Background: Platelets are a type of blood cell that play a critical role in bleeding, forming blood clots, and healing. Researchers want to know more about platelets work in healthy people. They want to look at how platelets clump together, how blood clots, and how genes and proteins work. They also want to study how these processes change over time and how they are affected by factors such diet, exercise, weight, and new health problems. Objective: To study how platelets function in healthy people. Eligibility: Healthy people aged 18 years and older. Design: Researchers will review participants medical history. They will ask about the participant s family history and any drugs they take. Participants will have a clinic visit once every 6 or 7 months for 10 years. Each visit will be 2 to 3 hours. At each visit, participants will have several tests and procedures: A physical exam, including vital signs. Hip and ankle circumference will be measured. Urine collection. Blood tests. About 10 tablespoons of blood will be drawn. Participants will be asked to fast for 10 hours and avoid drugs like aspirin or Advil for 7 days before each draw. Some of the blood may be used for gene studies. Some may be used to create stem cells for research. Stem cells are cells that can be used to make other types of cells. Surveys and questionnaires. Participants will answer questions about habitual activity, diet, smoking, drugs and alcohol, sleep, illness, and other health issues. These surveys may be done online, via email, or by phone.

Type: Observational

Start Date: Mar 2026

open study

Background: Turner Syndrome, galactosemia, and premature ovarian insufficiency are all conditions that may make it very hard or impossible for a person to become pregnant and have their own child. Researchers want to learn more about why this happens and if freezing Gonadal tissue allows for fertility preservation. Objective: To find out why people with certain conditions have can have premature ovarian insufficiency (POI or early menopause) and individuals with variations in sex characteristics have trouble getting pregnant and if freezing the gonads tissue from them will help to have their own child in the future. Eligibility: Individuals aged 2-21 who have Turner Syndrome or galactosemia. Also, females aged 13-21 with premature ovarian insufficiency, individuals with variations in sex characteristics, and individuals 2-35 receiving high-risk gonadotoxic therapy Design: Participants will be screened with a medical history. Participants may have a physical exam and blood tests. Their body measurements may be taken. These include weight, height, arm span, skin fold, and sitting height. They may fill out surveys about their quality of life, body image, and health. Participants may have a transabdominal pelvic ultrasound. A probe will be placed on their belly and will take pictures of the organs in the pelvis. They may have a transvaginal pelvic ultrasound performed while asleep in the operating room if needed. Participants may have surgery to remove an gonads and skin biopsy. The removed tissue will be frozen and stored. The tissue will have to be stored for many years. NIH will pay to store the tissue for 1 year. After that, participants will have to pay for storage. A piece of the gonads (no more than 20%) will be used for research Travel, lodging and meals for participants traveling greater than 50 miles will be reimbursed based off the government rate. Local participants will not be reimbursed. Participants will have a checkup 6 weeks after surgery one or more follow-up visits 6-18 months after surgery. They may have phone follow-up every 12-24 months after surgery. Participation will last 30 years.

Type: Observational

Start Date: Sep 2021

open study

Background: The body uses energy from calories for basic functions like breathing and digesting food. Over time, when a person eats more calories than they burn, they may become overweight or obese. Obesity is a major health concern. Researchers want to look at fat and muscle tissue to learn more about metabolism. That is how the body uses food and other nutrients for normal function and energy. This research may help to develop new treatments for obesity and related diseases. Objective: To learn more about the role of fat and muscle in metabolism, particularly how fat and muscle store and use energy. Eligibility: Adults 18 years and older who have a planned surgery at NIH in which tissue can be collected by the surgeon. Design: Participants will be screened by their regular NIH doctor. Then researchers will contact them about this study. Participants will not have to make extra visits to NIH for this study. Researchers will collect samples during the participant s surgery. These will be fat tissue and skeletal muscle tissue. Muscle tissue will only be taken from tissue that is going to be discarded. Collecting the tissue will not add any time or any extra incisions than what is required for the surgery. After surgery, blood will be drawn. Some participants will have this done in the pre-op or post-op room. Others will have this done during their hospital stay.

