Background: About 90,000 new cases of brain and spinal cord tumors are diagnosed annually in the United States. Most of these tumors are benign; however, about 30% are malignant, and 35% of people with malignant tumors in the brain and spinal cord will die within 5 years. Many of these people have changes in certain genes (MYC or MYCN) that drive the development of their cancers. Objective: To test a study drug (PLX038) in people with tumors of the brain or spinal cord. Eligibility: People aged 18 years or older with a tumor of the brain or spinal cord. Some participants must also have tumors with changes in the MYC or MYCN genes. Design: Participants will be screened. They will have a physical exam and blood tests. They will have imaging scans and a test of their heart function. They may need to have a biopsy: A sample of tissue will be removed from their tumor. PLX038 is given through a tube attached to a needle inserted into a vein in the arm. All participants will receive PLX038 on the first day of each 21-day treatment cycle. They will take a second drug 3 days later to help reduce the risk of infection; for this drug, participants will be shown how to inject themselves under the skin at home. Blood tests, imaging scans, and other tests will be repeated during study visits. Hair samples will also be collected during these visits. Some participants may have an additional biopsy. Study treatment will continue up to 7 months. Follow-up visits will continue every few months for up to 5 years.

Type: Interventional

Start Date: Jan 2024

open study

Background: Diseases involving blood, blood vessels, and immune systems are leading causes of death in the United States. Researchers studying these diseases need to compare blood samples from both healthy and sick individuals. Blood samples from healthy people are also used to establish what is normal when developing new tests for diseases and to make sure new testing equipment is working properly. Objective: This natural history study will collect blood samples from healthy people. The blood will be used for various kinds of research. Eligibility: Healthy adults aged 18 years or older. Pregnant or nursing women will be excluded. Design: Participants will have a telehealth visit or telephone call to review their medical history. They will come to the NIH Clinical Center. They will have a needle inserted into a vein in their arm or hand. About 10 tablespoons of blood will be drawn through the needle. Researchers may perform a complete blood count, a type of blood test that can help evaluate the participant s overall health. They may do a blood type test. The blood samples will also be used for genetic studies. Some blood samples may be stored for use in future research. Participants may choose to return for repeat visits for up to 10 years. Review of their medical history may also be repeated at later visits. They will receive $50 per blood collection visit. ...

Type: Observational

Start Date: Jul 2022

open study

Background: Ongoing and future research projects that study gastrointestinal diseases depend on access to biological samples and clinical data. Researchers want to study people who are seen and treated for these diseases. This may help them assess and treat these diseases better in the future. Objective: To collect data and samples from people being seen and/or treated for gastrointestinal problems at NIH, to use in future research. Eligibility: Adults aged 18 and older who have known or suspected gastrointestinal disorders or need screening, treatment, or follow-up per current medical guidelines. Design: Participants will be screened with a physical exam. Their medical records will be reviewed. Participants will be seen by doctors based on the ailment they have. Their condition will be treated just like it would at a doctor s office. But the data and samples collected will be used for future research. Participants may give blood, urine, and/or stool samples. If participants have an endoscopy or colonoscopy as part of their standard care and samples are taken, they may be asked to give their leftover samples to NIH. Or, they may be asked to have extra samples taken for NIH to use. These samples may include gastric acid and/or tissue from the lining of the stomach or intestines. If samples are not taken as part of their standard care, they may be asked to have samples taken for NIH to use. Data will be stored at NIH. The data systems are password protected. Samples will be coded. Participants will take part in the study for as long as they agree to be seen for their disease....

