Background: The genes a person is born with can sometimes cause serious diseases. Genetic diseases are rare, but they can have a big impact on the people they affect. Researchers have already made great strides in understanding how some genes cause disease. But they would like to have even better tools to analyze and understand genetic data. To create these new tools, they need to gather health and genetic data from a lot of people. Objective: This natural history study will gather medical information from people with genetic conditions. Eligibility: People of any age who (1) are known or suspected to have a genetic condition or (2) have a family member with a known or suspected genetic condition. Design: Participants will come to the clinic for up to 4 days. Tests to be performed will vary depending on the nature of each participant s health issue. The tests may include: Blood and saliva. Blood may be drawn from a vein; cells and saliva may be collected by rubbing the inside of the cheek with a swab. These would be used for genetic testing. Imaging scans. Participants may have X-rays or other scans of their bodies. They may lie still on a table while a machine records the images. Heart tests. Participants may lie still while a technician places a probe on their chest. They may also have stickers attached to wires placed on their chest. Photographs and recordings. Pictures may be taken of facial features, skin changes, or other effects of the genetic condition. Video and audio recordings may also be made. Some people may be able to participate via telehealth.

Type: Observational

Start Date: Apr 2026

open study

Background: Heart disease is a leading cause of death. People can reduce their heart disease risk by exercising more. Mobile health technology may make people more successful at increasing their exercise. This includes things like physical activity monitors and smartphone apps. Objective: To find out if mobile health technology can increase physical activity. Eligibility: African American women ages 21-75 who: - Are overweight or obese - Live in certain areas near Washington, DC - Have a smartphone that can use the study app Design: At visit 1, participants will - Answer survey questions. These may be about medical history, physical activity, and weight. They may also cover body image, health perception, and spirituality. - Have body size measured and get blood tests - Get a device to wear on the wrist. It will record physical activity and hours of sleep. - Learn how to download and use the study mobile app For 2 weeks, researchers will collect data about participants physical activity. Then participants will have a study visit with additional blood tests. All participants will get messages from the app that encourage exercise. Some participants will get data from the app about exercise near their home or work. Some participants may get face-to-face coaching. Participants may get wireless devices. These measure body weight, blood pressure, and blood glucose. Participants can measure these at home and upload the data to the app for the study. Participants will have visits after 3 and 6 months. They will repeat the visit 1 tests.

Type: Interventional

Start Date: Jun 2018

open study

Background: Runt-related transcription factor 1 (RUNX1) gene regulates the formation of blood cells. People with mutations of this gene may bleed or bruise easily; they are also at higher risk of getting cancers of the blood, bone marrow, and lymph nodes. Objective: The purpose of the study includes determining which dose of imatinib is best for people with pathogenic or likely pathogenic RUNX1 mutations without blood cancers, and to determine whether there are any changes in platelet function and inflammatory markers. Eligibility: Adults aged 18 and older with RUNX1 mutations. Healthy people without this mutation, including family members of affected participants, are also needed. Design: Participants with the RUNX1 mutation will be screened. They will have a physical exam with blood tests. They will have a test of their heart function. They may need a new bone marrow biopsy if they haven't had one in the past year. Imatinib is a tablet taken by mouth once a day, every day, at home. Affected participants in different parts of the study will take imatinib for either 28 days or up to 84 days. They will fill out questionnaires about how they are feeling. For the first part of the study, participants will have blood tests every 2 weeks, either at home or at the NIH, while they are taking the imatinib. They will have a follow up visit, at home or at the NIH, when they are done taking imatinib on Day 28. Participants on the second part of the study will come to NIH on days 1 and days 84. They will have blood tests every 2 weeks (at home or the NIH) while they are taking imatinib. They may opt to have a bone marrow biopsy repeated after they finish their course of imatinib. Participants will have a follow-up visit (at home or the NIH) 30 days after they stop taking imatinib. Participants who do not have the RUNX1 mutation will have 1 clinic visit. They will have blood tests. They will fill out questionnaires. They may opt to have a bone marrow biopsy.