Type: Observational

Start Date: Mar 2016

open study

Background The development of new technologies now allow scientists to investigate the molecular basis and clinical manifestations of monoclonal B cell lymphocytosis (MBL), chronic lymphocytic leukemia(CLL)/small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM), and splenic marginal zone lymphoma (SMZL). Applying these methods in a natural history study can help identify processes involved in disease progression, and possibly lead to the discovery or validation of treatment targets. Objectives Study the history of MBL/CLL/SLL/LPL/WM/SMZL in patients prior to and after treatment. Characterize clinical, biologic and molecular events of disease stability and progression of patients enrolled on this protocol. Eligibility: - Diagnosis of CLL/SLL and on treatment/previously treated/nearing treatment - Diagnosis of LPL/WM - As of February 5, 2025, patients with MBL and SMZL will no longer be enrolled. - Age greater than or equal to 18 years. - ECOG performance status of 0-2. Design Patients are typically followed every 6 to 24 months in the clinic and have blood drawn. Patients may be asked to undergo additional testing, including bone marrow biopsy and aspiration, lymph node biopsy, positron emission tomography, and CT and MRI scans. Some of these tests (e.g., blood draw) may be required to monitor CLL/SLL and LPL/WM. Other tests (e.g., lymph node biopsy) may not be clinically indicated, but patients may be asked to undergo these procedures for research purposes. No treatment will be administered on this study. If a patients requires treatment for their cancer, available NIH clinical trials and alternative treatment options will be discussed with the patient.

Type: Observational

Start Date: May 2008

open study

The goal of this study is to develop better methods of diagnosis, localization, and treatment for pheochromocytomas. These tumors, which usually arise from the adrenal glands, are often difficult to detect with current methods. Pheochromocytomas release chemicals called catecholamines, causing high blood pressure. Undetected, the tumors can lead to severe medical consequences, including stroke, heart attack and sudden death, in situations that would normally pose little or no risk, such as surgery, general anesthesia or childbirth. Patients with pheochromocytoma may be eligible for this study. Candidates will be screened with a medical history and physical examination, electrocardiogram, and blood and urine tests. Study participants will undergo blood, urine, and imaging tests, described below, to detect pheochromocytoma. If a tumor is found, the patient will be offered surgery. If surgery is not feasible (for example, if there are multiple tumors that cannot be removed), evaluations will continue in follow-up visits. If the tumor cannot be found, the patient will be offered medical treatment and efforts to detect the tumor will continue. Main diagnostic and research tests may include the following: 1. Blood tests - mainly measurements of plasma or urine catecholamines and metanephrines as well as methoxytyramine. If necessary the clonidine suppression test can be carried out. 2. Standard imaging tests - Non-investigational imaging tests include computed tomography (CT), magnetic resonance imaging (MRI), sonography, and 123I-MIBG scintigraphy and FDG (positron emission tomography) PET/CT. These scans may be done before and/or after surgical removal of pheochromocytoma. 3. Research PET scanning is done using an injection of radioactive compounds. Patients may undergo 18F-FDOPA, 18F-DA, as well as 68Ga-DOTATATE PET/CT . Each scan takes up to about 2 hours. 4. Genetic testing - A small blood sample is collected for DNA analysis and other analyses....

Type: Interventional

Start Date: Mar 2000

open study

Background: People use virtual reality (VR) technology to play games, socialize, work, or receive medical care. Some people have "cybersickness" after using VR. Cybersickness is similar to motion sickness. Symptoms include eye strain, nausea, dizziness, or headache. The symptoms are usually mild and go away after the person stops using VR. New software called Motion Reset is being designed to reduce symptoms of cybersickness during VR use. Objective: To see if Motion Reset software can reduce cybersickness in people using VR. Eligibility: Healthy adults aged 18 to 60 years. Design: Participants will have 1 clinic visit that will last about 1 hour. They will answer questions about how they are feeling. They will learn how to use the VR headset and the handheld game controllers. The study will be broken into 2 parts. For the first part, participants will be assigned to 1 of 3 groups: Group 1 will participate in a VR experience designed to prevent cybersickness. They will view screens and move around while they press buttons on a controller. Group 2 will participate in a VR experience that is not designed to prevent cybersickness. They will view screens and move around while they press buttons on a controller. Group 3 will have no VR experience. Participants will complete 2 questionnaires about their experiences in the first part of the study. For the second part, all participants will spend up to 20 minutes playing a commercial VR game called Jurassic World Aftermath. Every few minutes, they will be asked if they are experiencing discomfort. After playing the game, participants will complete 12 questionnaires about their experience....

