Background: Glucagon-like peptide 1 (GLP-1) agonist drugs are used to treat diabetes and aid weight loss. They may also help reduce cravings for drugs and alcohol. Researchers want to know if a GLP-1 drug (tirzepatide) can lessen the urge to drink in people with alcohol use disorder (AUD). Objective: To learn how the brains of people with AUD respond to a GLP-1 drug. Eligibility: People aged 21 to 65 years with AUD who are non-treatment seeking. They must be enrolled in protocol 14-AA-0181. Healthy volunteers are also needed. Design: This study consists of Part 1 and Part 2. Part 1 (Imaging Procedures): Five healthy volunteers will undergo 2 to 3 combined positron emission tomography/magnetic resonance imaging (PET/MRI) scans, with an interval of 2 to 3 weeks between scans. For each scan, a radioactive substance (tracer) will be administered intravenously. Participants will undergo PET/MRI scanning to assess brain activity during resting state. Methylphenidate (Ritalin) will be administered during each scan. Each imaging session will last approximately 2 hours. Tirzepatide and placebo will not be administered in Part 1. Participants with alcohol use disorder (AUD) are not included in Part 1. The purpose of this part of the study is to assess test/retest reproducibility of the PET/MRI combined scan measures. Part 2 (Randomization to Tirzepatide & Placebo): Participants will be randomized to receive either Tirzepatide or Placebo first. Healthy Volunteers and AUD participants will receive both treatments in a crossover design. Tirzepatide and placebo will be administered via subcutaneous injection (under the skin) once weekly for 2 to 3 weeks. This treatment period will be followed by 2 to 3 PET/MRI combined imaging scans described in the next paragraph. After a washout interval of approximately 2 to 3 weeks, participants will cross over to the alternate treatment (tirzepatide or placebo), administered once weekly for 2 to 3 weeks. This second treatment period will be followed by an additional 2 to 3 PET/MRI scans. Participants may receive up to 3 doses of tirzepatide and 3 doses of placebo. Part 2 (Imaging Procedures): Healthy Volunteers and participants with an AUD will undergo PET/MRI scans at two time points: following tirzepatide administration and following placebo administration. For each scan a radioactive substance (tracer) will be administered intravenously. Brain activity will be measured during PET/MRI acquisition during resting state. Methylphenidate will be administered during 1 of the scans at each time point. Each imaging session will last approximately 2 hours. Participants will wear a device to track their activity for at least 1 week before each set of scans. They will have tests of their thinking, memory, and attention.

Type: Interventional

Start Date: May 2026

open study

Background: Scientists have long used simple measures (such as height and weight) to estimate how much a person s body uses food (calories) as energy, as commonly called the metabolic rate. But metabolism varies among people with similar body sizes. Scientists now believe the old formulas for estimating metabolic rates may not work well for all people. Researchers want to find more accurate ways to measure a person s metabolism. Objective: This natural history study will examine the relationships between metabolism, body composition, and body surface area in a wide range of people. Eligibility: Healthy children and adults aged 2 years or older. Also, people aged 2 years or older with conditions that may alter metabolism. These may include diabetes, obesity, renal disease, or cancer. Design: Participants will spend 2 days and 1 night in the hospital. They will provide a medical history and answer questions about their activity levels, the foods they eat, and their lifestyle. They will also eat a special diet. Participants will undergo many tests: They will lie in a bed with a clear hood covering their head for 30 to 45 minutes to measure the gases in their breath. They will lie on a padded table for about 15 minutes while their body is scanned. They will stand on a platform while a 3D scanner measures their body. They will have a test to measure how fast an electric signal moves through their body. They will grip an instrument to measure the strength of their hands. They will drink salty water and provide blood and urine samples. Participants may be invited to return for these 2-day visits up to 8 times per year. Return visits must be at least 2 weeks apart.

