Background: People with alcohol use disorder (AUD) also often have bouts of depression called major depressive episodes (MDEs). People having MDEs have been found to have low levels of a protein called PDE4B in the brain. Researchers want to find out if people with AUD also have low levels of PDE4B. This research may help lead to better treatments for AUD. Objective: To find out (1) if PDE4B levels are lower in people who are withdrawing from AUD and (2) if their PDE4B levels go up after they abstain from alcohol for 3 to 4 weeks. Eligibility: Adults aged 18 to 70 years with AUD. They must be enrolled in protocol 14-AA-0181. Design: Participants enrolled in protocol 14-AA-0181 will stay in the clinic for 3 to 4 weeks for alcohol withdrawal. During this stay, they will have some added procedures for the current study. Within the first week, participants will have a positron emission tomography (PET) scan of the brain. A needle will be used to guide a thin plastic tube (catheter) into a vein in one arm. An experimental substance called a radioactive tracer will be injected through the catheter. This tracer binds to PDE4B and makes it easier to see the protein in the brain. For the scan, participants will lie on a table that slides into a doughnut-shaped machine. Participants will have a second PET scan toward the end of their stay in the clinic. Participants may also have a magnetic resonance imaging (MRI) scan of the brain. They will lie on a bed that slides into a tube....

Type: Interventional

Start Date: Mar 2025

open study

Background: Alcohol use disorder (AUD) is a leading cause of disease and death worldwide. New treatments for AUD are needed. Dopamine, a chemical that carries signals between brain cells, is thought to play a role in alcohol addiction. Researchers want to learn how Suvorexant, a drug used to treat sleep disorders, affects dopamine receptors in the brain. Objective: To see how Suvorexant affects dopamine receptors in people with AUD and in healthy people. Eligibility: People aged 18 to 75 years seeking treatment for AUD. Healthy volunteers are also needed. Design: Participants with AUD will stay in the clinic for at least 10-28 days for alcohol detoxification. They will receive normal treatment for AUD. Suvorexant is a medicine used to treat sleep problem that is taken taken by mouth, once a day. Some participants will take the study drug. Others 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 wear a device that looks like a wristwatch to track their movements during their clinic stay. Participants will have blood tests and 3 brain imaging scans before starting on the study drug: 2 positron emission tomography (PET) and 1 magnetic resonance imaging (MRI) scan. They will be injected with a radioactive tracer during each PET scan. Participants will have tests to assess their thinking, memory, and attention. They will have sleep studies. Imaging scans and other tests will be repeated at the end of the study. Healthy volunteers will have 1 MRI and 2 PET scans. They will have tests to assess of their thinking, memory, and attention. They will wear a wristwatch like movement monitor for 1 week. ...

Type: Interventional

Start Date: Nov 2024

open study

Background: Olfactory neuroblastoma (ONB) is a rare cancer. It grows from tissue in the upper part of the nose cavity, related to the sense of smell and can affect a person s sense of smell. Researchers want to better understand the health problems of people with ONB. This may help them design better treatment and supportive care studies. Objective: To better understand ONB-the course of the disease, tumor characteristics, response to treatments, and management of the treatment. Eligibility: People ages 3 years and older who have ONB. They must enroll in NIH studies #19-C-0016 and #18-DC-0051. Design: Participants will be screened with a medical history and medical record review. Participants do not have to visit NIH. Participants will give a blood sample. They will complete surveys to assess their emotional and physical wellbeing and needs. Leftover tissue from biopsies and surgeries will be collected. Participants will take smell tests. They will smell items and answer questions about them. Participants may take taste tests. They will get plastic taste strips that they will move around their mouth to determine the taste. Participants may have a physical exam. Their performance status may be assessed. Participants may give blood, saliva, urine, and nasal secretion samples. Participants may have computed tomography and/or magnetic resonance imaging scans. Participants may have one or more tumor biopsies. Participants will talk to the research team about the results of their medical record/tests evaluation. The team will recommend how to best manage and treat their disease. Participants may give samples and complete surveys every 12 months. Their medical records will be reviewed every year. They will be monitored for the rest of their life.