Type: Observational

Start Date: Jan 2022

open study

Background: - Best Vitelliform Dystrophy (Best disease), Late-Onset Retinal Degeneration (L-ORD), and Age-Related Macular Degeneration (AMD) all affect the retina, the light sensing area at the back of the eye. Doctors cannot safely obtain retinal cells to study these diseases. However, cells collected from hair follicles, skin, saliva, urine, and blood can be used for research. Researchers want to collect cells from people with Best disease, L-ORD, and AMD, and compare their cells with those of healthy volunteers. Objectives: - To collect hair, skin, saliva, urine, and/or blood samples to study three eye diseases that affect the retina: Best disease, L-ORD, and AMD. Eligibility: - Individuals affected with ocular condition is one year of age or older. - Individuals affected with Best disease, L-ORD, or AMD is 18 years of age or older. - Unaffected individuals are seven years of age or older. Design: - The study requires one visit to the National Eye Institute. - Participants will be screened with a medical and eye disease history. They may also have an eye exam. - Participants will provide a hair sample, saliva sample, urine sample, blood sample, and/or a skin biopsy. The hair will be collected from the back of the head, and the skin will be collected from the inside of the upper arm.

Type: Observational

Start Date: Sep 2011

open study

Background: Type 2 diabetes is a disease that affects blood sugar levels. Complications can include heart and blood vessel (vascular) diseases. Rates of type 2 diabetes have tripled in children and young adults over the last 40 years. Vascular diseases are also increasing in young people. Objective: To learn more about factors, including type 2 diabetes, that may cause vascular disease in young people. Eligibility: People aged 12 to 25 years who (1) have type 2 diabetes; (2) are overweight but not diabetic; (3) or are lean and healthy. Biological parents are also needed. Design: Young participants will visit the NIH clinic once a year for up to 25 years. Each visit will take 4 days. Before each visit, participants will wear devices to track their sleep, activity, and blood sugar levels for 7 to 10 days. At each visit, participants will have tests including: Samples: They will provide blood, urine, and stool samples. Heart: They will ride a stationary bike for 6 minutes with stickers applied to their chest. Scans: They will lie on a bed that slides into a tube; the machine will take pictures of the inside of their body. Energy: They will wear a hood over their head to measure the air they breathe. Social stress: They will give a speech for 10 minutes to show their body s response to stress. Glucose: They will drink a sweet drink to see how their blood sugar changes. Biological parents will have 1 study visit. They will have blood tests. They will fill in questionnaires about their lifestyle and stress. ...

Type: Observational

Start Date: Mar 2025

open study

Background: Chronic hepatitis B virus (HBV) infection affects 292 million people worldwide; 887,000 die each year from cirrhosis, liver cancer, and related issues. Treatment options are limited. Objective: To test 2 drugs (VIR-2218 and peginterferon) in people with mild or inactive HBV infection. Eligibility: People aged 18 to 65 years with mild or inactive HBV infection. Design: Participants will be screened. They will have blood tests and an eye exam. They will have imaging scans of the liver to check the health of the liver. Participants will be in the study for over 2 years. VIR-2218 is an injection given under the skin of the stomach, upper arm, or thigh. Participants will come to the clinic to receive this injection once a month for 6 months. Peginterferon is also injected under the skin. Participants will have this shot once a week for 6 months. They may either inject themselves at home or come to the clinic to get the injections. Participants will get just the VIR-2218 for 3 months, then both shots for 3 months, then just the peginterferon for 3 months. Participants will have two 3-day stays in the hospital. Tests will include: Liver biopsy. A sample of tissue will be taken from their liver. After the procedure, participants will lie on their right side for 2 hours and then on their back for 4 hours. Fine needle aspiration. A small needle will be used to collect cells from the liver. After the last injection of peginterferon, follow-up visits will continue in the outpatient clinic every 4 to 12 weeks.