Type: Observational

Start Date: Oct 2022

open study

Background: Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma. Most people with this cancer can be cured. But those who are not cured have a poor prognosis. Researchers want to add another drug to standard treatment see if it can improve the cure rate. Objective: To see if the drug acalabrutinib given with rituximab and standard combination chemotherapy can improve the cure rate of aggressive B-cell lymphomas such as diffuse large B-cell lymphoma. Eligibility: People ages 18 and older with an aggressive B-cell lymphomas that have not been treated Design: Participants will be screened with: Blood and urine tests Physical exam Medical history Tumor biopsy Bone marrow biopsy: A needle will remove marrow from the participant s hipbone. Lumbar puncture: If necessary, a needle will remove fluid from the participant s spinal canal. Imaging scans Participants will take the study drug for up to 14 days. It is a pill taken 2 times a day. Then they will have more scans. They will get rituximab and chemotherapy. They may get these drugs through a needle in an arm vein. Or they may them through a tube placed in a vein in their chest or in their neck. They might also keep taking the study drug. Each treatment cycle lasts 21 days. They will have up to 6 cycles. Participants may have 4 doses of another drug injected into their spinal fluid. Participants will have repeats of the screening tests throughout the study. Participants will have a follow-up visit 30 days after their last treatment, then every 3 months for 2 years, then every 6 months for 3 years, and then yearly.

Type: Interventional

Start Date: Aug 2019

open study

Background: Severe aplastic anemia (SAA), and myelodysplastic syndrome (MDS), and paroxysmal nocturnal hemoglobinuria (PNH) cause serious blood problems. Stem cell transplants using bone marrow or blood plus chemotherapy can help. Researchers want to see if using peripheral blood stem cells (PBSCs) rather than bone marrow cells works too. PBSCs are easier to collect and have more cells that help transplants. Objectives: To see how safely and effectively SAA, MDS and PNH are treated using peripheral blood hematopoietic stem cells from a family member plus chemotherapy. Eligibility: Recipients ages 4-60 with SAA, MDS or PNH and their relative donors ages 4-75 Design: Recipients will have: - Blood, urine, heart, and lung tests - Scans - Bone marrow sample Recipients will need a caregiver for several months. They may make fertility plans and a power of attorney. Donors will have blood and tissue tests, then injections to boost stem cells for 5-7 days. Donors will have blood collected from a tube in an arm or leg vein. A machine will separate stem cells and maybe white blood cells. The rest of the blood will be returned into the other arm or leg. In the hospital for about 1 month, recipients will have: - Central line inserted in the neck or chest - Medicines for side effects - Chemotherapy over 8 days and radiation 1 time - Stem cell transplant over 4 hours Up to 6 months after transplant, recipients will stay near NIH for weekly physical exams and blood tests. At day 180, recipients will go home. They will have tests at their doctor s office and NIH several times over 5 years.

Type: Interventional

Start Date: Feb 2019

open study

Background: - A number of rare inherited diseases affect only a few patients, and the genetic causes of these conditions remain unknown. Researchers are studying the use of a new technology called genome sequencing to learn which gene or genes cause these conditions. Understanding the genes that cause these diseases is important to improve diagnosis and treatment of affected patients. Objectives: - To identify the genetic cause of disorders that are difficult to identify with existing techniques. - To develop best practices for the medical and counseling challenges of genome sequencing. Eligibility: - Individuals who have one of the rare disorders under consideration in this study. These conditions are generally those in which the genetic cause of the disorder is unknown. The eligibility of most individual participants will be decided on a case-by-case basis by the researchers. - Family members of affected individuals, if that family member (often a parent) may provide genetic information. Design: Participants in this study will have at least one and in some cases several of the following procedures: - A medical genetics evaluation. - Other tests that may include x-rays, magnetic resonance imaging (MRI) exams, and consultations with other doctors. Not all studies are necessary for each person, but the information from the tests may be required to proceed with some of our gene sequencing studies. - Clinical photographs to document certain aspects of the disorder. - Blood, saliva, and skin biopsy samples, or other tissue samples, as required by the study doctors. - Genetic testing, as decided by the researchers. However, most participants in this study can expect to undergo genome sequencing, which is a technique to study all of a person s genes. - Participants will have choices about what kinds of results from genome sequencing they wish to learn. - After the tests have been completed and the results of the genetic studies are known, participants may be offered a return visit to the National Institutes of Health to learn these results, or the results may be returned by telephone or by a participant's home provider.