Type: Observational

Start Date: Jun 2022

open study

Background: Severe aplastic anemia (SAA) and myelodysplastic syndrome (MDS) are bone marrow diseases. People with these diseases usually need a bone marrow transplant. Researchers are testing ways to make stem cell transplant safer and more effective. Objective: To test if treating people with SAA or MDS with a co-infusion of blood stem cells from a family member and cord blood stem cells from an unrelated donor is safe and effective. Eligibility: Recipients ages 4-60 with SAA or MDS Donors ages 4-75 Design: Recipients will be screened with: - Blood, lung, and heart tests - Bone marrow biopsy - CT scan Recipients will have an IV line placed into a vein in the neck. Starting 11 days before the transplant they will have several chemotherapy infusions and 1 30-minute radiation dose. Recipients will get the donor cells through the IV line. They will stay in the hospital 3-4 weeks. After discharge, they will have visits: - First 3-4 months: 1-2 times weekly - Then every 6 months for 5 years Donors will be screened with: - Physical exam - Medical history - Blood tests Donors veins will be checked for suitability for stem cell collection. They may need an IV line to be placed in a thigh vein. Donors will get Filgrastim or biosimilar (G-CSF) injections daily for 5-7 days. On the last day, they will have apheresis: Blood drawn from one arm or leg runs through a machine and into the other arm or leg. This may be repeated 2 days or 2-4 weeks later.

Type: Interventional

Start Date: Jun 2017

open study

Patients with hepatic steatosis due to alcohol will be offered liver biopsies when they enter a detoxification program. The first biopsy will occur in the first week of admission and the second in the fourth week when the steatosis has resolved. The hepatic transcriptome will be compared,

Type: Observational

Start Date: Jul 2026

open study

Background: People with alcohol use disorder (AUD) often develop metabolic alcohol-associated liver disease (MetALD). MetALD is a term for the heart, liver, obesity, and other issues that can accompany AUD. MetALD can be fatal. An approved weight management drug (Tirzepatide) may be able to help people with AUD and MetALD control their alcohol intake. Objective: To test Tirzepatide in people with AUD and MetALD. Eligibility: People aged 21 years and older with AUD and MetALD. Design: Participants will be screened. They will have a physical exam with blood and urine tests. They will have a test of their heart function. They will have a Fibroscan: This test uses ultrasound to measure how stiff the liver is. They will answer questions about their alcohol drinking, eating habits, and mental health. Participants may opt to have imaging scans of their brain and liver. These tests will be repeated in a baseline visit. This visit will take up to 6 hours. Tirzepatide is injected under the skin once a week for 12 weeks. Participants will visit the clinic to receive each injection. Some participants will get a placebo. A placebo is given just like a Tirzepatide injection but contains no medicine. The physical exam and other tests will be repeated during clinic visits. The Fibroscan will be repeated every 2 weeks during the study. Each weekly visit will take up to 3 hours. All tests will be repeated on the last visit. These tests will include the imaging scans and Fibroscan. Participants will learn about treatment options for AUD; they will be given recommendations on ways to reduce alcohol intake. This visit will take up to 6 hours.

Type: Interventional

Start Date: Jun 2026

open study

Background: Ollier disease (OD) and Maffucci syndrome (MS) are rare disorders that increase the risk of cancers in cartilage tissue. These tumors can lead to severe skeletal deformities beginning in childhood. People with OD or MS are also at an increased risk of blood vessel disorders and specific cancers. Researchers want to learn more about what causes these disorders. Objective: To understand the genetic causes of OD and MS. Eligibility: People aged 2 years and older who have OD or MS with cartilage tumors or blood vessel disorders. Design: Participants will stay at the NIH clinic for 5 days. They will undergo these procedures: A physical exam with blood tests. DXA (dual-energy X-ray absorptiometry) scan. The DXA scan measures the density of bones. Participants will lie on a table while a machine uses low-level X-rays to scan their body. MRI (magnetic resonance imaging) scan. An MRI uses strong magnets to take pictures of the tissues inside the body. Participants will lie on a table that slides into a large tube. A contrast dye may be injected through a needle inserted into a vein in the arm. X-rays. Some participants may have full-body X-rays instead of an MRI. X-rays take pictures of bones and other internal tissues and organs, such as the heart, lungs, and airways. PET (positron emission tomography) and CT (computed tomography) scans. Adult participants will have 2 other scans. The PET scan will include a radioactive injection into a vein. They will also have a full-body CT scan.