Type: Interventional

Start Date: Jan 2025

open study

Background: Alcohol use disorder (AUD) is a problematic pattern of alcohol use accompanied by clinically significant medical consequences. Medications can help most people reduce their drinking, but the number is limited, and additional treatment options are needed. Objective: To test if a medication named Semaglutide may reduce alcohol drinking in people with AUD. Who can participate? All Adults aged 18 or older with AUD might be eligible to participate in the study. What will happen during the study? Participants will visit the National Institute on Drug Abuse (NIDA) in Baltimore once a week for about 20 weeks (5 months). Each visit will last between 2 and 6 hours depending on the tasks scheduled for that visit. Participants will be assigned by chance (like flipping a coin) to receive either Semaglutide or placebo. A placebo looks just like a real drug but contains no medicine. The study medication is given as a shot under the skin each week. Participants will undergo different tests throughout the study: They will give blood, urine, and saliva samples. They will engage in self-paced behavioral therapy on a computer. They will answer questions about their mood, diet, alcohol drinking and craving, tobacco use, etc. They will taste several sweet liquids and tell their preferences. They will sit in a bar-like room and be exposed to cues that might make them feel the urge to eat food or drink alcohol. They will wear a virtual reality headset that creates a cafeteria setting. They will walk the virtual cafeteria and choose food and drinks from a buffet. They will have a functional magnetic resonance imaging (fMRI) scan to take pictures of their brain. During the scans, participants will be shown pictures of alcohol-containing drinks, food, and other items.They will perform tasks on a computer screen. Participants will have a follow-up visit about 7 weeks after their last shot.

Type: Interventional

Start Date: Oct 2023

open study

Background: Lipodystrophy is a health problem in which the body does not have enough fat tissue. People with lipodystrophy may not make enough of the hormone leptin. Leptin regulates hunger. Low leptin levels trigger hunger. People with lipodystrophy can have many health problems. They may take a drug (metreleptin) that mimics leptin. Little is known about how taking metreleptin may affect a pregnancy. Metreleptin may be helpful or harmful to pregnant women. It may also affect the health of the child who is born. Objective: This natural history study will collect data about the effects of taking metreleptin while pregnant. Eligibility: Women aged 18 years or older with lipodystrophy who have been pregnant. Women who did and who did not take metreleptin during their pregnancies are needed. Children of women with lipodystrophy who took this drug during pregnancy are also needed. Design: Participants will have 1 study visit. This visit may be by phone, by telehealth, or in-person. Participants will answer questions about their pregnancies. They will discuss any health problems they had. They will be asked about any medicines they took before and during their pregnancies. They will be asked about the health of their children. Participants medical records will be reviewed. Participants may need to provide a blood sample. They may also be asked to provide a sample of breastmilk. Participants children may also be asked to provide a blood sample....

Type: Observational

Start Date: Sep 2022

open study

Background: In Fontan Associated Liver Disease (FALD), congestion of blood in the liver causes cirrhosis. This condition can cause death. Researchers want to understand what triggers this process and find new treatments for it. Objective: To understand how long-term congestion of blood in the liver causes liver scarring that eventually leads to cirrhosis. Eligibility: People aged 18 and older who are at risk of developing FALD from the Fontan procedure. Design: Participants will be screened with: Medical history Physical exam Blood and urine tests Liver ultrasound. This uses sound waves to take pictures of the body. Participants will have an outpatient visit within 12 weeks after screening. Within 24 weeks later, they will have a 3-day hospital stay. About 2 weeks later, they will have a follow-up visit. Visits will include repeats of the screening tests and: Heart tests Stool collection Questionnaires MRI of the liver. Participants will lie on a bed that slides in and out of the scanner. They will receive a contrast agent injected into a vein. While in the scanner, they will also have an MRCP to view the bile ducts and the pancreatic duct. Fibroscan exam. This is an ultrasound that uses a special probe to look at the toughness of the liver. Upper endoscopy. This uses a thin scope to look inside the upper digestive tract. Liver biopsy. This will be taken through large vein in the neck or through the chest. Just before the biopsy, participants will have pressure measurements inside their liver. For this, a catheter will be inserted into a neck vein and guided into the liver.