Type: Interventional

Start Date: Sep 2025

open study

Background: Atopic dermatitis (AD), also called eczema, is a chronic skin condition. AD can make skin dry and itchy, and sometimes it can lead to serious health problems, such as asthma, food allergies, eye infections, and sleep problems. No cure exists for AD. Researchers know that people with AD have different kinds of harmless bacteria on their skin than do people without AD. They want to see if adding a harmless bacteria (Roseomonas mucosa) to the skin can help people with AD. Objective: To test a skin treatment that contains R. mucosa and ground cardamom seeds in people with AD. Eligibility: People aged 2 years and older with AD. Design: All study visits will be remote. Participants will have 5 visits over about 7 months. Participants will be screened. Researchers will review their AD and medical history. Participants will receive a study product in the mail. The product comes as a powder in single-use packets. Participants will be shown how to mix the powder with water in a single-use spray vial. They will spray the solution onto their skin 2 to 3 times per week for 14 weeks. Half of participants will receive the study powder. Half will receive a placebo; the placebo looks just like the study powder but contains no bacteria. They will not know which one they have. During 3 study visits, participants will take a skin swab. They will receive supplies in the mail to rub a cotton swab on their skin and mail it back to the researchers. Participants may opt to have pictures taken of their AD. Participants will fill out 4 online questionnaires.

Type: Interventional

Start Date: Oct 2024

open study

Background: Genes tell the body and its cells how to work. Familial platelet disease (FPD) or FPD with associated malignancies (FPDMM) is caused by a variant in the gene RUNX1. People with this disease may have problems with their blood and bleed for a long time when they are injured. Researchers want to learn more about RUNX1 variants and FPD. Objective: To learn more about FPD in people with RUNX1 variants to lead to better diagnosis, monitoring, and treatment. Eligibility: People any age with a suspected or confirmed RUNX1 variant People who have a family member with the variant Design: All participants will be screened with a phone call and a blood, saliva, or cheek cell sample. Participants with a suspected or confirmed variant will have 1 visit. It will last about 2 days. They will then have visits at least once a year. Visits will include: - Medical history and physical exam - Blood tests or saliva sample - Possible skin biopsy: A small piece of the participant s skin will be removed. - Bone marrow aspiration or biopsy: The participant s bone marrow will be removed by needle from a large bone such as the hip bone. - Possible apheresis: Blood will be removed from the body and certain blood cells will be taken out. The rest of the blood is returned to the body. Between visits, participants with a suspected or confirmed variant will keep a diary of disease symptoms and signs. Samples from all participants may be used for genetic testing

Type: Observational

Start Date: Mar 2019

open study

Background: - Gum disease is a condition in which the tissue around the tooth root becomes swollen and infected. This condition can cause tooth loss if it is not treated. Who gets gum disease and how bad it will be depends on (1) the different bacteria in the mouth and (2) how the immune system of an individual handles these bacteria. Researchers want to look at the oral bacteria and genetic immune problems of different people to learn how these affect gum disease and other conditions of the mouth. Objectives: - To study how immune system problems may lead to problems in the mouth, including gum disease. Eligibility: - Children and adults at least 7 years of age who have genetic problems with their immune system. - Healthy adults that have periodontal disease - Health adults that do not have periodontal disease Design: - This study will involve a screening visit and a study visit. - Participants will be screened with a medical history, blood work and a full oral and dental exam, including dental x-rays and photos. - The study visit will involve collection of blood, urine, and other samples, including saliva, plaque, and gum swabs. Any abnormal tissue will sampled for a biopsy. Additional oral and dental exams will be performed. Participants will also answer questions about any current medical or dental problems.

