-boost interval is 4 weeks. Official Title ----------------- Open-Label, Dose-Escalation, Phase I Study of the Prime-Boost Investigational 2012/13 Seasonal Influenza DNA Vaccine, VRC-FLUDNA063-00-VP, Followed by the 2012/2013 Seasonal TIV Compared to TIV Prime-Boost in Children/Adolescents Ages 6-17 Conditions ----------------- Influenza Intervention / Treatment ----------------- * Biological: Seasonal Influenza DNA vaccine * Biological: TIV Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Children/adolescents aged 6 to 17 years inclusive and at least 20 kg in weight. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process. Willing to have blood drawn 5 times over 42 weeks, including blood stored for research purposes. In good general health as assessed by medical history, vital signs and targeted physical examination; stable medical conditions that, in the opinion of the investigator, will not compromise the subject's participation in the study are acceptable. Capability of the legal adult representative of the minor to understand and comply with planned study procedures. Capability of the legal adult representative of the minor to provide written informed consent; assent will be obtained from the child/adolescent per requirements of the site institutional review board (IRB). For female adolescent of child-bearing potential (as defined by onset of menses): agrees to avoid becoming pregnant and to use effective method of contraception or practice abstinence for at least 21 day prior to the first study vaccine administration, until at least 4 weeks after the second study vaccination. Within 70 days prior to enrollment, hemoglobin within institutional normal limits, creatinine less than the upper limit of normal (ULN) and ALT ≤1.5 X ULN for respective age group. Exclusion Criteria: History of Guillain-Barré syndrome. Active neoplasm or history of cancer. On-going immunosuppressive therapy or known to be immunosuppressed at the time of enrollment. Immunoglobulin (or similar blood product) therapy within 3 months prior to enrollment. Known to have HIV, hepatitis B or hepatitis C infection. Acute or chronic illness that, in the opinion of the investigator, precludes participation in the study. Developmental delay, neurologic disorder, or seizure disorder requiring ongoing medical management (note: history of febrile seizure is not an exclusion). Acute febrile and/or respiratory illness within one week prior to enrollment. Idiopathic urticaria within the year prior to enrollment. Allergy treatment with antigen injections, unless on maintenance schedule and allergy shots could be staggered with the study vaccinations, within 14 days (2 weeks) prior to enrollment. Asthma that is severe, unstable or required emergent care, urgent care, hospitalization or intubation during the previous two years or that is expected to require the use of oral, intravenous or high dose inhaled corticosteroids. Vaccination of any type within 2 weeks prior to enrollment or receipt of the 2012/2013 seasonal TIV any time prior to enrollment. Participating in or planning to begin participation in another investigational study during the projected time during which the subject would be in this study. Factors related to the legal representative that in the judgment of the investigator may affect the objective decision-making of the legal representative. For a female adolescent of child-bearing potential: breast-feeding, known pregnancy or positive urine or serum pregnancy test on day of study enrollment. Ages Eligible for Study ----------------- Minimum Age: 6 Years Maximum Age: 17 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: Group 1A (12-17yrs):1 mg DNA vaccine+TIV<br>2012/13 seasonal influenza DNA Vaccine (VRC-FLUDNA063-00-VP) at Day 0 and licensed 2012/13 TIV at Week 18±2 wks | Biological: Seasonal Influenza DNA vaccine<br>* VRC-FLUDNA063-00-VP is composed of 3 closed-circular DNA plasmids that encode for the hemagglutinin (HA) from the following 3 strains: A/California/04/2009 (H1); A/Victoria/361/2011 (H3), and B/Wisconsin/2010. DNA vaccine vials will be supplied at 4 mg/mL in single use vials. The 1 mg dosage is administered as 0.25 mL volume and the 4 mg dosage as a 1 mL volume.<br>* Other names: Seasonal influenza trivalent DNA vaccine;Biological: TIV<br>* 2012/13 Seasonal Influenza Trivalent Inactivated Vaccine (TIV)<br>* Other names: 2012/13 Seasonal Influenza Trivalent Inactivated Vaccine;| | Experimental: Group 1B (6-11yrs):1 mg DNA vaccine+TIV<br>2012/13 seasonal influenza DNA Vaccine (VRC-FLUDNA063-00-VP) at Day 0 and licensed 2012/13 TIV at Week 18±2 wks | Biological: Seasonal Influenza DNA vaccine<br>* VRC-FLUDNA063-00-VP is composed of 3 closed-circular DNA plasmids that encode for the hemagglutinin (HA) from the following 3 strains: A/California/04/2009 (H1); A/Victoria/361/2011 (H3), and B/Wisconsin/2010. DNA vaccine vials will be supplied at 4 mg/mL in single use vials. The 1 mg dosage is administered as 0.25 mL volume and the 4 mg dosage as a 1 mL volume.<br>* Other names: Seasonal influenza trivalent DNA vaccine;Biological: TIV<br>* 2012/13 Seasonal Influenza Trivalent Inactivated Vaccine (TIV)<br>* Other names: 2012/13 Seasonal Influenza Trivalent Inactivated Vaccine;| | Experimental: Group 2A (12-17yrs):4 mg DNA vaccine+TIV<br>2012/13 seasonal influenza DNA Vaccine (VRC-FLUDNA063-00-VP) at Day 0 and licensed 2012/13 TIV at Week 18±2 wks | Biological: Seasonal Influenza DNA vaccine<br>* VRC-FLUDNA063-00-VP is composed of 3 closed-circular DNA plasmids that encode for the hemagglutinin (HA) from the following 3 strains: A/California/04/2009 (H1); A/Victoria/361/2011 (H3), and B/Wisconsin/2010. DNA vaccine vials will be supplied at 4 mg/mL in single use vials. The 1 mg dosage is administered as 0.25 mL volume and the 4 mg dosage as a 1 mL volume.<br>* Other names: Seasonal influenza trivalent DNA vaccine;Biological: TIV<br>* 2012/13 Seasonal Influenza Trivalent Inactivated Vaccine (TIV)<br>* Other names: 2012/13 Seasonal Influenza Trivalent Inactivated Vaccine;| | Experimental: Group 2B (6-11yrs):4 mg DNA vaccine+TIV<br>2012/13 seasonal influenza DNA Vaccine (VRC-FLUDNA063-00-VP) at Day 0 and licensed 2012/13 TIV at Week 18±2 wks | Biological: Seasonal Influenza DNA vaccine<br>* VRC-FLUDNA063-00-VP is composed of 3 closed-circular DNA plasmids that encode for the hemagglutinin (HA) from the following 3 strains: A/California/04/2009 (H1); A/Victoria/361/2011 (H3), and B/Wisconsin/2010. DNA vaccine vials will be supplied at 4 mg/mL in single use vials. The 1 mg dosage is administered as 0.25 mL volume and the 4 mg dosage as a 1 mL volume.<br>* Other names: Seasonal influenza trivalent DNA vaccine;Biological: TIV<br>* 2012/13 Seasonal Influenza Trivalent Inactivated Vaccine (TIV)<br>* Other names: 2012/13 Seasonal Influenza Trivalent Inactivated Vaccine;| | Active Comparator: Group 3A: (12-17yrs): TIV+TIV<br>Licensed 2012/13 TIV at Day 0 and Week 18±2 wks | Biological: TIV<br>* 2012/13 Seasonal Influenza Trivalent Inactivated Vaccine (TIV)<br>* Other names: 2012/13 Seasonal Influenza Trivalent Inactivated Vaccine;| | Active Comparator: Group 3B: (6-11yrs): TIV+TIV<br>Licensed 2012/13 TIV at Day 0 and Week 18±2 wks | Biological: TIV<br>* 2012/13 Seasonal Influenza Trivalent Inactivated Vaccine (TIV)<br>* Other names: 2012/13 Seasonal Influenza Trivalent Inactivated Vaccine;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Incidence of solicited and unsolicited adverse events | Incidence is reported for solicited events for 7 days after each injection, for unsolicited adverse event (AE) of any severity for 28 days after each injection, and for serious adverse events or new chronic medical conditions through 24 weeks after the 2nd injection. | 7 days after injection for solicited events; from 1st injection to study completion for unsolicited events | | Mean change from baseline in safety laboratory measures | At day 28 (+/- 7 days) blood will be drawn prior to receiving the second injection to measure hemoglobin, creatinine, and alanine transaminase (ALT). | Day 28 | | Number of subjects with influenza or influenza-like illnesses | Participants who experience at least one influenza or influenza-like illness will be counted. | Day 0 through 24 weeks post TIV boost (Day 294) | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Proportion of subjects with either a baseline hemagglutination inhibition (HAI) titer <1:10 and post-vaccination HAI titer ≥1:40 or baseline HAI titer ≥1:10 and a minimum 4-fold rise in HAI titer for each of the 3 strains in the 2012/13 TIV at Week 22. | Blood is collected from all subjects at baseline and at 4 weeks after TIV boost(Week 22 +/- 7 days) for testing in an HAI assay for each of the 3 strains of influenza in the 2012/2013 TIV. | Week 22 (4 weeks after TIV boost) | | Proportion of subjects with a four-fold or greater rise from baseline (Day 0) and Week 22 in 2012/13 TIV specific H1, H3 and B neutralizing antibodies | Blood is collected from all subjects at baseline (Day 0) and 4 weeks after TIV boost (Week 22 +/- 7 days) for testing in a neutralizing antibody assays for 2012/13 strain-specific H1, H3 and B antigens. | Week 22 (4 weeks after TIV boost) | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Influenza A (H1), Influenza A (H3), Influenza B, DNA Vaccine, Trivalent Inactivated Vaccine (TIV), Healthy Adolescents, Healthy Children

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Evaluation of Novel Antimicrobial Hand Towels Study Overview ================= Brief Summary ----------------- In March 2012, the investigators initiated a prospective, cluster-randomized, controlled field trial in Kisumu County, located in an area in western Kenya which has the highest under-five mortality rate in Kenya with 149 childhood deaths per 1,000 live births 9. The study was designed to evaluate the effectiveness of an antimicrobial hand towel (hereafter referred to as towel) in preventing diarrheal diseases, acute respiratory infections, self-reported fever, and skin infections in children <2 years old. Detailed Description ----------------- In March 2012, the investigators initiated a prospective, cluster-randomized, controlled field trial in Kisumu County, located in an area in western Kenya which has the highest under-five mortality rate in Kenya with 149 childhood deaths per 1,000 live births 9. The study was designed to evaluate the effectiveness of an antimicrobial hand towel (hereafter referred to as towel) in preventing diarrheal diseases, acute respiratory infections (ARIs), self-reported fever, and skin infections in children <2 years old. Official Title ----------------- Evaluation of Novel Antimicrobial Hand Towels Conditions ----------------- Fever, Diarrheal Diseases, Acute Respiratory Infections, Skin Infection Intervention / Treatment ----------------- * Other: Antimicrobial Hand Towel Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Mother of a child <2 years old Exclusion Criteria: Inaccessible enumeration area in the rainy season Multiple eligible children in a single compound Moved between census and round 1 Sexes Eligible for Study ----------------- Female 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 | | --- | --- | | No Intervention: Comparison<br>Hand hygiene education. | | | Experimental: Intervention<br>Hand hygiene education and 4 antimicrobial hand towels | Other: Antimicrobial Hand Towel<br>* Novel antimicrobial hand towel.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Number of participants with diarrheal disease | The number of participants that experience 3 or more loose or watery stools | Within 48 hours of enrollment | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Number of participants with respiratory infections | | Within 48 hours of enrollment | | Number of participants with a subjective fever | | Within 48 hours of enrollment | | Number of participants with a skin infection | | Within 48 hours of enrollment |

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The RECHARGE Low Carbohydrate Diet Trial for Metastatic Cancer Study Overview ================= Brief Summary ----------------- This study is for people whose cancer: has resisted chemotherapy are taking a break from chemotherapy or are looking for an alternative to the toxic effects of chemotherapy The trial is looking to see if a very low carbohydrate diet can inhibit the growth of certain cancers. The two major goals of the RECHARGE study are to determine: whether a very low carbohydrate diet can help participants reduce the amount of cancer in their bodies (as measured by a PET scan at the beginning and end of the study) whether participants can feel well while maintaining their weight on a very low carbohydrate diet This research study is for people with advanced cancers who decline chemotherapy or want to take a break from chemotherapy and have cancers that primarily feed on blood sugar. Examples of such cancers include metastatic breast cancer, colon cancer, cervical and uterine cancers, ovarian cancers, and many others. The investigators' intervention consists of a 28-day diet of high protein foods such as fish, poultry, meats, eggs and cheese as well as plenty of vegetables. Participants may eat as much of the high protein foods as they wish and can eat up to two cups of vegetables per day. Participants strictly eliminate carbohydrate-containing foods. These foods include all starches and sweets (breads, pasta, rice, potatoes, cereals, fruit, cakes, candies, soda with sugar, etc.). Detailed Description ----------------- You may be eligible to participate in this one month research study if you are: An adult with metastatic cancer (especially breast, colon, cervical, endometrial, ovarian; others may qualify) that has resisted prior attempts to treat it with courses of chemotherapy; or if you decline chemotherapy or are looking for a break, or you seek an alternative to medicines or therapies due to toxic effects. Your tumor has shown up on a PET scan. Willing to closely follow a diet and strictly limit your carbohydrate intake. You will not be eligible to participate if you: Have heart or liver condition or any other disease or condition that makes it difficult or medically hazardous (determined by your doctor) for you to follow the diet recommended for this study. Have kidney or kidney stone disease. Procedures: We will obtain a PET/CT scan to determine your eligibility if you are otherwise interested in this protocol. We will also obtain a second PET/CT scan at the end of the dietary trial (28 days). We will also obtain blood and urine tests at weekly intervals during the trial. Visits and contacts: We will see you once/week for four weeks on the Albert Einstein, or Montefiore Medical Center Campus (your choice) for a total of 5 visits, and will call you on the phone at least one additional time each week. The first visit will take approximately one hour or as long as is needed to understand the diet correctly. The remaining visits will take approximately one-half hour. The PET/CT scan will take approximately 25 minutes in the camera. Waiting time varies for the procedure but is usually less than 20 minutes. Compensation: Low carbohydrate supplement shakes will be given to all participants. All procedures and visits are without cost to the subject. There are no funds for direct compensation. Description of the Intervention: The diet will severely restrict carbohydrates (that is, NO sugars or starches; no bread, pasta, rice, sugary drinks, potatoes or potato chips, cake, cookies, ice cream, etc). You will be allowed to eat AS MUCH AS YOU LIKE of foods that have very small amounts of carbohydrate, such as eggs, beef, poultry, fish, salads (except potatoes and other starchy vegetables). Official Title ----------------- Pilot Feasibility Study Of A Low Carbohydrate Diet In Patients With Advanced Cancer Conditions ----------------- Cancer, Breast Cancer, Colon Cancer, Cervical Cancer, Uterine Cancer, Ovarian Cancer Intervention / Treatment ----------------- * Behavioral: Very low carbohydrate diet (approximately 20 grams per day) Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: You're an adult with metastatic cancer (breast, colon; others may qualify) that has been resistant to chemotherapy or would like a break from chemotherapy. Your tumor shows up on a PET or PET/CT scan. You are willing to closely follow a diet which strictly limits your carbohydrate intake (sugars, starches, etc). We will help you with nutrition counseling but you must prepare your meals, or have someone help you prepare your meals. You are able to come to the Albert Einstein College of Medicine in Bronx, NY for an initial evaluation appointment and weekly nutrition counseling appointments for a four-week period. Exclusion Criteria: Have a heart condition, liver condition or any other disease or condition that makes it difficult or medically hazardous (as determined by your doctor) for you to follow the study diet. Have kidney or kidney stone disease. Are too thin or have lost too much weight. 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 Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Dietary modification<br>Patients are placed on a low carbohydrate diet (<30 grams/day) for 28 days. | Behavioral: Very low carbohydrate diet (approximately 20 grams per day)<br>* Very low carbohydrate diet for a duration of four weeks.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in tumor FDG uptake from PET/CT imaging over a 28 period. PET is done at baseline and 28 days | | 28 day trial | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Safety of a very low carbohydrate diet in individuals with metastatic cancer | | 28 days | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Diet, Cancer, Alternative, Breast, Colon, Cervix, Uterus, Ovary, Metastatic, Nutrition, Carbohydrate

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An Efficacy and Safety Study to Assess [18F]-ML-10 in Detecting Response of Tumors to Chemotherapy and Radiation Study Overview ================= Brief Summary ----------------- The purpose of this study is to determine whether [18F]-ML-10 used in conjunction with PET imaging is effective as an imaging tool for the early detection of response of oncological tumors in the lungs,head and neck to chemoradiation therapy. The study will evaluate the potential of [18F]-ML-10 used in conjunction with PET imaging to distinguish early during the course of chemoradiation therapy between a tumor that responds to the therapy, and a tumor that does not respond to the therapy. Currently, this distinction is available to the physician several weeks or months after completion of therapy, using anatomical imaging (for example Computed Tomography [CT] or Magnetic Resonance Imaging [MRI]). Official Title ----------------- A Prospective, Multicenter Study, to Evaluate the Efficacy and Safety of [18F]-ML-10, a Positron Emission Tomography (PET) Imaging Radiotracer, in Early Detection of Response of Non-Hematological Tumors to Concurrent Chemoradiotherapy Conditions ----------------- Carcinoma, Non-Small-Cell Lung, Head and Neck Neoplasms Intervention / Treatment ----------------- * Other: [18F]-ML-10 in conjunction with PET imaging Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Male or female patients with either: Newly diagnosed non small cell lung cancer (NSCLC) (Group A) who meet the following criteria: Previously untreated, histologically or cytologically confirmed stage IIB, IIIA or IIIB disease, without evidence of distant metastases A measurable primary tumor with at least one diameter > 2 cm or primary tumor extending to one or more lymph nodes which cannot be distinctively delineated as confirmed by a diagnostic quality chest CT performed within 4 weeks prior to initiation of the concurrent CRT. Planned to receive concurrent chemoradiotherapy as definitive treatment. The radiation dose should not exceed 70 Gy. Undergone the following minimum workup to confirm disease staging within 4 weeks prior to initiation of the concurrent CRT: GBCA-enhanced Brain MRI or contrast enhanced CT if there are signs or symptoms suggesting brain metastases within the past 2 months. If necessary to confirm stage of disease, an upper abdomen CT scan will be performed. whole-body FDG PET/CT; OR Newly diagnosed squamous cell carcinoma of the head and neck (SCCHN) (Group B) who meet the following criteria: Previously untreated, histologically or cytologically confirmed (from the primary tumor and/or lymph nodes) stage III-IV disease without evidence of distant metastases. A measurable (i) primary tumor with at least one diameter ≥2 cm and (ii) lymph node with at least one diameter ≥ 2 cm as confirmed by a diagnostic quality neck CT performed within 4 weeks prior to initiation of the concurrent CRT. Planned to receive concurrent chemoradiotherapy as definitive treatment. The radiation dose should not exceed 70 Gy. Have undergone the following minimum workup to confirm disease staging within 4 weeks prior to initiation of the concurrent CRT: Whole-body FDG PET/CT. Patients ≥ 18 years of age. Able to comply with lying still during the PET/CT imaging session which may last for up to 3 hrs with intermediate breaks. ECOG performance status of 0, 1 or 2. Adequate renal function and adequate hepatic function, as assessed by standard laboratory criteria and defined as: Serum creatinine ≤ 1.2 times the Upper Limit of Normal (ULN). Total bilirubin ≤ 1.5 times the ULN. Asparagine aminotransferase (AST) and/or alanineaminotransferase (ALT) ≤ 2.5 times the ULN (grade 1 according to the NCI-CTCAE v.3). Women of child-bearing potential must have a negative blood pregnancy test at screening and use an adequate and medically acceptable contraceptive method. Willing and able to comply with the protocol requirements. Able to provide written informed consent. Exclusion Criteria: Exclusion criteria specific to patients with NSCLC (Group A): Predominant small cell carcinoma histology. Pure bronchioalveolar cell carcinoma histology. Treatment planned with chemotherapy other than a platinum-based doublet regimen. Malignant pleural or pericardial effusions. Any contraindication to perform CT with IV contrast agent. Exclusion criteria specific to patients with SCCHN (Group B): Histology other than squamous cell carcinoma. Treatment planned with chemotherapy other than a platinum-based regimen. Treatment planned with cetuximab. Treatment with induction chemotherapy. Any contraindication to CT with IV contrast agent. Evidence of distant metastases. Patients who, based on the investigator's judgment, have other unstable medical conditions that may preclude safe and complete study participation. Treatment with any investigational drug, device or biologic agent within 30 days prior to administration of [18F]-ML-10. Pregnancy or lactation. 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 | | --- | --- | | Experimental: [18F]-ML-10<br> | Other: [18F]-ML-10 in conjunction with PET imaging<br>* Subjects will receive two to three intravenous (IV) doses of [18F]-ML-10. The dose for each [18F]-ML-10 dose will be 5.50 MBq/Kg or 0.15 mCi/Kg but will not exceed 500.00 MBq (13.50 mCi) per administration.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | To characterize changes in [18F]-ML-10 uptake in the target lesion in response to chemoradiotherapy. | | Between baseline and day 11 ± 1, and between baseline and day 18 ± 1 | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | To assess the correlation between the changes in the uptake of [18F]-ML-10 in the target lesion and the changes in the anatomical dimensions of the target lesion. | To assess the correlation between the changes in the uptake of [18F]-ML-10 in the target lesion following an accumulative radiation dose of 14.4-20.0 Gy, and the changes in the anatomical dimensions of the target lesion, as assessed by the follow-up anatomical imaging by CT, performed after completion of the concurrent chemoradiotherapy (CRT). | | | To identify at least one parameter, derived from the changes in [18F]-ML-10 uptake that can discriminate tumors responsive to treatment from tumors that are non-responsive. | For this parameter, various cut-off values of change will be evaluated, with corresponding estimates of sensitivity and specificity. | | | To perform additional analyses for all other lesions and lymph nodes with at least one diameter ≥ 2 cm treated by concurrent CRT. | | | | To assess the safety of [18F]-ML-10 administered to cancer patients receiving concurrent CRT. | | | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Carcinoma, non-small-cell lung, Head and neck neoplasms, Diagnostic imaging

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Transection of Sternothyroid Muscle Increases the Rate of Exposure of the External Laryngeal Nerve During Thyroidectomy Study Overview ================= Brief Summary ----------------- The sternothyroid (ST) muscle is closely adherent to the thyroid gland with oblique insertion into the thyroid cartilage. EBSLN passes through the sternothyroid laryngeal triangle with a parallel course deep to the ST muscle. This study evaluates the transection of the sternothyroid muscle as a key step during thyroidectomy to increase the rate of exposure and visual identification of EBSLN compared to ST muscle retraction as a traditional technique. Detailed Description ----------------- The study was conducted on patients eligible for total thyroidectomy, which meets the standard of the ATA Thyroid Guidelines. Preoperative biochemical thyroid function tests and neck ultrasound with FNAC of suspicious nodules confirmed the clinical diagnosis. Patients who had previously undergone neck surgery or irradiation or were preoperatively diagnosed with a vocal cord movement disorder, a vocal cord benign lesion, or speech disorders were excluded from the study. A random number was used to determine the patient group allocation. Data about patients were gathered via history, examinations, and investigations. The patients were randomized (computer-generated) with the use of an opaque-sealed envelope into two groups; group A: conventional method of thyroidectomy with ST muscle retraction, group B: transection of ST muscle. The study's primary endpoint was the identification rate of the EBSLN in both techniques. The secondary endpoints included: a comparison of operative time in both techniques as well as anatomical variability of the EBSLN according to Cernea classification, rate of injury of EBSLN, and changes in postoperative voice performance. Official Title ----------------- Transection of Sternothyroid Muscle Increases the Rate of Exposure of the External Branch of the Superior Laryngeal Nerve During Thyroidectomy Conditions ----------------- Thyroid, Surgery, Thyroid Disease Intervention / Treatment ----------------- * Procedure: thyroidectomy Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: eligible for total thyroidectomy no previous history of neck surgery or radiation no vocal cord pathology no voice disorders Exclusion Criteria: not fit for surgery previous history of neck surgery or radiation vocal cord pathology vocal cord movement disorders Ages Eligible for Study ----------------- Minimum Age: 15 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 Masking: Quadruple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: conventional approach of thyroidectomy<br>conventional method of thyroidectomy with ST muscle retraction | Procedure: thyroidectomy<br>* removal of the diseased thyroid gland by conventional method vs transection method of sternothryroid muscle<br>| | Active Comparator: transection approach of thyroidectomy<br>method of thyroidectomy with ST muscle transection | Procedure: thyroidectomy<br>* removal of the diseased thyroid gland by conventional method vs transection method of sternothryroid muscle<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | rate of identification and exposure of the external laryngeal nerve during thyroidectomy | | 1 year |