Type: Interventional

Start Date: Dec 2023

open study

Background: At least 30% of Americans have fatty liver disease. This means that they store too much fat in the liver. At the moment lifestyle changes are the only way to treat this problem. Objective: To test how (1) a low-carbohydrate diet and (2) a supplement called nicotinamide riboside (NR) affect how a person s body uses dietary fat. Eligibility: Men aged 18 to 65 and women aged 18 to 50 who are healthy volunteers with a body mass index (height to weight ratio) of 25 or more. Adults with maturity-onset diabetes of the young type 2 (MODY2) are also needed. Design: Participants with diabetes will have 1 screening visit and a 9-day clinic stay. Healthy volunteers will have 1 screening visit and 2 clinic stays of 1 to 2 weeks each. During screening, all participants will have a physical exam with blood and urine tests. They will have their heart rhythm measured while riding a gym bike. NR is a pill taken by mouth. Only healthy volunteers will take the NR, for 14 days at a time, during 1 clinic stay. During their other stay, they will take placebos; these are pills that look like the study supplement but contain no NR. During each clinic stay, all participants will eat a normal American diet. Then they will eat a ketogenic "low-carb" diet for 5 days. Participants will have many tests, including: Sleeping every night and having two 24-hour stays in a special room that measures the gases their body uses and produces. Drinking a high-fat shake, then remaining seated for 5 hours while their blood and breath are monitored. Having a substance injected into the arm and remaining seated for 3 hours while their blood is measured. Wearing monitors to measure their activity levels. Another monitor will measure their blood glucose levels. Having imaging scans. ...

Type: Interventional

Start Date: Jan 2024

open study

Background: Multiple sclerosis (MS) is a disease that damages the central nervous system (brain and spinal cord). This leads to increased physical disability over time. The disease is lifelong once it begins. Researchers want to learn more about MS s stages and follow them until a person s death. Objective: To understand how the physical and clinical signs of MS relate to its changes over time. Eligibility: Adults age 18 or older with MS or a disease of the brain and spinal cord that may act like MS. Design: Participants will have a medical history and a complete neurological exam. They may have timed tests of neurological function, such as a 25-foot walk and a 9-hole peg test. Participants will have multi-day visits about once a year. Participants will have blood drawn. Participants may have a brain magnetic resonance imaging (MRI) scan. They may also have an MRI of the spinal cord. They may get a contrast agent (dye) injected into a tube in an arm vein. During the MRI, participants will lie on a table that slides in and out of a metal cylinder. Participants will have the thickness of their retina measured using optical coherence tomography. A camera on top of a table uses lasers. Participants will look through a lens and follow instructions. Eye drops may be used to dilate the pupils. Participants will chew on a piece of sterile cotton for 1 minute to collect saliva. Participants agree to have an autopsy at the time of their death and to donate some of their organs to research, such as the brain and spinal cord.

Type: Observational

Start Date: Apr 2016

open study

Study Description: This study examines relations between neurocognitive and clinical features of pediatric anxiety disorders. The study uses neuro-cognitive tasks, functional magnetic resonance imaging (fMRI), as well as magneto- and electro-encephalography (M/EEG). Patients will be studied over one year, before and after receiving either one of two standard-of-care treatments: cognitive behavioral therapy (CBT) or fluoxetine, a serotonin reuptake inhibitor (SSRI). Healthy comparisons will be studied at comparable time points. Primary Objectives: To compare healthy youth and symptomatic, medication-free pediatric patients studied prior to receipt of treatment. The study seeks to detect relations between clinical features of anxiety disorders at baseline and a wide range of neurocognitive features associated with attention, memory, and response to motivational stimuli. Secondary Objectives: 1. To document relations between baseline neurocognitive features and response to Cognitive Behavioral Therapy (CBT) or fluoxetine, as defined by the Pediatric Anxiety Rating Scale (PARS) and Clinical Global Improvement (CGI) Scale. 2. To document relations between post-treatment changes in neurocognitive features and anxiety symptoms on the PARS following treatment with Cognitive Behavioral Therapy (CBT) or fluoxetine. 3. To document relations among broad arrays of clinical, cognitive, and neural measures Primary Endpoints: Indices of percent-signal change in hypothesized brain regions, comprising amygdala, striatum, and prefrontal cortex (PFC) for each fMRI and MEG paradigm. Secondary Endpoints: 1. Treatment-response as defined by a continuous measure, the Pediatric Anxiety Rating Scale score (PARS), and a categorial measure, the Clinical Global Improvement (CGI) score. 2. Levels of symptoms and behaviors evoked by tasks that engage attention, memory, and elicit responses to motivational stimuli.