Type: Observational

Start Date: Oct 2012

open study

This study will examine growth factors that promote and inhibit mast cell proliferation resulting in mastocytosis, a disease of excessive mast cells in the body. These cells can release chemicals that cause itching, blisters, flushing, bone pain and abdominal pain. Patients up to 80 years of age with mastocytosis may be eligible for this 1-day study. Participants will have one visit at NIH lasting up to 8 hours, during which they will undergo the following tests and procedures: - Medical history and physical examination. - Laboratory studies, if medically indicated. - Blood tests to identify genetic changes important in the growth, development, and functioning of mast cells. - Bone marrow aspiration and biopsy. For the bone marrow procedure, the skin over the hipbone and the outer surface of the bone itself are numbed with local anesthesia. Then, a special needle is inserted into the hipbone and about 1 tablespoon of bone marrow is drawn into a syringe. Another needle is inserted into the same area to collect a small piece of the bone marrow. Additional procedures may include allergen testing, urinalysis, and 24-hour urine collection. Participants will receive an evaluation of their mastocytosis.

Type: Observational

Start Date: Sep 2002

open study

This study will collect white blood cells and plasma for research on how the immune system controls HIV infection. The immune system of a very small group of people with HIV, called non-progressors, has been able to control HIV for long periods without antiretroviral therapy. Some immune system-related genes important for this control have been identified in these patients. People living with HIV who are 18 years of age and older, documented or suspected long-term nonprogressors in generally good health may be eligible to screen for the study. Participants will undergo apheresis (a method for collecting larger quantities of certain blood components than can safely be collected through a simple blood draw) if venous access is adequate once yearly. Some may be asked to return every six months. - Automated apheresis - Blood is drawn through a needle placed in an arm vein and spun in a machine, separating the blood components. The white cells are extracted and the red cells, with or without plasma (liquid part of the blood), are re-infused into the donor through a needle in the other arm. An anticoagulant (medication to prevent blood from clotting) is usually added to the blood while in the machine to prevent it from clotting during processing. - Blood draw - a needle placed in an arm vein for large volume (approx 75ml) blood draw if veins considered inadequate for apheresis procedure. Some of the blood collected through apheresis may be stored for future studies of HIV disease and immune function and for HLA testing, a genetic test of markers of the immune system.

Type: Observational

Start Date: Aug 2001

open study

Background: Kidney cancer is the 12th leading cause of cancer-related death in the United States. Some kidney tumors do not respond well to current treatments. Better treatments are needed. Objective: To test a pair of drugs (sasanlimab and palbociclib) in people with kidney cancers. Eligibility: People aged 18 years and older with kidney cancer; specifically, clear cell renal cell carcinoma (ccRCC) or papillary renal cell carcinoma (pRCC). Design: Participants will be screened. They will have a physical exam with blood tests. They will have an imaging scan and a test of their heart function. They may have a biopsy; that is, a sample of tissue will be cut from the tumor. Participants will be treated in 28-day cycles for up to 2 years. Palbociclib is a pill taken by mouth. Participants will take this drug once a day for 21 days during each 28-day treatment cycle. They will write down the dates and times they take these pills in a diary. Sasanlimab is an injection under the skin. Participants will receive this injection on the first day of each treatment cycle. Imaging scans and blood tests will be repeated throughout the treatment. Tumor biopsies may be repeated up to 3 times; these biopsies are optional. Participants will have follow-up visits every month for 3 months after treatment ends. They will continue to have imaging scans every 3 months; these scans may be done close to home. The results can be sent to researchers. Participants will remain in the study up to 6 years.

Type: Interventional

Start Date: Apr 2024

open study

This study is not a treatment protocol and no experimental treatments are involved. Study participants may be seen as needed for clinical, translational and basic research studies, or as medically indicated. Subjects will receive their general medical care outside the NIH and will be seen at our clinic or at CNHS with varying frequency. Subjects may be seen for multiple visits. Subjects may be asked to return for additional testing as needed. Clinical care for patients with sickle cell disease will be provided as appropriate through the Sickle Cell Clinic and the inpatient clinical center....

