All Clinical Trials

The primary purpose of the study is to transition participants into an extension study to collect long-term safety and efficacy data. The study will include participants who are safely tolerating bomedemstat, receiving clinical benefit from its use in estimation of the investigator, and have shown the following criteria: * Participants from the IMG-7289-202/MK-3543-005 (NCT05223920) study must have received at least 6 months of treatment with bomedemstat; * Essential thrombocythemia (ET) and polycythemia vera (PV) participants from studies other than IMG-7289-202/MK-3543-005 must have achieved confirmed hematologic remission. No hypothesis testing will be conducted in this study. Read Less

Background: Diseases related to the immune system, blood clots, and blood vessels can affect every part of the body. These diseases are now known to be interrelated: People who have strokes, blood clots in their legs, or autoimmune disease, for example, are at greater risk of complications in the heart, brain, and other organs. Researchers want to learn more about how these diseases start, how they change over time, and how they affect different organs. Objective: To learn more about how inflammation and diseases of the blood vessels start and how they change over time. Eligibility: People aged 5 years and older with a disease related to blood clots, the immune system, or blood vessels. Healthy relatives of people with these diseases and unrelated healthy volunteers are also needed. Design: Participants will have a baseline visit: They will provide a medical history, physical exam and blood test. All other tests and procedures are optional; these may be spread over more than 1 day: Tests of heart and lung function. Fill in a family tree form. Imaging scans Treadmill or bike stress tests and a 6-minute walk test. Tests of blood pressure and the flow of blood through vessels. Photos of the face and body. Eye exams, with photos taken of the retina. Saliva and urine samples. Biopsies (tissues samples) of the skin and fat. Tests of thinking and mental function. Evaluations by other medical specialists. Participants may opt to return for repeat testing for up to 90 months (7.5 years). Some visits may be done by telehealth. Read Less

The study is designed to evaluate the safety, immunogenicity, and efficacy of the intramuscular administration of a CS6 based vaccine (CssBA) against ETEC co-administered with double mutant labile toxin (dmLT) in preventing moderate-severe diarrhea (MSD) following challenge with ETEC strain B7A in healthy adults. Approximately 72 adult participants, divided into 4 cohorts of 18, will be randomized 1:1 to receive vaccine (45 micrograms CssBA with 0.5 micrograms dmLT) or placebo (normal saline) on an outpatient basis. All participants will receive 3 intramuscular (IM) doses of vaccine or placebo at 3-week intervals (days 1, 22 and 43). Following vaccination, participants will be followed as outpatients for safety using a memory aid from the time of each vaccination through 7 days post each vaccination. Approximately 28 days (plus or minus 1 day) after receipt of the 3rd dose of study agent, participants meeting challenge criteria will be admitted to an inpatient unit and be administered an oral dose of 1 x 10\^10 cfu (colony-forming unit) of ETEC strain B7A. Five days after challenge, participants will be treated with ciprofloxacin, except in cases of known allergy or intolerance. Participants will be discharged from the inpatient unit when they have completed their 3-day antibiotic course and are able to care for themselves. After discharge from the inpatient unit, participants will return for clinic visits and have a phone visit to provide any updates on medication, medical history and AE/SAEs. The primary objectives are: 1) Estimate CssBA+dmLT efficacy in preventing moderate-severe diarrhea (MSD) following challenge with ETEC strain B7A in healthy adults. 2) Evaluate the safety of intramuscular injection of CssBA+dmLT. Read Less

Magnetic Resonance Imaging (MRI) unlike X-rays and CT-scans does not use radiation to create a picture. MRI use as the name implies, magnetism to create pictures with excellent anatomical resolution. Functional MRIs are diagnostic tests that allow doctors to not only view anatomy, but physiology and function. It is for these reasons that MRIs are excellent methods for studying the brain. In this study, researchers will use MRI to assess brain anatomy and function in X and Y chromosome variation, healthy volunteers, and patients with a variety of childhood onset psychiatric disorders. The disorders include attention deficit disorder, autism, congenital adrenal hyperplasia, childhood-onset schizophrenia, dyslexia, obsessive compulsive disorder, Sydenham's chorea, and Tourette's syndrome. Results of the MRIs showing the anatomy of the brain and brain function will be compared across age, sex (gender), and diagnostic groups. Correlations between brain and behavioral measures will be examined for normal and clinical populations. Read Less