Type: Interventional

Start Date: Oct 2001

open study

Background: Irritability can be defined as an unusually strong response to frustration; these responses may include severe temper outbursts and a constant grumpy mood. Irritability is a common symptom of many mental health disorders. Little is known about how the brain responds to frustration, and few treatments are available for this problem. Researchers want to know more about how the brain responds to frustration. Objective: To learn how the brain responds to frustration. Eligibility: Healthy adults aged 18 to 55 years. They must have been screened through studies 01-M-0254 or 17-M-0181. Design: Participants will have up to 3 study visits in 2 months. Each visit will last up to 4 hours. Visit 1: Participants will be screened. They will have a physical exam. They will complete questionnaires about how often and how easily they get angry or grumpy. They will be trained to use a device that measures hand grip. Visit 2: Participants will have a magnetic resonance imaging (MRI) scan. They will lie on a table that slides into a tube. Padding will hold their head still. Visit 3: Participants will undergo magnetoencephalography (MEG). A cone with detectors will be lowered over their head while they are seated. The MEG will measure the magnetic fields in the participant s brain both while they are resting and while they are doing the frustration task. For the task, they will hold a grip device in each hand. They will use the devices to pick 1 of 2 doors on a computer screen. The task has 3 parts. The participant s face will be filmed during this task.

Type: Interventional

Start Date: Feb 2025

open study

Background: Kaposi sarcoma (KS) is a type of tumor caused by the Kaposi sarcoma herpesvirus. KS usually affects the skin, but lesions can also appear in the lymph nodes, lungs and digestive tract. KS is most common in people with compromised immunity, but it also appears in otherwise healthy people. Researchers want to understand more about how KS develops, why it may recur, and how it affects the immune system and organs. Objective: To learn more about the natural history of KS. Eligibility: People aged 18 years and older with KS. Design: Participants will be screened. They will have a physical exam with blood tests. They will have an imaging scan. They may need a new biopsy: Tissue samples may be cut from their tumor. Their ability to perform normal activities will be assessed. Participants will visit the clinic to have their KS evaluated. In addition to the imaging scans and other tests performed during screening, procedures may include: Eye exam. Ultrasound exam of the heart (electrocardiogram). Collection of saliva and urine samples. Biopsies of the skin or lymph nodes. Swabs of the anus and cervix. Photographs of skin lesions. Removal of fluid samples from the space around the lungs, intestine, or heart. The evaluation visit will be repeated 5 more times over 18 months and then yearly for up to 10 years. Participants will follow their standard treatment for KS during the study.

Type: Observational

Start Date: May 2024

open study

Background: The lymphatic system is a network of vessels that carry a clear fluid called lymph through the body. Problems in the lymphatic system can cause pain, fluid buildup, and issues with immunity. There is much researchers do not understand about lymphatic anomalies. In this natural history study, they will collect data from a lot of people over a long time. Objective: To better understand why lymphatic anomalies develop. The goal is to improve future treatments. Eligibility: People aged 0 days and older with a suspected or confirmed lymphatic anomaly. Their unaffected parents or siblings aged 7 years or older are also needed. Design: Participants may remain in the study indefinitely. Affected participants may be evaluated every 10 months to 2 years. Some participants will be seen over telemedicine. Others will be seen at the NIH Clinical Center for 2-5 days. All participants will have a physical exam. They may provide specimens including blood, saliva, hair follicles, stool, skin, and other tissues. Samples may be used for genetic testing. Participants may undergo other tests depending on their medical conditions. The NIH Clinical Center visit may include: Heart tests include placing stickers on the chest to measure electrical activity and using sound waves to capture pictures of the heart. A lung test measures the muscle strength in the chest. Participants will blow into a tube. Photographs may be taken of participants faces and other features. Imaging scans will take pictures of the inside of the body. One scan will measure bone density. One type of scan tracks how lymph fluid moves through the body. Participants will be under anesthesia, and they will be injected with a dye.

Type: Observational

Start Date: Mar 2023

open study

Background: - Recent advances in cancer research have led to new therapies to treat the disease. It is important to continue these advances and discover new ones. To do that, researchers need tissue samples from solid tumors. This study will collect such samples from people already scheduled to have a procedure at the National Institutes of Health Clinical Center (NIHCC). Objectives: - To collect tissue samples for use in studying new ways to treat tumors. Eligibility: - Adults 18 years and older, with a precancerous or cancerous solid tumor who are scheduled to have surgery or a biopsy at the NIHCC. - Children under the age of 18 but who are older than 2 years of age are eligible to be enrolled on the research sample collection portion of this study if they will have a biopsy or surgery as part of their medical care. Design: - Before their procedure, participants will have a small blood sample taken. - Some participants will undergo leukapheresis. In this procedure, blood is removed through a tube in one arm and circulated through a machine that removes white blood cells. The blood, minus the white blood cells, is returned through a tube in the other arm. The procedure takes 3-4 hours. - For all participants, during the surgery or biopsy, pieces of the tumor and pieces of normal tissue near it will be removed for this study. The rest of the tumor or precancerous growth will be sent to a lab for analysis. - Participants will return to the clinic about 6 weeks after the operation for a routine checkup. Some may have to return for additional follow-up.