Type: Observational

Start Date: Apr 2004

open study

Background: -A gene provides instructions to the body. Mutated genes can sometimes cause cancer. Germline mutations are those people are born with. These mutations in the BAP1 gene can cause mesothelioma and other cancers. Researchers want to study people with germline mutations of BAP1 and other genes known to cause cancer. Objective: -To learn how cancer might develop in people with BAP1 mutations. Eligibility: -People ages 2 and older with a germline mutation in BAP1 Design: - Participants will be screened with: - Medical and family history - Saliva test - Participants with mesothelioma will be in the NIH Group. Participants without mesothelioma can choose to be in either the NIH Group or the Remote Group. - Remote Group participants will have a medical and family history by phone. If they have tumor tissue from a previous surgery, it will be tested. They will be contacted once a year by phone. - NIH Group participants will have a baseline visit. This can take up to 4 days. They may have to stay in the area overnight. The visit will include: - Physical exam - Evaluation of tumor tissue if available - Optional tumor biopsy - Blood tests - Scans: A machine will take pictures of the body. - Photographs of skin lesions or other issues - Skin exam - Eye exam - NIH Group participants will have visits once or twice a year. These will include a physical exam, lab tests, scans, and other tests as needed. - Participants who have a confirmed mutation will be asked to contact any relatives who may be at risk and ask them about joining the study.

Type: Observational

Start Date: Mar 2019

open study

Background: A prospective cohort of Inherited Bone Marrow Failure Syndrome (IBMFS) will provide new information regarding cancer rates and types in these disorders. Pathogenic variant(s) in IBMFS genes are relevant to carcinogenesis in sporadic cancers. Patients with IBMFS who develop cancer differ in their genetic and/or environmental features from patients with IBMFS who do not develop cancer. These cancer-prone families are well suited for cancer screening and prevention trials targeting those at increased genetic risk of cancer. Carriers of IBMFS pathogenic variant(s) are at increased risk of cancer. The prototype disorder is Fanconi's Anemia (FA); other IBMFS will also be studied. Objectives: To determine the types and incidence of specific cancers in patients with an IBMFS. To investigate the relevance of IBMFS pathogenic variant(s) in the carcinogenesis pathway of the sporadic counterparts of IBMFS-associated cancers. To identify risk factors for IBMFS-related cancers in addition to the primary germline pathogenic variant(s). To determine the risk of cancer in IBMFS carriers. Eligibility: North American families with a proband with an IBMFS. IBMFS suspected by phenotype, confirmed by pathogenic variant(s) in an IBMFS gene, or by clinical diagnostic test. Fanconi's anemia: birth defects, marrow failure, early onset malignancy; positive chromosome breakage result. Diamond-Blackfan anemia: pure red cell aplasia; elevated red cell adenosine deaminase. Dyskeratosis congenita: dysplastic nails, lacey pigmentation, leukoplakia; marrow failure. Shwachman-Diamond Syndrome: malabsorption; neutropenia. Amegakaryocytic thrombocytopenia: early onset thrombocytopenia. Thrombocytopenia absent radii: absent radii; early onset thrombocytopenia. Severe Congenital Neutropenia: neutropenia, pyogenic infections, bone marrow maturation arrest. Pearson's Syndrome: malabsorption, neutropenia, marrow failure, metabolic acidosis; ringed sideroblasts. Other bone marrow failure syndromes: e.g. Revesz Syndrome, WT, IVIC, radio-ulnar synostosis, ataxia-pancytopenia. First degree relatives of IBMFS-affected subjects as defined here, i.e. siblings (half or full), biologic parents, and children. Grandparents of IBMFS-affected subjects. Patients in the general population with sporadic tumors of the types seen in the IBMFS (head and neck, gastrointestinal, and anogenital cancer), with none of the usual risk factors (e.g. smoking, drinking, HPV). Design: Natural history study, with questionnaires, clinical evaluations, clinical and research laboratory test, review of medical records, cancer surveillance. Primary endpoints are all cancers, solid tumors, and cancers specific to each type of IBMFS. Secondary endpoints are markers of pre-malignant conditions, such as leukoplakia, serum or tissue evidence of carcinogenic viruses, and bone marrow morphologic myelodyplastic syndrome or cytogenetic clones.