Type: Observational

Start Date: Sep 2022

open study

Background: There are no approved drugs to treat recurrent thymoma and thymic carcinoma. New therapies are needed for people with these cancers. Researchers want to see if the drug PT-112 can help. PT-112 kills cancer cells. It also helps the body s immune system fight cancer. Objective: To see if the study drug PT-112 can cause tumors to shrink. Eligibility: People ages 18 and older who have thymoma or thymic cancer and whose disease returned or progressed after treatment with at least one platinum-containing chemotherapy, or who have refused standard treatment. Design: Participants will be screened with: Review of medical history and medications Physical exam Blood and urine tests CT or MRI scans of parts of the body, including the brain Participants will get PT-112 in 28-day cycles, on days 1 and 15 of of the first cycle and on day 1 of each cycle after that. They will get the drug by infusion through a catheter. The catheter is a small plastic tube put into a vein. On days they receive the drug, participants will have physical exams and blood and urine tests. They will have an ECG to test heart function on day 1 of each cycle. Participants will have scans every 8 weeks. Participants may choose to have tumor biopsies on day 1 of cycles 1 and 3. Biopsies may be guided by an ultrasound or CT scan. Participants will continue treatment as long as they can handle the side effects and their disease does not get worse, for up to 8 years. Participants will have follow-up visits 2 weeks and 4 weeks after they stop therapy. Then the study team will check on participants every 3 months until 8 years after the participant joined the study.

Type: Interventional

Start Date: Apr 2022

open study

Background: Parathyroid disorders are very common in the general population and include disorders of parathyroid excess, deficiency, or defects in parathyroid hormone (PTH) signaling. PTH, the main secretory product of parathyroid glands is responsible for regulation of calcium-phosphate homeostasis. Objective: i) To investigate the cause of parathyroid disorders ii) To describe evolution, natural history, and longitudinal trends of parathyroid and related disorders seen in syndromic presentations like multiple endocrine neoplasia, hyperparathyroidism-jaw tumor syndrome Eligibility: People ages 6 months older who have, are at risk of having, or are related to a person with a parathyroid or related disorder. Design: Participants will be screened with a review of their medical records. Participants will be seen, tested, and treated by doctors based on their condition. Their visits may be in person or via telehealth. Participants will complete questionnaires. They will answer questions about their physical, mental, and social health. Participants may give samples such as saliva, blood, urine, or stool. Participants may give cheek cell samples. They will do this using a cheek swab or by spitting into a cup. Adult participants may give a skin biopsy. For this, a small bit of skin is removed with a punch tool. Participants may have medical photos taken. If participants have surgery during the course of their regular care either at the NIH or at a different hospital or doctor s office, researchers will ask for some of the leftover tissue. Participants will be in the study as long as they are being seen by their doctor.

Type: Observational

Start Date: Nov 2021

open study

Background: The adrenal gland makes the hormone aldosterone. This helps regulate blood pressure. An adrenal gland tumor that makes too much aldosterone can cause high blood pressure and low potassium. The cause of these tumors is unknown, but sometimes they are inherited. Objective: To study the genes that may cause primary aldosteronism in Black individuals. Eligibility: People ages 18-70 who: Are Black, African American, or of Caribbean descent And have difficult to control blood pressure or primary aldosteronism Relatives of people with primary aldosteronism Design: Participants who are relatives of people with primary aldosteronism will have only 1 visit, with medical history and blood tests. Participants with primary aldosteronism or difficult to control blood pressure (suspected to possibly have primary aldosteronism) will be screened with a 1-2 hour visit. If they qualify, they will return for a hospital stay for 7-10 days. Tests may include: Medical history Physical exam Blood tests: Participants will have a small tube (IV catheter) inserted in a vein in the arm. They may drink a glucose-containing liquid or get a salt solution. If medically indicated, they may have invasive blood tests with a separate consent. Urine tests: Some require a high-salt diet for 3 days. Heart tests Scans: Participants lie in a machine that takes pictures of the body. A dye may be injected through a vein. Small hair sample taken from near the scalp. Kidney ultrasound Bone density scan: Participants lie on a table while a camera passes over the body. If the doctors feel it is medically necessary, they will offer participants treatment depending on their results. These treatments may cure the patient of their disease and may include: 1. Having one adrenal gland removed by the Endocrine surgeon under anesthesia. Patients will have follow-up visits 2-4 weeks after surgery. 2. Taking drugs to block the effects of aldosterone Participants may return about 1 year later to repeat testing....