Type: Observational

Start Date: Jul 2013

open study

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.

Type: Observational

Start Date: Oct 2001

open study

Background: Magnetic resonance imaging (MRI) is a tool for getting pictures of the tissues and organs inside the body. MRI can help diagnose many injuries and diseases. But not all patients are equally likely to receive MRIs. Factors such as race or ethnicity, distance to imaging centers, mobility, and a lower income can limit some people s access to MRIs. A new ultra-low field (ULF) type of MRI, which can be used on a vehicle, may help take imaging scans to more people. But researchers need to know that UFL-MRI works just as well as standard MRIs. Objective: To learn whether UFL-MRI is as good as standard MRI at detecting neurological disorders. Eligibility: People aged 3 years or older who have or show symptoms of neurological disease (such as stroke, cancer, or epilepsy). Healthy adults are also needed. Design: Participants will have 1 or 2 study visits. Adult participants will have a physical exam. They will receive two MRI exams: - Standard MRI. They will lie still on a narrow bed that will move into a large tube. They will wear earplugs to muffle the sounds. - ULF-MRI. They will lie on a stretcher, and only their head will be inside a smaller tube. The noises will be quieter. They will wear earplugs to muffle the sounds. Some adults may receive a contrast agent given through a small tube attached to a needle in the arm. The contrast agent helps the researchers see differences in the body more clearly. This may be done during 1 or both MRIs. Children will have only 1 ULF-MRI. Some participants may be invited to have additional visits for up to 6 months.

Type: Observational

Start Date: Mar 2024

open study

Background: People living with HIV(PLWH) are at a higher risk for cancers that may be curable with a bone marrow transplant. HIV infection itself is no longer a reason to not get a transplant, for patients who otherwise have a standard reason to need transplant. Objective: This study is being done to see if a new combination of drugs (cyclophosphamide, maraviroc, and bortezomib) is both safe and effective at protecting against graft-versus-host disease after bone marrow transplant. The study will also test the transplant s impact on your survival and control of your cancer. Eligibility: People aged 18 years and older living with HIV and a blood cancer that is eligible for a transplant. Healthy family members aged 12 or older who are half matched to transplant recipients are also needed to donate bone marrow. Design: The study will be done in 2 phases. The first phase will be to see if we can safely use a new combination of drugs to prevent GVHD. If the combination is safe in the first phase, the study will proceed to the second phase. In the second phase, we will see if this new combination can better protect against GVHD after transplant. Participants will be screened. Their diagnoses, organ function and eligibility will be confirmed. Participants will have a catheter inserted into a vein in their chest or neck. Medications and transfusions will be given through the catheter; blood will be drawn from it. Participants will be in the hospital for 6 weeks or longer. They will receive various drugs for 2 weeks to prep their body for the transplant. The transplant cells will be administered through the catheter. Participants will continue to receive drug treatments after the transplant. Blood transfusions may also be needed. Participants will return 1-2 times per week for follow-up visits for 3 months after discharge. Participants will have visits 6, 12, 18, 24 months after transplant, then once a year for 5 years.

Type: Interventional

Start Date: Jan 2023

open study

Background: Proteus syndrome is a rare overgrowth disorder. Most people begin to have symptoms between 6 months and 2 years of age. There are very few living adults with this disease. There is also no known treatment for it. Researchers want to see if a new drug can slow down or stop overgrowth in people with Proteus syndrome. Objective: To learn if miransertib is a safe and effective treatment for Proteus syndrome. Eligibility: People ages 3 and older with Proteus syndrome. Design: Participants will be screened with a medical checkup. They will answer questions about their medical history and current health. They will have a physical exam with vital signs. They will have an electrocardiogram to measure their heartbeat. They will give blood and urine samples. They will repeat the screening tests during the study. Participants will take a miransertib pill once a day. They will bring their empty pill bottles with them to the NIH when they visit. If they can t swallow a pill, researchers will try to find other ways for them to take the drug. Participants will have X-rays, ultrasounds, and imaging scans. Photos may be taken of their feet and other parts of the body that have or develop signs of Proteus syndrome. Participants will have lung function tests to measure how much and how fast air moves out of their lungs. Participants will complete surveys about their levels of pain, physical functioning, and quality of life. Participants may have additional tests performed to assess their individual disease. They may have consultations with other specialists. Participation lasts about 4 years. Participants will have 20-30 visits at the NIH....