Type: Observational

Start Date: Feb 2010

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

Background: Major depressive disorder (MDD) is a serious mental illness that can put people at risk of self-harm and death. Many drugs are used to treat MDD, but it can take a long time for them to be effective. Researchers want to know if a faster-acting drug, (2R,6R)-hydroxynorketamine (HNK), can better treat the symptoms of MDD. Objective: To test a study drug (HNK) in people with MDD. Eligibility: People aged 18 to 70 years with MDD. They must have had a screening assessment under protocol 01-M-0254. Design: Participants will be tapered off their current MDD drugs over 2 to 5 weeks. They will stay off of the drugs for up to 2 weeks prior to starting the study medication and procedures. They will have a physical exam with blood tests. They will have tests of their heart function, mood, and thinking. They will answer questions about their symptoms. They may choose to have imaging scans and scans of their brain activity. HNK is given through a tube attached to a needle inserted into a vein. Participants will receive infusions on this schedule: They will receive 4 infusions over 2 weeks. They will stay in the clinical center overnight after each infusion or for the duration of the study. They will receive no drugs for 2 to 3 weeks. They will have 4 more infusions over 2 weeks, with overnight stays after each or for the duration of the study. One set of 4 infusions will be the HNK. The other set of 4 infusions will be a placebo. A placebo looks just like the real drug but contains no medicine. Participants will not know when they are getting the HNK or placebo. ...

Type: Interventional

Start Date: Nov 2024

open study

This study will investigate the genetic cause of Birt Hogg-Dube (BHD) syndrome and the relationship of this disorder to kidney cancer. BHD is a rare inherited condition characterized by papules, or bumps-benign tumors involving hair follicles-on the head and neck. People with BHD are at increased risk of developing kidney cancer. Scientists have identified the chromosome (strand of genetic material in the cell nucleus) that contains the BHD gene and the region of the gene on the chromosome. This study will try to learn more about: - The characteristics and type of kidney tumors associated with BHD - The risk of kidney cancer in people with BHD - Whether more than one gene causes BHD - The genetic mutations (changes) responsible for BHD Individuals with known or suspected Birt Hogg-Dube syndrome, and their family members, may be eligible for this study. Candidates will be screened with a family history and review of medical records, including pathology reports for tumors, and films of computed tomography (CT) and magnetic resonance imaging (MRI) scans. Participants may undergo various tests and procedures, including the following: - Physical examination - Review of personal and family history with a cancer doctor, cancer nurses, kidney surgeon, and genetic counselor - Chest and other x-rays - Ultrasound (imaging study using sound waves) - MRI (imaging study using radiowaves and a magnetic field) - CT scans of the chest and abdomen (imaging studies using radiation) - Blood tests for blood chemistries and genetic testing - Skin evaluation, including a skin biopsy (surgical removal of a small skin tissue sample for microscopic evaluation) - Cheek swab or mouthwash to collect cells for genetic analysis - Lung function studies - Medical photography of skin lesions These tests will be done on an outpatient basis in either one day or over 3 to 4 days. When the studies are complete, participants will receive counseling about the findings and recommendations. Individuals with kidney lesions may be asked to return periodically, such as every 3 to 36 months, based on their individual condition, to document the rate of progression of the lesions.