Type: Observational

Start Date: Dec 2017

open study

Background: - Noncirrhotic Portal Hypertension (NCPH) is caused by liver diseases that increase pressure in the blood vessels of the liver. It seems to start slowly and not have many warning signs. Many people may not even know that they have a liver disease. There are no specific treatments for NCPH. Objectives: - To learn more about how NCPH develops over time. Eligibility: - People age 12 and older who have NCPH or are at risk for getting it. In the past year, they cannot have had other types of liver disease that typically result in cirrhosis, liver cancer, or active substance abuse. Design: - Participants will have 2 screening visits. - Visit 1: to see if they have or may develop NCPH. - Medical history - Physical exam - Urine and stool studies - Abdominal ultrasound - Fibroscan. Sound waves measure liver stiffness. <TAB>- Visit 2: - Blood tests - Abdominal MRI - Echocardiogram - Questionnaire - Liver blood vessel pressure (hepatic venous portal gradient (HVPG)) measurement. This is done with a small tube inserted in a neck vein. - They may have a liver biopsy. - All participants will visit the clinic every 6 months for a history, physical exam, and blood tests. They will also repeat some of the screening tests yearly. - Participants with NCPH will also have: - Upper endoscopy test. A tube inserted in the mouth goes through the esophagus and stomach. - At least every 2 years: Esophagogastroduodenoscopy. - At least every 4 years: testing including HVPG measurements and liver biopsy. - Participants without NCPH will also have: - Liver biopsy and HVPG measurements to see if they have NCPH. - Every 2 years: abdominal MRI and stool studies. - The study will last indefinitely.

Type: Observational

Start Date: Jul 2015

open study

Background: The NCI Surgery Branch has developed an experimental therapy that involves taking white blood cells from patients' tumors, growing them in the laboratory in large numbers, and then giving the cells back to the patient. These cells are called Tumor Infiltrating Lymphocytes, or TIL and we have given this type of treatment to over 100 patients. In this study, we are selecting a specific subset of white blood cells from the tumor that we think are the most effective in fighting tumors and will use only these cells in making the tumor fighting cells. Objective: The purpose of this study is to see if these specifically selected tumor fighting cells can cause non-small cell lung cancer (NSCLC) tumors to shrink and to see if this treatment is safe. Eligibility: - Adults age 18-72 with NSCLC who have a tumor that can be safely removed. Design: - Work up stage: Patients will be seen as an outpatient at the NIH clinical Center and undergo a history and physical examination, scans, x-rays, lab tests, and other tests as needed - Surgery: If the patients meet all of the requirements for the study they will undergo surgery to remove a tumor that can be used to grow the TIL product. - Leukapheresis: Patients may undergo leukapheresis to obtain additional white blood cells. {Leukapheresis is a common procedure, which removes only the white blood cells from the patient.} - Treatment: Once their cells have grown, the patients will be admitted to the hospital for the conditioning chemotherapy, the TIL cells and aldesleukin. They will stay in the hospital for about 4 weeks for the treatment. Follow up: Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1 year as long as their tumors are shrinking. Follow up visits take up to 2 days.

Type: Interventional

Start Date: Oct 2014

open study

Idiopathic CD4 lymphocytopenia (ICL) is a rare syndrome defined by consistently low CD4 T cell counts (<300/mm3) without evidence of HIV infection or other known immunodeficiency. Patients with ICL are at risk for opportunistic infections typically associated with HIV/AIDS such as disseminated cryptococcal infection and severe human papillomavirus-related dysplasia. More than 20 years since the description of ICL, its etiology, pathogenesis, and management remain unclear. In this study we propose to administer the combination of granulocyte colony stimulating factor (G-CSF) and plerixafor to ICL patients and healthy volunteers with the objective of harvesting mobilized CD34+ hematopoietic progenitor cells (HPCs) by apheresis for transfer into immunocompromised mice and for study with in vitro assays. The mice studies would serve to investigate thymic development, survival, and trafficking of the mobilized human cells within murine lymphoid and non-lymphoid organs. HPCs are used for various therapies and there is an increasing use of agents that stimulate the bone marrow to produce progenitor cells and move them into the bloodstream where they may be harvested by apheresis. Not all patients respond to GCSF with vigorous HPC mobilization. The binding of chemokine receptor CXCR4 to stromal cell derived factor (SDF-1 or CXCL12) is an important interaction between a hematopoietic progenitor cell and its marrow environment. Plerixafor is a CXCR4 inhibitor which blocks binding to SDF-1 resulting in the release of hematopoietic progenitor cells (CD34+) into peripheral circulation. In pharmacodynamic studies of plerixafor in conjunction with G-CSF compared to G-CSF and placebo, a two-fold increase in CD34+ cell count was observed. Due to the important role CXCR4 plays in immune cell trafficking and its potential role in the pathogenesis of ICL, we propose as a secondary objective to assess peripheral CD4 T cell and CD34+ hematopoietic progenitor cell numbers and functions in ICL patients compared to controls following G-CSF and plerixafor administration. Study participants will be screened within 12 weeks prior to the study period. Eligible participants will receive G-CSF for 5 days with hospitalization on Day 4 for plerixafor injection followed by apheresis on Day 5. Participants will return for examinations and blood draws on Days 8 and 12.