Type: Interventional

Start Date: May 2022

open study

Background: - Chromatin is is the structural building block of a chromosome. It is found inside the nucleus of the cell and consists of a complex of DNA and protein. - Cancers of the lung, pleura (lung lining) and esophagus show profound changes in chromatin structure that may affect the course of disease in patients. - A better understanding of these diseases and the genetic changes associated with them may be helpful in developing new treatments for them. Objectives: - To evaluate people with cancer of the lung, pleura or esophagus for participation in NCI clinical trials. - To obtain biopsies (small pieces of tissue) from tumor, normal tissue and blood samples to learn more about the cellular changes in blood and tissue in tumors of the lung, esophagus and pleura and surrounding structures in the chest. Eligibility: Patients 2 years of age and older with cancer of the lung, esophagus, pleura, mediastinum or chest wall, or cancers of other origin that have invaded the lung. Note: Patients >= 2 years of age and under 18 years of age may only participate in research sample collection. Design: - Up to 1310 patients may be included in this study. - Patients undergo standard tests for evaluating the stage of their disease and for determining eligibility for an NCI investigational treatment study. - All patients undergo bronchoscopy and bronchoalveolar lavage ("washing" with salt water) to assess their tumor and collect a sample of normal tissue. Patients whose tumor is located on the outside portion of the lung may also undergo thoracoscopy to obtain a tumor sample. For bronchoscopy and bronchoalveolar lavage a tube with a light is passed through the nose or mouth into the lungs to examine the airways. Salt water is injected through the tube and then withdrawn to obtain cells for laboratory studies. For the thoracoscopy a small tube with a light is put through a small hole in the chest to obtain the tumor sample. Both procedures are usually done under general anesthesia. The tissue is examined to identify cell characteristics of people who respond to certain therapies and to identify markers on the surface of the tissue that may be useful in future research and treatment. - Blood and urine samples are collected from patients. - Patients who are eligible for a treatment study at NCI are offered participation in the study. - Patients for whom standard surgery, radiation or chemotherapy is more appropriate may receive treatment at NCI or with their own physician. - Patients who receive treatment at NCI return for follow-up examinations 4 weeks after discharge and then every 2 to 4 months depending on the nature of their cancer.

Type: Observational

Start Date: Nov 2005

open study

Background: Hereditary hearing loss is one of the most common sensory disabilities affecting newborns. The main options for people with hereditary hearing loss are hearing aids and cochlear implants. Both options have their limitations and do not restore biological hearing. Researchers want to learn if gene editing might be a treatment option. Objective: To understand the genes that cause non-syndromic autosomal dominant hearing loss (DFNA) in people with DFNA as well as their family members. Eligibility: People age 3 99 who have DFNA, affected family members of enrolled participants with DFNA, and unaffected family members of enrolled participants Design: Participants will be screened with a medical and hearing history. Their medical records will be reviewed. Participants will have hearing tests. They will wear headphones or earplugs. They will listen to tones, sounds, and words and may be asked to describe what they hear. Participants will have balance tests. For these, they will wear googles as they watch moving lights or as cold or warm air is blown into their ears. They will sit in a spinning chair in a quiet, dark booth. From a reclined position, they will raise their head while listening to clicking sounds. Participants will have blood drawn through a needle in the arm. Some blood will be used for gene testing. Some participants will have 2 skin biopsies. The skin will be washed, and a numbing medicine will be injected. Two small pieces of skin will be removed. Participants may have a physical exam. Participation will last for up to 20 years. Participants may give medical updates once a year.

Type: Observational

Start Date: Feb 2021

open study

This study aims to understand the causes and progression of Common Variable Immunodeficiency (CVID) and related inborn errors of immunity (IEI). These are conditions where the immune system does not function properly, leading to frequent infections and other complications such as gastrointestinal inflammation, lung and liver disease, autoimmune conditions, and an increased risk of certain cancers. By studying patients with CVI and related immune disorders, we hope to develop better ways to diagnose, treat, and prevent complications associated with these conditions. Patients diagnosed with CVID or related immune disorders must be referred by their physician and medical records reviewed by the study team to confirm eligibility to participate in this study. Once enrolled, participants will undergo various tests, including blood draws, physical exams, and imaging studies like CT scans to track changes over time. We may collect samples such as blood, urine, stool, or saliva for research purposes. If a surgical procedure or biopsy is performed because it is medically necessary, we may collect an additional sample for research testing. Family members of patients may be asked to provide blood samples for comparison. Some tests may be done remotely if participants or family members cannot travel to the study site. Who Can Participate - Patients diagnosed with CVI or related IEI, such as X-linked agammaglobulinemia, Blau Syndrome or Yao Syndrome. - Participants must be at least 2 years old. - Family members of patients may include parents, siblings, grandparents, children, aunts, uncles, and cousins. - Pregnant women already enrolled in the study will continue to participate, but new pregnant participants will not be enrolled. Potential Risks and Benefits - Risks: Blood draws may cause discomfort, bruising, or infection. Apheresis may cause dizziness, nausea, or muscle cramps; this procedure is to collect specific cells in the blood and is infrequently done on this protocol. Extra biopsies during clinically indicated procedures may increase the risk of complications; they will only be collected after the medically necessary biopsies are taken and if it is safe to collect any extra biopsies. - Benefits: Participants may not receive direct medical benefits, but the study will contribute to a better understanding of CVID and related conditions, potentially leading to improved treatments.