Type: Observational

Start Date: Nov 2001

open study

Background: Memory consolidation is the process by which memories become stable, long-term representations in the brain. Consolidation of a motor skill is dependent upon sleep. Some research shows that daytime naps improve people s motor performance and memory retention. Researchers want to find out how daytime naps may contribute to learning and support consolidation of motor skill memories. Objective: To learn the role of memory replay during wakeful rest and sleep (naps) in retaining a newly learned skill. Eligibility: English-speaking adults ages 18 and older with chronic stroke, or healthy, right-handed, English-speaking adults ages 18-35 and 50-80 Design: Participants will be screened with: - medical history - neurological history - medicine review - medical exam - neurological exam. Participants will have a magnetic resonance imaging (MRI) scan of the brain. For this, they will lie down in a scanner. The scanner makes loud noises, so they will wear earplugs. They will fill out an MRI screening form before each MRI. Participants will also have magnetoencephalography (MEG). MEG maps brain activity. It does this by recording the magnetic fields produced by naturally occurring electrical currents in the brain. For MEG, participants will lie down in the MEG room. Their eye movements may be recorded by a video camera. Participants will have behavior testing. They will practice typing random keys. Then they will repeatedly type a custom sequence that they see on a computer screen. Then they will take a 2-hour nap. Then they will type the same sequence again. Participants will have no more than 4 visits at the NIH over 3 months. Visits will last 2-4 hours each.

Type: Observational

Start Date: Mar 2021

open study

Background: People with B cell malignancies (blood cancers) often cannot mount a full immune response to infections or certain vaccines. Bruton tyrosine kinase inhibitors (BTKis), which are used to treat blood cancers, may also negatively affect a person s response to certain vaccines. Researchers want to learn more about vaccine responses in people with certain types of blood cancers. The findings may help develop better vaccine strategies for people with these cancers. Objective: To learn how well vaccines work in people who have certain types of blood cancers. Eligibility: Adults aged 18 years or older who have chronic lymphocytic leukemia (CLL), Waldenstrom macroglobulinemia, or certain non-Hodgkin lymphomas. Design: Participants will get one or more vaccines for illnesses, such as vaccines for hepatitis B, shingles, pneumonia, and respiratory syncytial virus (RSV). They may get more than 1 type of vaccine during the study. Not all participants will get all vaccines. Some vaccines require 2 doses. Participants will give a blood sample before they get each vaccine. About 4 weeks after they finish each vaccine series, they will give another blood sample. Some vaccines require a second dose 3-6 weeks later. For vaccines that require a second dose, participants may also have study procedures at that visit. Participants may have 2 to 3 study visits per vaccine series. Participants may receive a booster dose for some vaccines. The booster dose is optional. For this study, a booster means repeating the full vaccine series. Participants who receive a booster may have additional blood samples to measure their vaccine response. Participants will have pregnancy tests, if needed. Participants with CLL who receive BTKis may be assigned to either continue treatment or pause treatment around the time of vaccination. Participants may give follow-up blood samples once a year for up to 5 years after each vaccine series. These blood samples are optional. Participation will last for up to 5 years after each vaccine series is received.

Type: Interventional

Start Date: Sep 2022

open study

Background: Research has identified some of the genes involved in inherited eye diseases. But for many of these diseases, the genes are not yet known. Researchers want to try to find these genes. They also hope to learn more about how symptoms differ in people with similar gene changes. Objective: To learn more about genes involved in eye diseases. Eligibility: People who have a known or suspected inherited eye disease, and their relatives. Design: - All participants will have a medical history, physical exam, and eye exam. They will have blood taken. - Participants with an eye disease may have eye cell samples taken using a swab or biopsy procedure. - Participants may have a skin biopsy. A 3mm piece of skin will be removed. - Participants may provide samples of tears, urine, saliva, stool, hair, or inner cheek cells. - Participants may have a retina test. They may also have a test that uses light to measure retina thickness. - Participants may have an eye movement test. Electrodes will be placed on the skin next to both eyes. - Participants may have a fluorescein angiography. A dye will be given through an intravenous line in the arm. A camera will take pictures of the dye as it flows through the eyes blood vessels. - Participants may have microperimetry. They will sit at a computer screen and press a button when they see a light. - Participants may have an eye movement test. They will wear contact lenses or goggles and watch a series of spots on a computer screen. - Participants may complete a color vision test. - Participants will provide a specimen for genetic testing. - Participants may have a MRI. - Participants may complete questionnaires.