Type: Observational

Start Date: May 2002

open study

Background: Human intestines are home to a complex gut flora, also called microbiome; this is a natural occurring community of bacteria, fungi, yeast, and viruses. Changes in the balances of the gut flora can lead to illnesses, such as diabetes, colorectal cancer, and inflammatory bowel diseases. Synbiotics are dietary supplements people take to maintain proper balances of their gut flora aiming to improve health. Objective: To find out if a synbiotic supplement can increase the type and amount of beneficial gut bacteria in healthy people as well as improve cardio-vascular protection markers. The supplement contains a natural sugar from human milk. Eligibility: Healthy people aged 18 years or older who eat a typical western diet. They must take no medications (with a few exceptions). Design: Participants will have 2 clinic visits. The first visit will start with screening. They will have a blood test and wait around 2 hours for the results of the blood test. The test will determine if they are eligible for the study. Eligible participants will have additional blood drawn during the screening visit. They will be given a kit to collect a stool sample at home with instructions. They may complete a 3-day food diary. They will meet with a nutritionist and a physician by phone, telehealth, or in person. The supplement is a powder that is mixed with water or another noncarbonated drink. Participants will drink 2 doses per day. Each dose will be 1 hour before or after a meal. The second visit will be about 8 weeks after the first. Participants may repeat the 3-day food diary and nutrition visit. The physical exam, blood tests, and stool sample will be repeated.

Type: Interventional

Start Date: Nov 2024

open study

Background: Alcohol use disorder (AUD) is the most common substance use disorder in the world. Long-term AUD can affect a person s sense of taste and smell. This natural history study will compare alcohol drinking behaviors and measures of taste and smell in people with and without AUD. Objective: To understand how alcohol use changes the senses of taste and smell. Eligibility: People aged 18 to 65 years with or without AUD. Design: Participants will be screened. They will have several tests to assess their smell and taste functions. They will answer questions about their eating, alcohol use, and smoking or vaping habits. Participants will have 2 study visits. They will give samples of blood, nasal mucous, saliva, stool, and urine. Their bodies will be measured. They will undergo a type of scan that uses X-rays to measure their body composition. They will complete taste measurements. They will taste liquids by swishing them in their mouth, without swallowing. Then, they will be asked what they can detect and which flavors they preferred. They will also complete smell measurements. They will be asked if they can identify strong odors on a metal wand. They will be asked to rate the intensity and pleasantness of odors. Their brain activity in the frontal regions will be measured while they smell various odors. For this, we will use a brain imaging tool called functional near infrared spectroscopy. They will have sensory testing. Sensations such as pressure, pinpricks, heat, or vibrations will be applied to their skin. Then, they will be asked what they felt. They will keep diaries. They will write down what they eat (for 3 days), the alcohol they drink (3 days), and how much they sleep (14 days). They will wear a wristwatch-like device that records their activity for 14 days.

Type: Observational

Start Date: Jan 2024

open study

Background: Chronic graft-versus-host disease (cGVHD) is an immune system disorder that can occur in people who have had a stem cell transplant. cGVHD can affect multiple organs and increase risk of disability and death. New treatments are needed to treat cGVHD after stem cell transplant. Objective: To test a drug (pacritinib) in people with moderate or severe cGVHD that has not responded to previous treatment. Eligibility: People aged 18 years and older with moderate or severe cGVHD that has not responded to 2 or more lines of previous treatment. Design: Participants will be screened. They will have blood and urine tests. They will have tests of their heart and lung function. They may also have a CT scan. Some may have other specialized tests. Participants will take the study drug at home every day. Pacritinib is a capsule taken by mouth. The study doctor will determine the dosage and schedule. Participants will keep a medication diary. They will record the date and time of each drug dose and any missed doses. Participants will visit the clinic every 2 weeks for the first 4 months. Then they will visit the clinic once every 4 weeks. They will have blood and urine tests. During some visits, other screening tests will be repeated, and participants will fill out questionnaires about their quality of life. Photographs may be taken of skin rashes and joints affected by cGVHD. Participants will give saliva samples. Optional biopsies may be taken of the skin and mouth. Participants will take pacritinib for 6 to 12 months if no side effects develop. Follow-up visits will continue for up to 2 years. ...