Type: Observational

Start Date: Jan 1990

open study

Background: Neuroblastoma is a type of cancer that causes tumors in nerves. It affects mainly infants and toddlers, and it causes about 15 percent of cancer-related deaths in children. Objective: To test a new drug (rhIL-15), combined with 3 standard cancer drugs, in people with neuroblastoma. Eligibility: People aged 3 to 35 years with neuroblastoma that did not respond or returned after standard treatment. Design: Participants will be screened. They will have a physical exam with blood and urine tests. They will have imaging scans and tests of their heart and lungs. They will have a bone marrow biopsy: A sample of tissue and fluid from inside a bone will be removed with a large needle. Participants will be treated in 21-day cycles. They may have up to 4 treatment cycles. rhIL-15 is given through a needle into a vein over 5 to 7 days during the first week of each cycle. Participants will stay in the hospital while they are receiving the rhIL-15. Starting in the second week of the second cycle, participants will receive other drugs for treating cancer. They will have no study treatments during the third week of each cycle. Participants will visit the clinic at least 2 times a week throughout all 4 treatment cycles. They will have a physical exam and blood tests during these visits. Imaging scans, bone marrow biopsy, and other tests will be repeated at the end of cycles 2 and 4. Participants will have a follow-up visit 6 months after treatment ends. This visit will include a physical exam with blood and urine tests.

Type: Interventional

Start Date: Oct 2025

open study

Background: The current standard treatment of prostate cancer is either surgery or radiation. Typically, this includes either the removal or radiation of the whole prostate gland. Many people now seek out focal therapy options to decrease the side effects of treatment. Until now, several forms of physical destruction with heat (thermal ablation), cold (cryotherapy), sound waves (HIFU), laser (FLA), and electrical energy (IRE). A new type of radiation (SBRT) may be an effective way to cure men of early-stage prostate cancer with fewer side effects than standard treatments. Objective: To see how people with untreated localized prostate cancer will respond to focal therapy with SBRT. Eligibility: People aged 18 years and older with untreated localized prostate cancer (prostate cancer which has not spread outside of the prostate gland). Design: - Participants will undergo screening including blood tests, an MRI, a PSMA PET/CT (18F-DCFPyL), and a biopsy. - Small, non-radioactive, gold seeds about the size of a grain of rice will be placed in and/or around the tumor to help target the radiation treatment. - Radiation (SBRT) will occur in 2 separate sessions about 1 week apart. No sedation is used, these sessions are painless. Each session will take about 1-2 hours. Participants can go home afterwards. - Follow-up will continue for 2 years with repeat scans (MRI and PSMA PET/CT) and blood (PSA) tests. - After two years, a biopsy will be done to understand the impact of this new treatment on prostate cancer.

Type: Interventional

Start Date: Oct 2023

open study

Background: Eosinophilic esophagitis (EoE) is a disease that causes inflammation in the esophagus. The esophagus is the tube that moves food from the mouth to the stomach. Diagnosing EoE currently requires a specialized tool called an endoscope. The esophageal string test (EST) is another test; the EST collects fluid from the upper digestive tract. An EST is simpler and cheaper than an endoscopy. Researchers want to know if an EST can diagnose EoE. Objective: To test if the EST can diagnose EoE in people who have trouble swallowing. Eligibility: Adults aged 18 to 65 years with trouble swallowing. They must have been born in the African continent or their parents were born in Africa. Design: Participants will be screened. They will give blood, stool, urine, and skin swab samples. They will complete surveys about their medical history, diet, symptoms, and home environment. They will bring a sample of their drinking water for testing. Participants will have an EST. They will swallow a pill capsule that contains a nylon string. One end of the string will be taped to their cheek. The string will unravel down the esophagus and into the stomach. It will be pulled out after 1 hour. Fluids that soaked into the string will be tested. At a different visit, participants will have an endoscopic exam. An endoscope is a flexible tube that is inserted down the mouth; it can be used to take tissue samples from the esophagus, stomach, and small intestine. Participants will have a final visit in person, online, or by phone. They will take a survey and talk about their test results.