Type: Observational

Start Date: Jan 2025

open study

Background: Neuroendocrine neoplasms (NENs) are rare cancers in the gastrointestinal tract, pancreas, lungs, adrenal glands, and other areas of the body. Many of these cancers have a high risk of relapse and a low chance of survival. Better treatments are needed. Objective: To test a new drug, ADCT-701, in people with NENs. Eligibility: Adults aged 18 and older with NENs. Design: Participants will be screened. They will have a physical exam with blood and urine tests. They will have imaging scans and tests of heart functioning. Their ability to perform normal daily activities will be tested. A biopsy may be needed: A sample of tissue will be removed from the tumor. ADCT-701 is given through a tube attached to a needle inserted into a vein in the arm. Participants will receive the drug treatment on the first day of 21-day treatment cycles. They will visit the clinic a total of 10 times during the first two cycles. After that, they will visit the clinic 2 times during each cycle. Imaging scans, blood draws, heart function tests, and other tests will be repeated during study visits. Each visit will last up to 8 hours. Participants may continue receiving treatment with the study drug for up to 2 years. After treatment ends, participants will have follow-up clinic visits 4 times in 4 months. They will have a physical exam, with heart and blood tests, at each visit. After that, they will have follow-up clinic visits every 9 weeks; these visits will include imaging scans. Follow-up visits will continue for up to 5 years after treatment began....

Type: Interventional

Start Date: Jun 2024

open study

Background: Gulf War illness (GWI) affects up to 210,000 U.S. veterans who served in the Middle East during the Gulf War in 1990-1991. Symptoms include fatigue, muscle and joint pain, forgetfulness, headaches, rashes, and sleep disturbances. Routine exams cannot determine the cause of GWI. Researchers need more information to understand this disease. Objective: This natural history study will look for differences in Gulf War veterans who experienced GWI and those who did not. Eligibility: Gulf War veterans with GWI. Healthy Gulf War veterans who do not have GWI are also needed. Design: Participants will stay in the NIH Clinical Center as an inpatient for 2 weeks. They will undergo many tests. Blood will be drawn many times throughout the study. Participants will also give urine, saliva, and stool samples. Scans to measure the brain, leg muscles, bone density and body mass will be done. They will have an exercise stress test and muscle strength tests. They will have a sleep study. They will have tests to look at how well the brain, heart and lungs are working. Participants will sleep in a specialized room that measures the amount of oxygen they use and the carbon dioxide they produce on four consecutive nights. A sample of fluid will be collected from inside the spine. Participants will take many surveys. Some will ask about their activities. Some will be about emotional and mental health. Some will be about thinking, memory, and behavior. Optional tests include other imaging scans and testing the autonomic nervous system. Samples of skin and muscle may be taken. After discharge, participants will wear activity monitors for 14 days. They will keep a diary of their symptoms, including fatigue, pain, and sleep, while wearing the monitors.