Type: Observational

Start Date: Jun 2015

open study

Background: - Radiation is a common treatment for prostate cancer. It helps damage tumor cells and causes them to die. Radiation can be effective, but some tumors may be harder to treat with radiation or even with surgery. This happens to a small number of men who have either radiation or surgery for prostate cancer. Most men who have these hard-to-treat tumors do not know if the tumor has recurred only in the prostate or has spread to another area. Also, men whose prostate cancer has recurred only after radiation may have different treatment options. This study will use improved imaging studies to better understand why some men do not respond as well to initial radiation treatments. Objectives: - To use detailed imaging studies to look at the results of local radiation therapy for prostate cancer. Eligibility: - Men at least 18 years of age who are scheduled to have radiation for prostate cancer. - Men at least 18 years of age whose prostate cancer has returned after earlier treatments. Design: - All participants will have a medical history and physical exam. Blood and urine samples will be collected. Imaging studies will be used to evaluate the cancer at the start of the study. - All participants will have an initial full magnetic resonance imaging (MRI) scan of the prostate. Tumor and healthy tissue samples will be collected. - Those whose cancer has recurred after treatment will discuss possible treatment options with the study doctors. - Participants who are scheduled to have radiation will have radiation therapy. This will be given according to the current standard of treatment. - After radiation, participants will have regular follow-up tests and imaging studies. They will have another full MRI scan 6 months after the end of radiation treatment.

Type: Observational

Start Date: Nov 2013

open study

We are studying virologic and/or immunologic parameters of HIV infection and other infectious or non-infectious immune deficiency diseases in order to better understand the pathogenesis of HIV. Because of the lack of an adequate animal model it is generally necessary to utilize human peripheral blood cells for studying aspects of either in vivo or in vitro HIV infection. We wish to be able to continue to elucidate many pathogenic aspects of HIV infection in relation to other infectious or non-infectious immune regulation and dysregulation using human peripheral blood mononuclear cells as a model....

Type: Observational

Start Date: Mar 1993

open study

Background: Progressive multifocal leukoencephalopathy (PML) is a rare and often fatal brain infection caused by the JC virus. The JC virus is common. More than half of adults have been exposed to it. Most people do not get sick from the JC virus, but in people with weakened immune systems, it can cause PML. Brincidofovir (BCV) is an antiviral drug approved to treat smallpox. Researchers want to know if it can help people with PML. Objective: To test BCV in people with PML. Eligibility: People aged 18 years or older with PML. Design: Participants will be screened. They will have a physical exam with blood tests. They will have an imaging scan of the brain with contrast dye. They will have a lumbar puncture (spinal tap): A thin needle will be inserted into their lower back to draw out a sample of the fluid around their spinal cord. BCV will be given through a tube attached to a needle inserted into a vein. Participants will receive the drug 2 times a week for 4 weeks (this is 1 cycle). If the drug is helping them, they may have up to 3 drug cycles (12 weeks). Imaging scans, spinal taps, and other tests will be repeated after every 4 weeks of treatment. Participants will have 6 follow-up visits in 1 year after treatment ends. The imaging scan, spinal tap, and other tests will be repeated at each visit.

Type: Interventional

Start Date: Jun 2026

open study

Background: Aldesleukin is used to treat metastatic or advanced melanoma and renal cell carcinoma. Pembrolizumab is used to treat many cancers including melanoma. Researchers want to see if these drugs can be used together to produce better results in people with these types of cancer. Objective: To learn if the combination of pembrolizumab and aldesleukin can be used to treat metastatic or advanced melanoma and renal cell cancer. Eligibility: Adults aged 18 years or older who have metastatic or advanced melanoma or renal cell carcinoma. Design: Participants will be screened with: - Medical history - Physical exam - Electrocardiogram - Blood and urine tests - Ability to perform tasks of daily living - Imaging scans (CT, MRI, PET, and/or X-rays). They may get a contrast agent to enhance the images. - Photographs, if needed Some of these tests will be repeated during the study. Participants will receive the study drugs by IV (a plastic tube that is put into a vein) for 4 days. A second cycle of treatment will be given 21 days later. They will stay in the hospital for each of the cycles in the first course of treatment. After 2 months, their cancer will be evaluated. They may receive a second course of pembrolizumab alone on Days 1 and 21. They will not have to stay in the hospital for this course. About 30 days after treatment ends, participants will have a safety follow-up visit. Then they will have visits every 3 months for up to 1 year, and then every 6 months for up to 4 years. Follow-up can also be done by phone, email, and mail. If their cancer gets worse, they will stop having visits. Participation will last for 5 years....