Type: Interventional

Start Date: Jan 2014

open study

The purpose of this investigation is to develop improved magnetic resonance imaging (MRI) techniques and hardware for studying brain function. MRI is a diagnostic tool that provides information about brain chemistry and physiology. This study will evaluate new MRI methods for monitoring blood flow to regions of the brain in response to simple tasks. The MRI machine used in this study is more powerful than those in most hospitals, permitting a higher visual resolution. Normal healthy volunteers over 18 years old may be eligible for this study. Candidates will be screened with a medical history and questionnaire, and a neurological examination. Study participants will have a yearly MRI scan. For this procedure, the subject lies on a stretcher that is moved into a donut-shaped machine with a strong magnetic field. A lightweight circular or rectangular coil-a device that improves the quality of the images-may be placed on the head. The scan time varies from 20 minutes to 3 hours; most scans last between 45 and 90 minutes. During the scan, the subject may perform simple tasks, such as listening to tapes, tapping a finger, moving a hand, watching a screen, or smelling a fragrance. More complex tasks may require thinking about tones or pictures and responding to them by pressing buttons. Information from this study will be used to develop better imaging methods that will, in turn, permit a greater understanding of normal and abnormal brain behaviors. ...

Type: Observational

Start Date: Jul 2000

open study

Kidney diseases related to the immune system include, nephrotic syndrome, glomerulonephritis, membranous nephropathy, lupus nephritis, and nephritis associated with connective tissue disorders. This study will allow researchers to admit and follow patients suffering from autoimmune diseases of the kidney. It will attempt to provide information about the causes and specific abnormalities associated with autoimmune kidney disease. Patients with kidney disease as a result of their immune system, and patients with diseases of the immune system who may later develop kidney disease, will be potential subjects for this study. Patients will undergo a history and physical examination, and standard laboratory test to more closely understand the causes, signs, symptoms, and responses to medication of these diseases. Based on these evaluations the patients may qualify as candidates for other experimental studies. At any time these patients may be asked to submit blood or urine samples for further research.

Type: Observational

Start Date: Jun 1992

open study

Hermansky-Pudlak Syndrome (HPS) is an inherited disease which results in decreased pigmentation (oculocutaneous albinism), bleeding problems due to a platelet abnormality (platelet storage pool defect), and storage of an abnormal fat-protein compound (lysosomal accumulation of ceroid lipofuscin). The disease can cause poor functioning of the lungs, intestine, kidneys, or heart. The major complication of the disease is pulmonary fibrosis and typically causes death in patients ages 40 - 50 years old. The disorder is common in Puerto Rico, where many of the clinical research studies on the disease have been conducted. Neither the full extent of the disease nor the basic cause of the disease is known. There is no known treatment for HPS. The purpose of this study is to perform research into the medical complications of HPS and begin to understand what causes these complications. Researchers will clinically evaluate patients with HPS of all ethnic backgrounds. They will obtain cells, blood components (plasma), and urine for future studies. Genetic tests (mutation analysis) to detect HPS-causing genes will also be conducted.<TAB>

Type: Observational

Start Date: Nov 1995

open study

Hypoglycemia is the term used to refer to lower than normal levels of blood sugar. This study will continue to research the causes of hypoglycemia. Patients involved in the study will be admitted to the Clinical Center of the National Institutes of Health and undergo tests for evaluating blood sugar. Patients will be required to refrain from eating for a set period of time and will undergo blood tests for insulin levels and several other specific diagnostic tests related to insulin secretion. The patients will be under supervision and will be provided with appropriate medical and surgical attention as needed.