Type: Interventional

Start Date: Apr 2026

open study

Background: Phosphodiesterase-4B (PDE4B) is a protein in the brain that may play a role in several mental health disorders. Researchers want to know if drinking alcohol increases the binding of a radioactive tracer to PDE4B in the brain because of increased activity and/or amount of the protein. This knowledge may help create new ways to treat people with alcohol use disorder (AUD). Objective: To learn if alcohol increases PDE4B activity in the brain. Eligibility: Healthy people aged 21 to 70 years who drink socially but do not have AUD. They must be enrolled in protocol 14-AA-0181"NIAAA Natural History Protocol". Design: Participants will have up to 4 clinic visits with up to 3 imaging scans of the brain; these will include 1 or 2 positron emission tomography (PET) scans and 1 magnetic resonance imaging (MRI) scan. The first PET scan will be a baseline. Participants will receive a radioactive tracer through a tube inserted into a vein. A second tube will be inserted so that blood can be drawn during the scan. Participants will lie on a bed that slides into a doughnut-shaped machine. This visit will take about 6 hours. For the next PET scan, participants will receive alcohol (ethanol) through a tube in a vein until they have a blood alcohol concentration that is equal to the legal driving limit. This is the same as 4 or 5 drinks for most people. After the scan, participants must remain at the clinic for a few hours until their blood alcohol drops. This visit will take 14 to 16 hours. The MRI scan of the brain will take up to 2 hours in a separate clinic visit.

Type: Interventional

Start Date: Dec 2025

open study

Background: Myelodysplastic syndromes (MDS) are disorders of blood stem cells that can develop into blood cancers. Treatment options are limited. To find better treatments, researchers need to better understand how MDS develops. To do that, they must be able to compare biospecimens from people with the disease to those of healthy people. Objective: This study will create a database of biospecimens collected from healthy volunteers. Eligibility: Healthy people aged 18 and older. Design: Participants will be screened. They will have a physical exam with blood and urine tests. Up to 5 types of samples will be collected on 1 or more days within 1 month of screening: Blood: Blood will be drawn by inserting a needle into a vein. Saliva: Participants will scrape the insides of their cheeks with a brush. Stool: Participants will be given a container to collect stool at home. They will use a prepaid envelope to mail in the sample. Bone marrow: A sample of the soft tissue inside the bones will be drawn out. The area to be biopsied, usually the lower back, will be numbed. A needle will be inserted through a small cut to remove the sample. Participants' pain will be monitored; additional numbing medicine may be used. Skin: A piece of skin about 1/6 of an inch across will be cut away. Stitches may be used to close the wound. Participants will return to the clinic to have the stitches removed. Participants do not have to provide all of the samples listed. They will give each sample only once.

Type: Observational

Start Date: Jan 2023

open study

Background: - Pleuropulmonary blastoma (PPB) is a rare fast-growing lung tumor that is associated with other, rare tumor types. Most cases of PPB appear in children younger than 6 years of age. Recently, it has been shown that this condition can be inherited (e.g., mutation of the DICER1 gene). Researchers are studying both clinical and genetic aspects of this newly described condition. They are interested in collecting further medical history and genetic information on individuals and close relatives of individuals who have PPB or other rare associated tumors. Objectives: - To study individuals with a personal or a family history of pleuropulmonary blastoma (PPB) or other rare tumors that can be associated with PPB (e.g., cystic nephroma, nasal chondromesenchymal hamartoma, ovarian Sertoli-Leydig cell tumors, ocular medulloepithelioma). Eligibility: - Individuals who have been diagnosed with PPB and/or PPB-related tumors. - Close blood relatives (e.g., parents, siblings, grandparents) of individuals who have been diagnosed with PPB and/or PPB-related tumors. Design: - Interested participants can enroll or inquire about this study by calling 1-800-518-8474. - Participants will be asked to complete family history and medical history questionnaires. They will complete the questionnaire if they are at least 18 years of age, or another person will complete the questionnaire if the key family member is too young to do so on his or her own. - Participants will be asked to sign a medical record release form to allow researchers to examine detailed medical history information. - Participants may be asked to have a physical examination and imaging studies, provide blood and saliva samples, or provide tumor tissue from prior biopsies or cancer surgeries. - Annually, participants will update the family history and individual information questionnaires to document important changes in medical history, and will also update the medical record release form. Participants may be asked to provide additional cheek lining cells and/or blood samples, as well as tumor tissue from any new or planned biopsies or tumor surgeries. - Treatment will not be provided as part of this protocol.