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Evaluation of Impaired Microcirculation During Septic Shock With Contrast Enhanced Ultrasound Study Overview ================= Brief Summary ----------------- Microcirculatory disorders play a central role in the pathogenesis of sepsis and septic shock. Without adequate therapy that may lead to multi-organ failure and death. Therefore useful therapeutic measures aim to improve the microcirculation, to avoid tissue hypoxia and thus multiple organ failure or death. Clinically, the microcirculation can currently be indirectly evaluated using the diuresis and metabolic parameters (eg, lactate). The aim of the present study is to measure the microcirculation in septic shock by means of contrast-enhanced sonography of the calf muscles. For this purpose, the method is applied to 24 subjects during and after septic shock. It will be investigated in this study whether the microcirculation measurement with ultrasound contrast reflects the severity of the disease. As well as to evaluate whether the use of this diagnostic method could lead to better treatment of the septic shock. Official Title ----------------- Messung Von Mikrozirkulationsstörungen im Septischen Schock Mit Kontrastmittel- verstärkter Sonographie Evaluation of Impaired Microcirculation During Septic Shock With Contrast Enhanced Ultrasound Conditions ----------------- Sepsis Intervention / Treatment ----------------- * Other: Contrast enhanced ultrasound Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: septic shock Exclusion Criteria: myocardial infarction 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 | | --- | --- | | Experimental: Contrast enhanced ultrasound<br>Contrast enhanced ultrasound during septic shock | Other: Contrast enhanced ultrasound<br>* Contrat enhanced ultrasound during septic shock<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Contrast transit time during and after septic shock | | 24 months | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- sepsis, septic shock, contrast-enhanced ultrasound, microcirculation

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Dermal Cryotherapy in Patients Undergoing Abdominoplasty Study Overview ================= Brief Summary ----------------- A prospective, interventional, single-arm study to evaluate histologic changes in skin following cryotherapy with the study device. Detailed Description ----------------- This study is to include healthy adults who intend to undergo an abdominoplasty surgery, and agree to have small areas of their middle and lower abdomen exposed to cooling with the Dermal Cooling System within 180 days before the planned surgery. Exposure of multiple test sites will be completed in areas of skin that will be excised as part of the abdominoplasty procedure. Clinical assessments of the treatment sites at 1-week post-treatment and at 1-month post-treatment intervals throughout the time period prior to surgical excision, and histologic evaluation of the treated skin will be conducted to assess skin changes. Official Title ----------------- Dermal Cryotherapy in Patients Undergoing Abdominoplasty Conditions ----------------- Skin Laxity Intervention / Treatment ----------------- * Device: Dermal Cooling System Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Male or female subjects > 18 years of age. Subjects eligible, consented, and scheduled for abdominoplasty. Subject is willing to use photoprotection (e.g., sun avoidance) of the treated areas during the duration of the follow-up period. Subject has read and signed a written informed consent form. - Exclusion Criteria: Subject has medical or surgical treatment in the area of intended treatment in the previous 6 months (e.g., liposuction, mesotherapy, hydroquinone, corticosteroids, laser surgery). Subject has a known history of subcutaneous injections into the abdomen within the past six months (e.g., insulin, Enbrel). Subject has a known history of illness or adverse reaction to cold insult (e.g., cryoglobulinemia, cold urticaria, paroxysmal cold hemoglobinuria, Reynaud's disease). Subject is taking methylxanthines (phosphodiesterase-inhibitors like amino- or theophylline) Artificial tanning in the area of intended treatment within 1 month (e.g., spray, lotion, tanning bed) or intention to use artificial tanning within the follow-up period. Subject is unable or unwilling to comply with the study requirements. Subject has any dermatological conditions or scars (other than stretch marks) within the area of planned abdominoplasty excision that may interfere with the ability to obtain test sites for treatment or evaluation. Subject has a history of abnormal wound healing or abnormal scarring. Subject is currently enrolled in a clinical study of any other unapproved investigational drug or device. Patient is pregnant or intending to become pregnant within the next 6 months. Patient is lactating or has been lactating in the past 9 months. Any other condition or laboratory value that would, in the professional opinion of the investigator, potentially affect response or participation in this clinical study, or would pose an unacceptable risk to the patient. 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: Treatment with cryotherapy<br>Treatment with dermal cooling system. | Device: Dermal Cooling System<br>* Treatment with dermal cooling system.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Histologic evaluation of treated skin | Identify a range of treatment parameters which elicits a response in melanocytes based upon histologic assessments. | 1-180 days | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Access device or procedure-related adverse events | Assess adverse events and side effects. | 1 - 180 days |

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Colon Cancer Surgery in the Aged; Postoperative Outcome, Functional Recovery and Survival. Study Overview ================= Brief Summary ----------------- Patients aged > 80 years represent an increasing proportion of colon cancer diagnoses. It is important to have relevant and trustable data concerning elderly colorectal cancer patients surgery and postoperative morbidity, functional ability, life quality and survival numbers. With possibly compromised health status and functional decline the benefits of surgical management and outcomes can diminish life quality and overall survival. With proper patients selection, preoperative health evaluation and thus patient information, colorectal cancer surgery can be performed with lower morbidity and mortality rates with comparative survival numbers. The aim of this prospectively collected, observational study is to acquire data from colorectal cancer surgery in aged over 80 years and perform statistical analysis of the preoperative risk factors affecting postoperative morbidity, functional recovery, mortality and overall survival. Detailed Description ----------------- 9 Finnish hospitals including three university hospitals participate in the study. The data is collected from the hospitals using a specially designed and secure web application (RedCap). The preoperative patients' data include comorbidities, clinical frailty scale (CFS) and functional status, postoperative surgical and medical outcomes and survival data. The patient questionnaire is based on the G-8 geriatric screening tool and MNA-short form. The questionnaire is filled out preoperatively and 1, 3, 6 and 12 months postoperatively. The patient data concerning procedures is collected from the hospitals prospectively recording data. Mortality data on causes of death are obtained from Statistics Finland. All colon cancer patients aged over 80 years with curative disease (stage I-III) are included. Patients with metastatic disease or severe Alzheimer disease are excluded. They are treated either non-operatively or with curative resection or palliative procedure. Patients fill out the approval form. The study is acknowledged by the ethics committee of the participating hospitals. Official Title ----------------- Colon Cancer Surgery in the Aged; Postoperative Outcome, Functional Recovery and Survival Conditions ----------------- Colon Cancer Intervention / Treatment ----------------- * Procedure: Curative operation Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: primary colon cancer, which is surgically treated with curative intent (stage I-III) Exclusion Criteria: metastatic colon cancer, severe dementia, life expectancy less than six months Ages Eligible for Study ----------------- Minimum Age: 80 Years Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Intervention/Treatment | | --- | |Procedure: Curative operation|Postoperative morbidity, mortality, functional outcome, survival| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Postoperative morbidity | Clavien-Dindo classification (0-V) | 30 days | | Postoperative mortality | Date of death | 12 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Functional performance | Patient questionnaire ( nutritional status, mobility, use of implements, medication, weight, housing, homeaid), scale 0-3; 0= no, 1= sometimes, 2= often, 3= always | 12 months | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Colon cancer surgery octogenarian postoperative outcome

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Dose-finding Study of SPK-8016 Gene Therapy in Patients With Hemophilia A to Support Evaluation in Individuals With FVIII Inhibitors Study Overview ================= Brief Summary ----------------- SPK-8016 is in development for the treatment of patients with inhibitors to FVIII. This Phase 1/2, open-label, non-randomized, dose-finding study is part one of a planned two part study of SPK-8016. Part one will evaluate the safety, efficacy, and tolerability of SPK-8016 in adult males with clinically severe hemophilia A and no measurable inhibitor against FVIII. Data obtained from Part 1 will inform the study design and dose selection for Part 2 in patients with FVIII inhibitors. Official Title ----------------- Dose-finding Study of SPK-8016 Gene Therapy in Patients With Hemophilia A to Support Evaluation in Individuals With FVIII Inhibitors Conditions ----------------- Vector, Adeno-Associated Virus (AAV), Blood Coagulation Disorder, Blood Coagulation Disorders, Inherited, Coagulation Protein Disorders, Factor VIII (FVIII), Factor VIII (FVIII) Deficiency, Factor VIII (FVIII) Gene, Factor VIII (FVIII) Protein, Genetic Diseases, Inborn, Genetic Diseases, X-Linked, Gene Therapy, Gene Transfer, Hematologic Diseases, Hemorrhagic Disorders, Recombinant, Inhibitors Intervention / Treatment ----------------- * Genetic: SPK-8016 Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria for Part 1: Be male and ≥18 years of age; Have clinically severe hemophilia A, defined as: <1% (<1 IU/dL) endogenous FVIII activity levels as historically documented by a certified laboratory or screening data results; OR 1-2% (1-2 IU/dL) endogenous FVIII activity levels and > 10 bleeding events per year (in the last 52 weeks prior to screening); OR 1-2% (1-2 IU/dL) endogenous FVIII activity levels and on prophylaxis; Have had >150 exposure days (EDs) to any recombinant and/or plasma-derived FVIII concentrates or cryoprecipitates Have no prior history of hypersensitivity or anaphylaxis associated with any FVIII or IV immunoglobulin administration Have no measurable inhibitor against FVIII as assessed by central laboratory, have no confirmed history of clinically significant FVIII inhibitor, and no clinical signs or symptoms of decreased response to FVIII administration (Note: family history of inhibitors will not exclude study participation) Agree to use reliable barrier contraception after the administration of SPK-8016 until notified by the Investigator. Exclusion Criteria for Part 1: Have active hepatitis B or C Have significant underlying liver disease. Have serological evidence of HIV-1 or HIV-2 with CD4 counts ≤200/mm3. Participants who are HIV-positive and stable, with an adequate CD4 count (>200/mm3) and undetectable viral load, and are on an antiretroviral drug regimen are eligible to enroll Have detectable antibodies reactive with AAV-Spark capsid Have history of chronic infection or other chronic disease Have been dosed in a previous gene therapy research trial within the last 52 weeks or with an investigational drug within the last 12 weeks Any concurrent clinically significant major disease (such as liver abnormalities or type I diabetes) or other condition that, in the opinion of the Investigator and/or Sponsor, makes the subject unsuitable for participation in the study; Unable or unwilling to comply with the schedule of visits and study assessments described in the clinical protocol. Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- Male 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: SPK-8016<br>All participants who meet the eligibility criteria will receive an outpatient single intravenous (i.v.) administration of SPK-8016. | Genetic: SPK-8016<br>* adeno-associated viral vector<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Number of study-related adverse events, including clinically significant abnormal laboratory values. | Adverse events. | 52 weeks | | Occurrence of hepatic transaminase elevation requiring immunosuppression. | Number of incidences of hepatic transaminase elevation where immunosuppression is required. | 52 weeks | | Number of bleeding events (spontaneous and traumatic) after vector administration. | Bleeding events. | 52 weeks | | Number of FVIII infusions after vector administration. | FVIII infusions. | 52 weeks | | Peak and steady-state FVIII activity levels. | Peak and steady-state FVIII activity levels assessed by coagulation clotting assays. | 52 weeks | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Vector shedding of SPK-8016 in bodily fluids. | Vector shedding. | 52 weeks | | Incidence of immune response to AAV capsid protein and transgene product. | | 52 weeks |

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Role of Color Doppler Ultrasonography in Assessment of Vascular Access Surveillance in Hemodialysis Patients. Study Overview ================= Brief Summary ----------------- The aim of this study is to provide an overview of the possible applications of DUS during the maturation and postoperative follow-up of vascular access, with particular emphasis to establish a relationship between doppler Ultrasound parameters including: Flow volume. Outflow vein diameter. Outflow vein depth. Resistive index. Official Title ----------------- Role of Color Doppler Ultrasonography in Assessment of Vascular Access Surveillance in Hemodialysis Patients. Conditions ----------------- Arteriovenous Fistula Intervention / Treatment ----------------- * Device: doppler ultrasound Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: ESRD patients on dialysis with heamodialysis vascular access with adult age group (18 years and above). Exclusion Criteria: Patients with chronically occluded vascular access with failed surgical or interventional attempts. 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 | | --- | |Device: doppler ultrasound|a 7.5 MHz ultrasound (US) linear probe is needed, grey-scale ultrasound and Color Doppler and a minimum display facility of the Doppler velocity spectrum for blood flow calculation are mandatory tools.| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Maturation of arteriovenous fistulas | Assess the role of grey scale and color Doppler US in the early detection of failure in the hemodialysis vascular access. Maturation and monitoring\ surveillance of arteriovenous fistula. | 6 weeks duration follow up |

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Dietary Quality During Adolescence is Associated With Mother's Dietary Quality During Pregnancy Study Overview ================= Brief Summary ----------------- We will examine the association between diet quality in offspring at age 14 years and maternal diet quality during pregnancy in the Danish National Birth Cohort Detailed Description ----------------- Background: Dietary exposures in fetal life may have long lasting impact on the individual's susceptibility for several non-communicable diseases. Although offspring's own dietary habits become increasingly independent from parental influence other external factors are likely to exist. Further insights are needed to interpret and separate potential influence from exposures in pregnancy from later dietary habits on later disease risk. Objectives: We will examine the association between diet quality in offspring at age 14 years and maternal diet quality during pregnancy in the Danish National Birth Cohort (DNBC). Design: A total of 19620 DNBC offspring-mother pairs will be matched by offspring dietary intake assessed at age 14 years with a 150-item food frequency questionnaire (FFQ) and dietary intake assessed with a 300-item FFQ during mid-pregnancy (1996-2003). A Healthy Eating Index (HEI) will be developed as an indicator for diet quality based on current Danish Food-Based Dietary Guidelines including 8 components; fruit and vegetables, fish, dietary fibers, red meat, saturated fatty acids, sodium, sugar-sweetened beverages, and added sugar. Official Title ----------------- Dietary Quality During Adolescence is Associated With Mother's Dietary Quality During Pregnancy: 15 Years Follow up From a Large National Birth Cohort Conditions ----------------- Eating Behavior Intervention / Treatment ----------------- * Behavioral: Observational Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Participants in the Danish National Birth Cohort Exclusion Criteria: If mother did not complete a food frequency questionnaire during pregnancy Ages Eligible for Study ----------------- Minimum Age: 14 Years Maximum Age: 14 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 | | --- | --- | | Danish National Birth Cohort<br> | Behavioral: Observational<br> <br> | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Diet quality | Healthy Eating Index depicting diet quality | Reported intake during one year | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- diet quality, pregnancy, adolescence, longitudinal study, food frequency questionnaire

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Study to Evaluate Efficacy and Safety of Wound Dressing Solution Containing EGF in Patients With Peptic Ulcers Bleeding Study Overview ================= Brief Summary ----------------- This is a prospective, single-blinded, randomized study to evaluate the efficacy and safety of CEGP003 in patients with acute peptic ulcers bleeding, compared to endoscopic epinephrine injection therapy. Detailed Description ----------------- CEGP003 is wound dressing solution containing Hydroxyethyl-cellulose and EGF. Epidermal growth factor (EGF) stimulates cell growth and differentiation by binding to its receptor, which can enhance wound healing and regeneration of new tissue, finally may provide a new option in treating a peptic ulcers bleeding. Official Title ----------------- Clinical Study to Evaluate Efficacy and Safety of CEGP003(Wound Dressing Solution Containing EGF) for Achieving Hemostasis and Protecting Ulcer in Patients With Acute Peptic Ulcer Bleeding: A Prospective, Randomized Trial Conditions ----------------- Peptic Ulcer Bleeding Intervention / Treatment ----------------- * Device: CEGP003 * Device: Injection Tx Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Peptic ulcer with high-risk stigmata of recent hemorrhage (Forrest class IA, IB, IIA and IIB) Exclusion Criteria: Subjects who have a history of malignant tumor in upper gastro-intestinal site Subjects with platelet and coagulation dysfunction (PLT < 50E9/L, INR > 2) Subjects that have taken anticoagulant drugs or non-steroidal anti-inflammatory drugs within 72 hours after the treatment Subjects with one or more bleeding sources Subjects who are pregnant or breast-feeding Subject who are allergic or have a hypersensitive reaction to Hydroxyethyl-cellulose or EGF Subjects who have undergone endoscopically therapies within the last 7 days Subjects who are considered not suitable for the study by significant disease Subjects who are not able to comply with the study requirements Subjects who are currently enrolled in another clinical study which can impact the study within 30 days of screening Subjects who are considered not suitable for the study by the investigator Ages Eligible for Study ----------------- Minimum Age: 20 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: CEGP003<br> | Device: CEGP003<br>* Application of CEGP003 to peptic ulcer bleeding<br>* Other names: EGF;| | Active Comparator: Injection Tx<br> | Device: Injection Tx<br>* Injection of epinephrine to peptic ulcer bleeding<br>* Other names: epinephrine injection;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Initial hemostasis rate | Endoscopically verified cessation of bleeding for at least 10 minutes after treatment. | Within 10 minutes after first endoscopy session | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Recurrent bleeding rate | If any of the following conditions are met, an endoscopy will verify for rebleeding. Associated with overt signs of GI bleed (melena, and/or hematemesis) Instability of Vital signs (<80/60 mmHg of blood pressure, and/or >120 beats/min of pulse) Decrease in hemoglobin of at least 2 g/dl after Initial hemostasis bleeding can be confirmed directly (direct visualization) | Within 72 hours | | Time required for treatment | The time from when the endoscope is inserted to when the endoscope treatment is completed. | 0 day | | Wound healing effect of peptic ulcer | Evaluation of Stage Classification of Gastric Ulcer by Sakita-Miwa. | After 3 days (72 hours) | | Usability for the delivery system | Evaluation of success for the delivery system | 0 day | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Bleeding

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The PK/PD Study of SHR7280 Tablets in Healthy Subjects. Study Overview ================= Brief Summary ----------------- The primary objective of this study is to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of SHR7280 tablets in healthy subjects. Detailed Description ----------------- GNRH antagonists can be used to treat sex hormone-dependent diseases, and SHR7280 is an oral GNRH antagonist. The purpose of this study is to observe the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple oral doses of SHR7280 in healthy subjects. Official Title ----------------- A Randomized, Double-blind, Dose-escalation, Placebo-controlled Phase I Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Oral Doses of SHR7280 Tablets in Healthy Subjects. Conditions ----------------- Healthy Subjects Intervention / Treatment ----------------- * Drug: SHR7280 * Drug: Placebo oral tablet Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: PART 1: Healthy males , aged 18-65; BMI 18 30 kg/m2; Subjects in general good health. No clinically significant findings in Physical examination and auxiliary examination. PART 2: premenopausal females, aged 18-45; BMI 18 30 kg/m2; Subjects in general good health. No clinically significant findings in Physical examination and auxiliary examination. Exclusion Criteria: PART 1 Testosterone (T) < 12 nmol/L; ALT or AST or total bilirubin exceeds the upper limit of normal; Those with positive nicotine test and alcohol breath test before administration, and those with positive drug screening before administration; Use of any medication within 1 month before administration; or use of medication that does not exceed 5 half-lives, whichever is longer; Subjects with chronic diseases or serious diseases that affect drug absorption, distribution, metabolism and excretion; Blood donation or donation of blood components within 1 month before screening, or loss of blood equivalent to at least 200 mL, or transfusion within 2 months; Use of GnRH agonists and GnRH antagonists within 6 months before screening and use of any androgens and antiandrogens within 5 half-lives before screening; Subjects with severe infection, severe trauma or major surgery within 6 months before screening; Positive results of infectious disease screening . Allergic constitution or allergy to two or more kinds of food and drugs, including known history of allergy to the study drug or any component of the study drug. PART 2: Pregnant or breast feeding; FSH≥25U/L; Positive serum pregnancy test (serum β-HCG test) result; Abnormal uterine bleeding within 3 months prior to screening ALT or AST or total bilirubin exceeds the upper limit of normal; Those with positive nicotine test and alcohol breath test before administration, and those with positive drug screening before administration; Use of any medication within 1 month before administration; or use of medication that does not exceed 5 half-lives, whichever is longer; Subjects with chronic diseases or serious diseases that affect drug absorption, distribution, metabolism and excretion; Blood donation or donation of blood components within 1 month before screening, or loss of blood equivalent to at least 200 mL, or transfusion within 2 months; GnRH agonist use 6 months prior to Screening and GnRH antagonist or any sex hormone use 2 months prior to Screening. Subjects with severe infection, severe trauma or major surgery within 6 months before screening Positive results of infectious disease screening . Allergic constitution or allergy to two or more kinds of food and drugs, including known history of allergy to the study drug or any component of the study drug. 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: Randomized Intervention Model: Parallel Assignment Masking: Quadruple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: SHR7280 dose 1(male)<br>oral administration for 14 days,Phase I(PART 1) | Drug: SHR7280<br>* treatment<br>Drug: Placebo oral tablet<br>* blank control<br>| | Experimental: SHR7280 dose 2(male)<br>oral administration for 14 days,Phase I(PART 1) | Drug: SHR7280<br>* treatment<br>Drug: Placebo oral tablet<br>* blank control<br>| | Experimental: SHR7280 dose 3(male)<br>oral administration for 14 days,Phase I(PART 1) | Drug: SHR7280<br>* treatment<br>Drug: Placebo oral tablet<br>* blank control<br>| | Experimental: SHR7280 dose 4(male)<br>oral administration for 14 days,Phase I(PART 1) | Drug: SHR7280<br>* treatment<br>Drug: Placebo oral tablet<br>* blank control<br>| | Experimental: SHR7280 dose 5(male)<br>oral administration for 14 days,Phase I(PART 1) | Drug: SHR7280<br>* treatment<br>Drug: Placebo oral tablet<br>* blank control<br>| | Experimental: SHR7280 dose 1(female)<br>oral administration for 21 days,Phase I(PART 2) | Drug: SHR7280<br>* treatment<br>Drug: Placebo oral tablet<br>* blank control<br>| | Experimental: SHR7280 dose 2(female)<br>oral administration for 21 days,Phase I(PART 2) | Drug: SHR7280<br>* treatment<br>Drug: Placebo oral tablet<br>* blank control<br>| | Experimental: SHR7280 dose 3(female)<br>oral administration for 21 days,Phase I(PART 2) | Drug: SHR7280<br>* treatment<br>Drug: Placebo oral tablet<br>* blank control<br>| | Experimental: SHR7280 dose 4(female)<br>oral administration for 21 days,Phase I(PART 2) | Drug: SHR7280<br>* treatment<br>Drug: Placebo oral tablet<br>* blank control<br>| | Experimental: SHR7280 dose 6(male)<br>oral administration for 14 days,Phase I(PART 1) | Drug: SHR7280<br>* treatment<br>Drug: Placebo oral tablet<br>* blank control<br>| | Experimental: SHR7280 dose 7(male)<br>oral administration for 14 days,Phase I(PART 1) | Drug: SHR7280<br>* treatment<br>Drug: Placebo oral tablet<br>* blank control<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Number of Participants with Adverse events | Part 1 and Part 2 | Pre-dose to 28±2 days after dose administration | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Area under the plasma concentration versus time curve (AUCτ) after the first dose of SHR7280; | Part 1 and Part 2 | At pre-defined intervals from initial dose through final study visit( 28±2 days after dose administration) | | Maximum observed serum concentration (Cmax) after the first dose of SHR7280; | Part 1 and Part 2 | At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration) | | Time to maximum observed serum concentration (Tmax) after the first dose of SHR7280; | Part 1 and Part 2 | At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration) | | Time to elimination half-life (T1/2) ; | Part 1 and Part 2 | At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration) | | Apparent total clearance(CL/F) of the drug from plasma after last morning dose of SHR7280; | Part 1 and Part 2 | At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration) | | Apparent volume of distribution(Vz/F) after last morning dose of SHR7280; | Part 1 and Part 2 | At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration) | | Maximum observed serum concentration (Cmax) after last morning dose of SHR7280; | Part 1 and Part 2 | At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration) | | Time to maximum observed serum concentration (Tmax) after last morning dose of SHR7280; | Part 1 and Part 2 | At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration) | | Trough observed serum concentration (Ctrough) after last morning dose of SHR7280; | Part 1 and Part 2 | At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration) | | Accumulation Factor（Racc）after last morning dose of SHR7280; | Part 1 and Part 2 | At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration) | | Area under the plasma concentration versus time curve (AUCτ) after last morning dose of SHR7280; | Part 1 and Part 2 | At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration) | | Endocrine Parameters: Testosterone | Part 1 | At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration) | | Endocrine Parameters: Estuarial | Part 2 | At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration) | | Endocrine Parameters:Progesterone | Part 2 | At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration) | | Endocrine Parameters: Luteinizing hormone | Part 2 | At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration) | | Endocrine Parameters: Follicle stimulating hormone | Part 2 | At pre-defined intervals from initial dose through final study visit (28±2 days after dose administration) |