This study will explore the causes of rheumatic diseases and why many of them affect certain minority communities more severely. Rheumatic diseases may cause joint pain, stiffness or swelling. Some can involve bones, muscles, tendons or ligaments. Some cause abnormalities of the immune system the body s defense against disease. Some rheumatic diseases are painful or deforming and some can be life threatening. Information obtained from this study will be used to learn about the disparities in rheumatic disease in the minority community and to design further, more targeted, research studies to address this issue. Patients with known or suspected rheumatic disease 18 years of age or older may be eligible for this study. Candidates will undergo a medical history and physical examination to confirm the diagnosis of rheumatic disease and determine what is needed for evaluation and treatment. Participants will receive standard medical care for rheumatic disease and arthritis. No experimental treatments, medications or procedures will be included in this study. Procedures may include routine blood tests for blood chemistries, cell counts, and antibodies commonly found in patients with rheumatic disease; a urine test for proteins and cells; and X-rays and other imaging tests to check for abnormalities in the lungs or other organs. All medical information will be kept confidential. Patients who are found to be eligible for other current NIH research studies will be offered an opportunity to participate in these studies. ... Read Less

Eosinophils are a type of white blood cell. Elevated eosinophil levels can damage the heart, nerves, and other organs, in the syndrome known as hypereosinophilic syndrome (HES). Some individuals have a hereditary form of HES known as familial eosinophilia (FE). More research on the causation and mechanisms of HES is needed in order to design more effective and less toxic therapies. This study will investigate FE and its genetic causes, damage mechanisms, and disease markers (such as blood test abnormalities). It will enroll approximately 50 individuals (both adults and children) from a previously studied family with FE. This is a long-term study of indefinite duration. Participants will undergo yearly clinical examinations including medical history, physical examination, bloodwork, EKG, echocardiogram, and pulmonary function tests, with additional or more frequent examinations and tests as required. In addition, participants will donate blood and tissue for research purposes. Both adult and child participants will donate blood. At the initial evaluation, adult participants will donate bone marrow. During the study, some adult participants will also undergo a limited number of leukaopheresis sessions, in which blood is donated from one arm, the blood is separated into red blood cells and other components, and the red blood cells are returned into the donor's other arm. ... Read Less

Background: * Endocrine neoplasms (tumors) are among the fastest growing tumors in incidence in the United States. Furthermore, it is often difficult to distinguish between benign or malignant tumors in cancers of the thyroid, parathyroid, adrenal gland, and pancreas. More research is needed to improve detection and treatment options for patients who develop these kinds of cancer. * Researchers are interested in studying the molecular changes that are involved in endocrine cancer development and growth. To collect a sample of tumor specimens and healthy tissue for further study, researchers are specifically looking for samples from patients who are scheduled for surgery or biopsy on endocrine tumors. Objectives: - To collect samples of precancerous, cancerous, and healthy tissue from individuals who are scheduled for surgery or biopsy of endocrine system tumors. Eligibility: - Individuals who have a tumor in or around their thyroid, parathyroid, adrenal gland, pancreas, or any neuroendocrine tissue, and are scheduled for surgery at the National Institutes of Health Clinical Center. Design: * Participants in this study will provide blood and urine samples prior to surgery. * During the surgery or biopsy, pieces of the tumor or precancerous growth and pieces of normal tissue near to the tumor will be removed for ongoing and future research. The rest of the tumor or growth will be sent for analysis. * After surgery, participants will receive routine care until discharge, and doctors will discuss possible treatment options. If there is an appropriate NIH protocol, participants may choose to be treated at the NIH. * After discharge, participants will return to the clinic for a routine postoperative check about 6 weeks following the operation, and then may be followed yearly at the Clinical Center or by phone. Read Less

Background: - Researchers at the National Institutes of Health give many tests of hearing and balance. These tests can help detect problems that affect hearing or balance. It is important to know exactly how healthy people perform on each of these tests. This information will indicate when a test result is normal and when a test result shows a problem. Researchers also want to determine the best methods for each test. Objectives: - To test different types of hearing and balance tests, and collect information on normal values for each test. Eligibility: - Healthy volunteers between 5 and 80 years of age. Design: * This study will require a single visit to the National Institutes of Health Clinical Center. It will include both screening tests and study tests of hearing and balance. Sometimes, a second visit may be required if a test is designed to measure the same thing on 2 different days. Each visit will last between 2 and 5 hours, depending on the number of tests scheduled per visit. * Participants will have a physical exam and medical history. They will also have basic tests to check for normal hearing and balance. * Participants may have different hearing tests, including the following: * Auditory Evoked Potentials to study how the ears and brain handle sound information. * Auditory Processing Tests to study how a person processes complex sounds like speech in background noise. * Tests of middle ear and inner ear function. * Participants may have different balance and inner ear tests, including the following: * Balance test on a tilting platform. * Different tests to measure how well the eyes, ears, and brain work together to help maintain balance. * Treatment will not be needed as part of this study. Read Less