Type: Interventional

Start Date: Aug 2022

open study

Background: As people age, the cells in the pancreas that produce insulin begin to release less of this hormone, and levels of blood glucose (sugar) rise. This can lead to illnesses such as diabetes. Urolithin A (UA) is a natural nutritional supplement that may improve how the body controls blood glucose. Objective: To learn if UA improves levels of insulin and other hormones that help control blood glucose. Eligibility: People aged 55 years and older with a body mass index of 27 or higher. Design: Participants will have 6 clinic visits over 8 weeks. Participants will be screened. They will have a physical exam with blood and urine tests and a test of their heart function. UA gelcaps are taken by mouth every morning at home. Half of participants will take UA. The other half will take a placebo. The placebo looks like the study drug but does not contain any medicine. Participants will not know which they are taking. Participants will have tests during the study including: Oral glucose tolerance: Participants will drink a sweet liquid. Blood will be drawn at intervals over the next 3 hours. Continuous glucose monitor: A sensor with a needle that goes just under the skin will be placed on the upper arm. Participants will wear this sensor throughout the study. Exercise. Participants will walk on a treadmill while their heart rate, hearth rhythm, and blood pressure are monitored. They will walk in a hallway at normal and fast paces. Imaging scans of the thigh; scans of the brain are optional....

Type: Interventional

Start Date: Aug 2026

open study

Background: Idiopathic CD4 lymphopenia (ICL) is a syndrome characterized by low levels of certain immune cells called CD4 T cells. The low CD4 T cells renders people with ICL prone to many types of severe infections, autoimmune diseases, and cancers. Although these infections and diseases can be treated whenever occur, there is currently no treatment that targeting the underlying deficiency of CD4 T cells can provide a definitive treatment for people with ICL. Objective: To test a new drug (NT-17) in people with ICL which can increase the number of CD4 T cells Eligibility: People aged 18 to 75 years with ICL who are also enrolled in NIH protocol 09-I-0102. Design: Participants will be screened. They will have a physical exam and blood tests. Some participants with high suspicion of central nervous system infection or history of such infections may also undergo a lumbar puncture. A thin needle will be inserted into their lower back to draw out a sample of the fluid around their spinal cord. Participants will receive 3 doses of NT-17, each about 12 weeks apart. NT-17 is injected into the muscle of the upper arm, thigh, or buttock. They will visit the clinic 5 days before each dose and again 2 and 4 weeks after each dose. Blood will be drawn at all visits. Participants will undergo leukapheresis 3 times. Blood will be drawn from a needle in one arm. The blood will pass through a machine that separates out the white blood cells. The remaining blood will be given back through a second needle in the other arm. Some visits will include a rectal swab. Some participants may have additional tests, including a skin exam, skin biopsies, and medical imaging. Participants will have 3 follow-up visits every 3 months after they finish treatment.

Type: Interventional

Start Date: Nov 2024

open study

Background: Bone marrow failure diseases are rare. Much is known about the diseases at the time of diagnosis, but long-term data about the effects of the diseases and treatments are lacking. Researchers want to better understand long-term outcomes in people with these diseases. Objective: To follow people diagnosed with acquired or inherited bone marrow failure disease and study the long-term effects of the disease and its treatments on organ function. Eligibility: People aged 2 years and older who have been diagnosed with acquired or inherited bone marrow failure or Telomere Biology Disorder. First degree family members may also be able to take part in the study. Design: Participants will be screened with a medical history, physical exam, and blood tests. They may have a bone marrow biopsy and aspiration. For this, a large needle will be inserted in the hip through a small cut. Marrow will be drawn from the bone. A small piece of bone may be removed. Participants may also be screened with some of the following: Cheek swab or hair follicle sample Skin biopsy Urine or saliva sample Evaluation by disease specialists (e.g., lung, liver, heart) Imaging scan of the chest Liver ultrasounds Six-Minute Walk Test Lung function test Participants will be put into groups based on their disease. They will have visits every 1 to 3 years. At visits, they may repeat some screening tests. They may fill out yearly surveys about their medicines, transfusions, pregnancy, bleeding, and so on. They may have other specialized procedures, such as imaging scans and ultrasounds. Participation will last for up to 20 years.

Type: Observational

Start Date: Oct 2021

open study