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In Vitro Follicle Activation in Patient With Premature Ovarian Failure Under 36 Years Old Study Overview ================= Brief Summary ----------------- This is a clinical trial that the investigators aim to validate In-vitro Activation (IVA) treatment protocol, which was previously defined by Kazuhiro Kawamura (MD) and Aaron Hsueh (PhD), in Turkish patient with Premature Ovarian Insufficiency (POI) under age 36. Detailed Description ----------------- The objectives of the study is as following; Validation of the previously defined In-Vitro Activation Protocol approach in Turkish patients under 36 years old with Premature Ovarian Insufficiency (POI). Giving an opportunity to young POI patient in Turkey for having genetically own baby. Primary outcome measure would be live birth. For activation of primordial follicles, phosphatase and tensin homolog (PTEN) inhibitor and protein kinase B (AKT) stimulator will be used. Official Title ----------------- In Vitro Follicle Activation of Dormant Follicles in Patient With Premature Ovarian Failure Under 36 Years Old Conditions ----------------- Activation of Primordial Follicles Intervention / Treatment ----------------- * Procedure: In vitro activation of primordial follicles by PTEN inhibitor and AKT stimulator Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patient with POI Short amenorrhea period (1 - 2 years) Exclusion Criteria: Having been treated with chemotherapy and/or radiotherapy; Having been diagnosed with advanced stage of endometriosis (endometriomas) Having been diagnosed with the chronic diseases such as diabetes, cardiac failure, kidney insufficiency, morbid obesity etc.. Presence of chromosomal abnormality (Turner, Fragile-X etc.) Previous multiple laparotomies Menopause >10 years Accompanied azoospermia Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 36 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 Masking: None (Open Label) Arms and Interventions | Intervention/Treatment | | --- | |Procedure: In vitro activation of primordial follicles by PTEN inhibitor and AKT stimulator|After laparoscopic unilateral oophorectomy, ovarian medulla would be dissected from cortex. After fragmentation of 2 cm square ovarian cortex into smaller pieces they would be incubated PTEN inhibitor and AKT stimulator for 48 hours. Finally we will auto graft these fragments beneath to the fallopian tube peritoneal surface.| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Live birth | The primary outcome is live birth, defined as the delivery of a live-born infant at 24 weeks of gestation | 2 years | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Follicle growth rate | Number of ovulation induction cycle achieved to growth follicle | 1 year | | M-II oocyte rate | Number of mature oocyte rate among retrieved oocytes | 1 year | | Day 2-3 good quality embryo rate | Good quality embryo rate of fertilized oocytes (2PN) | 1 year | | Clinical pregnancy rate | A clinical pregnancy is a pregnancy that is confirmed by both high levels of human chorionic gonadotropin (hCG) and ultrasound confirmation of a gestational sac or heartbeat (fetal pole) | 2 years |

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Intestinal-Specific Organ Function Assessment (iSOFA Study) Study Overview ================= Brief Summary ----------------- Importance of gastrointestinal (GI) function in critically ill patients has been recognized, but until now there is no validated clinical tool to monitor GI dysfunction as part of multiple organ dysfunction syndrome (MODS). The general aim of current project is to develop a five grade score (0-4 points) for assessment of GI function similar to SOFA sub-scores used for assessment of other organ systems. 500 consecutive adult patients admitted to the intensive care unit will be monitored for gastrointestinal symptoms, intra-abdominal pressure (IAP) and acute gastrointestinal injury (AGI) grades [1]. In 200 patients from these, plasma and urinary levels of possible biochemical markers of intestinal injury will be assessed. Objectives: To determine the prognostic value of gastrointestinal symptoms alone and in combination with intra-abdominal pressure (IAP), and acute gastro-intestinal injury (AGI) grades in predicting the ICU-, 28 days and 90 days mortality of adult intensive care patients (Part A of the study) To describe the blood and urine levels of biochemical markers of intestinal injury in general cohort of intensive care patients (Part B of the study). To compare the prognostic values of the intestinal-specific plasma parameters (IFABP, citrulline, ILBP, and D-lactate) with the gastrointestinal symptoms, AGI grades, and the SOFA score in predicting of ICU-, 28 days and 90 days mortality of adult intensive care patients (Part B of the study) Study design: prospective, observational, multicenter study Patient population: All consecutive adult critically ill patients (25 to 50 patients for each study site, 500 patients in total) in need for intensive care admission during maximum 4 weeks of study period. Duration of the study: for the individual patient 7 days and follow-up of 90 days Primary study outcome: 28 and 90 days all-cause mortality Secondary outcomes: ICU and hospital mortality, ICU length of stay, hospital length of stay, duration of mechanical ventilation, multiple organ failure as a cause of mortality, plasma and urinary levels of intestinal fatty-acid binding protein (I-FABP), citrulline, ileal lipid binding protein (ILBP), and D-lactate in general cohort of intensive care patients. Detailed Description ----------------- Objectives To determine the prognostic value of gastrointestinal symptoms alone and in combination with intra-abdominal pressure (IAP), and acute gastro-intestinal injury (AGI) grades in predicting the ICU-, 28 days and 90 days mortality of adult intensive care patients. To describe the blood and urine levels of the intestinal-specific plasma parameters (I-FABP, citrulline, ILBP, and D-lactate) in general cohort of intensive care patients. To compare the prognostic values of the intestinal-specific plasma parameters (I-FABP, citrulline, ILBP, and D-lactate) with the gastrointestinal symptoms, AGI grades, and the SOFA score in predicting of ICU-, 28 days and 90 days mortality of adult intensive care patients. Hypothesis GI symptoms, alone or in combination with IAP, and AGI grades as defined by WGAP statement improve the predictive capability of the SOFA score in critically ill patients. Intestinal-specific plasma and urinary markers are good to excellent predictors of outcome in critically ill patients. Best prediction is achieved by combination of GI symptoms, IAP and plasma markers. A clinical score developed based on the data from this study can be combined with existing SOFA score and thereby the predictive value of the SOFA score will be improved. To test these hypotheses, the study has two parts: Part A. Clinical data and routine laboratory parameters of 500 consecutive patients will be collected for 7 days after ICU admission. Standard treatment is implemented; no additional interventions solely for the study will be performed. Waived consent is expected. Part B. Blood and urinary samples for intestinal-specific laboratory markers will be drawn once daily from 200 patients enrolled in Part A, and analyzed in addition to standard clinical and laboratory data. First blood sample will be taken at admission to the intensive care unit. Informed consent will therefore be obtained from the patient or the next of kin after blood and urine sampling (delayed consent). Research questions Part A. What is the predictive capability of gastrointestinal symptoms, IAP and AGI grades in intensive care patients? Does the use of the AGI grades or a new AGI score based on GI symptoms alone or in combination with IAP improve the predictive capability of the SOFA score in the intensive care patients? Part B. What is the relationship between the intestinal-specific markers and the disease severity of the organ dysfunction, as described with the APACHE and the SOFA score? What is the predictive value of the intestinal-specific markers in predicting ICU-, 28 days and 90 days all-cause mortality, ICU and hospital length of stay, and duration of mechanical ventilation? Is there a correlation between the intestinal-specific markers and the gastrointestinal signs and symptoms? Is the predictive value of the intestinal specific markers higher compared to the GI symptoms, IAP and AGI grades in predicting ICU-, 28 days and 90 days all-cause mortality, ICU and hospital length of stay, and duration of mechanical ventilation? Does the addition of the intestinal-specific plasma and urinary markers increase the predictive value of the SOFA score in predicting outcome? Is the combination of the intestinal-specific markers with the GI symptoms, IAP and AGI grades better in predicting outcome compared to two individual items? What in these comparisons is the best marker or combination of markers? Methods/design 1. Study design, setting and patient population This is a prospective multicenter cohort study where 500 consecutive adult patients admitted to the intensive care unit will be monitored for gastrointestinal symptoms, IAP and AGI grades. Of these 500 patients, 200 patients will be included in part B. All consecutive adult critically ill patients (25 to 50 patients for each study site) in need for intensive care admission during maximum 6 weeks. The study will consist of three phases: Screening assessment, documentation of admission parameters; Study period of 7 days for the individual patient; Follow-up period of 90 days. 2. Study sites and the duration of the study The study will be conducted in ICUs of both university teaching hospitals and general (non-academic) hospitals. 20 ICUs from different countries will be invited and expected to participate, and each site is expected to enrol 25 to 50 patients during the maximum period of 6 weeks. For individual patient the study period is 7 days or till ICU discharge and follow-up of 90 days. Official Title ----------------- Prospective, Multicenter Cohort Study on Prognostic Value of Gastrointestinal Symptoms and Intestinal-specific Biomarkers in Prediction of Outcome of Intensive Care Patients Conditions ----------------- Critical Illness, Multiple Organ Failure Intervention / Treatment ----------------- * Other: No intervention Participation Criteria ================= Eligibility Criteria ----------------- Part A Inclusion criteria Admission to ICU during the study period (the patients already in the ICU at the time the study starts will not be included) Age at least 18 years Exclusion criteria Age <18 years Restriction of care at admission (i.e any limitation of intensive care measures) Readmission 7 or more days after initial admission to ICU Part B Inclusion criteria Admission to ICU during the study period (the patients already in the ICU at the time the study starts will not be included) Age at least 18 years Signed informed consent by patient or next of kin or legal representative for blood sampling. Exclusion criteria Age <18 years Restriction of care at admission (i.e any limitation of intensive care measures) Readmission 7 or more days after initial admission to ICU Absence of signed 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? ----------------- Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | All enrolled patients/Group A<br>500 consecutive adult patients will be enrolled in Part A (clinical data) | Other: No intervention<br> <br> | | Patients with blood and urine sampling/Group B<br>Patients with informed consent signed (anticipated 200 out of 500 patients) will participate in Part A (clinical data) and B (intestinal-specific biomarkers from blood and urine) | Other: No intervention<br> <br> | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | all-cause mortality | | 90 days |

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The Effect of Dairy and Non-Dairy Snacks on Food Intake, Subjective Appetite in Children Study Overview ================= Brief Summary ----------------- Dairy products have the potential to be healthy snack foods for children and are provided in a variety of food matrices. For instance, milk represents a fluid product, yogurt can be classified as a semi-solid food, and finally, cheese is the example of solid food. This experiment is aimed to examine the effect of dairy products with different food matrices on satiety and food intake in children. Dairy products will be compared with other non-dairy snacks popular among children including cookies and potato chips. Official Title ----------------- The Effect of Solid, Semi-Solid and Fluid Dairy Products on Short-Term Food Intake and Satiety in Children Conditions ----------------- Food, Eating, Appetite Intervention / Treatment ----------------- * Other: Potato chips * Other: Greek yogurt * Other: Cookies * Other: Cheese * Other: Milk Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Born at full-term within the normal weight range 9-14 year old Exclusion Criteria: Food sensitivities or allergies, Dietary restrictions, Health, learning, emotional or behavioural problems Receiving medication Ages Eligible for Study ----------------- Minimum Age: 9 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: Basic Science Allocation: Randomized Intervention Model: Crossover Assignment Interventional Model Description: Randomized crossover Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Potato chips<br>Commercial potato chips, 180 kcal | Other: Potato chips<br>* Commercially available potato chips, 180 kcal<br>| | Experimental: Greek yogurt<br>Greek yogurt, 180 kcal | Other: Greek yogurt<br>* Commercially available Greek yogurt, 180 kcal<br>| | Experimental: Cookies<br>Sandwich-type cookies, 180 kcal | Other: Cookies<br>* Commercially available cookies, 180 kcal<br>| | Experimental: Cheese<br>Mozzarella cheese, 180 kcal | Other: Cheese<br>* Commercially available cheese, 180 kcal<br>| | Experimental: Milk (fluid)<br>Milk, 2% m.f., 180 kcal | Other: Milk<br>* Commercially available milk, 180 kcal<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Food intake (grams and kcal) measured with a test meal | The amount of energy (kcal) consumed ad libitum with the test meal (pizza lunch) two hours later. | 120 min | | Subjective appetite measured with Visual Analogue Scales | The subjective assessment of appetite parameters including a desire to eat, fullness, hunger and a prospective food consumption measured with 100 mm Visual Analogue Scales with two opposite statements at each end (e.g., for the hunger scale, 0 mm means not hungry at all, and 100 mm means very hungry). | 0-120 min | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Cortisol | The concentration of salivary cortisol | 0-120 min | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Snacking, Food Intake, Satiety, Obesity

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Pretreatment With Norethindrone Acetate Prior to Levonorgestrel IUS Insertion for Heavy Menstrual Bleeding Study Overview ================= Brief Summary ----------------- Problematic uterine bleeding after the insertion of the LNG IUS is a well documented side effect. The levonorgestrel intrauterine system (LNG IUS) was approved for treatment of heavy menstrual bleeding (HMB) by the FDA in October 2009. To reduce the incidence and severity of post-insertional uterine bleeding, pretreatment with norethindrone acetate may effectively slough the endometrium prior to insertion of the LNG IUS. Detailed Description ----------------- This study will examine whether or not pretreatment with oral norethindrone acetate prior to the insertion of a hormonal intrauterine device will affect post-insertional uterine bleeding. The subjects enrolling in the study will have documented heavy menstrual bleeding (HMB) and desire the levonorgestrel intrauterine system (LNG IUS) (Mirena®, Bayer, Inc. Pittsburgh, PA) for symptomatic relief. HMB for this study is defined as heavy bleeding at regular intervals at least 20-40 days apart. Subjects will be randomized to one of two groups. One group will receive norethindrone acetate for two consecutive months prior to LNG IUS insertion while the other group will proceed with direct insertion of the LNG IUS with no hormonal pre-treatment. Subjects will be followed for a period of 180 days post LNG IUS insertion. Bleeding patterns will be recorded daily. Official Title ----------------- Pretreatment With Norethindrone Acetate Prior to Levonorgestrel IUS Insertion for Heavy Menstrual Bleeding Conditions ----------------- Heavy Menstrual Bleeding, Menorrhagia, Hypermenorrhea Intervention / Treatment ----------------- * Drug: Norethindrone acetate pretreatment * Other: No pretreatment Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: You must be between 18-45 years old You have Heavy Periods Exclusion Criteria: You are pregnant You are currently using hormonal contraception or hormonal therapy You have a history of pelvic inflammatory disease (and have not had a normal pregnancy since) You had an infected abortion within the last three months You have abnormal or cancerous cells of the cervix or uterus You have an actine infection in your genital organs Known or suspected breast cancer Active liver disease or tumors Allergy to levonorgestrel or norethindrone You currently have deep vein thrombosis, pulmonary embolism, or history of these conditions you currently have active or recent (within the past year) arterial thromboembolic disease (such as a stroke or myocardial infarction) these conditions Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 45 Years Sexes Eligible for Study ----------------- Female 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: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Active Comparator: Norethindrone acetate pretreatment<br>This arm will receive two cycles of norethindrone acetate before LVN IUS insertion. | Drug: Norethindrone acetate pretreatment<br>* 5 mg tablets, three times a day for 21 days for 2 menstrual cycles.<br>* Other names: Aygestin;| | Other: No pretreatment<br>LVN IUS is placed without norethindrone acetate pretreatment. | Other: No pretreatment<br>* LVN IUS is placed withour Norethindrone acetate pretreatment.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Total number of bleeding days | Number of days on study calendars with menstrual flow | up to 180 days | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Menorrhagia Questionnaire | Patients will assess the impact of their menstrual bleeding on their lifestyle. | up to 180 days | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Intrauterine system, reproductive age, menstrual bleeding

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Study of Sulphonylurea Synergy With Incretins Study Overview ================= Brief Summary ----------------- The Study of Sulphonylurea Synergy with Incretins (LOGIC) is a Proof-of-Concept Physiological study in the form of two matched isoglycaemic clamps. A matched clamp consists of an of oral glucose tolerance test followed by an isoglycaemic intravenous glucose infusion (IGII). The study will investigate whether there is synergy between a physiological sulphonylurea (SU) stimulus and the incretin effect, causing augmentation of insulin secretion in patients with type 2 diabetes mellitus (T2DM). The study will take place at The Clinical Research Centre at Ninewells Hospital in Dundee over five visits. It will evaluate 20 patients with T2DM on no diabetes therapy, or metformin monotherapy. All participants will undergo two matched clamps. The first matched clamp will be with no intervention. The second intervention matched clamp, low-dose liquid gliclazide will be administered 1-hour prior to each test. The sulphonylurea, Gliclazide, in this this instance will be used as a physiological stimulus and will only be given on two occasions as part of the second matched clamp. The first eight participants will participate in the dose-ranging phase. They will receive either 10mg or 20mg gliclazide as a stimulus to augment the incretin effect. A further twelve participants will then be recruited to complete the study utilising the dose which caused the greatest increment in insulin secretion. LOGIC will also evaluate the cohort for effect of KCNJ11 genotype on physiological response. Detailed Description ----------------- The Study of Sulphonylurea Synergy with Incretins (LOGIC) is a Proof-of-Concept Physiological study in the form of two matched isoglycaemic clamps. A matched clamp consists of an of oral glucose bolus test followed by an isoglycaemic intravenous glucose infusion (IGII) the next day. The study will investigate whether there is synergy between a physiological sulphonylurea (SU) stimulus and the incretin effect, causing augmentation of insulin secretion in patients with type 2 diabetes mellitus (T2DM). The study will take place at The Clinical Research Centre at Ninewells Hospital in Dundee over five visits. It will evaluate 20 patients with T2DM on no diabetes therapy, or metformin monotherapy. The first visit is a screening visit to ensure the participant meets inclusion and exclusion criteria, and, if so, to obtain written informed consent for study. Visits 2-5 will all occur following an overnight 10-hour fast at home. The second and third visits will make up the first matched clamp. In visit 2, the participant will undergo a 75-gram oral glucose bolus with frequent blood sampling to assess the glucose variance, insulin secretion and incretin hormone response from an oral glucose stimulus. Blood glucose level (BGL) will be sampled every 5 minutes along with hormone biochemical analysis at regular defined time points. The third visit consists of an IGII to replicate the glucose curve from the OGTT to allow measurement of incretin effect. BGL will again be sampled every 5 minutes with regular biochemical analysis of hormones. The investigators aim to establish whether a low-dose of sulphonylurea will have a synergistic role on insulin secretion with endogenously secreted GLP-1 and GIP, therefore visits four and five will complete the same matched clamp, however, low-dose liquid gliclazide will be administered 1-hour prior to each test. The sulphonylurea, Gliclazide, in this this instance will be used as a physiological stimulus and will only be given on two occasions as part of the second matched clamp. The first eight participants will receive either 10mg or 20mg gliclazide as a stimulus to augment the incretin effect. A further twelve patients will then be recruited to complete the study utilising the dose which caused the greatest increment in insulin secretion. The comparison of these tests will investigate the hypothesis that there is a synergistic effect between low-dose sulphonylurea and augmentation of the incretin effect on the beta cell. LOGIC will also evaluate the cohort for effect of KCNJ11 genotype on physiological response. Participants will be consented for genotyping as part of this study. Official Title ----------------- Study of Sulphonylurea Synergy With Incretins Conditions ----------------- Type 2 Diabetes Mellitus Intervention / Treatment ----------------- * Drug: Gliclazide Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Age 40 - 80, Age of Diabetes Diagnoses ≥ 35 T2DM on no treatment or metformin monotherapy White British HbA1c ≤ 8% (64mmol/mol) eGFR ≥ 50ml/min-1 ALT ≤ 2.5 x ULN Able to consent Exclusion Criteria: Type 1 Diabetes Mellitus HbA1c > 8.0% (> 64mmol/mol) eGFR <50ml/min-1 ALT >2.5 x ULN Anaemia (Haemoglobin <12.0 g/dL for women, <13.0 g/dL for men) Pregnancy, lactation or a female planning to conceive within the study period Established pancreatic disease Participating in clinical phase of another interventional trial/study or have done so within the last 30 days Any other significant medical reason for exclusion as determined by the investigator Ages Eligible for Study ----------------- Minimum Age: 40 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: Basic Science Allocation: Non-Randomized Intervention Model: Parallel Assignment Interventional Model Description: Proof-of-Concept Physiological Study Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | No Intervention: No Intervention<br>All participants in study will complete two matched clamp studies (OGTT + IGII). The first matched clamp without any intervention the second matched clamp with low dose gliclazide | | | Experimental: Low Dose Gliclazide<br>The first 8 participants will complete the dose-ranging phase of LOGIC study. Low dose gliclazide is being used a physiological stimulus. In the dose-ranging phase, 4 participants will receive 10mg gliclazide, the remaining 4 will receive 20mg gliclazide. The allocation to 10mg or 20mg will be randomised and unblinded. The study will analyse after the first 8 participants to assess which dose produces the greatest augmentation of insulin secretion when acting synergistically with the incretin effect. The further 12 participants will complete the study with the identified best dose. | Drug: Gliclazide<br>* Low dose liquid gliclazide will be used with the second matched clamp (OGTT/IGII) in visits 4 & 5.<br>* Other names: Zicron;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Difference in insulin secretion and incretin effect between two matched clamps (presence and absence of low dose gliclazide) | Comparison of two matched clamps (oral glucose tolerance test + isoglycaemic intravenous glucose infusion). Matched clamp 1 - control. Matched clamp 2 - low dose gliclazide. Levels of insulin/c-peptide, incretin hormones and plasma glucose will be compared in the presence and absence of low dose gliclazide | Through four study visits completed over 4 weeks | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Insulin secretory response analysed by KCNJ11 Genotype (E23K, E23E, K23K) | Difference in insulin secretory response to low dose gliclazide calculated by insulin/cpeptide levels in matched clamp(gliclazide). Differences will then be compared by participants genotype e.g. insulin secretory response for E23K, E23E, K23K variants. | Through four study visits completed over 4 weeks |