Type: Observational

Start Date: Apr 2023

open study

Background: Metastatic castration sensitive and castration resistant prostate cancer (mCSPC and mCRPC) are prostate cancers that have spread to other parts of the body. Use of the drug docetaxel with androgen deprivation therapy can improve survival for men with mCSPC. Researchers want to see if combining this treatment with other drugs can help delay the time it takes for mCSPC and mCRPC to get worse. Objective: To learn if giving docetaxel with PDS01ADC is safe and effective for men with prostate cancer. Eligibility: Men age 18 and older with mCSPC or mCRPC. Design: Participants will be screened with a medical history and physical exam. Their diagnosis will be confirmed. Their symptoms and how well they do their normal activities will be reviewed. They will have blood and urine tests. Their heart will be evaluated. They will have imaging scans of the chest, abdomen, and pelvis. They will have bone scans with intravenous (IV) injections of Tc99 to check for tumor spread in the bones. Some screening tests will be repeated during the study. Participants may have tumor biopsies. Participants will get treatment in cycles. Each cycle will last 21 days. They will get docetaxel through IV infusion. They will get PDS01ADC as an injection under the skin. Participants with mCSPC will have up to 6 cycles. Those with mCRPC will be treated until they cannot tolerate the side effects or their disease gets worse. Participants will have a follow-up visit 30 days after treatment ends. Those with mCSPC will then have follow-up visits at the clinic every 3 months.

Type: Interventional

Start Date: Feb 2021

open study

Background: Mitochondrial disease is a rare disorder. It can cause poor growth, developmental delays, muscle weakness, and other symptoms. The disease is usually inherited. It can be present at birth or develop later in life. Infection is a major cause of disease and death in people with this disease. Researchers want to learn more about these infections and the declining health of people who have this disease. To do this, researchers will study the DNA of people who become ill. Their DNA will be compared to the DNA of their household/family members. Objective: To learn more about how genes affect people with mitochondrial disease. Eligibility: People age 2 months and older with mitochondrial disease and their household/family members. .<TAB> Design: Participants will complete a questionnaire about their health history. Their medical records may be reviewed. They will give a blood sample. If the participant becomes ill, they may have a videoconference with a doctor or nurse at the NIH to perform a physical exam. They may be contacted after their illness to give updates on their health. They may be asked to give extra blood samples or complete extra questionnaires. Participants genetic data will be put into a database. The data will be labeled with a code and not their name. The data will be shared with other researchers. Participation lasts about 1 year. This may be extended if the participant is very ill.

Type: Observational

Start Date: Oct 2020

open study

Background: - Biomarkers are substances in people s blood and tissues. They help researchers understand diseases and signs of aging. Scientists want to do more research on biomarkers to find ways to improve quality of life in old age. Objective: - To learn more about biomarkers and their relationship to aging. Eligibility: - Adults at least 20 years old who weigh at least 110 pounds and have a body mass index below 30. They must agree that their genetic samples can be collected, studied, and stored. Design: - Participants will be screened with medical history, physical exam, EKG and blood and urine tests. - Participants will have 3-day visits. They will return every 2 years. - All visits include: - Blood and urine collection - Physical performance tests - Health questionnaires - Memory and problem-solving tests - Magnetic Resonance Imaging (MRI) and Computerized Tomography (CT) scans. - Muscle metabolism/ exercise tests - Taste strips - Muscle and/or skin biopsies/ red light therapy - Retinal imaging/ eye tracking - Sleep study - ODD visits also include: - Cytapheresis - Bone marrow aspirate - EVEN visits also include: - Hyperglycemic CLAMP - Lumbar Puncture (LP) - Continuous Glucose Monitor (CGM)