Background: There are no good treatments for people considering suicide. Researchers want to study suicide with questions, blood tests, brain imaging, and sleep studies. They hope to better understand suicide, so they can help suicidal people. Objective: To understand what happens in the brain when someone has thought about or attempted suicide. Eligibility: Group 1: Adults ages 18 70 who have thought about or attempted suicide recently Group 2: Adults ages 18 70 who have thought about or attempted suicide in the past Group 3: Adults ages 18 70 who have depression or anxiety, but have never thought about suicide Group 4: Healthy volunteers the same ages. Design: Participants will be screened in another protocol. Adults who have recently thought about or attempted suicide must be referred by a doctor. They may do up to 3 phases of this study. Groups 2, 3 and 4 will do only Phase 1 and will not get ketamine. Phase 1: 1 week in hospital. Participants will have: Physical exam. Questions about thoughts and feelings. Thinking and memory tests and simple tasks. Blood and urine tests. Two MRI scans. Participants will lie on a table that slides into a metal cylinder that takes pictures. They will have a coil over their head and earplugs and do a computer task. Sleep test. Disks and bands will be placed on the body to monitor it during sleep. Magnetic detectors on their head while they perform tasks. A wrist monitor for activity and sleep. Lumbar puncture (optional). A needle will collect fluid from the back. Shock experiments (optional). Participants will observe pictures and sounds and feel a small shock on the hand. Phase 2: 4 days in hospital. A thin plastic tube will be placed in each arm, one for blood draws, the other to get the drug ketamine once. Participants will repeat most of the Phase 1 tests. Phase 3: up to 4 more ketamine doses over 2 weeks. Participants will have follow-up calls or visits at 6 months and then maybe yearly for 5 years. Read Less

Background: Lymphoma is a type of blood cancer. Blood cell transplant can cure some people with lymphoma. Researchers want to see if they can limit the complications transplant can cause. Objective: To test if a stem cell transplant can cure or control lymphoma. Also to test if new ways of getting a recipient ready for a transplant may result in fewer problems and side effects. Eligibility: Recipients: People ages 12 and older with peripheral T cell lymphoma that does not respond to standard treatments Donors: Healthy people ages 18 and older whose relative has lymphoma Design: Participants will be screened with: Physical exam Blood and urine tests Bone marrow biopsy: A needle inserted into the participant s hip bone will remove marrow. Donors will also be screened with: X-rays Recipients will also be screened with: Lying in scanners that take pictures of the body Tumor sample Donors may donate blood. They will take daily shots for 5 7 days. They will have apheresis: A machine will take blood from one arm and take out their stem cells. The blood will be returned into the other arm. Recipients will be hospitalized at least 2 weeks before transplant. They will get a catheter: A plastic tube will be inserted into a vein in the neck or upper chest. They will get antibody therapy or chemotherapy. Recipients will get the transplant through their catheter. Recipients will stay in the hospital several weeks after transplant. They will get blood transfusions. They will take drugs including chemotherapy for about 2 months. Recipients will have visits 6, 12, 18, 24 months after transplant, then once a year for 5 years. Read Less

Background: Primary sclerosing cholangitis is a rare chronic liver disease. It affects the bile ducts of the liver. It can result in bile duct infections, cirrhosis, cancer, and end stage liver disease. Researchers want to learn more about this disease. Objective: To understand the biological causes of primary sclerosing cholangitis. Eligibility: Adults age 18 and older who have primary sclerosing cholangitis. Design: Participants will be screened with a medical history, physical exam, and blood tests. Participants will give blood, saliva, urine, and stool samples. They will have nasal swabs. They will complete surveys. Participants will get an intravenous (IV) catheter. A plastic tube is inserted into an arm vein. Participants will have a colonoscopy. A tube with a video camera at the end is inserted into the rectum. Participants will have an upper endoscopy. A scope with a light and camera at its tip is used to look inside the upper digestive tract. Participants will have a liver biopsy, entering through the chest wall or a neck vein. Blood is drawn from a blood vessel that carries blood to the liver. A liver tissue sample is taken. Participants will have magnetic resonance imaging or spectroscopy. They will get a contrast agent through an IV. Participants may have an optional bone marrow aspiration. A large needle is inserted into the hip to withdraw marrow. Participants will have a liver ultrasound. Participants will complete a 3-day food diary. They will have a nutrition assessment. Participants may give contact details for people who live with them, to also take part in this study. Participation will last for 12 months.... Read Less

Study CDFV890G12101 is an open-label, phase 1b, multicenter study with a randomized two-dose optimization part, and a dose expansion part consisting of two groups evaluating DFV890 in patients with myeloid diseases. The purpose of this study is to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, efficacy and recommended dose for single agent DFV890 in patients with lower risk (LR: very low, low or intermediate risk) myelodysplastic syndromes (LR MDS) and lower risk chronic myelomonocytic leukemia (LR CMML). Read Less