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Baby Detect : Genomic Newborn Screening Study Overview ================= Brief Summary ----------------- Newborn screening (NBS) is a global initiative of systematic testing at birth to identify babies with pre-defined severe but treatable conditions. With a simple blood test, rare genetic conditions can be easily detected, and the early start of transformative treatment will help avoid severe disabilities and increase the quality of life. Baby Detect Project is an innovative NBS program using a panel of target sequencing that aims to identify 126 treatable severe early onset genetic diseases at birth caused by 361 genes. The list of diseases has been established in close collaboration with the Paediatricians of the University Hospital in Liege. The investigators use dedicated dried blood spots collected between the first day and 28 days of life of babies, after a consent sign by parents. Detailed Description ----------------- Every year, thousands of children around the world are born with rare genetic diseases leading to death or lifelong disability. With technological advancements in the field of genetics and medicine, the rate of introduction of treatments for these rare conditions has grown remarkably. However, timing is of great importance for medication administration. The benefit that can be measured in a patient who has already suffered from a long irreversible degenerative disorder is small and, sometimes, it hardly justifies the cost and the burden of the treatment. Early diagnosis is, thus, of primary importance both to obtain the best effect of the innovative medications and to accelerate their development. The investigators are pioneered in the field of genetic newborn screening (NBS) in rare diseases by funding, designing, and leading an innovative genetic NBS program initiated in March 2018 in Southern Belgium for Spinal Muscular Atrophy (SMA) that allowed, so far, for 11 children to be detected and treated early and avoid the terrible fate of the disease. The program was disseminated in 17 countries and included public dissemination and health-economic analysis since the very beginning [1]. (www.facebook.com/sunmayariseonsma). Drawing upon our experience with SMA screening, the investigators have designed a project to screen up to 40,000 newborns/year progressively in 3 years for virtually all the rare diseases that can benefit from treatment or a pre-symptomatic clinical trial. The methodology of Baby Detect includes sequencing of target genes on dried blood spots collected from the NBS cards in a timely and cost-efficient manner, and its high dynamicity allows for any newly treatable rare disease to be included in its scheme in no longer than 6 months. Baby Detect, as a multidisciplinary newborn screening program, involves expertise in areas from genetics and medicine to laboratory studies, computer science, Data Protection, Ethics, and health economy. It will constitute the proof of concept that is needed before moving to a whole region-scale population. Official Title ----------------- Universal Genomic Newborn Screening in the Wallonia-Brussels Federation: Baby Detect Conditions ----------------- Fructosemia, Fructose-1,6-Diphosphatase Deficiency, Citrullinemia 1, Adrenoleukodystrophy, Shwachman-Diamond Syndrome, Crigler-Najjar Syndrome, Charcot-Marie-Tooth Disease, Type 6C, Mucopolysaccharidosis I, Creatine Deficiency Syndrome, Jervell-Lange Nielsen Syndrome, Systemic Primary Carnitine Deficiency, Congenital Adrenal Hyperplasia, Familial Hyperinsulinemic Hypoglycemia 1, Phosphoglucomutase 1 Deficiency, Maturity Onset Diabetes of the Young, Cystic Fibrosis, Hypophosphatasia, Infantile, Congenital Hypothyroidism, Deficit in Anterior Pituitary Function and Variable Immunodeficiency, Diamond Blackfan Anemia, Wiskott-Aldrich Syndrome, Fanconi Anemia, Hemophilia A, Hemophilia B, Glucose 6 Phosphate Dehydrogenase Deficiency, Alpha-Thalassemia, Alpha 1-Antitrypsin Deficiency, Inflammatory Bowel Disease 25, Autosomal Recessive, Wilson Disease, Progressive Familial Intrahepatic Cholestasis, Familial Chylomicronemia, Lysosomal Acid Lipase Deficiency, Familial Hemophagocytic Lymphocytosis, Griscelli Syndrome, Chediak-Higashi Syndrome, Chronic Granulomatous Disease, Menkes Disease, Smith-Lemli-Opitz Syndrome, Ataxia With Vitamin E Deficiency, Thiamine Metabolism Dysfunction Syndrome 5 (Episodic Encephalopathy Type), Thiamine Metabolism Dysfunction Syndrome 4 (Bilateral Striatal Degeneration and Progressive Polyneuropathy Type), Thiamine-Responsive Megaloblastic Anemia, Thiamine Metabolism Dysfunction Syndrome 2, Sepiapterin Reductase Deficiency, Dopamine Beta Hydroxylase Deficiency, Glut1 Deficiency Syndrome, Late-Infantile Neuronal Ceroid Lipofuscinosis, Aromatic L-amino Acid Decarboxylase Deficiency, Hereditary Hyperekplexia, Brain Dopamine-Serotonin Vesicular Transport Disease, Very Long Chain Hydroxy Acyl Dehydrogenase Deficiency, Tyrosinemia, Type I, Disaccharide Intolerance I, Beta Ketothiolase Deficiency, Phosphoglycerate Dehydrogenase Deficiency, Succinyl-Coa:3-Ketoacid Coa-Transferase Deficiency, Pyridoxine-5'-Phosphate Oxidase Deficiency, Pompe Disease, Phenylalanine Hydroxylase Deficiency, Ornithine Transcarbamylase Deficiency, N Acetyl Glutamate Synthetase Deficiency, Riboflavin Deficiency, Isovaleric Acidemia, Phosphoserine Aminotransferase Deficiency, Phosphoserine Phosphatase Deficiency, Hyperornithinemia-Hyperammonemia-Homocitrullinuria, S-Adenosylhomocysteine Hydrolase Deficiency, Mucopolysaccharidosis VI, Mucopolysaccharidosis IV A, Mucopolysaccharidosis II, Transcobalamin Deficiency, Isolated Methylmalonic Acidemia, Cobalamin Deficiency, Homocystinuria, Holocarboxylase Synthetase Deficiency, Fanconi Bickel Syndrome, Glycogen Storage Disease, Glycine Encephalopathy, Glutaric Acidemia I, Glucose Galactose Malabsorption, Gaucher Disease, Type 1, Carbamoyl Phosphate Synthase 1 Deficiency, Citrullinemia Type II, Carnitine Palmitoyltransferase Deficiency 2, Carnitine Palmitoyltransferase Deficiency 1, Carnitine Acylcarnitine Translocase Deficiency, Riboflavin Transporter Deficiency, Andersen Tawil Syndrome, Timothy Syndrome, Catecholaminergic Polymorphic Ventricular Tachycardia, Familial Hypertrophic Cardiomyopathy Type 4, Primary Hyperoxaluria, X Linked Hypophosphatemia, Hereditary Nephrogenic Diabetes Insipidus, Cystinosis, Congenital Nephrotic Syndrome, Finnish Type, Alport Syndrome, Hereditary Retinoblastoma, Biotinidase Deficiency, Aciduria, Argininosuccinic, Argininemia, Acyl-CoA Dehydrogenase Family, Member 9, Deficiency of, 3-Hydroxy 3-Methyl Glutaric Aciduria, 3-Hydroxy-3-Methylglutaryl-CoA Synthase 2 Deficiency, Maple Syrup Urine Disease, Medium Chain Acyl CoA Dehydrogenase Deficiency, Long-chain 3-hydroxyacyl-CoA Dehydrogenase Deficiency, Malonic Acidemia, Sickle Cell Disease, Severe Congenital Neutropenia, Severe Combined Immune Deficiency, Deficiency of GOT2, Cerebral Folate Transport Deficiency, Segawa Syndrome, Autosomal Recessive, Congenital Myasthenic Syndrome, Metachromatic Leukodystrophy, Pyridoxine-Dependent Epilepsy, Propionic Acidemia, Mucopolysaccharidosis VII, Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency, Pseudohypoaldosteronism, Type II, Pseudohypoaldosteronism Type 1, Pituitary Hormone Deficiency, Combined, Galactosemias Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: newborn between birth and 28 days of life consent of parent Exclusion Criteria: + 28 days Non consent of parent Ages Eligible for Study ----------------- Maximum Age: 28 Days 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 | | --- | --- | | Newborns with consent<br>Newborns with parent's consent | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Acceptability | The percentage of parents accepting the proposed screening in comparison with the number of mothers approached for consent | through study completion, an average of 1 year | | Feasibility - timing | The Turn-around time for the different mutations that are screened | through study completion, an average of 1 year | | Feasibility - reliability | The percentage of false positives and the predicted value for each test The estimation of the false negatives through collaboration with physicians treating the different diseases. | through study completion, an average of 1 year | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Consequence of NBS on early treatment access - timing | The time passed between the birth of diagnostic-positive newborns to the initiation of their treatment | through study completion, an average of 1 year | | Consequence of NBS on early treatment access - frequency | The number of patients offered early treatment | through study completion, an average of 1 year | | To improve the detection technique for disease related mutations that are not detected in classical screening by improving the classification of unspecified variants. | The number of new mutations implemented yearly in the NBS. | through study completion, an average of 1 year |

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Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders Study Overview ================= Brief Summary ----------------- This is an open-label extension protocol that will provide necessary data on the safety, tolerability, pharmacokinetics and efficacy of STX209 among subjects with ASD. Detailed Description ----------------- This is an open label extension study enrolling by invitation only to those subjects that have completed Seaside protocols 209AS208 and 22007. Protocol 209AS208, A Randomized,Double-Blind, Placebo-Controlled, Study of the Efficacy, Safety, and Tolerability of STX209 (Arbaclofen) Administered for the Treatment of Social Withdrawal in Subjects with Autism Spectrum Disorders. Protocol 22007, An Open Label Extension Study to Evaluate the Safety, Tolerability and Pharmacokinetics of STX209 in Subjects with Autism Spectrum Disorder. This open-label extension will provide data on the following: Evaluate the safety and tolerability of long term use of STX209 (Arbaclofen) Provide supporting pharmacokinetic analyses Assess long term efficacy on social behaviors in subjects with ASD. Official Title ----------------- An Open-Label Extension Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of STX209 (Arbaclofen) in Subjects With Autism Spectrum Disorders Conditions ----------------- Autism Spectrum Disorders Intervention / Treatment ----------------- * Drug: STX209 (arbaclofen) Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Subject completed study 22007 or 209AS208, and showed he can adequately follow the protocol, and with adequate medical justification to enter this study. Parent or other legally-authorized representative or caregiver is willing and able to perform all protocol-specified functions. Treatment with no more than 2 psychoactive medications Subjects with a history of seizure disorder must be adequately well-controlled, as specified in the study protocol For female subjects, negative pregnancy test Exclusion Criteria: Comorbid conditions that might interfere with the conduct of the study or confound the interpretation of the study data, or endanger the subject. Current use of illicit drugs or alcohol abuse. Subjects with a serious adverse event or other adverse event in study 22007 or 209AS208 that was related to STX209, and that endangers the subject, in the opinion of the investigator Current use of another investigational drug, or of vigabatrin, tiagabine, or riluzole Ages Eligible for Study ----------------- Minimum Age: 5 Years 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: STX209<br>Active treatment with STX209 | Drug: STX209 (arbaclofen)<br>* Long-term, daily, orally-administered STX209<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Safety and tolerability of STX209 | Spontaneously-reported adverse events, physical examination, and clinical laboratory assessments | 100 weeks | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Aberrant Behavior Checklist | Open-label assessment of change from baseline on the ABC | 100 weeks | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Autism Spectrum Disorders, Autism, Asperger, Pervasive Developmental Disorder - Not otherwise specified

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Effect of Anti-inflammatory Diet on Inflammatory, Oxidative and Nutritional Markers in Hemodialysis Patients Study Overview ================= Brief Summary ----------------- The purpose of this study is to evaluate the effect of especial diet therapy Anti-inflammatory Diet on inflammatory, oxidative stress, and nutritional markers in the context of protein-energy wasting syndrome(PEW) in hemodialysis patients. Official Title ----------------- Effect of Anti-inflammatory Diet on Inflammatory, Oxidative and Nutritional Markers in Hemodialysis Patients Conditions ----------------- Inflammation, Malnutrition, Protein Energy Wasting Syndrome, Oxidative Stress, Diet Therapy Intervention / Treatment ----------------- * Other: Diet Therapy * Other: Control Group Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patients who are on hemodialysis(HD) at least two times a week for 3months or more without any internment illness or admission Exclusion Criteria: Hospitalization because of sepsis or surgery 3 months prior to intervention Cirrhosis Hepatitis virus infection Human Immunodeficiency virus infection Acquired Immunodeficiency Syndrome Active malignancy Active infection Absence of communication Mental Impairment Terminal illness Tube feedings Total parenteral nutrition Pregnancy Not previously seen by a dietitian within 3 months prior to enrollment in the study Not expected to be transplanted within 6 months after the enrollment in the study Absence of malnutrition from a cause other than end stage renal disease(ESRD) Psychiatric conditions, preventing adherence to intervention Consuming immunosuppressive drugs or taking antioxidant supplements including Vitamin E, Vitamin C, N-acetyl- cysteine (NAC), Pentoxifylline, Lipoic acid,Fish-oil extracts (omega-3 fatty acids), Soy extracts(isoflavones), Green-tea preparations, Pomegranate extracts, Grape extracts within 2 months prior to enrollment in the study Ages Eligible for Study ----------------- Minimum Age: 18 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: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Diet therapy<br>The patients in this arm were educated to follow a especial type of diet (anti-inflammatory diet)in addition to nutrition counseling for 10 weeks. | Other: Diet Therapy<br>* The patients in this arm were educated to follow a especial type of diet (anti-inflammatory diet)in addition to nutrition counseling for 10 weeks.<br>| | Other: Control Group<br>The patients in this arm received nutrition counseling and education in general based on their needs as a control group for 10 weeks. | Other: Control Group<br>* The patients in this arm received nutrition counseling and education in general based on their needs as a control group for 10 weeks.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in serum Albumin | | 10 weeks | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in Subjective Global Assessment (SGA) score | | 10 weeks | | Change in Malnutrition-inflammation score(MIS) | | 10 weeks | | Change in serum C-Reactive Protein(CRP) | | 10 weeks | | Change in serum malondialdehyde(MDA) | | 10 weeks | | Change in serum Interleukin-6(IL-6) | | 10 weeks | | Change in serum total antioxidant capacity(TAC) | | 10 weeks | | Change in serum ferritin | | 10 weeks | | Change in serum total iron binding capacity(TIBC) | | 10 weeks | | Change in serum urea nitrogen | | 10 weeks | | Change in serum creatinine | | 10 weeks | | Change in serum phosphorus | | 10 weeks | | Change in body fat mass index(BFMI) | | 10 weeks | | Change in fat free mass index(FFMI) | | 10 weeks | | Change in body cell mass(BCM) | | 10 weeks | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Hemodialysis, Diet, Inflammation, Malnutrition

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A Randomized, Double-Blind, Placebo-Controlled Dose-Escalation Study to Determine the Safety and Efficacy of Intravenous Infusion of Human Placenta-Derived Cells (PDA001) for the Treatment of Crohn's Disease Study Overview ================= Brief Summary ----------------- To assess the safety and efficacy of intravenous (IV) PDA001 infused every two weeks for up to 5 total infusions in subjects with Crohn's disease who are refractory to one or more standard Crohn's disease therapies. Detailed Description ----------------- This is a randomized, double-blind, placebo-controlled, dose-escalation study to study 3 cohorts of subjects with Crohn's Disease including (but not limited to) those with colonic involvement. Each cohort (n = 9) will include PDA001 treated subjects (n = 6) as well as placebo (vehicle control) treated subjects (n = 3). Cohorts will be enrolled sequentially, beginning with the lowest dose cohort (1/4 unit PDA001) and progressing until the maximum tolerated dose of IV PDA001 is determined. Official Title ----------------- A Randomized, Double-Blind, Placebo-Controlled Dose Escalation Study to Determine the Safety and Efficacy of Intravenous Infusion of Human Placenta-Derived Cells (PDA001) for the Treatment of Crohn's Disease Conditions ----------------- Crohns Disease Intervention / Treatment ----------------- * Biological: PDA001 * Drug: Vehicle Controlled Placebo Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: • Males and females 18 - 75 years of age at the time of signing the informed consent document. Minimum weight of subject is 40 kg at screening. Subject must have inflammatory Crohn's Disease (CD) diagnosed at least 6 months but no greater than 15 years prior to treatment with Investigational Product (IP). Subject must have confirmation of ongoing CD by ileocolonoscopy at screening. Subject must have a Crohn's Disease Activity Index (CDAI) score ≥ 220 and ≤ 450 as assessed between Visit 1 and Visit 2. Exclusion Criteria: Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study including but not limited to Liver Function Tests Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) > 2.5 x the upper limit of normal at screening. Serum creatinine concentration > 2.0 mg/dl at screening. Alkaline phosphatase > 2.5 x the upper limit of normal at screening. Bilirubin level > 2 mg/dL (unless subject has known Gilbert's disease). Pregnant or lactating females. Morbidly obese subjects Body Mass Index (BMI) > 35 at screening). Subject has untreated chronic infection including Clostridium difficile toxin positive at screening or treatment of any infection with antibiotics within 4 weeks prior to dosing with IP (other than a treated urinary tract infection or drained perianal abscess). Note: Stable doses of antibiotics used to treat Crohn's Disease are allowed. Subject has organic heart disease (eg, congestive heart failure), clinically significant arrhythmia or clinically significant abnormal findings on Electrocardiograms (ECG). Subject has a history of other malignancies within 5 years (except basal cell carcinoma of the skin that is surgically cured, remote history of cancer now considered cured or positive Pap smear with subsequent negative follow up). Subject has had a stricture of the bowel requiring hospitalization within 182 days prior to treatment with IP. Subject has had bowel surgery other than perianal (for example, fistulotomy, seton placement, or abscess drainage) or previous abscess drainage within 182 days prior to treatment with IP. Subject has had any surgery within 28 days prior to treatment with IP. Subject has a colostomy, ileostomy or ileal pouch anal anastomosis. Subject has received an investigational agent -an agent or device not approved by FDA for marketed use in any indication-within 90 days (or 5 half-lives, whichever is longer) prior to treatment with investigational product. Subject has received previous cell therapy. Subject is expecting to have elective surgery at any time between Visit 1 (screening) and Visit 7 (end of induction phase). Subject has concurrent diagnosis of ulcerative colitis. Subjects with protein C or S deficiency. Subjects with prior history of thrombophlebitis or other pathological arterial or venous thrombosis. 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: Quadruple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Human Placenta-Derived Cells PDA001 Intravenous Infusion<br>Intravenous infusion of Human Placenta-Derived Cells PDA001 over the course of 2 hours. | Biological: PDA001<br>* Cohort 1 Dose Level 1: ¼ unit Human Placenta-Derived Cells PDA001 infused a total of 5 times 2 weeks apart. Cohort 2 Dose Level 2: ½ unit Human Placenta-Derived Cells PDA001 infused a total of 5 times 2 weeks apart. Cohort 3 Dose Level 3: 1 unit Human Placenta-Derived Cells PDA001 infused a total of 5 times 2 weeks apart.<br>| | Placebo Comparator: Vehicle controlled placebo<br>Intravenous infusion of Vehicle Controlled Placebo over the course of 2 hours | Drug: Vehicle Controlled Placebo<br>* Cohort 1 Dose Level 1: ¼ unit vehicle controlled placebo infused a total of 5 times 2 weeks apart. Cohort 2 Dose Level 2: ½ unit vehicle controlled placebo infused a total of 5 times 2 weeks apart. Cohort 3 Dose Level 3: 1 unit vehicle controlled placebo infused a total of 5 times 2 weeks apart.<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Adverse Events | Number of participants experiencing adverse events during the initial and extended follow-up periods | Up to 1 year | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Clinical Response | A clinical response is defined as a reduction from baseline by 25% and/or ≥ 100 points in the Crohn's Disease Activity Index (CDAI) score. The Crohn's Disease Activity Index or CDAI is a research tool used to quantify the symptoms of patients with Crohn's disease. | Up to 1 year | | Clinical Remission | Clinical remission is defined as a Crohn's Disease Activity Index (CDAI) score CDAI score of ≤ 150 points | Up to 1 year | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Crohn's disease, Fistula, Diarrhea, Colon, Stem cells

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Study of a Topical Gentamicin-Collagen Sponge Along With Systemic Antibiotic in Infected Diabetic Foot Ulcers Study Overview ================= Brief Summary ----------------- This is a phase 3, randomized, controlled, blinded, multicenter study conducted in 3 parallel cohorts of diabetic patients with at least 1 infected foot ulcer. Patients will be randomized to receive 1 of 3 study treatments; systemic antibiotic therapy and standard ulcer care with either (A) daily application of a gentamicin-sponge, (B) daily application of a placebo-sponge or (C) no-sponge, in the ratio 2:1:1. Patients will be treated for approximately 28 days and return to the clinic weekly for safety and efficacy assessments. After completing treatment, patients will return to the clinic for scheduled follow-up visits approximately 10, 30, 60 and 90 days after treatment is stopped. Detailed Description ----------------- This is a phase 3, randomized, controlled, blinded, multicenter study conducted in 3 parallel cohorts of diabetic patients with at least 1 infected foot ulcer. Patients will be randomized using an electronic randomization system to receive 1 of 3 study treatments; systemic antibiotic therapy and standard ulcer care with either (A) daily application of a gentamicin-sponge, (B) daily application of a placebo-sponge or (C) no-sponge, in the ratio 2:1:1. The investigator will be blinded to the patient's treatment group assignment and patients randomized to one of the 2 sponge groups will be blinded as to whether the sponge is active or placebo. If a patient has multiple infected ulcers, the assigned treatment will be administered to all infected ulcers. The investigator will determine the highest severity ulcer to be used for all efficacy evaluations and will also determine the size and number of sponges (up to 4) that a patient will use in order to completely cover all infected ulcers. The investigator will prescribe an empiric systemic antibiotic therapy based on protocol instructions. Patients will be treated for approximately 28 days and return to the clinic weekly for safety and efficacy assessments. The investigator will stop study treatment if a patient achieves clinical cure by or after the 3rd treatment visit (approximately study day 15). After completing treatment, patients will return to the clinic for scheduled follow-up visits or until ulcer closure. The final efficacy assessments used in the primary efficacy analyses will be obtained at the first follow-up visit approximately 10 days after treatment is stopped. The remaining follow-up visits will occur at approximately 30, 60 and 90 days after treatment is stopped when patients will be assessed for ulcer closure and any re-infection. Official Title ----------------- A Phase 3 Randomized, Placebo-Controlled, Blinded Study to Investigate the Safety and Efficacy of a Topical Gentamicin-Collagen Sponge in Combination With Systemic Antibiotic Therapy in Diabetic Patients With an Infected Foot Ulcer Conditions ----------------- Foot Ulcer, Diabetic, Infection Intervention / Treatment ----------------- * Drug: Gentamicin collagen sponge * Other: Placebo Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Has diabetes mellitus, according to the American Diabetes Association (ADA) criteria. Has at least 1 skin ulcer located on or below the malleolus that presents with the following clinical manifestations of a moderate or severe infection based on the Infectious Disease Society of America guidelines for the Diagnosis and Treatment of Diabetic Foot Infections (CID 2012; 54:132-173) (IDSA guidelines): has ≥ 2 manifestations of inflammation (local swelling or induration, erythema, local tenderness or pain, local warmth, purulent discharge (thick, opaque to white or sanguineous secretion) has ≥ 1 of the following characteristics: erythema > 2cm, or involving structures deeper than skin and subcutaneous tissues (e.g. abscess, osteomyelitis, septic arthritis, fasciitis) For patients with multiple infected ulcers, the ulcer with the highest Diabetic Foot Infection Wound score (DFI score) must be on or below the malleolus and all infected ulcers must be completely coverable using no more than 4 sponges (sponges cannot be cut). Has documented adequate arterial perfusion in the affected limb(s) (either palpable dorsalis pedis and posterior tibial pulses, or normal Doppler wave forms, a toe blood pressure ≥ 45 mm Hg or participation is approved by a vascular surgeon) Has received appropriate surgical intervention to remove all necrotic and infected bone if diagnosed with osteomyelitis. Has received appropriate surgical debridement to remove all gangrenous tissue. Exclusion Criteria: Has a known history of hypersensitivity to gentamicin (or other aminoglycosides). Has a known or suspected hypersensitivity to bovine collagen. Has an ulcer infection which, based upon the patient's known history of hypersensitivity and/or as otherwise in the opinion of the investigator, cannot be adequately treated with at least one of the empiric systemic antibiotic regimens allowed by this protocol. Has an ulcer associated with prosthetic material or an implanted device. Has received any systemic or topical antibiotic therapy for any reason within 7 days of randomization unless it was administered to specifically treat the infected ulcer(s) and only within 36 hours of randomization. Requires or is likely to require treatment with any concomitant topical product or wound therapy before the first follow-up study visit. Is severely immunocompromised, or likely to become severely immunocompromised during the study, in the opinion of the investigator. Has a history of myasthenia gravis or other neurological condition where gentamicin use is contraindicated as determined by the investigator. Has a history of epilepsy. Has a history of alcohol or substance abuse in the past 12 months. Has an uncontrolled illness that, in the opinion of the investigator, is likely to cause the patient to be withdrawn from the trial or would otherwise interfere with interpreting the results of the study Ages Eligible for Study ----------------- Minimum Age: 18 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: Treatment Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Gentamicin sponge group<br>Topical Gentamicin Collagen Sponge: Up to four collagen sponges each containing 50 mg of gentamicin sulfate (equivalent to 32.5 mg of gentamicin base) administered daily, with systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days. | Drug: Gentamicin collagen sponge<br>* Up to 4 topical Gentamicin Collagen Sponges each containing 50 mg of gentamicin sulfate (equivalent to 32.5 mg of gentamicin base)<br>* Other names: Cogenzia;| | Placebo Comparator: Placebo sponge group<br>Matching placebo collagen sponge administered daily, with systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days. | Other: Placebo<br>* Matching collagen sponge<br>| | No Intervention: No sponge group<br>Systemic antibiotic therapy and standard ulcer care (gentamicin-sponge group) for up to 28 days. | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Clinical Cure (Resolution of All Clinical Signs and Symptoms of Infection) | The primary efficacy variable is the percent of patients with a clinical outcome of clinical cure (Resolution of all clinical signs and symptoms of infection) at F/U visit 1 | approximately 10 days after end of treatment | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Clinical Cure and Baseline Pathogen Eradication (Resolution of All Clinical Signs and Symptoms of Infection) and Baseline Pathogen Eradication) | Percent of patients with both a clinical outcome of clinical cure (Resolution of all clinical signs and symptoms of infection) and baseline pathogen eradication at F/U visit 1 | Approximately 10 days after end of treatment | | Reinfection (Percent of Patients With Re-infection) | Percent of patients with re-infection | Approximately 90 days after end of treatment | | Time to Clinical Cure | Actual time to clinical cure (Resolution of all clinical signs and symptoms of infection) | Approximately 10 days after end of treatment | | Amputation (Percent of Patients That Have an Amputation Associated With the Target Ulcer) | Percent of patients that have an amputation associated with the target ulcer | Within approximately 90 days of end of treatment | | Ulcer Closure (Percent of Patients With Target Ulcer Closure) | Percent of patients with ulcer closure within approximately 30 days of end of treatment | within approximately 30 days of end of treatment |