Type: Interventional

Start Date: Mar 2023

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: A person s genome is the collection of all their genes. A gene instructs individual cells to make proteins. Proteins are involved in all of our body s chemical processes. Genome sequencing allows researchers to find variations in genes. Some of these are normal and are not known to cause disease. Some variants are known to cause or affect diseases like cancer. Researchers want to study genetic variants in people with cancer who also have an immunologic disease like HIV. Objective: To study the biology of cancer in order to improve ways to prevent, detect, and treat it. Eligibility: Adults at least 18 years old with certain cancers and/or immunodeficiencies Design: Participants will be screened with medical history, physical exam, and lab tests. Participants will give samples of one or more tissue type. They may give blood or urine samples. Researchers may get samples of tissue when participants have surgery or when the participants are on other protocols in the NCI. Participants may have a procedure to have tissue samples removed. Researchers may collect data from participant medical records. Researchers will compare the genes in a participant s cancer tissue to their normal tissue. They may use the tissue cells to grow new cells in a lab. Participants may be contacted about the results. The samples will be stored for future research. No personal data will be kept with them. ...

Type: Observational

Start Date: Dec 2017

open study

Inflammatory or degenerative diseases of the brain and spinal cord, such as multiple sclerosis, may be related to problems with an individual s immune system. However, more information is needed on the ways in which the cells of the immune system interact with the central nervous system (CNS). This study will compare tests performed on both healthy volunteers and individuals who have signs or symptoms of immune-related damage to their CNS. This study will include two groups of subjects at least 12 years old. Subjects will either have symptoms of immune-related CNS damage, or will be healthy volunteers selected for comparison purposes. Study participants will visit the NIH Clinical Center on an outpatient basis for an initial evaluation visit. During the visit, patients will provide a comprehensive medical history and undergo a neurological examination, and will provide blood samples for research purposes. The healthy volunteers will be asked to schedule a return visit for a magnetic resonance imaging (MRI) procedure, and may be asked to undergo other tests requested by the study researchers on an as-needed basis. The group of patients with symptoms of immune-related CNS damage will be asked to undergo a series of tests, including the following: - MRI procedures, with a minimum of three brain MRIs and one spinal cord MRI taken approximately 4 weeks apart - A diagnostic lumbar puncture, performed on an outpatient basis - Tests of brain and vision activity - Additional blood and tissue samples Patients with symptoms of immune-related CNS damage may be offered the opportunity to participate in additional followup tests with NIH researchers. ...

Type: Observational

Start Date: Oct 2008

open study

This study will examine microbes (e.g., bacteria, fungi, viruses) that live on human skin and how microbes contribute to health and disease. It will analyze healthy human skin and how the these microorganisms might change in patients with atopic dermatitis (AD), a skin condition also known as eczema. Healthy volunteers, as well as patients with moderate to severe eczema (AD), between 2 and 40 years of age may be eligible for this study. We also wish to enroll children and adults aged 2-40 who have been diagnosed with inherited immune disorders known as HIES (hyperimmunoglobulin-E syndrome), WAS (Wiskott-Aldrich syndrome), or DOCK8 immunodeficiency because they frequently have skin problems similar to AD. Eligible participants undergo the following tests and procedures: - Medical family and medication history - Skin examination - Blood tests (research blood as well as serum IgE, and complete blood count) - Skin samples to analyze microbes. Samples are obtained by the following methods: swabbing the skin with a cotton swab; scraping (scratching) the skin gently with a blade to remove only the outermost skin layers; and, only in adults, biopsy (surgical removal) of a small skin sample less than 1/4-inch (5 mm) in diameter. - Nose swabs to analyze microbes. - Patients with eczema may have photographs of their skin taken to help monitor the skin rashes. Participants may be contacted periodically for follow-up studies. Patients with atopic dermatitis may have additional skin samples collected to examine changes in the skin bacteria over time and during all of the stages of eczema. In addition, patients who have a flare of their eczema are asked to undergo a skin sample collection as soon as possible. ...