Type: Observational

Start Date: Mar 2015

open study

Background: Most people with hairy cell leukemia have a BRAF gene mutation. They can be treated with BRAF inhibitors, drugs that target this mutation. For people who do not have this mutation, BRAF inhibitors are not a treatment option. We found that in hairy cell leukemia, when BRAF is not mutated, the MEK gene frequently is. Binimetinib is a MEK inhibitor which targets MEK. It is important to determine if this drug can be a good treatment option in those who cannot benefit treatment with BRAF inhibitors. Objective: To see if binimetinib is an effective treatment for hairy cell leukemia that does not have a BRAF mutation. Eligibility: People ages 18 and older with hairy cell leukemia without a mutation in the BRAF gene and whose disease either did not respond to treatment or came back after treatment Design: Participants will be screened with: - Medical history - Physical exam - Blood and urine tests - Lung and heart tests - Eye exam - Bone marrow biopsy: A needle will be injected through the participant s skin into the bone to remove a sample of marrow. - CT or MRI scan: Participants will lie in a machine that takes pictures of the body. They might receive a contrast agent by vein. Before they start treatment, participants will have an abdominal ultrasound, pulmonary function tests, and exercise stress tests. Participants will take binimetinib by mouth twice daily in 28-day cycles. They will keep a medication diary. Participants will have at least one visit before every cycle. Visits will include repeats of some screening tests. Participants may continue treatment as long as their disease does not get worse and they do not have bad side effects. About a month after their last dose of treatment, participants will have a follow-up visit. They will then have visits once a year....

Type: Interventional

Start Date: Jan 2021

open study

Background: - Researchers are interested in studying individuals who have known or suspected metabolic, inflammatory or genetic diseases that may put them at a high risk for heart diseases or diseases of their blood vessels. Depending on the condition being studied, both affected and nonaffected individuals may be asked to provide blood and other samples and may undergo tests to evaluate the heart, blood vessels and lung function. The testing is tailored to the individual and/or condition being studied. Nonaffected individuals may include relatives of affected individuals and healthy nonrelated volunteers. Objectives: - To study individuals who have or are at risk for cardiovascular diseases, and in some cases their unaffected relatives and healthy volunteers. Eligibility: - Individuals between 1 and 100 years of age. Participants may be healthy volunteers, individuals with cardiovascular diseases, or unaffected relatives of individuals with cardiovascular diseases. Design: - Participants will have some or all of the following tests, as directed by the study researchers: - Photography of the face and full body - Body measurements - Radiography, including chest or limb x-rays - Metabolic stress testing to study heart and muscle function - Echocardiography to study heart function - Magnetic resonance imaging (MRI) studies, including cardiovascular MRI, angiography, and contrast MRI, to study heart function and performance - Computed tomography (CT) angiogram to obtain images of the heart and lungs - Positron emission tomography (PET) imaging to study possible fat infiltration of the heart - Six-minute walk test to study heart, lung, and muscle function and performance - Vascular ultrasound to study blood vessel walls - Blood, tissue, and other specimens will be collected for research and testing, and will be taken either as part of the clinical study or during surgical procedures. - Follow-up studies may be performed under separate research protocols.

Type: Observational

Start Date: Jul 2010

open study

Background: Autoimmune lymphoproliferative syndrome (ALPS) is a rare disorder of the immune system caused by a mutation in the FAS gene. In ALPS, the body stores too many germ-fighting cells called lymphocytes. This can lead to an enlarged spleen and lymph nodes. Current treatments for ALPS can have many adverse effects. Better treatments for ALPS are needed. Objective: To test a study drug (soquelitinib) in people with ALPS. Eligibility: People aged 16 years and older with ALPS. Design: Participants will have 8 clinic visits and 6 remote visits within 1 year. Participants will be screened. They will have a physical exam with blood and urine tests. Some may have tests of their lung function. Soquelitinib is a tablet taken by mouth twice a day. Participants will record their doses and any symptoms on a paper or online form. Blood tests and other procedures will be repeated during study visits. Three visits will include imaging scans. Participants will lie on a table that slides through a doughnut-shaped machine while X-rays capture pictures of the inside of their body. Some participants may be able to remain in the study for a second year.

Type: Interventional

Start Date: Mar 2025

open study

Background: Laboratory tests that use blood and urine can provide a great deal of information about human health and disease. To develop even better tests and to improve the ways samples are handled for testing researchers need to experiment with samples from healthy people. Objective: This natural history study will collect blood and urine from healthy people. The samples will build a repository that will be used for all kinds of research. Eligibility: Healthy people aged 18 years or older. Design: Participants will have 1 study visit. The visit will last up to 2 hours. Participants will be screened. They will answer questions about their health history. They will list any medications they take. They will consent to donate samples for research and future use: Blood: Up to 4.5 tablespoons of blood may be collected from a needle inserted into a vein. Urine: Participants will be given a sterile container to provide a sample. Some participants may be asked to provide other types of samples. Some participants may be asked to provide new samples if their first ones are depleted.