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A Study of Siliphos in Adults With Non-alcoholic Steatohepatitis (NASH) Study Overview ================= Brief Summary ----------------- The purpose of this study is to evaluate the dietary supplement Siliphos, which comes from milk thistle, to determine whether it is safe and well-tolerated in adults who have non-alcoholic steatohepatitis (NASH). An additional aim of this study is to determine whether Siliphos may be beneficial in treatment of NASH as indicated by improvement in liver enzymes (ALT and AST). The study hypothesis is that Siliphos will be safe and well-tolerated in people with NASH and will result in a decrease in the liver enzymes ALT and AST. Detailed Description ----------------- Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver conditions characterized by fat accumulation in the liver. Non-alcoholic steatohepatitis (NASH) is one form of NAFLD that may progress to cirrhosis in some people. Currently, there are no medications that are approved for the treatment of NASH. Milk thistle is sold over-the-counter as a dietary supplement. Milk thistle has been used for hundreds of years as a supplement to support liver function, and is commonly taken by people with a variety of liver conditions. Milk thistle may help to reduce inflammation and fibrosis (scar tissue) in the liver, so it may be beneficial in the treatment of NASH. As NAFLD is very common in the population, there are probably many people with NAFLD taking milk thistle supplements. However, there are no published studies of milk thistle in NAFLD. Therefore, this study is designed to provide preliminary evidence of the safety, tolerability, and efficacy of milk thistle in people with NASH. Comparison: The milk thistle supplement (called Siliphos) will be compared to a placebo (sugar pill) in this study. Official Title ----------------- A Single-center, Single-blinded, Placebo-controlled Pilot Study of IdB 1016 (Siliphos) in Adult Patients With Non-alcoholic Steatohepatitis (NASH) Conditions ----------------- Fatty Liver Intervention / Treatment ----------------- * Drug: IdB 1016 (Siliphos) * Drug: Matched placebo Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Liver biopsy within 12 months demonstrating NASH Abnormal ALT Exclusion Criteria: Uncontrolled diabetes Hepatitis B, hepatitis C, or other chronic liver conditions Abnormal kidney function Excess alcohol consumption 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: Crossover Assignment Masking: Single Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Siliphos/Placebo<br>Received study medication first followed by placebo | Drug: IdB 1016 (Siliphos)<br>* 1 pill 3 times daily x 6 weeks<br>Drug: Matched placebo<br>* 1 pill 3 times daily x 6 weeks<br>| | Experimental: Placebo/Siliphos<br>Received placebo first followed by study medicaiton | Drug: IdB 1016 (Siliphos)<br>* 1 pill 3 times daily x 6 weeks<br>Drug: Matched placebo<br>* 1 pill 3 times daily x 6 weeks<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Number of Study Participants With Adverse Events | Side effect profile was collected at each study visit as tracked by study participants. Any new onset symptoms reported by study participants were recorded as side effects of treatment and analyzed according to whether they occurred while participants were treated with placebo or Siliphos. An increase in ALT value to greater than or equal to 2 x baseline value was also evaluated for possible drug induced liver injury. | 6 weeks | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Number of Participants With a Decrease in ALT Value Greater Than or Equal to 15 U/L From Baseline to the End of the Treatment Era | Change in ALT value from baseline to end of treatment arm during the time treated with Placebo in comparison to the time treated with Siliphos. Significant change in ALT was defined as a decrease by 15 or more units from baseline to end of treatment period. | 6 weeks | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Clinical Trials, Pilot Projects, Milk Thistle, Liver Function Tests

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Correlation Between Specific Gene Mutationand Local Immune Microenvironment and Immunotherapy Efficacy in NSCLC Study Overview ================= Brief Summary ----------------- Immunotherapy for PD-L1 positive patients is still ineffective in some patients，which may be related to the complex immune microenvironment.In view of this bottleneck, further refinement of immunotyping and in-depth study of drug resistance mechanism are the most important tasks. In this observational study, we evaluated the difference of gene mutation and immune microenvironment and therapeutic effect in primary NSCLC. Detailed Description ----------------- There are still some patients with PD-L1 positive who are ineffective in immunotherapy, which may be related to the complex immune microenvironment. In view of this bottleneck, further refinement of immunotyping and in-depth study of drug resistance mechanism are the most important tasks. Recently, studies have shown that the core elements of tumor microenvironment that have a significant impact on immunotherapy are:1. Infiltration abundance of specific killer T cells; 2. PD-L1 expression dependent on IFN - γ pathway, down-regulation of various active molecules and up-regulation of inhibitory molecules; 3. Activation and clearance of various inhibitory T cells. Although the classification has achieved further refinement of immune cells and molecular level, there are still some problems to be solved urgently: first, the classification of TIL cells needs further refinement, and different types of TIL infiltration have different guiding significance for prognosis; second, the subjective second-order semi quantitative scoring is often used for til count scoring, with low repeatability and different centers It is not easy for different pathologists to reach an agreement on the results of reading and interpretation. Thirdly, conventional methods are difficult to meet the requirements of tumor microenvironment analysis. In conclusion, it is urgent to develop a multi molecular marker landscape analysis system for tumor microenvironment, and establish a standardized detection process for each molecule to meet the needs of clinical positioning, quantitative and qualitative analysis for key molecular markers of immune microenvironment. In this observational study, we evaluated the difference of gene mutation and immune microenvironment and therapeutic effect in primary NSCLC. Official Title ----------------- Correlation Between Specific Gene Mutationand Local Immune Microenvironment and Immunotherapy Efficacy in NSCLC Conditions ----------------- NSCLC Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Non small cell lung cancer was diagnosed by cytology or histopathology; Patients to be treated with PD-1 / PD-L1 inhibitors; Who signed the informed consent for participating in the research plan Exclusion Criteria: History of other malignancies Cancer meningitis in subjects Incomplete clinical follow-up data Failure to sign informed consent to participate in the research program 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? ----------------- What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Correlation between specific gene mutation and immune microenvironment | Correlation between specific gene mutation and immune microenvironment | up to 1year | | Correlation between specific gene mutations and ORR and PFS in immunotherapy patients with lung cancerof lung cancer patients with immunotherapy | Correlation between specific gene mutations and ORR and PFS in immunotherapy patients with lung cancer | up to 1year | | Correlation between immune microenvironment and ORR and PFS in immunotherapy lung cancer patients | Correlation between immune microenvironment and ORR and PFS in immunotherapy lung cancer patients | up to 1year | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Correlation of OS with specific gene mutation in immunotherapy of lung cancer | Correlation of OS with specific gene mutation in immunotherapy of lung cancer | up to 1year | | Correlation between immune microenvironment and OS in immunotherapy lung cancer patients | Correlation between immune microenvironment and OS in immunotherapy lung cancer patients | up to 1year | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- PD-L1, NSCLC, Biomarker, mIHC, immune microenvironment, mutation, sequencing

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Evaluation and Standardization of Ginseng and it's Components for Blood Pressure Regulation Study Overview ================= Brief Summary ----------------- Ginseng has been used for many years in a wide array of anecdotal medicinal properties. Animal and limited clinical research points to the vascular effects of Korean Red Ginseng (KRG). The present project aims to assess the efficacy of KRG and contribution of its factionated components on various indices of vascular function in healthy individuals. Our primary objective is to compare the acute effects of KRG and placebo on endothelial function. Moreover, our secondary objective is to evaluate the effect of isolated KRG factions on arterial stiffness, blood pressure and vasoactive markers. We hypothesize that (1) consumption of KRG will cause an improvement in endothelial function in healthy individuals, as compared to placebo; (2) consumption of KRG will cause an improvement in arterial stiffness and blood pressure in healthy individuals, as compared to placebo; (3) the ginsenoside faction of KRG is primarily responsible for the anticipated vascular effects. Official Title ----------------- Evaluation and Standardization of Ginseng and it's Components for Blood Pressure Regulation Conditions ----------------- Hypertension, Blood Pressure, Endothelial Function Intervention / Treatment ----------------- * Dietary Supplement: Korean Red Ginseng * Dietary Supplement: Korean Red Ginseng (Panax ginseng) * Dietary Supplement: Cornstarch * Dietary Supplement: Korean Red Ginseng (Panax Ginseng) Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Age: between 18 and 70 years of age Healthy individuals (absence of major illnesses) Exclusion Criteria: Primary hypertension (defined by the use of antihypertensive agents or a seated systolic blood pressure greater than or equal to 140mmHg or diastolic blood pressure greater than 90mmHg) Secondary hypertension (defined as SBP greater than 180mmHg and DBP greater than 110mmHg) Grade 3 hypertension (defined as SBP greater than 180mmHg and DBP greater than 110mmHg) Diabetes Chronic kidney disease Liver disease Estrogen-sensitive cancer Heavy alcohol use Bleeding disorders Planned surgery Angina CHF Coronary revascularization Peripheral vascular disease Coronary/cerebrovascular event in the last 6 months Prescriptions of MAO inhibitors, SSRIs, diuretics, sympathomimetics, herbal therapies, medication affecting nitric oxide synthesis, and/or anticoagulent medications within the last 6 months Sensitivity to any of the ingredients in the treatments or placebo Chronic use of or frequent prescriptions for NSAIDs Women of childbearing potential must not be pregnant or breast-feeding Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 70 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: Crossover Assignment Masking: Quadruple Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Placebo Comparator: 1<br>Placebo capsules (3g) | Dietary Supplement: Cornstarch<br>* Placebo<br>| | Experimental: 2<br>Whole Korean Red Ginseng root (3g) | Dietary Supplement: Korean Red Ginseng<br>* Cultivated KRG-B (central body Korean Red Ginseng) obtained from Kyonggi-do Farm, Kyonggi-do Province, Korea. Dosage form: whole root in capsules (3g)<br>* Other names: C. A. Meyer;| | Experimental: 3<br>Ginsenoside fraction of Korean Red Ginseng B (0.22g); bioequivalent to the original whole KRG root | Dietary Supplement: Korean Red Ginseng (Panax ginseng)<br>* Cultivated KRG-B (central body Korean Red Ginseng) obtained from Kyonggi-do Farm, Kyonggi-do Province, Korea. Dosage form: total ginsenoside fraction in capsules<br>* Other names: C. A. Meyer;| | Experimental: 4<br>Polysaccharide fraction of KRG root (0.21g); bioequivalent to the original whole KRG root | Dietary Supplement: Korean Red Ginseng (Panax Ginseng)<br>* Cultivated KRG-B (central body Korean Red Ginseng) obtained from Kyonggi-do Farm, Kyonggi-do Province, Korea. Dosage form: total polysaccharide fraction (panaxans) in capsules<br>* Other names: C. A. Meyer;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Flow-mediated dilation of the brachial artery | | Start and finish of each treatment arm | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Augmentation Index | | Start and finish of each treatment arm | | Nitric Oxide and Cyclic GMP | | Beginning of and 3 hours into clinical visit | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Ginseng, Korean Red Ginseng, Ginsenoside, Flow Mediated Dilation, Endothelial Function, Hypertension

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Antibiotic Prophylaxis for Elective Cesarean Section Study Overview ================= Brief Summary ----------------- A randomized controlled study comparing the effect of administration of 1 gm ceftriaxone in elective cesarean section 30-60 min before skin incision versus after cord clamping. Detailed Description ----------------- comparing the effect of administration of 1 gm ceftriaxone in elective cesarean section 30-60 min before skin incision versus after cord clamping.on post-cesarean section infection(wound infection as a primary outcome) Official Title ----------------- Timing of Antibiotic Prophylaxis for Elective Cesarean Section: A Randomized Controlled Trial Conditions ----------------- Infection of Cesarian Section Wound Following Delivery Intervention / Treatment ----------------- * Drug: ceftriaxone 1gm for intravenous infusion Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Patients undergoing elective cesarean section with Gestational age 37 weeks or more Exclusion Criteria: Fever greater than 38°C or maternal sepsis. Cephalosporin allergy. Exposure to any antibiotic agent within 1week before delivery. Patents having premature rupture of membranes and acute chorioamnionitis. Patients with chronic diseases (diabetes mellitus, renal disease and Cardiac disease). 3) Morbid obesity (BMI>30) Ages Eligible for Study ----------------- Minimum Age: 18 Years Maximum Age: 35 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: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Group A ceftriaxone after cord clamping<br>165 patients pregnant at 37weeks or more undergoing elective cesarean section randomly distributed to receive 1 gm. ceftriaxone via l intravenous infusion single dose after cord clamping. | Drug: ceftriaxone 1gm for intravenous infusion<br>* Patients undergoing elective cesarean section with Gestational age 37 weeks or more. comparing the effect of administration of 1 gm ceftriaxone in elective cesarean section 30-60 min before skin incision versus after cord clamping.on post-cesarean section infection(wound infection as a primary outcome)<br>* Other names: cefaxon;| | Active Comparator: Group B ceftriaxone before skin incision<br>165 patients pregnant at 37weeks or more undergoing elective cesarean section randomly distributed to receive 1 gm. ceftriaxone vial intravenous infusion single dose 30-60 minutes before skin incision. | Drug: ceftriaxone 1gm for intravenous infusion<br>* Patients undergoing elective cesarean section with Gestational age 37 weeks or more. comparing the effect of administration of 1 gm ceftriaxone in elective cesarean section 30-60 min before skin incision versus after cord clamping.on post-cesarean section infection(wound infection as a primary outcome)<br>* Other names: cefaxon;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | The primary outcome is the rate of post cesarean section surgical site infection. | postoperative assessment of SSI. Patients will be followed up at 48-72 hours postoperative, at 7th days (skin suture removal) and at 6 weeks (contraception application).all patients will be contacted by telephone and interviewed. They will be rescheduled for a clinic visit if they reported signs and symptoms of wound infection (purulent discharge or erythema >1 cm in diameter, induration of the incision site and fever). | administration of 1gm ceftriaxone prophylaxis for elective cs and follow up surgical site infection till 40 days | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | other post cesarean section maternal and neonatal infection | Maternal complications: other post cesarean section maternal complications, namely endometritis, pyrexia, urinary tract infection and complication of drug administration such as anaphylaxis. Neonatal complications: such as neonatal sepsis | follow up ofother post cesarean section maternal and neonatal infection till 40 days of delivery | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Elective Cesarean Section, Antibiotic prophylaxis, Timing of Antibiotic prophylaxis, post cesarean section infection

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Hybrid Procedure in Patients With Persistent Atrial Fibrillation Study Overview ================= Brief Summary ----------------- In this study, the investigators therefore comparatively analyzed the mid-term results (at 1 year) including electrocardiogram, 24 hour Holter monitoring, and 2 week long-term electrocardiogram of thoracoscopic ablation and RFCA performed individually or as a hybrid procedure in patients with long-lasting persistent atrial fibrillation. Antiarrhythmic medication, discontinuation of anticoagulation medication, and echocardiographic findings were also analyzed. Detailed Description ----------------- Atrial fibrillation is highly associated with sudden death and stroke, requiring definitive treatment. In Korea, atrial fibrillation is a common disease predicted to affect more than 5% of the population over 65 years of age and more than 10% over 80 years. Totally thoracoscopic ablation has been adopted and performed successfully on February 2012 at Samsung Medical Center for the first time in Korea. More than 120 operations have been performed up to date. In Korea, treatment for atrial fibrillation is still dependent on percutaneous RFCA, and life-long medication and anticoagulation is needed when recurrent atrial fibrillation occurs. The investigators expected thoracoscopic ablation to be an alternative to overcome this limitation. Also, thoracoscopic ablation and RFCA are recently being performed simultaneously or stage by stage as a hybrid procedure, and the results are being reported. In this study, the investigators therefore comparatively analyzed the mid-term results (at 1 year) including electrocardiogram and 24 hour Holter monitoring of thoracoscopic ablation and RFCA performed individually or as a hybrid procedure in patients with long-lasting persistent atrial fibrillation. Antiarrhythmic medication, discontinuation of anticoagulation medication, and echocardiographic findings were also analyzed. Official Title ----------------- Comparison of Success Rate of Totally Thoracoscopic Ablation Versus Hybrid Procedure in Patients With Persistent Atrial Fibrillation Conditions ----------------- Atrial Fibrillation Intervention / Treatment ----------------- * Procedure: Hybrid procedure Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Long-lasting persistent atrial fibrillation Persistent atrial fibrillation refractory to antiarrhythmic drug therapy over 18 years Exclusion Criteria: Valvular heart disease of more than moderate degree Unresponsive ischemic cardiomyopathy Follow-up of over 1 year was not possible Warfarin was unable to be used Refusal of informed consent Left atrial thrombus 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 | | --- | --- | | No Intervention: Thoracoscopic ablation group<br>Patients who will undergo thoracoscopic ablation only | | | Active Comparator: Hybrid procedure<br>Patients who will undergo hybrid procedure (thoracoscopic ablation and eletrophyologic study with or without additional ablation) | Procedure: Hybrid procedure<br>* Eletrophysiologic study via femoral vein approach to confirm pulmonary vein isolation lesion and box lesions in left atrium<br>* Other names: Postprocedural electrophysiological study;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Cardiac related death | medical records review | one year | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Stroke | medical records review at 3, 6 and 12 months follow up | postoperative one year | | Bleeding | medical records review at 3, 6 and 12 months follow up | postoperative one year | | Embolism | medical records review at 3, 6 and 12 months follow up | postoperative one year | | Recurred atrial arrhythmia | medical records review at 3, 6 and 12 months follow up | postoperative one year | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Atrial fibrillation, Ablation, Hybrid

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An Intervention to Reduce Prolonged Sitting in Police Staff Study Overview ================= Brief Summary ----------------- The primary aim of this study is to assess the feasibility of an intervention to reduce and break up prolonged sitting time in full-time police staff. The secondary aims of this study are to assess preliminary effects on patterns of sedentary behaviour (number of breaks, number of prolonged sitting bouts, average duration of prolonged sitting bouts, and total prolonged sitting duration), additional measures of sedentary behaviour (total sitting time, standing, and stepping), cardiometabolic risk markers, physiological stress (cortisol levels), physical health (self-report and postural stability), psychological wellbeing and mood, work stress (self-reported), and work performance (job satisfaction and productivity). Detailed Description ----------------- Prolonged sedentary behaviour is associated with a higher incidence of cardiovascular disease and type 2 diabetes. A large proportion of daily sedentary time (sitting) occurs in the workplace. On average, full time office workers spend upwards of 70% of their working day seated with the majority of this time accumulated in sitting bouts ≥ 20 minutes. A recent cross-sectional investigation into the occupational characteristics of over 5,000 British police force employees reported at least 30% identifying as having mainly office-based duties. When trying to reduce prolonged sitting in the workplace, one of the most effective strategies is the use of multi-component interventions. At the present time, sedentary workplace intervention studies in the police are limited. The primary aim of this study is to assess the feasibility of an intervention to reduce and break up prolonged sitting time at work in full-time police staff. The secondary aims of this study are to assess preliminary effects on sedentary behaviour, cardiometabolic risk markers, physiological stress, physical health, psychological wellbeing and mood, work stress, and work performance. This has a single-arm, pre-post study design. Participants will receive a multi-component intervention to break up and reduce prolonged sitting including: a presentation/workshop, electronic support, minor environmental modifications, organisational support, and team competition. Assessments will take place at baseline and post-intervention (week 10). Official Title ----------------- A-REST (Activity to Reduce Excessive Sitting Time): a Cluster Randomised Controlled Feasibility Trial to Reduce Prolonged Sitting in Police Staff Conditions ----------------- Sedentary Behavior, Metabolic Syndrome, Affect, Stress, Physiological, Stress, Psychological, Musculoskeletal Pain Intervention / Treatment ----------------- * Behavioral: Breaks Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: ≥ 0.6 Full Time Equivalent (FTE) work hours Ambulatory Predominantly desk-based (spend on average ≥ 5-h/day seated at work by self-report) Own a smartphone, with ability to keep phone with them during work hours Exclusion Criteria: Planned absence of two weeks or more during the intervention period Work part time (< 0.6 FTE) Health contraindications to standing and walking Planned relocation to another site, office or workplace Have personal access to an active workstation (sit-stand desk, seat cycle, treadmill desk or similar) Participating simultaneously in another workplace intervention (for sedentary behaviour, physical activity, diet, lifestyle, or combination thereof) Health contraindications to postural stability testing (e.g., injury to the lower extremities in the past six months, dizziness, or epilepsy) 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 Intervention Model: Single Group Assignment Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Intervention<br>The intervention group will aim to regularly break up participants' prolonged sitting time with three-minute incidental movement breaks every half hour at work. Support for behaviour change will include a lecture/workshop, electronic prompts, break logging, team competition, health champions, and email support. | Behavioral: Breaks<br>* 3-min breaks every half hour at work<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Feasibility - Adherence: Drop-out rates in control and intervention group | Analyses of drop-out rates (%) in control and intervention group. | From recruitment (typically 4 weeks prior to baseline) up to study completion (typically 12 weeks) | | Feasibility - Acceptability: Perceptions of the intervention | Asking participants' to qualitatively reflect on the intervention via semi-structured interview. | At week 11 | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in the number of breaks (sit-stand transitions) from sedentary time per hour (workplace and daily) | Participants will wear a thigh-based accelerometer/inclinometer (ActivPAL3), which provides a well established measure of sit-stand transitions. | This measure will be assessed at baseline and 10 weeks. At each time point the accelerometer will be worn for 7 days. | | Change in sitting time accrued in prolonged bouts (≥ 30 minutes) (workplace and daily) | Participants will wear a thigh-based accelerometer/inclinometer (ActivPAL3), which provides a well established measure of sitting time accrued in prolonged bouts (≥ 30 minutes). | This measure will be assessed at baseline and 10 weeks. At each time point the accelerometer will be worn for 7 days. | | Change in the average duration (minutes) of prolonged sitting bouts (≥ 30 minutes) (workplace and daily) | Participants will wear a thigh-based accelerometer/inclinometer (ActivPAL3), which provides a well established measure of the average duration (minutes) of prolonged sitting bouts (≥ 30 minutes). | This measure will be assessed at baseline and 10 weeks. At each time point the accelerometer will be worn for 7 days. | | Change in the number of prolonged sitting bouts (≥ 30 minutes) (workplace and daily) | Participants will wear a thigh-based accelerometer/inclinometer (ActivPAL3), which provides a well established measure of the number of prolonged sitting bouts (≥ 30 minutes). | This measure will be assessed at baseline and 10 weeks. At each time point the accelerometer will be worn for 7 days. | | Change in the total duration (minutes) of sitting time (workplace and daily) | Participants will wear a thigh-based accelerometer/inclinometer (ActivPAL3), which provides a well established measure of sitting time. | This measure will be assessed at baseline and 10 weeks. At each time point the accelerometer will be worn for 7 days. | | Change in step count (workplace and daily) | Participants will wear a thigh-based accelerometer/inclinometer (ActivPAL3), which provides a well established measure of step count. | This measure will be assessed at baseline and 10 weeks. At each time point the accelerometer will be worn for 7 days. | | Change in total stepping time (in minutes) (workplace and daily) | Participants will wear a thigh-based accelerometer/inclinometer (ActivPAL3), which provides a well established measure of total stepping time (in minutes). | This measure will be assessed at baseline and 10 weeks. At each time point the accelerometer will be worn for 7 days. | | Change in total standing time (in minutes) (workplace and daily) | Participants will wear a thigh-based accelerometer/inclinometer (ActivPAL3), which provides a well established measure of total standing time (in minutes). | This measure will be assessed at baseline and 10 weeks. At each time point the accelerometer will be worn for 7 days. | | Weight (kg) | Changes in weight via Tanita scale. | Baseline and at week 11 | | Body mass index (BMI) | Changes in BMI will be computed by dividing participants' weight (in kilograms) by their height (in metres) squared. | Baseline and at week 11 | | Waist circumference (cm) | Changes in waist circumference will be assessed by tape measure. | Baseline and at week 11 | | Body fat % | Changes in body fat percentage will be assessed via a bioelectric impedance spectroscopy device. | Baseline and at week 11 | | Body fat mass (kg) | Changes in body fat mass via a bioelectric impedance spectroscopy device. | Baseline and at week 11 | | Lean body mass (kg) | Changes in lean body mass via a bioelectric impedance spectroscopy device. | Baseline and at week 11 | | Blood pressure (mmHg) | Changes in blood pressure measured via electronic sphygmomanometer. | Baseline and at week 11 | | Fasted blood cholesterol (mg/dL) | Changes in total, high density lipoprotein (HDL), and low density lipoprotein (LDL) cholesterol measured via fasting blood tests using a Cholestech machine. | Baseline and at week 11 | | Fasted blood triglycerides (mg/dL) | Changes in triglycerides measured via fasting blood tests using a Cholestech machine. | Baseline and at week 11 | | Fasted blood glucose (mg/dL) | Changes in glucose levels measured via fasting blood tests using a Cholestech machine. | Baseline and at week 11 | | Salivary cortisol (nmol/L) | Changes in the cortisol awakening response and diurnal cortisol levels will be assessed via saliva samples (provided by chewing on a cotton swab for 60secs) collected seven times over the course of one day. | Baseline and at week 11. At each time point saliva samples will be collected at 7 time points over the course of one day. | | Nordic musculoskeletal questionnaire | The Nordic musculoskeletal questionnaire is comprised of 40 forced-choice questions pertaining to low back, neck, shoulder and general physical complaints most often experienced in the work setting. A visual diagram aids the viewer by labelling the nine regions of the body referred to in the questionnaire. Acceptable reliability for this tool has been demonstrated. | Baseline and at week 11 | | Postural sway velocity (mm/s) | Change in postural sway velocity (bipedal-eyes-open, bipedal-eyes-closed, unipedal-eyes-open, unipedal-eyes-closed) will be evaluated via dynamic plantar pressure sensor (RS Footscan). | Baseline and at week 11 | | Postural sway range (mm) | Change in postural sway range (bipedal-eyes-open, bipedal-eyes-closed, unipedal-eyes-open, unipedal-eyes-closed) will be evaluated via dynamic plantar pressure sensor (RS Footscan). | Baseline and at week 11 | | International Physical Activity Questionnaire short form (IPAQ) | Changes in self-reported physical activity and total sitting time. The International Physical Activity Questionnaire short form (IPAQ) measures self-reported physical activity and sitting time in the last seven days. Participants are asked to report frequency of participation (0-7 days) and duration of activity on one of those days (in hours and minutes). The IPAQ has demonstrated acceptable reliability and validity in measuring activity in the last seven days. | Baseline and at week 11 | | Marshall sitting questionnaire | The Marshall sitting questionnaire has five questions that measure self-reported domain-specific sitting time (hours and minutes) on weekend days and weekdays. This questionnaire has good reliability and validity for sitting time on weekdays and weekend days. | Baseline and at week 11 | | Warwick-Edinburgh mental well-being scale (WEMWBS) | The Warwick-Edinburgh mental well-being scale (WEMWBS) is a 14-item questionnaire used to assess various aspects of positive mental health (e.g., I've been feeling optimistic about the future). Participants are asked to rate their experience of each wellbeing statement between 1 and 5 (1 = none of the time and 5 = all of the time). Item scores are then combined to provide a total score (between 14 - 70). The higher the score the better the overall mental wellbeing. For intervention purposes, a change in the total score of 3-8 points between two time points may be considered a meaningful change. | Baseline and at week 11 | | Positive and negative affect schedule (PANAS) | Changes in self-reported mood via the positive and negative affect schedule (PANAS) consisting of two 10-item subscales to measure positive and negative affect (i.e., mood). A number of words that describe different feelings and emotions (e.g., interested, distressed, excited) are presented and participants are asked to indicate on a 5-point scale to what extent over the past week they have felt these feelings/emotions (1 = very slightly or not at all and 5 = extremely). These scales are internally consistent with very good convergent and discriminant correlations. Negative Affect subscale Item scores on the negative affect scale are then combined to provide a total score (between 10 - 50). The higher the score the more negative emotions experienced. Positive Affect subscale Item scores on the positive affect scale are then combined to provide a total score (between 10 - 50). The higher the score the more positive emotions experienced. | Baseline and at week 11 | | Operational police stress questionnaire (PSQ-Op) | Changes in ratings of 20 operational stressors for police (PSQ-Org). Participants will be asked to rate items on how much stress it has caused you over the past 6 months using a 7-point Likert scale (1 = no stress at all and 7 = a lot of stress). Item scores are then combined to provide a total score (between 20 - 140). The higher the score the worse the stress level. This instrument has demonstrated acceptable reliability and validity for measuring police-specific occupational stressors. | Baseline and at week 11 | | Organisational police stress questionnaire (PSQ-Org) | Changes in ratings of 20 organisational stressors for police (PSQ-Org). Participants will be asked to rate items on how much stress it has caused you over the past 6 months using a 7-point Likert scale (1 = no stress at all and 7 = a lot of stress). Item scores are then combined to provide a total score (between 20 - 140). The higher the score the worse the stress level. This instrument has demonstrated acceptable reliability and validity for measuring police-specific occupational stressors. | Baseline and at week 11 | | Job satisfaction | Changes in self-reported job satisfaction and will be evaluated via a single-item questionnaire (How satisfied are you with your job in general?) assessed on a 7-point Likert scale (1 = dissatisfied and 7 = extremely satisfied). A higher score represents more satisfaction with one's job. | Baseline and at week 11 | | Job performance | Changes in self-reported job performance will be evaluated via a single-item questionnaire (How well do you think you have performed in your job recently?) with a 7-point Likert scale (1 = very poorly and 7 = extremely well). A higher score represents a more positive assessment of job performance. | Baseline and at week 11 |