Type: Observational

Start Date: May 1991

open study

Participants in this study will be patients diagnosed with or suspected to have a thyroid function disorder. These conditions may include: hypothyroidism, hyperthyroidism, thyroid hormone resistance, Graves' Dermopathy, and thyroid-stimulating hormone (TSH) secreting pituitary adenomas. The main purpose of this study is to further understand the natural history, clinical presentation, and genetics of thyroid function disorders. Many of the tests performed are in the context of standard medical care that is offered to all patients with thyroid function disorders. In addition, blood and tissue samples may be taken for research and genetic studies....

Type: Observational

Start Date: Feb 1977

open study

Background: People with substance use disorder (SUD) often have changes in brain function that can make it difficult to control drug-seeking behavior. These changes may heighten the urge to use drugs or lessen the desire to seek nondrug-related rewards. Researchers want to know how a technique called transcranial magnetic stimulation (TMS) may cause changes in brain activity that may help people with SUD. Objective: To test TMS in healthy volunteers. Eligibility: Healthy people aged 18 to 45 years who are right-handed. Design: Participants can volunteer for up to 5 different experiments. Each experiment requires 2 to 8 clinic visits. Each visit will last 3 to 7 hours. Some visits will include TMS. A coil will be placed on the participant s head. A brief electrical current will pass through the coil to create a magnetic field. Participants may feel a tapping or pulling sensation on the skin under the coil. They may feel a twitch in their face, neck, arm, or leg muscles. Participants may be asked to tense certain muscles during TMS. Some visits will include functional magnetic resonance imaging (fMRI) scans. Participants will lie on a bed that slides into a large tube. They will perform tasks on a computer inside the tube. The fMRI will show which parts of the brain are used during each task. Participants will perform tasks on a computer. Some tasks may be done at a desk as well as during TMS and fMRI. Participants may look at images, listen to sounds, smell odors, or taste flavored liquids. Their vital signs may be monitored and their eye movements may be tracked during tasks.

Type: Interventional

Start Date: May 2026

open study

Background: Myelodysplastic syndromes (MDS) occur when the cells that make blood cells are abnormal. There are limited treatment options for MDS. Researchers want to learn more through this natural history study so they can develop better treatments. Objective: To study the natural course of MDS and MDS/myeloproliferative neoplasms (MPN) and collect biological samples that can help researchers understand the disease. Eligibility: People with suspected or confirmed MDS or MDS/MPN. Healthy donors are also needed. They can be people who are scheduled to donate bone marrow at NIH for a relative, or they may be providing bone marrow in another study. Design: Participants will be screened with a medical history. Participants will have a physical exam. They will give blood and urine samples. They will discuss their symptoms, medications, and ability to perform their normal activities. They will complete surveys about how they are feeling. Participants will have a bone marrow biopsy. A needle will be inserted through a small cut. Bone marrow will be removed. A small piece of bone may be removed. Participants may have an optional skin biopsy. Participants may give optional saliva and stool samples. They may collect these samples at home and mail them to NIH. Participants may undergo optional apheresis. One or two needles or intravenous (IV) lines will be placed in their arm, neck, or groin veins. Blood will be removed. A machine will separate out the white cells. The rest of the blood will be returned to the participant. Participants will be contacted for follow-up once a year for up to 20 years. Healthy donors will have marrow collected for this study during their scheduled procedure with no follow-up.