Type: Observational

Start Date: Jul 2024

open study

Background: The National Cancer Institute, part of the National Institutes of Health, has partnered with nine health care systems across the U.S. to establish the Connect for Cancer Prevention Study. While researchers have made important discoveries, there is more to learn to lower the number of people affected by cancer. By taking part in Connect, participants can help researchers learn how the way we live, our genetics, and our health history may affect cancer risk. Objective: To study and better understand the causes of cancer and to find new ways to prevent it. Eligibility: The study will include 200,000 adults who get their health care from a partner health care system, are between 30 and 70 years old at enrollment, and have never had cancer. People remain eligible to join if they have or once had non-melanoma skin cancer, or a condition that may raise cancer risk (such as ductal carcinoma in situ, or DCIS). Design: Eligible recruits can sign up for Connect online by creating an account on MyConnect using their email address or phone number. After creating an account, they will complete the informed consent process. All information shared through MyConnect is secure to protect participant privacy. After joining the study, participants will be asked to answer online health surveys a few times a year, donate samples of blood, urine, and saliva every two to three years, and safely share access to their electronic health records with Connect. In the future, participants may donate unused samples that are collected at clinical visits, like tissue, stool, or blood, and may mail in samples collected at home. Participants may also share information from personal health trackers, like wearable devices or apps. This information will help researchers study the health and behavior patterns that may affect cancer risk. It takes time to understand the causes of cancer, so Connect will go on for many years. The longer people participate, the more researchers may learn. Participants can leave the study at any time. Learn more about Connect by visiting cancer.gov/connectstudy.

Type: Observational

Start Date: Jul 2021

open study

This study will examine the natural history of Leishmanial infections and their treatments. It will provide an opportunity for NIAID staff to learn more about leishmaniasis and perhaps to improve diagnostic tests for these infections. Patients between 2 and 80 years of age with known or suspected leishmaniasis are eligible for this study. Participants will have routine blood tests and a biopsy to confirm leishmanial infection. The biopsy procedure will be determined by the type of infection local cutaneous leishmaniasis (LCL), mucocutaneous leishmaniasis (MCL) or visceral leishmaniasis (VL). CL will be confirmed with a punch biopsy, in which a cookie-cutter type razor is used to remove a small circular piece of skin tissue. MCL will be confirmed using a thin flexible tube inserted into the nose. This tube is used to examine the nose and upper airway and to remove a tissue sample, if an affected area is seen. VL will be confirmed with either a bone marrow or liver biopsy or a splenic aspirate. For these procedures, a small tissue sample is withdrawn through a needle placed in the hipbone, liver or spleen, respectively. Some patients may also have a skin test for leishmaniasis similar to tuberculin skin testing. Treatment and length of hospital stay are determined by the type of infection. CL may be treated with Pentostam, amphotericin, amphotericin B, itraconazole or ketoconazole; ML with amphotericin B, or encapsulated amphotericin; and VL with Pentostam or encapsulated amphotericin. Pentostam is infused daily for 18 to 28 doses, most as an outpatient. Blood is drawn 3 times a week for safety tests and an electrocardiogram is done 2 to 3 times a week to monitor heart rhythm. Amphotericin B is infused every day or every other day for about 30 doses, all on an inpatient basis. Patients undergo hydration (infusion of a large amount of fluid) just before and immediately after each infusion to protect the kidneys. Blood is drawn every other day and urine samples are collected occasionally for routine urinalysis. Encapsulated amphotericin is infused every other day, on an outpatient basis. Blood is generally drawn every other day to every 2 days and urinalyses are done periodically. Itraconazole and ketoconazole are taken orally for at least 1 to 3 months, with blood drawn every 2 to 3 weeks. Patients may be asked to have photographs taken before, during and after treatment to document progress. They may also be asked to provide extra blood samples for research purposes, either through a vein in the arm or through apheresis, a method for collecting large numbers of cells. For apheresis, whole blood is collected through a needle in an arm vein and circulated through a machine that separates it into its components. The desired cells are then removed, and the rest of the blood is returned to the body, either through the same needle used to draw the blood or through a second needle in the other arm. Patients with cutaneous leishmaniasis will have a follow-up clinic visit 2 weeks to 3 months after treatment is completed. If there are no complications, their participation will end at that time. Patients with mucocutaneous leishmaniasis and visceral leishmaniasis will be followed every 3 to 6 months indefinitely for routine evaluations and re-treatment if the infection recurs. ...