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Optimising an Online Self-help Program for Coping With the Loss of a Spouse Study Overview ================= Brief Summary ----------------- When someone has lost his or her partner, feelings of grief are normal and usually diminish over time. However, for some people, strong feelings of grief persist. For coping with grief, it is important to learn to accept the loss, experience the pain of grief, adjust to an environment without the deceased person, and withdraw emotional energy and focus it on other relationships. Loss-oriented tasks, such as grief work, and restoration-oriented tasks, such as attending to life changes, engaging in new activities and finding new roles and identities, are both essential. The program is designed to be completed in 10 weeks and recommends that mourners complete one module or topic a week. To examine the benefits of SOLENA, this study will compare the answers of mourners that completed the intervention with the mourners of the control group, which will wait to complete the intervention. The group that completed the intervention is divided in two sub-groups. One group of mourners will complete the intervention in a fixed order, while the other will complete it in a self-tailored order according to their own needs at each moment. Specifically, the study examines how well the self-help program reduces grief, depression symptoms, and loneliness and examines whether the topics of the study modules are presented in a given order or whether participants can work on the topics according to their current needs makes a difference. Ultimately, it is expected that the self-tailored version leads to more benefits than completing SOLENA's modules in a fixed order. Detailed Description ----------------- BACKGROUND AND RATIONALE The death of a spouse is a frequent and very stressful critical life event in later life. The loss of a partner involves the adaptation of daily routines which can be even more challenging when social, physical, and financial resources decline in later life. Grief and psychological distress after the loss of a spouse are normative reactions. For most people, grief intensity weakens to a manageable degree within several weeks or months. However, some individuals are less able to cope with bereavement and show symptoms of disturbed or prolonged grief or adaptation problems. To support coping with the loss of a significant person, the Task model identifies four tasks of mourning, namely accepting the reality of the loss, experiencing the pain of grief, adjusting to an environment without the deceased person, and withdrawing emotional energy and reinvesting it in another relationship. Moreover, the dual-process model of coping with bereavement posits that a dynamic coping process oscillating between loss-oriented tasks such as grief work and restoration-oriented tasks such as attending to life changes is essential for adjustment. Based in these two models, Brodbeck and colleagues developed LIVIA, a text-based self-help online program to support the loss of the spouse, which has proved its efficacy for mourning older adults from a general population. LIVIA is rooted in cognitive behavioural therapy, including the most relevant treatment elements to support the mourning process: exposure, cognitive reappraisal, integration, and restoration as well as self-care and social reengagement treatment components. LIVIA confirmed that the intervention is also efficacious for milder grief symptoms. Compared to the control group, the intervention resulted in significant reductions in grief (d = 0.81), depression (d = 0.59), psychopathological distress (d = 0.39) (primary outcomes), embitterment (d = 0.37), loneliness (d = 0.37) and an increase in life satisfaction (d = -0.41) (secondary outcomes). These gains were maintained over three months. Improvements were similar among participants with low, medium, or high levels of grief at baseline. Therefore, LIVIA provides a promising basis for the development of a more sophisticated and attractive intervention with a more inclusive target group, e.g., mourners of all ages who lost their spouse within the previous six months, while still seeking help for coping with the loss. Apart from extending the target population of the intervention, SOLENA also aims to examine whether the efficacy of LIVIA can be increased by providing a self-tailored version, in which the users can chose the content that is relevant for them and that best fits their current needs. MAIN HYPOTHESES Primary outcome: Grief Efficacy of SOLENA: It is hypothesized that SOLENA will decrease grief significantly compared to the waiting list control group. Stability of the effects: It is hypothesized that SOLENA leads to stable effects on grief across 10 weeks. Comparison of the two active arms: When assessing the presentation format of SOLENA, it is hypothesized that self-tailored arm will lead to higher decrease of grief than the standardised arm. Secondary outcomes: Depression symptoms and perceived loneliness Efficacy of SOLENA: It is hypothesized that SOLENA will decrease depression symptoms and perceived loneliness significantly compared to the waiting list control or treatment as usual group. Stability of the effects: It is hypothesized that SOLENA leads to stable effects on depression symptoms and loneliness across 10 weeks. Comparison of the two active arms: When assessing the presentation format of SOLENA, it is hypothesized that self-tailored arm will lead to higher depression symptoms and loneliness than the standardised arm (superiority hypothesis). RECRUITMENT AND PROCEDURE Recruitment of participants will be conducted via newspaper articles, social media, internet forums, and personal contacts to healthcare workers and churches. Potential participants will find a description of the study and the intervention on the project website, from where they can register at the study. All potential participants can contact the study management to ask questions or clear eventual doubts about the study. This presentation is compiled in accordance with the general guidelines for clinical trials published by the Swiss Ethics Committees on research involving humans for the creation of an informed consent form (ICF) for information transfer. After receiving adequate and sufficient information about the study, the participants will declare consent by signing the ICF. All participants must confirm to have read this information before being allowed to participate in the study. After sending back the signed informed consent, participants will be invited to fill out the baseline measures on REDCap and take part in a short telephone call for screening the inclusion and exclusion criteria. Participants will be randomised to one of the three study arms (fixed-standardized, self-tailored or waiting list control group) and will receive the participant code to connect their data with study condition, ensuring confidentiality and privacy. For 10 weeks, starting at t0, participants will be asked to use the text-based program, SOLENA, to support their grief process and to complete the working alliance (goal & task), change mechanisms measures, and the self-check mood monitoring. At week 10 (t1, post-intervention), participants of the active arms will be asked to complete the primary and secondary measures. At this moment, the waiting-list control group starts using SOLENA and complete baseline measures. At week 20 (t2, follow-up), participants of the active arms will be asked to complete primary and secondary outcome measures to assess stability of program's effects. Also at this time, participants in the waiting list control group will complete post-intervention measures. At week 30 (t3), participants in the waiting list control group will complete follow-up measures. STATISTICAL ANALYSES PLAN Statistical analyses Analyses will be conducted according to the intention-to-treat paradigm. Linear mixed-models, which will be used in this study, allow a different number of measurement points per participants and are thus less sensitive to missing data. Time will be included (pre vs post intervention measures and post intervention vs follow-up measures), group (self-tailored and standardised vs. waiting list control condition) and interaction terms as predictors of the outcome variables. Cohens d will be calculated as effect size for all observed outcome variables. To analyse the longitudinal interplay of predictor and mediator variables, path analyses will be conducted. Analyses will be conducted in SPSS, R and Mplus. Any deviation from the original statistical plan will be described and justified in the final trial report. There are no statistical stopping rules in this trial. SAMPLE SIZE CALCULATIONS The study is mainly powered for the efficacy and stability hypotheses, i.e., the main and interaction effects of the active conditions compared to the waiting list control on the reduction of grief, depression symptoms, and loneliness. The sample size needed was obtained conducting a power analysis with a probability level of .05 and a power of 0.80 with G*Power based on the results of the evaluation of LIVIA, i.e., large to moderate effects. For the comparison of SOLENA and a waiting list condition, it is expected a large effect size of d > .80 or f > .4. For the comparison of the standardised and the self-tailored arms, it is expected a small to moderate effect between f = .25 and .15 in favour of the self-tailored arm. Figure 4 presents the power analyses for a repeated measures ANOVA with a within-between interaction for three groups. A minimum of 85 participants will be included, with an allocation ratio of 35:35:15 for the two active conditions and the waiting list control group. There is no statistical criterion for terminating the trial as more than 85 participants allow more sophisticated moderator analyses for example regarding the time since the loss. Data collection and analysis Data are assessed using online questionnaires programmed in REDCap. Data integrity is enforced through a variety of mechanisms, i.e., referential data rules, valid values, range checks, and consistency checks. The option to choose a value from a list of valid codes and a description of what each code means is available where applicable. Checks are applied at the time of data entry into a specific field. In addition, data on the use of the self-help sessions are collected within the platform. All data will be saved in an anonymous way only identified by a code which is not related to the participant's identity. Servers are protected by high-end firewall systems. Only the researchers directly involved in the study have access to the data. Handling of missing data and drop-outs Dropout are defined as participants who withdraw actively from the intervention after randomisation or who do not fill out the post-intervention in spite of two reminders. As for missing data, by withdrawing actively from the intervention, an e-mail will be sent with a REDCap link to the respective participants asking them to complete the post and follow-up questionnaires, nonetheless, thereby enabling us to conduct intention-to-treat analyses. In any case, all drop-outs are a part of the intent-to-treat sample as they have been randomised and are included in the analyses. Analyses of the extent of missing data will be conducted to explore the missing data patterns and determine the type of missing data (Missing Completely at Random, Missing at Random, Not Missing at Random). Missing values will be substituted using multiple imputations. Sensitivity analyses will explore the impact of the imputation of missing values. Official Title ----------------- An Online Self-help Intervention for Coping With the Loss of a Partner: Randomised Controlled Trial Conditions ----------------- Grief Intervention / Treatment ----------------- * Behavioral: SOLENA - Online self-help program for older adults who lost the partner Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Experience of spousal bereavement Seeking help for coping with grief or the psychosocial adaptation to a life without the partner Having access to an internet connection and adequate equipment Mastery of the German language An informed consent by the participant. Exclusion Criteria: Loss less than one month ago Acute suicidality Inability to follow the procedures of the study, e.g., due to comprehension problems, visual impairment, lack of sufficient motor skills or severe psychological or somatic disorders which require immediate treatment which impedes the continuous work on the self-help programme. 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 Interventional Model Description: The study is a single-centered randomized control trial with three arms: Two active arms correspond to the two intervention conditions in which the content is presented in a fixed standardised order (SOLENA-F) and a self-tailored order in which the participants select the modules and their sequence (SOLENA-ST) as well as the waiting list control group. Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Fixed standardized - SOLENA-F<br>In the fixed standardized arm participants will be asked to complete the study modules of the intervention (CBT intervention itself) in a fixed standardized order from module 1 to module 10. Participants will only be able to start the following module once they complete the previous one. At the beginning and at the end of each module it is emphasized what participants will do in the following module. | Behavioral: SOLENA - Online self-help program for older adults who lost the partner<br>* SOLENA follows the most relevant CBT elements of interventions for prolonged grief: 1) Exposure, e.g., telling the story of the loss; 2) cognitive reappraisal or restructuring of individual dysfunctional thoughts associated with the loss; 3) integration and restoration including self-care and social reengagement; and 4) behavioural activation. SOLENA's content is provided through a conversational virtual agent, Sol, who guides the user through the Study section the CBT intervention itself. In 10 study modules that address either the acceptance of the loss or the restoration and adaptation to a new life, SOLENA includes 1) readings, i.e., texts based about grief related topics that provide the background and rational for the module; and 2) exercises to encourage mourners to actively reflect on their grief and apply their new knowledge to their daily life and to practise the new routines regularly. SOLENA also provides users with the Notebook, Activities, and My Support sections.<br>* Other names: SOLENA;| | Experimental: Self-tailored - SOLENA-ST<br>In the self-tailored arm participants will be asked to complete most of the study modules of the intervention (CBT intervention itself) in a flexible format, according to their own needs at each moment. Participants will be asked to start the intervention by completing the preparatory modules (modules 1 and 2) following a fixed order. After completion of module 2, all the remaining modules become available at the same time. At the beginning and at the end of each module, participants are invited to reflect on their own needs and to complete the modules that better meet them. | Behavioral: SOLENA - Online self-help program for older adults who lost the partner<br>* SOLENA follows the most relevant CBT elements of interventions for prolonged grief: 1) Exposure, e.g., telling the story of the loss; 2) cognitive reappraisal or restructuring of individual dysfunctional thoughts associated with the loss; 3) integration and restoration including self-care and social reengagement; and 4) behavioural activation. SOLENA's content is provided through a conversational virtual agent, Sol, who guides the user through the Study section the CBT intervention itself. In 10 study modules that address either the acceptance of the loss or the restoration and adaptation to a new life, SOLENA includes 1) readings, i.e., texts based about grief related topics that provide the background and rational for the module; and 2) exercises to encourage mourners to actively reflect on their grief and apply their new knowledge to their daily life and to practise the new routines regularly. SOLENA also provides users with the Notebook, Activities, and My Support sections.<br>* Other names: SOLENA;| | No Intervention: Waiting list control group<br>Participants in this group will start the intervention 10 weeks after the randomization. Participants in the waiting list control group will be randomly distributed by the fixed standardised and self-tailored arms. This arm will follow the exact same procedure of the active arms. | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Grief: Texas Revised Inventory of Grief - German Version | Grief is assessed with the Texas Revised Inventory of Grief - German Version. The TRIG is a widely used measure to assess the severity of grief. The TRIG German version is a 16-item measure to assess the severity of grief from 1 = completely true to 5 = completely false. The scale ranges from 1 to 80, higher values indicate higher levels of grief. | At week 10 (post-intervention) | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Depression symptoms measured by The Patient Health Questionnaire (PHQ-9) German version. | Depression symptoms will be measured by the Patient Health Questionnaire (PHQ-9). The PHQ-9 corresponds to the depression assessment module, which scores each of the nine diagnostic criteria for major depression in Diagnostic and Statistical Manual Fourth Edition. For each item, answer format is a scale from '0' (not at all) to '3' (nearly every day). The scale ranges from 0 to 27, higher values indicate higher levels of depression. | At week 10 (post-intervention) | | Perceived loneliness measured by the Jong Gierveld Loneliness Scale | Perceived loneliness will be measured with the de Jong Gierveld Loneliness Scale. This will use the revised and shortened version of the scale that 6 items that resolve into social and emotional subscales. The items can be answered on a 5-point scale from '1' (yes) to '5' (no). The scale ranges from 1 to 30, higher values indicate lower levels of loneliness. | At week 10 (post-intervention) | Terms related to the study ================= Keywords Provided by Centre Hospitalier Valida ----------------- Grief symptoms, Depression symptoms, Loneliness, Prolonged grief, Self-help online program