Type: Observational

Start Date: Jan 2008

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: Mesothelioma is an aggressive cancer that grows in the linings of the body; this can include the membranes that line the heart, lungs, and internal organs. Mesothelin (MSLN) is a protein that appears in high numbers in many tumors, including mesothelioma. Researchers are developing a new treatment that collects a person s own immune cells (T cells); the T cells are genetically modified to target and kill tumor cells with high levels of MSLN. Objective: To test a new treatment (TNhYP218 CAR T cells) in people with solid tumors including mesothelioma. Eligibility: People aged 18 and older with solid tumors including mesothelioma that returned or spread after standard treatment. Design: Participants will be screened. A small piece of tissue will be cut from a tumor (biopsy). The sample will be tested to see if it has enough MSLN. Participants will undergo leukapheresis: Blood will be taken from their body through a vein. The blood will pass through a machine that separates out the T cells. The remaining blood will be returned to the body through a different vein. Participant s T cells will be modified in a lab to produce TNhYP218 CAR T cells. Participants will enter the hospital. For 7 days, they will receive drugs to prepare their bodies for the study treatment. TNhYP218 CAR T cells will be administered into a vein. Participants will remain in the hospital for at least 7 more days. After discharge, participants will have follow-up visits for 5 years. These visits may include imaging scans, blood and heart tests, and a new biopsy. Long-term follow-up will continue another 10 years....

Type: Interventional

Start Date: Jul 2025

open study

Background: Certain blood cancers can be treated with blood or bone marrow transplants. Sometimes the donor cells attack the recipient's body, called graft-versus-host disease (GVHD). The chemotherapy drug cyclophosphamide helps reduce the risk and severity of GVHD. Researchers want to learn if using a lower dose of cyclophosphamide may reduce the drug's side effects while maintaining its effectiveness. Such an approach is being used in an ongoing clinical study at the NIH with promising results, but this approach has not been tested for transplants using lower doses of chemotherapy/radiation prior to the transplant. Objective: To learn if using a lower dose of cyclophosphamide will help people have a successful transplant and have fewer problems and side effects. Eligibility: Adults ages 18-85 who have a blood cancer that did not respond well to standard treatments or is at high risk for relapse without transplant, and their donors. Design: Participants may be screened with the following: Medical history Physical exam Blood and urine tests Heart and lung tests Body imaging scans (they may get a contrast agent) Spinal tap Bone marrow biopsy Participants will be hospitalized for 4-6 weeks. They will have a central venous catheter placed in a chest or neck vein. It will be used to give medicines, transfusions, and the donor cells, and to take blood. In the week before transplant, they will get 2 chemotherapy drugs and radiation. After the transplant, they will get the study drug for 2 days. They will take other drugs for up to 2 months. Participants must stay near NIH for 3 months after discharge for weekly study visits. Then they will have visits every 3-12 months until 5 years after transplant. Participants and donors will give blood, bone marrow, saliva, cheek swab, urine, and stool samples for research.

Type: Interventional

Start Date: Sep 2021

open study

Background: RASopathies are a group of conditions caused by a genetic change. People with a RASopathy may have developmental issues, cognitive disability, poor growth, and birth defects. They may also have an increased risk for developing cancer. Researchers want to learn more. Objective: To learn more about RASopathies, how genes and environmental factors contribute to cancer development in people with RASopathies, and the best way to find these cancers and other conditions early or prevent them. Eligibility: People of any age who have or may have a RASopathy, and their family members. Design: Participants will complete questionnaires about their personal and family medical history. Their medical records will be reviewed. Participants will give blood and urine samples. They will give a saliva or cheek cell sample. Some samples will be used for genetic testing. Participants may have a skin biopsy. Participants may have a physical exam by the RASopathies study team. They may also have exams by additional specialists, such as dentists; urologists; ear, nose, and throat doctors; and neurologists. Participants may have computed tomography of the face and mouth. They may have an ultrasound of the abdomen. They may have a bone density scan. They may have skeletal and/or spine x-rays. They may have magnetic resonance imaging of the brain, low back, chest, and/or heart. They may be photographed. Participants may have other tests, such as sleep, brain and heart electrical activity, speech and swallow, metabolism, hearing, eye, and colon function tests. Participants may sign separate consent forms for some tests. Participation will last indefinitely. Participants may be contacted once in a while by phone or mail. They may have follow-up visits.