Type: Observational

Start Date: Nov 2001

open study

Background: - The Baltimore Longitudinal Study of Aging (BLSA) is a clinical research program on human aging that began in 1958. Volunteers of different ages join the study when they are healthy, and have follow-up visits for life. Visits last for multiple days. Participants are evaluated for many physical elements as well as for brain function. Physical tests are given. Information on mood, personality, and social aspects of life is also collected. This program has contributed more than any other research project to our understanding of aging. Objectives: - To characterize the many aspects of the aging process and learn how people can successfully adapt to aging. Eligibility: - Healthy individuals at least 20 years old. Design: - Participants will receive a booklet and video describing the tests they will take. - During a 3-day visit at the study hospital, participants will take the following tests: - Urine will be collected for 24 hours. Blood samples will be taken. A small piece of muscle tissue may be collected by a needle. - A medical questionnaire and a physical exam will be given. - Participants hearts will be tested, including with blood pressure tests and electronic monitors. They will breathe into a tube to test their lungs. - Participants will perform several exercises, including treadmill walking. - Vision, hearing, and taste will be tested. - Bone and joint X-rays may be taken. - Imaging tests will be given, such as an MRI. - Participants will answer questions to test their mental abilities. - Participants will return for follow-up visits every few years for life. The tests listed above will be given at every visit.

Type: Observational

Start Date: Feb 2014

open study

Background: The National Cancer Institute Surgery Branch (NCI-SB) has developed experimental therapies that involve taking white blood cells from patients' tumor or from their blood, growing them in the laboratory in large numbers, and then giving the cells back to the patient. Objective: This study will allow patients to under screening and evaluation for participation in NC-SB Protocols. Eligibility: Patients 18 years or older must meet the minimum eligibility criteria for an NCI-SB treatment protocol. Design Patients will undergo testing and evaluations as required by the appropriate NCI-SB treatment protocol.

Type: Observational

Start Date: Jul 1999

open study

Background: Some people with the same disorder on a genetic level have more complications than others. Researchers want to look for a link between the PKLR gene and sickle cell disease (SCD) symptoms. The PKLR gene helps create a protein, called pyruvate kinase that is essential in normal functioning of the red blood cell. Differences in the PKLR gene, called genetic variants, may cause some changes in the pyruvate kinase protein and other proteins, that can affect functioning of the red blood cell adding to the effect of SCD. Researchers can study these differences by looking at DNA (the material that determines inherited characteristics). Objective: To study how the PKLR gene affects sickle cell disease. Eligibility: Adults ages 18-80 of African descent. They may have sickle cell disease or not. They must not have had a transfusion recently or have a known deficiency of pyruvate kinase. They cannot be pregnant. Design: Participants will be screened with questions. Participants will have blood drawn by needle in an arm vein. The blood will be genetically tested. Not much is known about how genes affect SCD, so the test results will not be shared with participants or their doctors. ...