Type: Observational

Start Date: Feb 2011

open study

Dermatomyositis (DM) is a rare autoimmune disease that causes muscle weakness, skin rashes, and other symptoms. Researchers think both genetic and environmental factors play a role in this disease. They want to find out more about how diet and lifestyle choices affect people with DM/JDM. Objective: To see if omega-3 fatty acid supplements from fish oil, combined with a healthy diet, can help people with DM/JDM. Eligibility: Adults 18-60 years old, who live in the United States, can read English, and access Internet to complete questionnaires can participate. Design: Participants will have 5 or 6 inpatient visits. For 5 visits they may need to stay in the Clinical Center for up to 5 days. Participants will be screened. They will have a physical exam with blood, urine and stool tests. They will have tests of their heart and lung function. Their muscle strength will be measured. They may have an imaging scan of their thighs and pelvis. They will complete online questionnaires about their health and lifestyle. They may complete two optional skin biopsies. Participants will take 4 small capsules by mouth twice a day for up to 6 months. The capsules will contain omega-3 fatty acids from fish oil or a placebo. The placebo looks just like the regular capsule but contains no active ingredients. Participants will not know which capsules they are taking. They will follow a healthy diet based on the General Healthy Eating Pattern. Participants will receive dietary coaching and will have virtual check-ins throughout the study. For two 7-day periods, they will wear a watch-like device to track their daily activity and sleep patterns. Participants may opt to remain in the study for an additional 12 weeks. All will receive the fish oil supplements during this stage.

Type: Interventional

Start Date: Apr 2026

open study

Study Description: Despite the availability of pharmacotherapy for some substance use disorders, relapse vulnerability is still a significant issue. This suggests medications with alternative mechanisms of action should be explored to address this unmet need. Substantial preclinical research indicates that orexin antagonism blunts the internally and externally triggered motivation to attain abused substances. This research project will translate these preclinical findings into the clinical domain by administering the FDA approved orexin antagonist, suvorexant, to those with a substance use disorder. Suvorexant s ability to blunt neurobiological correlates of substance misuse will be assessed. This will be assessed following acute and repeated drug administration. Baseline individual differences will be considered to determine whether neurobiological variance influences suvorexant s impact in those with nicotine dependence. In an independent arm, the interaction between suvorexant and a dopamine agonist (methylphenidate) on cognitive function will be assessed in non-smoking individuals. Objectives: The objective is to determine the acute and chronic impact of the orexin antagonist, suvorexant, on neurobiological and behavioral factors linked with substance use disorders. Whether such effects are mediated by baseline characteristics will be tested. Given suvorexant is an FDA approved treatment for insomnia, sleep will be evaluated as well in the nicotine dependent arm. Endpoints: In nicotine-dependent individuals, suvorexant s impact on brain function will be assessed several ways by evaluating: 1) resting function, 2) reactivity to drug cues, 3) reactivity to non-drug related cognitive tasks. Sleep and nicotine use will be measured throughout the study period. In those without nicotine-dependence, the impact of suvorexant and the interaction of acute methylphenidate and suvorexant on brain function will be assessed. This arm will provide insight into how suvorexant impacts reward/cognition as well as impacts the pharmacological influence of methylphenidate on those same measures. Study Population:<TAB> Nicotine dependence arm:140 subjects; Volunteers who are between the ages of 18-60 and are daily smokers/vapers. Control arm: 80 subjects; Volunteers who are between the ages of 18-60 and are non-smokers/vapers This study will be conducted at the NIDA-IRP, Biomedical Research Center, in Baltimore, MD. Description of Study Intervention: Nicotine dependence arm: Suvorexant at 10 mg single dose, and Suvorexant at 10 mg daily for approximately 7 days. Control arm: 1. Tolerability visit with one MRI scan post-20mg methylphenidate, 4 acute drug administration (6-14 days in randomized order: 1. Placebo + placebo; 2. 20mg suvorexant + Placebo; 3. Placebo + 40mg methylphenidate; 4. 20 mg suvorexant + 40mg methylphenidate max) Study Duration: 5 years Participant Duration: 1-2 months

Type: Interventional

Start Date: Feb 2023

open study