Type: Observational

Start Date: Apr 2022

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: Omega-7 fatty acids are found in the oil extracted from certain fish and nuts like macadamia. Palmitoleic acid is one of the most common omega-7 fatty acids. Many studies suggest that this oil is good for heart health. Researchers want to find out more about these potential benefits. Objective: To study how oil enriched with palmitoleic acid (Omega-7 oil) affects metabolism. Eligibility: Healthy adults at least 18 years old with no known history of cardiovascular disease. Subjects not allergic to fish oil and fish products Females that are not pregnant and are not planning a pregnancy during the length of the study Design: Participants will be screened with questions about their health, medical history, and medicines they take. Participants will have 4 visits over 24 weeks. The visits may include: - Blood drawn from a vein in the arm by a needle stick. Sometimes participants will have to fast before the blood draw. - Vital signs (blood pressure, heart rate, and temperature) taken - Body mass index measured - Cardio-Ankle Vascular Index test may be performed. The stiffness of the participant s arteries will be measured by reading blood pressure in the arms and legs and monitoring the heart. - Optional stool samples - Pregnancy test - A short review of participants physical activity and diet - A supply of dietary supplements to take between visits. Participants will take 4 gel capsules a day. Participants will keep a food and exercise journal Compensation will be provided to subjects that complete the study Check your eligibility for this study by clicking here: https://www.surveymonkey.com/r/DietaryOmega

Type: Interventional

Start Date: Jul 2018

open study

Background: Some cancers have high levels of proteins called somatostatin receptors (SSTRs) on the surface of the tumors. These tumors can be in the lung, head and neck, digestive tract, kidneys, and in or near the adrenal glands. Researchers want to know if drug treatments that target SSTRs can help shrink these types of tumors. Objective: To test a study drug ([212Pb]VMT-Alpha-NET) in people with tumors that have SSTRs. Eligibility: People aged 18 years and older with tumors of the lung, kidneys, head and neck, digestive tract, or adrenal glands that have SSTRs. Their tumors must have spread to other organs and cannot be removed with surgery. Design: Participants will be screened. They will have a physical exam with blood and urine tests. They will have imaging scans and a test of their heart function. A sample of tumor tissue may be collected if one is not already available. [212Pb]VMT-Alpha-NET is given through a tube attached to a needle inserted into a vein. The drug will be given on the first day of four 8-week cycles. Participants will stay in the hospital for a few nights after each dose. They will have blood tests once a week during each cycle. Some participants will also get a related study drug ([203Pb]VMT-Alpha-NET). They will receive this drug a few days before the first 2 cycles. At 4, 24, and 48 hours after each infusion, they will have whole body scans. These scans will show where the study drug went in their body. Follow-up visits will continue up to 6 years after the last treatment.

Type: Interventional

Start Date: Aug 2025

open study

Background: - Many psychiatric, behavioral, and developmental disorders are genetic. This means that they tend to run in families. Some begin in childhood, while others do not appear until adulthood. Researchers want to look at people of all ages who have these disorders that started in childhood. They will also look at relatives of people with these disorders. This information will allow doctors to learn more about childhood behavioral problems and how they are inherited. It may also help doctors treat those disorders. Objectives: - To study the onset and treatment of childhood behavioral, psychiatric, and developmental disorders. Eligibility: - Individuals of any age who have a psychiatric, autism spectrum, or developmental disorder, or other behavioral problems. - Family members of individuals with the above disorders. This group may include parents, grandparents, siblings, aunts/uncles, cousins, and children. Design: - Participants will be screened with a medical history and physical exam. They may have a psychiatric history with tests of thinking, judgment, and behavior. Brain imaging scans may be performed to look at brain function....

Type: Observational

Start Date: Dec 2012

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: - 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