Type: Observational

Start Date: Oct 2018

open study

Background: In a previous study, participants were lived at the NIH and randomly received either a low-fat or a low-carbohydrate diet for 2 weeks and then switched to the other diet for 2 more weeks. Participants who received the low-carbohydrate diet first lost more body fat at the end of the study than those who received the low-fat diet first. Researchers want to see if they can repeat that result in a longer weight loss study when participants live at home. Objective: To test the effects of diet order in people receiving either a low-fat or low-carbohydrate diet first for 4 weeks and then immediately switched to the other diet for another 4 weeks. Eligibility: Adults aged 19 to 50 years with a body mass index of 25 or more. Design: Participants will complete the study at their homes, but there will be 3 required visits to the NIH. Participants will drink a special type of water 2 weeks before the baseline NIH visit and collect urine samples at home to measure how many calories they burn. Before the diets begin, participants will visit the NIH for baseline testing when they will have a metabolism test while relaxing in a bed with a plastic hood over their head to collect the air they breathe out. They will have scans to measure their bone density and how much muscle and body fat they have. They will give stool, blood, and urine samples. Participants will be asked to eat a specific diet for 4 weeks followed by a different diet for 4 weeks. All meals will be delivered to the participants' homes. They will eat only the foods delivered. Participants will weigh themselves daily. They will wear a monitor to track their physical activity and a sensor to measure their glucose levels. They will prick their finger each morning to test a drop of blood for ketones. Participants will meet virtually as a group with the study team weekly. Participants will have two more NIH visits towards the end of each diet period....

Type: Interventional

Start Date: Aug 2024

open study

Background: Rare tumors of the genitourinary (GU) tract can appear in the kidney, bladder, ureters, and penis. Rare tumors are difficult to study because there are not enough people to conduct large trials for new treatments. Two drugs-sacituzumab govitecan (SG) and atezolizumab-are each approved to treat other cancers. Researchers want to find out if the two drugs used together can help people with GU. Objective: To test SG, either alone or combined with atezolizumab, in people with rare GU tumors. Eligibility: Adults aged 18 years and older with rare GU tumors. These may include high grade neuroendocrine carcinomas; squamous cell carcinoma of the bladder; primary adenocarcinoma of the bladder; renal medullary carcinoma; or squamous cell carcinoma of the penis. Design: Participants will be screened. They will have a physical exam with blood and urine tests. They will have tests of heart function. They will have imaging scans. They may need a biopsy: A small needle will be used to remove a sample of tissue from the tumor. Both SG and atezolizumab are given through a tube attached to a needle inserted into a vein in the arm. All participants will receive SG on days 1 and 8 of each 21-day treatment cycle. Some participants will also receive atezolizumab on day 1 of each cycle. Blood and urine tests, imaging scans, and other exams will be repeated during study visits. Treatment may continue for up to 5 years. Follow-up visits will continue for 5 more years. ...

Type: Interventional

Start Date: Aug 2024

open study

Background: Genitourinary cancers are some of the most common types of cancer. They are lethal when they spread. The drug M7824 blocks the paths that cancer cells use to stop the immune system from fighting cancer. The drug PDS01ADC triggers the immune system to fight cancer. Researchers want to learn if these drugs can help fight these cancers when given with and without Stereotactic Body Radiation Therapy (SBRT) radiation. Objective: To learn if M7824 and PDS01ADC, with or without SBRT, can help the immune system to fight cancer better. Eligibility: People 18 and older with cancer that started in the bladder, kidneys, or other genitourinary organs (but not the prostate) and has spread to other parts of the body. Design: Participants will be screened with: medical history physical exam ability to do their normal activities blood tests urine tests electrocardiogram body scans. Participants will give a tumor sample or have a tumor biopsy. Screening tests will be repeated during the study. Participants will get PDS01ADC . It is injected under the skin every 4 weeks. They will also get M7824 through an intravenous (IV) infusion every 2 weeks. For this, a small plastic tube is put into a vein in the arm. They will get these drugs in 28-day cycles until they leave the study. They may have SBRT. Participants will give tissue and saliva samples. Participants will have a follow-up visit 30 days after treatment ends. Then they will get phone calls or emails every 12 weeks indefinitely.

Type: Interventional

Start Date: Jul 2020

open study

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. ...

Type: Interventional

Start Date: Apr 2019

open study