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Better Nights, Better Days for Typically Developing Children Study Overview ================= Brief Summary ----------------- Up to 25% of children suffer from sleep problems categorized as insomnia: difficulty settling, falling asleep, and staying asleep. This leads to daytime sleepiness and negatively effects behaviour, mood, and academic performance. It also has negative effects on primary caregiver's sleep and their daytime functioning. Despite robust evidence supporting the efficacy of behavioural treatments for insomnia in children, very few receive these treatments. The most common treatment for insomnia in children is medication. This pattern of care is troubling because there are no approved medications for insomnia in children, and there are concerns about the safety and side effects of these medications. One of the primary reasons for the low rate of evidence-based treatment is the shortage of available treatment resources for both parents and health care providers. When evidence-based treatments are available, they are usually provided in a traditional service delivery framework. These traditional approaches are often very difficult for parents to access due to scheduling conflicts, incidental costs, and travel difficulties. Thus, there is a critical need for access to effective interventions focused on insomnia for children, and increased knowledge for parents and health care providers about appropriate treatments for insomnia. The Better Nights, Better Days (BNBD) program will provide a potential solution to one of the most common treatment barriers: access to care. BNBD will provide a readily accessible distance treatment via the internet, to increase access to evidence-based care for insomnia in typically developing children aged 1 to 10. BNBD was developed based on evidence-based programs and extant literature. The investigators will conduct a randomized controlled trial (RCT) in which participants (primary caregivers of children ages 1 to 10 years with insomnia) will be assigned to Intervention or Usual Care based on a 1-to-1 allocation. The effects of this behavioural sleep intervention will be assessed at 4 and 8 months post baseline assessment. Assessment will include both sleep and daytime functioning of the children, and daytime functioning of their caregivers. This study aligns with the recognized need to more rapidly transfer new scientific knowledge to improve patient care and population health, and targets the validation of new treatment delivery models to increase availability of effective treatment. Detailed Description ----------------- Rationale: Evidence demonstrates that behavioural interventions should be the first line of treatment for children with insomnia, but this is not typically the case. Evidence-based behavioural intervention protocols are not readily available for clinical use, and their lack of implementation indicates inadequate knowledge translation. When evidence-based treatments are available, they are usually provided in a traditional service delivery framework (i.e., face-to-face therapy, small group therapy). These traditional approaches are often very difficult for parents to access due to scheduling conflicts, incidental costs, and travel difficulties. Thus, there is a critical need for access to effective interventions focused on insomnia for children, and increased knowledge for parents and health care providers about appropriate treatments for insomnia. The Better Nights, Better Days (BNBD) program will bridge this gap as we will provide a potential solution to one of the most common treatment barriers, access to care. Intervention: The BNBD intervention for children aged 1 to 10 years with insomnia is a bilingual, self-guided program delivered online. The intervention incorporates evidence-based strategies, including sleep education, positive routines, faded bedtime with response cost, sleep restriction, extinction/graduated extinction, stimulus fading, and scheduled awakenings. The intervention is comprised of five sessions made available sequentially to participants. The completion time of the intervention will range from 5-10 weeks. Each session will provide factual information to parents, strategies for implementation of best practices to address sleep problems, and access to additional help and advice. There is also a Reward Centre where parents can learn how to use reinforcement for children (e.g., sticker charts) to help support the implementation of these sleep intervention strategies. Participants complete a short Sleep Diary for a minimum of 5 days for each session throughout this intervention so that they can receive feedback on their progress. The intervention delivers the interactive, personalized cognitive and behavioural change strategies accessed through participants' desktops, laptops, tablets and smartphones. The program can be used at a time that is convenient for the participants, removing barriers to care and providing services in the comfort and privacy of their own homes. Objectives and Hypotheses: The study will evaluate the effectiveness of the BNBD online intervention for insomnia in children 1-10 years of age. The primary objective is to assess the immediate impact (Baseline vs. 4 month) of the intervention on children's sleep. The two hypotheses for the primary outcomes are: Improvements in sleep efficiency calculated using actigraphy data in the Intervention Group compared with the Usual Care Group, and Improvements in sleep efficiency calculated using Sleep Diary data in the Intervention Group compared with the Usual Care Group The secondary objectives are: a) to evaluate the longer-term impact (baseline, 4, 8 months) on children's sleep and psychosocial health and, b) to examine the impact on parent daytime fatigue and psychosocial health outcomes. The four hypotheses of the secondary outcomes are: Children in the Intervention Group will show improvement compared to children in the Usual Care Group at the two follow-up time points in their symptoms of insomnia based on improvements in sleep efficiency calculated using actigraphy and Sleep Diary data in the Intervention group compared with the Usual Care group. Children in the Intervention Group will show improvement compared to children in the Usual Care Group at the two follow-up time points in their symptoms of insomnia based on the total score from the Behavioural Insomnia Questionnaire (BIQ) and Tayside Children's Sleep Questionnaire (TCSQ; toddler and pre-schoolers) / Sleep Disturbance Scale for Children (SDSC; school-age). Children in the Intervention group, compared to children in the Usual Care Group, will show improved psychosocial health based on the internalizing and externalizing total scores from the Child Behaviour Checklist (CBCL/1 ½-5 and CBCL/6-18) and the total score from the Pediatric Quality of Life (Peds- QL). Parents randomized to the Intervention Group, compared to parents randomized to the Usual Care group, will show at all follow-up time points: 1.Decreased daytime fatigue based on the Single Item Fatigue Impact Scale (SIFIS) 2.Improved psychosocial health as assessed by the total score of the Depression, Anxiety and Stress Scales (DASS-21) 3.Improved parenting strategies as assessed by the total score of the Parenting Scale (PS) Exploratory analyses will examine age effects, the impact of the intervention on children's physical health, as well as process-level evaluation and implementation questions, exploring how BNBD works (e.g., changes in specific sleep behaviours such as bedtime routines, and predictors of treatment success). Study Design: The study is a two-arm Randomized Controlled Tiral (RCT) design, using 1-to-1 allocation, comparing participants assigned to receive either the BNBD online program for parents (Intervention Group) or the control group (Usual Care Group) who will not receive the intervention. The intervention will be delivered across Canada. The study will be coordinated through Corkum LABS at Dalhousie University. Randomization will be used to minimize bias in the assignment of participants to either group, to increase the likelihood that known and unknown participant attributes (e.g., demographic and baseline characteristics) are evenly balanced, and to enhance the validity of statistical comparisons across groups. Participants will be stratified at randomization by three age groups (Toddler, Pre-School, School-Aged) and two primary languages (English and French). Targets will be set for each variable - 1/3 of sample in each age group and 20% of sample French speaking, modelling the Canadian populatipm. This will ensure the study population is representative and balanced. Within each stratum, subjects will be randomized using an equal allocation ratio of 1:1. Both the Intervention Group and Usual Care Group will be able to access alternative resources and additional programs and services while enrolled in the study. Blocks of 6 will be used to randomize the participants for each strata. The block size is short enough to prevent imbalance, and long enough to prevent guessing allocation in trials. The power analyses indicate the need to have 250 participants in total who complete the final follow-up assessment at 8 months post randomization. Based on the Investigators past intervention research as well as sleep intervention trials in the literature, 500 participants who have successfully completed eligibility will be needed using an estimated 50% drop out rate from post-eligibility to the final follow-up assessment at 8 months. More specifically, loss of participants at each stage is estimated to be the following: 22% from post eligibility to end of baseline, 15% from post-randomization to 4 month assessment, and 13% from the 4 month to 8 month assessment. Outcome measures will be administered to all participants at Baseline and at 4 and 8 months post-randomization online through the REDCap database. Data collected at 8 months will assess the degree of maintenance of any initial treatment effects on children's sleep in each age group, as well as examine the longer-term impact of the intervention on child and parent psychosocial health. The REDCap database will automatically contact participants via email to complete assessments. There will be automated emails from REDCap followed by phone calls from the research staff to ensure that outcome data is collected. Study participation ends for participants in both study groups after completing the 8 month follow-up assessment. Participants in the Usual Care group will gain access to the BNBD program after their study participation is complete. The BNBD program will be accessible for the Usual Care group for 3 months. Subject Population: A total of 500 participants will be eligible to participate in the study. Participants will be recruited from across all Canadian provinces and territories. A target of 100 English-speaking participants will be recruited from across four geographical regions of Canada (Atlantic, Central, Prairies, West Coast and Northern Territories). Data Analysis: The primary outcome measures that will be used to evaluate the impact of the intervention program on insomnia symptoms are sleep efficiency based on actigraphy data and sleep efficiency based on Sleep Diary data. Two primary outcome measures are included in order to capture the variables of interest using both an objective measure of sleep (i.e., actigraphy) and a parent-report/subjective measure of sleep (i.e., Sleep Diary), thus allowing for comparison with existing research in the field. Another reason for using both objective and subjective measures is that it has been found that unblinded RCTs (i.e., in which participants know their group assignment such as the current study) have been demonstrated to be biased in favour of the active treatment, and it has been suggested that an objective measure (e.g., actigraphy) should be utilized in the assessment of outcomes. Secondary outcomes will examine the longer-term impact of change in sleep as well as the impact on the child's psychosocial health (behavioural, attentional, and emotional functioning) over the duration of the 8 month trial. We will also examine the impact on parents' fatigue levels and psychosocial health. Primary Outcome: A mixed effect General Linear Models will be fit to the data to test if the Intervention group demonstrates improved outcomes compared to the Usual Care group. The dependent variables will be the primary outcomes assessed at 4 and 8 months post-randomization (sleep efficiency on actigraphy and the Sleep Diary). Participants will be modelled as random effects group (Intervention vs. Usual Care) and baseline covariates (age and language) will be modelled as fixed effects. A significant interaction effect between time (baseline, 4 and 8 month) and group will indicate an intervention effect for treatment. Secondary Outcome: All secondary outcomes will be separately analyzed using Hierarchical Linear Modelling and will test differences between the two groups (Intervention vs. Usual Care) in the growth curves modelling changes in the outcome variables across the four points of measurement, controlling for age, language and other covariates. Exploratory analyses: The investigators will examine the possibility of differential response to treatment across the three age groups using growth curve modelling of the two primary outcomes (actigraphy and Sleep Diary). Official Title ----------------- Better Nights, Better Days: Improving Psychosocial Health Outcomes in Children With Behavioural Insomnia Conditions ----------------- Nonorganic Insomnia, Primary Insomnia Intervention / Treatment ----------------- * Behavioral: Intervention Group Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Potential participants must meet the following criteria to be eligible to participate in the study: Primary caregiver of a child aged 1 to 10 years. Live in any province or territory in Canada. Have regular access to high speed internet connection and an email account. Comfortable communicating in English or French for day-to-day tasks (e.g., listening to the news on the radio or watching TV, reading books, magazines, etc.). Child has insomnia, defined as having Sleep Onset Disturbance. For Sleep Onset Disturbance, child must meet two of the following three criteria. These episodes must have been occurring for at least one month: 1. More than three reunions for 12-24 month olds/more than two reunions for >24 month olds that occur two or more nights per week 2. 30 or more minutes to fall asleep for 12-24 month olds/20 or more minutes to fall asleep for >24 month olds 3. Parent remains in room for sleep onset for two or more nights per week Exclusion Criteria: Potential participants who meet any of the following criteria are not eligible to participate in the study: Parent wishes to bed-share with his/her child. Child has a probable intrinsic sleep disorder (e.g., sleep apnea) as assessed using the Pediatric Sleep Questionnaire (PSQ). Child has a significant medical disorder that interferes with sleep (e.g., asthma attacks during night, tube feeding, non-ambulatory, severe developmental disability affecting sensory systems such as vision). Child has a mental health disorder that has required hospitalization or residential care and/or current use of psychotropic medications which are known to interfere with sleep (e.g., stimulant medication for ADHD). Ages Eligible for Study ----------------- Minimum Age: 1 Year Maximum Age: 10 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: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Experimental: Intervention Group<br>The Intervention Group receives access to the BNBD intervention, and can access alternative resources while enrolled in the study. The BNBD intervention for caregivers of children 1 to 10 years with insomnia is a self-guided program delivered online. The intervention is conceptually consistent across age groups. Interactive and personalized content and evidence-based strategies are incorporated: sleep education, positive routines, faded bedtime with response cost, sleep restriction, extinction/graduated extinction, stimulus fading, and scheduled awakenings. BNBD includes five sessions available sequentially: Sleep Information; Healthy Sleep Practices; Settling to Sleep; Going Back to Sleep; Looking Back and Ahead. The completion time of the intervention will range from 5-10 weeks. | Behavioral: Intervention Group<br>* The BNBD intervention for caregivers of children 1 to 10 years with insomnia is a self-guided program delivered online. The intervention is conceptually consistent across age groups. Interactive and personalized content and evidence-based strategies are incorporated: sleep education, positive routines, faded bedtime with response cost, sleep restriction, extinction/graduated extinction, stimulus fading, and scheduled awakenings. BNBD includes five sessions available sequentially: Sleep Information; Healthy Sleep Practices; Settling to Sleep; Going Back to Sleep; Looking Back and Ahead. The completion time of the intervention will range from 5-10 weeks.<br>* Other names: Better Nights, Better Days;| | No Intervention: Usual Care Group<br>The Usual Care Group will receive no treatment until after the 8 month follow-up assessment. The Usual Care Group can access alternative resources and additional programs and services while enrolled in the study. | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in Sleep Efficiency and Onset Latency from Baseline to 8 Month Follow-up with Actigraphy | Actigraphy involves measurement of motor activity using an accelerometer-based, battery-operated device. The investigators will use actigraphy to collect information about changes in children's sleep efficiency (captured from lights out to awakening), sleep onset, total sleep time, and night wakings from baseline to 4 month and 8 month follow-up. Actigraphy data have been shown to be highly concordant with polysomnographic (PSG) data for identifying sleep and waking (85-90%) and to distinguish effectively between sleep-disturbed children and controls. The investigators will use Philps Respironics Actiwatch 2 actigraphs. Actigraphy data will be collected for a one week period at baseline, and 4 months and 8 months post randomization. Participants are instructed to ensure their child wears their actigraph during the 7 days of Sleep Diary collection. | 8 months | | Change in Sleep Efficiency and Onset Latency from Baseline to 8 Month Follow-up with Sleep Diary | Sleep Diaries will be used to document sleep variables over a number of days/nights. A composite score will capture bedtime resistance, difficulties falling asleep and night wakings, as these are the key features of insomnia in children. Parents record information about their children's sleep and sleep behaviours for a one week. The Sleep Diary contains 25 items specifically measuring; sleep duration, night time sleep duration, daytime sleep duration, sleep onset latency, bedtime, wake time, presence and frequency of night awakening, and the presence and frequency of bedtime resistance. Sleep Diaries also provide a measure of time spent in bed extracted from the time the light was turned off (Down for the night) to the time lights were turned on (Up for the day). Sleep Diaries are administered to participants at the 3 assessment periods to assess change over baseline to 4 month and 8 month follow-up. Sleep diaries have demonstrated good face validity and high internal consistency. | 8 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Tayside Children's Sleep Questionnaire (TCSQ) | Two questionnaires will be used to assess children's sleep / insomnia, depending on the age of the child, at baseline, 4 month and 8 month assessment periods. The Tayside Children's Sleep Questionnaire (TCSQ) consists of 10 items and will be used to measure insomnia symptoms in children aged 1-5 years. Only the first 9 items are used for scoring, and the last item is included to assess how parents view their child's sleep problem, but is excluded from data analysis. The TCSQ has been validated for its use to accurately measure sleep problems. | 8 months | | Pediatric Quality of Life (Peds-QL) | The Pediatric Quality of Life (Peds-QL) questionnaire is used to assess children's physical and psychosocial health at baseline, 4 month and 8 month assessment periods. The participant will complete the form for ages 2-4, 5-7, or 8-12. The Peds-QL is a validated, 23-item modular tool designed to measure health related quality of life (HRQoL) in children and adolescents across 4 domains: physical, emotion, social and school functioning. The questionnaire uses a Likert Scale anchored 0 never to 4 almost always, with reverse-scored answers linearly transformed to a 0-100 scale, with higher scores reflecting higher health related quality of life. The cut-off score assigned to physical health is any value 1 SD below the population sample mean, and this is also applied to psychosocial health. | 8 months | | Child Behaviour Checklist (CBCL) | The Child Behavior Checklist (CBCL) for ages 1 ½-5 and 6-18 will be used to assess the child's daytime functioning and psychosocial health at the three assessment periods. CBCL/1 ½-5 responses are scored and summed across subscales (Emotionally Reactive, Anxious/Depressed, Somatic Complaints, Withdrawn, Sleep Problems, Attention Problems, Aggressive Behaviour), combined into internalizing and externalizing, and compared to a normative sample indicating the child's behaviour falling within normal limits, borderline clinical, or clinical. CBCL/6-18 responses are scored and summed across subscales (Anxious/Depressed, Withdrawn/Depressed, Somatic Complaints, Social Problems, Thought Problems, Attention Problems, Rule-breaking Behaviour and Aggressive Behaviour), grouped into either internalizing or externalizing factors with total scores, compared to a normative sample indicating where the child's behaviour falls. The CBCL is psychometrically sound. | 8 months | | Teacher Report Form (TRF) | The Caregiver Teacher Report Form (C-TRF) for children 1 ½ to 5 and Teacher Report Form (TRF) 6-18 is used to assess children's daytime functioning and psychosocial health, obtained from an informant to validate parent reports. The forms received by teachers are dependent on the child's age. The TRF measures a child's adaptive functioning and behavioural problems with 100 items on a 3-point Likert-scale anchored from 0 not true to 2 very true or often true, with the added textboxes for qualitative feedback. Both TRFs are optional measures that participants may forward to their child's teachers, and are administered at baseline, 4 months and 8-months follow up. The TRF has demonstrated good psychometric properties, high test-retest reliability and internal consistency. | 8 months | | Single Item Fatigue Impact Scale (SIFIS) | The SIFIS is a single item that measures the severity of fatigue on caregivers. Responses are recorded on a Likert-scale anchored from 0 none to 10 a severely disabling effect. Participants receive the SIFIS at baseline, 4 and 8 month assessment periods. The SIFIS was adapted from Chan and colleagues' (2003) 40-item Fatigue Impact Scale, a measure with sound psychometric properties, demonstrating high internal consistency and the adequate correlations between each item's rating and the summed ordinal ratings of the remaining items, high construct validity and responsiveness. | 8 months | | Depression Anxiety Stress Scale (DASS-21) | The Depression Anxiety and Stress Scale (DASS-21) is used to measure self-reported parent distress. Using 21 items, participants indicate to what extent they have experienced certain mental health disorder symptoms in the past month. Items are anchored from 0 did not apply to me at all to 3 applied to me very much or most of the time. Responses are scored into three subscales: depression, anxiety and stress. These subscales are combined to obtain a measure of general stress, which is the variable that used in this study. The DASS-21 has been validated for its use to measure parent distress in a community, nonclinical sample with strong internal consistency. Concurrent validity was also validated, and the DASS-21 also demonstrates high sensitivity to effects of parent-focused interventions. | 8 months | | Parenting Scale (PS) | The Parenting Scale (PS) is used to measure dysfunctional parenting practices consisting of 30 items. This rating scale was designed to measure dysfunctional parenting across three stable factors; laxness, over reactivity, and verbosity. Participants are instructed to select a circle on a visual analogue scale to identify to what extent they engage in certain parenting practices (e.g. giving child several reminders/warnings as opposed to one reminder/warning). The measure has established test reliability and validity. | 8 months | | Sleep Disturbance Scale for Children (SDSC) | Two questionnaires will be used to assess children's sleep / insomnia, depending on the age of the child, at baseline, 4 month and 8 month assessment periods. The Sleep Disturbance Scale for Children (SDSC) will be used to measure insomnia in children aged 6-10. The SDSC will be used to measure initiation and maintenance of sleep. The SDSC has been validated with high sensitivity specificity, and reliability coefficients. | 8 months |

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Efficacy of a Multiplex BangasureTM RT-PCR Kit for the Detection of COVID-19 Study Overview ================= Brief Summary ----------------- The outbreak of the severe acute respiratory syndrome (SARS) corona virus (CoV)-2 continues to increase globally. To control the coronavirus disease 2019 (COVID-19) transmission, diagnose is very important step which would help in the process of quarantine, isolation of the infected person and also in contact tracing. Among the various techniques real-time reverse transcription polymerase chain reaction (rRT-PCR) is mostly used and considers as gold standard method for viral nucleic acid detection as per World Health Organization (WHO) and Centre for Diseases Control (CDC), USA. However, possible false-negative and false-positive results produce misleading consequences, making it necessary to improve existing methods. So, investigators need a robust and reliable PCR kit to detect different kinds of variant of SARS-CoV-2 virus to reduce its transmissibility and take preventive management plan. Beside that to manage the increasing number of testing, investigators are mostly dependent on imported test kit which seems to be very difficult at this pandemic situation and costly. Hence, virulence of SARS-CoV-2 virus may change rapidly due to mutation and country become hot spot so, gene detection RT-PCR kit is time demand. In this point of view, investigator's aim to develop an validate multiplex rRT-PCR qualitative diagnostic method, which targets two viral genes E (envelope protein), N (nucleocapsid gene, according to the CDC, USA guidelines for the development of RT-PCR kit and one human gene RNase P as internal control simultaneously. This is a case control study where will analyze 120 samples (60 COVID-19 positive and 60 COVID-19 negative both fresh and frozen) from Institute of Epidemiology, Disease Control and Research (IEDCR). This specimen will be blinded before supplying over to NILMRC/Contact ROL/ Bangladesh Clinical Trail Limited (BCTL), Dhaka, Bangladesh for Bangladesh Reference Institute for Chemical Measurements (BRiCM) RT-PCR Kit. Required in house validation will also be conducted as per International Council for Harmonization (ICH) and FDA guideline and also external validation will be carried in different Director General of Health Service (DGHS), Bangladesh approved COVID-19 diagnostic laboratory. Data will be analyzed by computer using Statistical Package for the Social Sciences (SPSS) software and will be presented into the frequency table, graph and chart according to the requirements. Detailed Description ----------------- Introduction: The corona virus COVID-19 pandemic is the defining global health crisis of our time and the greatest challenge that have faced since World War Two. The pandemic is much more than a health crisis; it's also an unprecedented socio-economic crisis. Since its identification in the region of Wuhan, China, not only the virus has spread across 213 countries/territories with 209 million cases and 4.39 million globally but also could put 400million people out of their jobs as The International Labor Organization estimates. To contain the spread of disease, multidisciplinary strategies have been launched in different regions of the world, including implementing social distancing, maintaining personal hygiene, contact tracing, and implementing quarantine, travel restrictions, and lock downs. A widely accepted method is testing for SARS-CoV-2, typically utilizing nasopharyngeal swab specimens. Patients tested positive require appropriate clinical management by either effective isolation or quarantine at home for mild symptoms or within health care facilities for moderate to severe symptoms. In addition, wide-scale testing provides more informative epidemiologic data for drafting policies on disease monitoring and control. Many approaches have been proposed to detect SARS-CoV-2 virus in nasopharyngeal fluids such as multiplex RT-PCR, CRISPR/Cas12, and CRISPR-Cas3, lateral flow immunoassay, paper-based bimolecular sensors, SHERLOCK testing in one pot, DNA aptamer, loop-mediated isothermal amplification (LAMP), etc. Among these methods, nucleic acid amplification-based tests are the most common for the diagnosis of SARS-CoV-2. In addition, US CDC suggest a protocol for the detection of SARS-CoV-2, based on the amplification of two regions of the nucleocapsid gene, namely N1and N2, and a human internal control gene RNase P (RP). In addition to these strategies, efforts to develop SARS-CoV-2 detection methods with high efficiency and accuracy, with less reaction time and effort, are still ongoing. However, despite being considered as the gold standard for SARS CoV-2 detection, testing has lagged behind in many countries because of various factors, most important being supply chain issues with lack of reagents and adequate test kits. Therefore, many patients (both symptomatic and asymptomatic) remain untested and hence are potentially contributing to community spread of the virus. If Bangladesh can produce its own RT-PCR kits which is no less in quality in terms of sensitivity, specificity etc. than that would mitigate the shortage of RT-PCR kit as investigators are totally dependent on imported test kits and also save foreign currency. Moreover, RT-PCR test kits are very temperature sensitive and need to maintain the cold chain for its quality which can be mitigated by developing local RT PCR kit. Additionally, many variant of SARS-CoV-2 has been developed due to mutation, which has shown more virulence and high transmission rate. So, development of new RT PCR kit which can detect newer strain can be extremely helpful. So, here investigator's aim to develop the three gene detectable robust RT-PCR kit that will be country first and give reliable result of different kinds of variant of SARS-CoV-2 virus for reducing its transmissibility and taking preventive management plan 2. Objectives of the Study: General Objectives: Primary objectives are aimed to develop multiplex real-time reverse transcription polymerase chain reaction (rRT-PCR) to detect of SARS-CoV-2. Secondary Objectives: For the best RT-PCR performance, the combination of E and N gene targets should be optimized. 3. Methodology: 3.1. Study type & purpose: This is a case control and observational study in which two existing groups frozen and fresh samples are identified and compared. 3.2. Place of study: Institute Epidemiology Disease Control and Research (IEDCR) M/S. Clinical Research Organization Ltd 3.3. Sample Collection Site(s): Institute Epidemiology Disease Control and Research (IEDCR) or National Institute of Laboratory Medicine & Referral Centre (NILMRC), Dhaka, Bangladesh. 3.4. Duration of study: • 3 months (November, 2021 to January, 2022) after getting Ethical Clearance from Bangladesh Medical Research Council. 3.5. Study Population/sample selection 3.5.1 CRO will receive testing samples from IEDCR. IEDCR and BCTL/CROL as CRO have memorandum of understanding (MoU) for different collaborative research work. So, NILMRC/ BCTL/CROL will receive a total 120 sample from IEDCR for the evaluation of RT-PCR kit efficiency. Of the 120 samples, 60 will be stored samples (30 COVID-19 known positive and 30 COVID-19 negative samples) which have been kept at -80°C lab freezers at IEDCR facilities and another 60 fresh specimens (30 COVID-19 positive and 30 COVID-19 negative samples) which are being tested at IEDCR. Samples with discordant results will be rejected before testing by BRiCM RT PCR kit. That is, more than 120 identified samples from IEDCR might be needed to analyze by imported RT-PCR kits and extraction kit at BCTL/CROL. This is how 120 samples will be selected for performance evaluation of BRiCM RT-PCR kit. 3.5.2 To avoid biasedness and conflicts of interest, sponsor and PI/co-investigators will be blinded to the sample ID and positive/negative status of the samples and clinical records of the patients. The positive/negative status of both stored and fresh samples will be identified at IEDCR before sending to BCTL/CROL. That is, BCTL/CROL personnel will also be blinded to sample identity document (ID) and positive negative/negative status before analysis. Finally, the CRO head will send the performance evaluation certificate to the PI or Sponsor. 3.5.3. Statistical Basis of Sample Size: Formulae: The study is conducted on 120 participants (60 stored known positive & negative and 60 fresh known positive & negative). To achieve desire absolute accuracy (n) in estimating efficiency of RT-PCR the minimum sample size estimated following following the Discrete Bernoulli Probability Function as follows: Alfa= 5% D= absolute Accuracy (%) with 95% confidence. Desired Absolute accuracy n D Alfa=5% Z=1.96 10 30.99% n D= (1.96)/(2* Square Root (SQRT) (n)) 20 21.91% 100 9.80% 30 17.89% 120 8.94% 100 9.80% 200 6.93% 300 5.66% 400 4.90% 1000 3.10% 10000 0.98% 20000 0.69% 30000 0.57% 100000 0.3% 3.6 Sample Selection Criteria 3.6.1 Inclusion criteria: Samples with Positives RT-PCR results with Ct value≤35 for the COVID-19 genes at IEDCR will be selected as COVID-19 positive. Samples with negative RT-PCR results with no amplification for the COVID-19 genes at IEDCR will be selected as COVID-19. Gender: All Age: 5 to 70 years (Child, Adult, Older Adult) 7.8.2. Exclusion criteria Samples with equivocal/ambiguous RT-PCR results in terms of sigmoidal curve and Ct value will be excluded. Consents from the patients are not required because the CRO will receive the specimens from IEDCR as per MOU with IEDCR. So there is no requirement of patient's enrollment and consents and CRF from the CRO side. 3.7 Data Collection Procedure: COVID-19 positive samples will be confirmed by laboratory findings of positive RT-PCR results for the viral RNA. 3.8 Data Analysis: The sensitivity, specificity, positive predictive value and negative predictive value of BRiCM COVID-19 real time RT-PCR kit will be determined. The chi-square test (two sided) will be performed for comparing categorical variables. A p value of ≤0.05 will be considered as the level of significant association. Alongside sensitivity, specificity, positive predictive value and negative predictive value, Kappa coefficient, positive likelihood ratio, and negative likelihood ratio will also be calculated. 3.9 The database is safeguarded against unauthorized access by established security procedures; appropriate backup copies of the database and related software files shall be maintained. Databases are backed up by the database administrator in conjunction with any updates or changes to the database. 3.10 The Investigator must make study data accessible to the monitor and authorized representatives. The Investigator must provide interim study report with data at every three months interval to the principle investigator. As per requirement study report and data may be provided to Bangladesh Medical Research Council (BMRC) and Directorate General of Drug Administration (DGDA). The Investigator must ensure the reliability and availability of source documents. 3.11 Monitoring visits will be conducted by principle investigator, co- investigator as well as the representatives according to Guidelines for Good Clinical Practice (GCP). 3.12 In order to maintain subject confidentiality, only a site number, subject number and subject initials will identify all study subjects on Case Records Forms (CRF) and other documentation submitted to the investigator. Additional subject confidentiality issues (if applicable) are covered in the Clinical Study Agreement. 3.13 All records will be kept secret to the PI, co-investigators, sponsor except IEDCR responsible persons who are in charge. Samples will be identified as code/ID number and date at IEDCR before sending to BCTL/Contact Research Organization Limited (CROL) 4. For this study the mentioned institute IEDCR/Bangladesh Clinical Trail Limited (BTCL)/CRO Ltd. has the capability to conduct the clinical trial to find out the efficacy of kit through their existing resource. Beside that CRO can manage the chemical, reagent and technology if any needed for the study as per MoU between funding agencies. 5. Conflict of the interest BRiCM is the funding agency of proposed COVID-19 RT-PCR kit, is a statutory body functioning under the administrative control of the Ministry of Science and Technology. It is a research organization and a reference institute in the area of chemical measurements. It is neither a commercial enterprise nor a profit making organization. According to constitutional sanction the principal responsibility of BRiCM is to carry on research leading to such innovation that will add value to the government effort for ensuring welfare of the people. Official Title ----------------- Development of a Multiplex BangasureTM RT-PCR Kit for the Detection of SARS-Corona Virus-2 Conditions ----------------- COVID-19 Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Samples with Positives RT-PCR results with Ct value≤35 for the COVID-19 genes at IEDCR will be selected as COVID-19 positive. Samples with negative RT-PCR results with no amplification for the COVID-19 genes at IEDCR will be selected as COVID-19. Exclusion Criteria: Samples with equivocal/ambiguous RT-PCR results in terms of sigmoidal curve and Ct value will be excluded. Ages Eligible for Study ----------------- Minimum Age: 5 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 | | --- | --- | | Cases (Current/fresh)<br>Cases (current/fresh) are defined as those samples which has been tested positive by RT-PCR at IEDCR as a regular screening program and have not been stored in the freezer. | | | Cases(stored)<br>Cases (stored) are defined as those samples which has been tested positive by RT-PCR at IEDCR as a regular screening program and have been stored in the -80°C freezer at IEDCR. | | | Control (Current/fresh)<br>Control (Current/fresh) are defined as those samples which has been tested negative by RT-PCR at IEDCR as a regular screening program and have not been stored in the freezer. | | | Control (stored)<br>Control (stored) are defined as those samples which has been tested negative by RT-PCR at IEDCR as a regular screening program and have been stored in the -80°C freezer at IEDCR | | What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Performance evaluation of BRiCM COVID-19 RT-PCR | Determine Performance evaluation of BRiCM COVID-19 RT-PCR with extracted viral RNA by using standard viral RNA extraction kit for the detection of SARS-CoV-2 virus in nasopharyngeal swab specimens collected in the nationwide COVID-19 screening program. RNA extraction from fresh Nasopharyngeal Swab sample in the Viral Transport Medium (VTM) of COVID-19 patients from IEDCR (30 positive and 30 negative) Analysis of COVID-19 RNA samples using RT-PCR. | 1 month | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Reduce the price and enhance the efficiency to detect COVID-19 by BRiCM COVID-19 RT-PCR kit | Supply locally manufacturer COVID-19 reverse transcription polymerase chain reaction (RT-PCR) kit to govt. and private hospitals for diagnosis of COVID-19 patients. RNA extraction from frozen nasopharyngeal swab sample in viral transport medium (VTM) of COVID-19 patients from IEDCR (30 positive and 30 negative) analysis of COVID-19 RNA samples using reverse transcription polymerase chain reaction (RT-PCR). | 1 month |