Type: Observational

Start Date: Aug 2022

open study

Background: - Salivary glands in and around the mouth and throat make saliva. Salivary gland disorders can affect a person s quality of life. Studying people who have a disease that affects their salivary gland(s) may teach researchers about the disorders and their genetics. Objectives: - To study salivary gland diseases and disorders. To collect data and samples from people with salivary gland problems and their relatives. Eligibility: - People more than 4 years old who have or are suspected to have a disease involving salivary glands. - Their relatives more than 4 years old. - Healthy volunteers 18 years or older. Design: - Participants may be screened with: - Medical history - Physical exam - Blood and urine tests - General oral and dental history and exam - Saliva collection - Eye exam and test for dry eyes - Health questionnaires (adults) - Biopsy of some minor salivary glands. A small incision will be made on the inside of the lower lip and several tiny salivary glands will be removed. - Participants will have 2-3 visits. These may include: - Repeats of some screening tests - Ultrasounds of some glands. Researchers will put some gel on the face, then press on it with a smooth wand. - Adults may have other biopsies - A small catheter inserted into the opening of the parotid gland duct on the inside of the cheek. A saline solution (in a syringe) will fill the duct. - Swishing a saltwater solution in the mouth for 10 seconds and then spitting into a cup - Scrapings collected from teeth, tongue, and cheeks

Type: Observational

Start Date: Apr 2015

open study

Background: - By the time diseases of the retina are detected, serious damage has often already been done. Researchers want to find better ways of viewing the retina. One way called adaptive optics may help detect problems earlier. Objectives: - To study if adaptive optics can help find better ways to diagnose, treat, and manage retinal diseases. Eligibility: - People over age 12 with an eye disease. - Healthy volunteers over age 12. Design: - Participants will be screened with medical history and eye exams. These may include dilating pupils and taking pictures of the eyes. - Participants will have 1 or more study visits. They will have: - Medical and eye history. - Questions about their medications. - Eye exam including pupil dilation. - Adaptive optics imaging. After dilation, participants sit still while looking into an adaptive optics instrument. They look at specific places and images are taken of their retina. - They may also have: - More images. - Perimetry. Participants look into a lens and press a button when they see a light. - Color vision tests. - Electroretinogram. Participants will get numbing eye drops and special contact lenses. A small metal electrode will be put on their forehead. They will look at flashing lights and try not to blink.

Type: Observational

Start Date: Feb 2015

open study

Background: The NCI Surgery Branch has developed an experimental therapy that involves taking white blood cells from patients' tumors, growing them in the laboratory in large numbers, and then giving the cells back to the patient. These cells are called Tumor Infiltrating Lymphocytes, or TIL and we have given this type of treatment to over 200 patients with melanoma. Researchers want to know if TIL shrink s tumors in people with digestive tract, urothelial, breast, or ovarian/endometrial cancers. In this study, we are selecting a specific subset of white blood cells from the tumor that we think are the most effective in fighting tumors and will use only these cells in making the tumor fighting cells. Objective: The purpose of this study is to see if these specifically selected tumor fighting cells can cause digestive tract, urothelial, breast, or ovarian/endometrial tumors to shrink and to see if this treatment is safe. Eligibility: - Adults age 18-72 with upper or lower gastrointestinal, hepatobiliary, genitourinary, breast, ovarian/endometrial cancer, or glioblastoma refractory to standard chemotherapy. Design: Work up stage: Patients will be seen as an outpatient at the NIH clinical Center and undergo a history and physical examination, scans, x-rays, lab tests, and other tests as needed. Surgery: If the patients meet all of the requirements for the study they will undergo surgery to remove a tumor that can be used to grow the TIL product. Leukapheresis: Patients may undergo leukapheresis to obtain additional white blood cells. (Leukapheresis is a common procedure, which removes only the white blood cells from the patient.) Treatment: Once their cells have grown, the patients will be admitted to the hospital for the conditioning chemotherapy, the TIL cells and aldesleukin. They will stay in the hospital for about 4 weeks for the treatment. Follow up: Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1 year as long as their tumors are shrinking. Follow up visits will take up to 2 days. ...

Type: Interventional

Start Date: Aug 2010

open study