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New Therapeutic Approach Against BK Virus Infection Based on Monoclonal Antibodies Study Overview ================= Brief Summary ----------------- BK virus (BKV) infection has a major negative impact on transplant recipients. No BKV-specific antiviral therapy is available, so there is an urgent need to develop new anti-BKV preventive and therapeutic strategies. Official Title ----------------- New Therapeutic Approach Against BK Virus Infection Based on Monoclonal Antibodies Conditions ----------------- BK Virus Infection Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: BK positive adult ok to participed to research Exclusion Criteria: under guardianship under curatorship opposed to research deprived of liberty 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 | | --- | --- | --- | | Ability of the isolated monoclonal antibodies to neutralize all 3 BKV genotypes | The neutralization titer will be defined as the dilution of the sample that produced 50% inhibition of pseudovirion infectivity (IC50) | 5 years |

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The Diagnostic Observatory: Combating Diagnostic Wandering and Impasse Within the AnDDI-Rares Network Study Overview ================= Brief Summary ----------------- The Direction Générale de l'Organisation des Soins (DGOS) and the Banque Nationale de Données Maladies Rares (BNDMR) have launched a call for a letter of commitment for the implementation of a diagnostic observatory in order to fight against diagnostic wandering and impasse. In this context, the AnDDI-Rares network proposes 3 work packages (WP) to respond to the missions entrusted to it. Work package 1 of the diagnostic observatory includes a retrospective and prospective study to evaluate how diagnostic wandering and impasse has evolved within the network, with regard to the integration of new technologies, and the expectations of patients and their families. Work package 2 of the diagnostic observatory includes a reassessment of sporadic copy number variations (CNV) of unknown significance of more than 1 Mb obtained since the beginning of CGH array analyses in the territory. Work package 3 of the diagnostic observatory aims to help put an end to diagnostic wandering for patients with certain emblematic syndromes by proposing genome and RNA analysis, which provides a certain diagnosis and negative targeted molecular study. Official Title ----------------- The Diagnostic Observatory: Combating Diagnostic Wandering and Impasse Within the AnDDI-Rares Network Conditions ----------------- Developmental Abnormality Intervention / Treatment ----------------- * Other: Questionnaire to assess expectations of a diagnosis * Other: Questionnaire to assess understanding of previously reported results and expectations of a diagnosis * Biological: Blood sample +/- skin biopsy Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: WP1: - Children or adult patients who did not obtain a diagnosis after consulting for a developmental abnormality (that may include isolated or multiple, minor or major malformations, facial dysmorphia associated or not with learning disabilities and/or intellectual disability). These patients had a diagnostic evaluation over the 2 weeks randomly drawn from 2012 and 2022. Patients agreeing to resume a diagnostic approach requiring new blood samples. For genome sequencing through the platforms of the France Genomic Medicine Plan, when they correspond to the criteria of existing preindications, the parents' sample will be proposed. - Patients (adults or their parents) affiliated to national health insurance or beneficiaries of such a system WP2: For the identification of patients eligible for reanalysis (Part 1 Lab) : Patients, children or adults with developmental anomalies with or without neurodevelopmental disorders, Patients in whim a de novo CNV of unknown significance of more than 1 Mb has been detected since the implementation of the CGH array platforms The CNV remained of unknown significance or classified as (probably) benign after reanalysis* *reanalysis other than that performed in the context of the diagnostic observatory For reanalysis, in addition to the previous inclusion criteria (Part 2 Clinical): CNV remained of unknown significance or classified as (probably) benign after reanalysis** Patients and/or their parents agreeing to resume diagnostic testing Patients (adults or their parents) affiliated to national health insurance or beneficiaries of such a system ** After reanalysis in the framework of the diagnostic observatory WP3: Patients (children or adults) with a syndrome that corresponds to the study criteria: Established clinical diagnosis for one of the characteristic syndromes of the AnDDI-Rares pipeline (list may be revised in the future): Noonan syndrome, CHARGE syndrome, Kabuki syndrome, Cornelia de Lange syndrome, Rubinstein-Taybi syndrome ; Known gene(s) but patient's molecular diagnosis is negative. Patients and their parents agreeing to a new blood sample for genome ± RNA sequencing and/or skin biopsy for conditions where gene transcription is not satisfactory from RNA extracted from blood; or agreeing to perform these analyses from previously stored samples; Parents of legal age who are affiliated with national health insurance or who are beneficiaries of such a system; Signed informed consent from both biological parents and/or the index case if they are of legal age; Ability of both biological parents to understand correctly. Exclusion Criteria: WP1: Patients without a developmental abnormality ; Patients with a previously identified diagnosis at the time of consultations on the weeks drawn randomly from 2012 and 2022. WP3: Unlikely clinical diagnosis ; Family not wishing to pursue molecular investigations; Index case having already benefited from the investigations through another research project. The parents of the index case are under court protection ; Families where one of the 2 parental authority holders is not a biological parent Sexes Eligible for Study ----------------- All Accepts Healthy Volunteers ----------------- No Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Work package 1 (WP1)<br>Patients without a diagnosis who consulted for a developmental anomaly in 2012 and 2022 and agree to resume a diagnostic approach | Other: Questionnaire to assess expectations of a diagnosis<br>* Duration 45 minutes<br>| | Work package 2 (WP2)<br>Part 1 (Lab): Patients with developmental abnormalities with or without neurodevelopmental disorders who have had a CNV (Copy Number Variation) rendering that remained of unknown significance or classified as (probably) benign Part 2 (Clinical part): Patients who agree to resume the diagnostic process following a CNV report of unknown significance or classified as (probably) benign | Other: Questionnaire to assess understanding of previously reported results and expectations of a diagnosis<br>* Duration 30 minutes<br>| | Work package 3 (WP3)<br>Patients with an established clinical diagnosis belonging to the characteristic syndromes of the AnDDI-Rares network (known gene(s) but negative molecular diagnosis) | Biological: Blood sample +/- skin biopsy<br>* 8 ml of blood biopsy: size 3 to 5 mm<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Consultations leading to a causal genetic diagnosis in 2012 and 2022 | | through study completion, an average of 24 months | | CNVs reclassified as pathogenic/probably pathogenic or benign/probably benign. | | through study completion, an average of 24 months | | Molecular diagnosis identified by sequencing of the genome ± associated RNA. | | through study completion, an average of 36 months |

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SASH Study - Sonographic Assessment for Severe Hypertension in Pregnancy Study Overview ================= Brief Summary ----------------- • Adjunctive use of easily-obtainable maternal sonographic vascular measurements assessing volume status, cardiac output, and systemic vascular resistance by means of inferior vena cava collapsibility/caval index (ICV CI), end-point septal separation (EPSS) for determining left ventricular ejection fraction (LVEF), cardiac output determination (stroke volume x heart rate), stroke volume variation, & radial artery resistance index) augments standard vital sign assessment (pulse pressure and systolic / diastolic predominance) in clinical decision-making potentially leading to more appropriate pharmacologic and clinical therapies with faster resolution of severe hypertension among pregnant women and women in the postpartum period. Detailed Description ----------------- Minutes count when it comes to treating and preventing serious complications associated with hypertensive emergencies in pregnancy. The rates of maternal morbidity and mortality are on the rise within the United States whereas the rates are falling in the rest of the developed world. Cardiovascular and neurologic injury associated with the severe hypertension witnessed among women with preeclampsia/eclampsia represent two of the leading causes of maternal mortality within the U.S. Optimizing the clinical identification and response to these perinatal complications represents one means of reducing overall maternal mortality. Point-of-care use of ultrasound technology to augment clinical diagnosis and management is gaining traction throughout nearly all fields of medicine. Obstetricians utilize this technology frequently to assess the fetus and maternal-fetal interface, and our ability to expand its use to assess a deeper understanding of maternal physiology is underutilized. Exploration into the ability to apply clinically-proven point-of-care sonographic techniques to augment maternal care and reduce maternal mortality is warranted. The purpose of this study is to gain a deeper understanding of maternal physiologic changes using easily-obtainable sonographic vascular measurements in the setting of hypertensive emergencies and to assess the utility of these adjunctive maternal sonographic measurements in augmenting clinical decision-making. Official Title ----------------- SASH Study - Sonographic Assessment for Severe Hypertension in Pregnancy Conditions ----------------- Hypertension in Pregnancy Intervention / Treatment ----------------- * Other: Cardiovascular Sonographic Assessment Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: For symptomatic women, those presenting to triage, admitted to Labor & Delivery or any of the above units who are at risk for developing a hypertensive emergency will be identified by the OBGYN resident staff or attending physicians as at risk for hypertensive emergency as based on current chronic hypertension, gestational hypertension, or preeclampsia). Women presenting with or developing new onset hypertensive emergency can be offered recruitment as well given that the performance of these sonographic measures will not interfere with initiating antihypertensive therapy. Exclusion Criteria: Age < 18 years Non-pregnant Without the capacity to provide informed written consent Non-English speaking without the ability to obtain a hospital interpreter Known atrial-ventricular heart block History of heart failure Moderate-to-Severe bronchial asthma Allergy to the medications used as part of regular care treatment of the patient population Lack of intravenous IV access Concurrent use of antihypertensive medications Congenital heart disease in the mother Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- Female Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Symptomatic patients<br>All pregnant women (under the care of the Maternal-Fetal Medicine physicians or Faculty Medical Center physicians with MFM involvement) experiencing a hypertensive emergency (sustained systolic blood pressure > 160 mmHg or sustained diastolic blood pressure > 110 mmHg {or both} on at least two consecutive occasions 15 minutes apart). All participants must be over the age of 18 and capable of consenting to the study (conscious, with capacity for medical decision making for themselves). | Other: Cardiovascular Sonographic Assessment<br>* Maternal sonographic vascular measurements assessing volume status, cardiac output, and systemic vascular resistance by means of inferior vena cava collapsibility/caval index (ICV CI), end-point septal separation (EPSS) for determining left ventricular ejection fraction (LVEF), cardiac output determination (stroke volume x heart rate), stroke volume variation, & radial artery resistance index) augments standard vital sign assessment (pulse pressure and systolic / diastolic predominance)<br>| | Asymptomatic patients<br>All asymptomatic pregnant women who are undergoing routine obstetric ultrasound evaluations at any gestational age who elect to undergo cardiovascular sonographic assessment for research purposes at no cost. All participants must be over the age of 18 and capable of consenting to the study (conscious, with capacity for medical decision making for themselves). | Other: Cardiovascular Sonographic Assessment<br>* Maternal sonographic vascular measurements assessing volume status, cardiac output, and systemic vascular resistance by means of inferior vena cava collapsibility/caval index (ICV CI), end-point septal separation (EPSS) for determining left ventricular ejection fraction (LVEF), cardiac output determination (stroke volume x heart rate), stroke volume variation, & radial artery resistance index) augments standard vital sign assessment (pulse pressure and systolic / diastolic predominance)<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Systolic Blood Pressure | Systolic Blood Pressure at Enrollment into the Study | At Enrollment into the Study |

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Erector Spinae Block, Epidural Analgesia and Intrathecal Analgesia in Thoracic Surgery Study Overview ================= Brief Summary ----------------- Pulmonary thoracic surgery is often responsible for severe postoperative pain, which is associated with an increase in postoperative morbidity and mortality. Moreover, postoperative thoracic pain has a strong impact on patient rehabilitation and is associated with an increase in hospital stay. Various analgesic techniques allow effective management of pain in the context of thoracic surgery. Regional anesthesia, particularly, allows a powerful analgesia, and limits the use of opioids and their side effects. Among regional anesthesia techniques, thoracic epidural analgesia has become the gold standard for post-thoracotomy analgesia. However, it induces a sympathetic block that promotes in particular per and postoperative hypotension and acute urinary retentions. Thus, new regional anesthesia techniques have been developed and assessed in thoracic surgery in order to avoid side effects related to epidural analgesia, particularly paravertebral block and erector spinae block, but also intrathecal analgesia. Paravertebral block has shown analgesic efficacy after thoracic surgery, and its interest in reducing the risk of hypotension, acute urinary retention, pruritus and postoperative nausea and vomiting compared with the epidural analgesia. Erector spinae block, recently described and evaluated in this context of thoracic surgery, seems to have the same interests and to be easier to achieve than the paravertebral block, but has been little studied. Finally, intrathecal morphine is frequently used because of an easy and rapid realization, and because it allows an adequate analgesia and the reduction of the duration of stay in intensive care compared to the epidural one. However, despite its frequent use, very few studies have compared intrathecal anesthesia with the epidural and other peri-spinal blocks. These three types of analgesia, epidural analgesia, intrathecal morphine, and erector spinae block are regional anesthesia methods regularly used for pulmonary surgery in the department of the investigators. All of these techniques have shown their analgesic efficacy, but each seems to have particular respective interests, in terms of achievement, management, or perioperative rehabilitation. The objective of the investigators study is to evaluate the effectiveness of each of its techniques to treat postoperative pain and improve the rehabilitation of these patients. Official Title ----------------- Efficacités comparées du Bloc Des Muscles érecteurs du Rachis, du Bloc péridural et de la rachianalgésie en Chirurgie Thoracique Majeure. Conditions ----------------- Pulmonary Surgery Intervention / Treatment ----------------- * Procedure: Epidural anesthesia * Procedure: Intrathecal morphine * Procedure: Erector spinae block Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Thoracic surgery for pulmonary resection Scheduled regional anesthesia: epidural anesthesia, intrathecal morphine or erector spinae block Exclusion Criteria: No epidural anesthesia or no intrathecal morphine or no erector spinae block performed Ages Eligible for Study ----------------- Minimum Age: 18 Years Sexes Eligible for Study ----------------- All Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Epidural anesthesia<br>At physician discretion (observational study) | Procedure: Epidural anesthesia<br>* Preoperative epidural anesthesia at physician discretion<br>| | Intrathecal morphine<br>At physician discretion (observational study) | Procedure: Intrathecal morphine<br>* Preoperative intrathecal morphine at physician discretion<br>| | Erector spinae block<br>At physician discretion (observational study) | Procedure: Erector spinae block<br>* Preoperative erector spinae block at physician discretion<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Pain assessment at H+48 | Numerical pain rating scale: 0 (no pain at all) to 10 (worst imaginable pain) | Day 2 after surgery | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Total consumption of morphine (per and postoperative) | | Hour 2, Day 1, Day 2 and Day 3 after surgery. | | Length of stay in intensive care unit | | Through study completion, an average of 1 year | | Length of hospital stay | | Through study completion, an average of 1 year | | Impact on respiratory function | Peak Flow in L/min | Day 1, Day 2 and Day 3 after surgery. | | Frequency of adverse effects related to morphine Frequency of morphine side effects | | Hour 2, Day 1, Day 2 and Day 3 after surgery. | | Postoperative pain assessment at other times | Numerical pain rating scale: 0 (no pain at all) to 10 (worst imaginable pain) | Hour 2, Day 1, and Day 3 after surgery. |

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Impact of Bariatric Surgery on Women Fertility Study Overview ================= Brief Summary ----------------- Obesity is a multifactorial risk factor for subfertility, in relation to chronic hormonal change induced by adipose tissue. This prospective cohort study aims to evaluate the impact of bariatric surgery induced weight loss on women fertility. Detailed Description ----------------- Females undergoing sleeve gastrectomy will be assessed for improvement of fertility indicators Official Title ----------------- Impact of Bariatric Surgery Induced Weight Loss on Women Fertility: A Prospective Cohort Study Conditions ----------------- Fertility Issues Intervention / Treatment ----------------- * Procedure: Sleeve gastrectomy Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: Age from 20-40 years. BMI >35 kg/m2 Exclusion Criteria: Women with medical endocrinal disorders as DM, thyroid, hyperprolactinaemia, etc. Women using any hormonal treatment or fertility drugs like oral contraceptive pills and/or metformin. Women have any surgical complication intra-operatively or post operatively. Women refused to participate in the study. Ages Eligible for Study ----------------- Minimum Age: 20 Years Maximum Age: 40 Years Sexes Eligible for Study ----------------- Female Accepts Healthy Volunteers ----------------- Accepts Healthy Volunteers Study Plan ================= How is the study designed? ----------------- Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Sleeve gastrectomy<br>Sleeve gastrectomy for weight loss | Procedure: Sleeve gastrectomy<br>* Bariatric surgery<br>| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in Antimullerian hormone level | Change in antimullerian hormone level | 3 months | Secondary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Change in serum FSH level | | 3 months | | Change in serum LH level | | 3 months |

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COVID-19 ThromboprophylaXIs Study of Novel FXIa Inhibitor Frunexian (EP-7041) in ICU Patients Study Overview ================= Brief Summary ----------------- This is a multicenter, open-label, single cohort study of patients with confirmed COVID-19 syndrome who based on clinical judgment require care in an intensive care unit, regardless of whether or not mechanical ventilation is in use or is anticipated. Patients should be enrolled on the first day of the ICU stay; withdrawal of prior thromboprophylaxis, if any, will follow specific protocol guidance. Enrolled patients will thereafter be administered intravenous frunexian (EP-7041) until disposition from the hospital (including post-ICU non-critical care management) Detailed Description ----------------- The goal of the COVID-ThromboprophylaXIs Study is to determine the safety and tolerability of two doses of frunexian (EP-7041) for the prevention of thromboembolism in the management of COVID-19 patients, compared to control patients managed with institutional standard care thromboprophylaxis regimens. Dosing of frunexian for the first 15 patients enrolled will be randomized to 0.6 mg/kg/hr IV (n=15) and next 15 patients will be randomized to 1.0 mg/kg/hr IV (n=15) for the duration of the index hospitalization. Enrollment will be paused after treatment of these 30 patients, at which time a dedicated DSMB will evaluate all collected safety data through 7 days post-index hospital discharge. If no adverse safety signal is identified for the 1.0 mg/kg/hr dose, enrollment will be resumed with the study dose of frunexian randomized 2:1 to 1.0 mg/kg/hr or institutional standard care for thromboprophylaxis in ICU patients with COVID-19. If safety concerns are identified for the higher dose and not for the lower dose, then open-label randomized enrollment vs institutional standard of care for thromboprophylaxis will proceed with an frunexian dose of 0.6 mg/kg/hr. The second phase of the study will enroll 60 additional patients, with 40 in the frunexian dosing arm, and 20 in the standard care arm. Official Title ----------------- Prospective, Open-Label Single Ascending Dose Study of Two Dose Levels of Frunexian (EP-7041), Followed by a Randomized Comparison of One Dose With Institutional Standard Care, for Thromboprophylaxis in Patients Managed in Intensive Care Settings for COVID-19 Syndrome: The COVID-ThromboprophylaXIs Study Conditions ----------------- Thrombopenia, Covid19 Intervention / Treatment ----------------- * Drug: EP-7041 Injection Participation Criteria ================= Eligibility Criteria ----------------- Inclusion Criteria: SARS-CoV-2 test (by local evaluation) positive Symptom severity and general risk of decompensation warrants, in the opinion of the treating clinician, admission to/care in an intensive care unit setting Patient or legally authorized representative (LAR) able and willing to provide written informed consent No contraindication to receiving anticoagulation At least one D-dimer value ≥2 times local ULN (within 72 hours of hospital admission) Exclusion criteria Patients who meet ANY of the following criteria are not eligible for inclusion: Moribund patient not expected to survive 24 hours ICU length of stay > 24 hours prior to initiation of frunexian infusion Existing venous thromboembolism Known immune compromise (HIV/AIDS, chemotherapy, chronic corticosteroid therapy, transplant patient, etc.) Active cancer diagnosis Pregnant, lactating, or parturient woman bodyweight <40kg hemoglobin <8.0 g/L in the last 72 hours platelet count <50 x 109/L in the last 72 hours known fibrinogen <1.5 g/L (if testing deemed clinically indicated by the treating physician prior to the initiation of anticoagulation) known INR >1.8 (if testing deemed clinically indicated by the treating physician prior to the initiation of anticoagulation) patient already on therapeutic anticoagulation at the time of screening (low or high dose nomogram UFH, LMWH, warfarin, or any regular dose of a direct oral anticoagulant) patient on dual antiplatelet therapy, when at least one of the agents cannot be stopped safely history of spontaneous intracranial bleeding; gastrointestinal bleeding requiring hospitalization and/or transfusion within prior 3 months major surgery within prior 30 days known bleeding within the last 30 days requiring emergency department presentation or hospitalization known history of a bleeding disorder of an inherited or active acquired bleeding disorder recent (<48 hours) or planned spinal or epidural anesthesia or puncture anticipated transfer to another hospital that is not a study site within 72 hours enrollment in other trials related to anticoagulation or antiplatelet therapy use of pneumatic compression devices for thromboprophylaxis Failure to meet ALL Inclusion Criteria 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: Multicenter, Open Label, Single Dose Escalation Study Masking: None (Open Label) Arms and Interventions | Participant Group/Arm | Intervention/Treatment | | --- | --- | | Other: Active<br>Frunexian infusion 0.6 mg/kg/hr or 1 mg/kg/hr. 0.6 mg/kg/hr dose will be completed first. | Drug: EP-7041 Injection<br>* EP-7041 infusion<br>* Other names: Frunexian;| | Active Comparator: Institutional Standard<br>Clinician's choice of prophylaxis strategy | Drug: EP-7041 Injection<br>* EP-7041 infusion<br>* Other names: Frunexian;| What is the study measuring? ----------------- Primary Outcome Measures | Outcome Measure | Measure Description | Time Frame | | --- | --- | --- | | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | Identify the appropriate dose of EP-7041 that demonstrates safety as defined by incidence of treatment-emergent adverse events | 30 days after discharge |

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