Background: Alcohol use disorder (AUD) is a chronic disease that causes more than 140,000 US deaths each year. AUD treatment often includes therapy and medication. Some people with AUD may also benefit from behavioral and lifestyle changes. Objective: To evaluate the effects of different activities and environments on drinking behaviors and mental health in people with AUD. Eligibility: People aged 21 years and older with AUD. Design: Participants will have up to 10 study visits in Baltimore. Participants will have a baseline visit. They will have a physical exam with blood and urine tests. They will have a breath test for alcohol and a test that measures body composition. They will answer questions about their alcohol and substance use; mental and physical health; mood and anxiety; and sleep quality. Participants will download an app called MetricWire. The app will send 3 sets of questions to be answered at different times throughout the day. The study visits will include 2 stages: 1. Active stage. On these visits, participants will use a virtual reality system called the Meta Quest Pro (MQP) as they choose. Then they may choose among video games, puzzles, books, crafts, and other activities.. These sessions will last for 3 hours. 2. Passive stage. On these visits, participants will watch videos selected by the research team. These sessions will last for 3 hours. On the last visit of each stage, participants will sit in a room that looks like a bar. They will answer questions about their cravings, their urge to drink, and how many drinks they would buy. Participants will be served 1 drink containing alcohol. They will be asked about their cravings and subjective effects of alcohol after drinking it.

Type: Interventional

Start Date: Jun 2026

open study

Background: Obstructive sleep apnea (OSA) occurs when the blockage of the airway causes a person to stop breathing involuntarily for 10 seconds or more throughout the night during sleep. Pediatric OSA can be especially concerning and can have long-term effects. Researchers want to see how a monitoring device called near-infrared spectroscopy (NIRS) compares with the traditional techniques used in children s sleep studies. Objective: To learn about oxygen levels in the brain and limbs in children with and without sleep apnea using a wearable, point-of-care biosensor. Eligibility: Children aged 3-12 who have OSA and plan to receive treatment (OSA group) or who do not have OSA (NORM group). Design: Participants will be screened with a review of their medical records. If they have taken part in other NIH studies, that data will be reviewed as well. Participants in the NORM group will have 1 overnight study visit. Those in the OSA group will have 2 overnight study visits. Participants will do an overnight sleep study. They will have a physical exam and medical history. They will have a sleep study electroencephalography (EEG). For this, electrodes will be placed on their head. They will wear a gauze cap to keep the electrodes in place. Two NIRS probes made of a soft silicon will be placed on their forehead and arm. They will follow their normal bedtime routine. Their parent will stay overnight. The OSA group will have a second study visit 2 weeks to 12 months after they start treatment for their sleep apnea. They will repeat the sleep study.

Type: Observational

Start Date: Aug 2022

open study

Background: Genes are the basic units of heredity. When genes are changed, certain cells don t work like they should. Researchers want to try to better understand the genetic conditions that are linked with inherited eye diseases. Objective: To try to identify the genes linked to the development of inherited eye diseases. Eligibility: People ages 4 and older who have or have a family member with an inherited eye disease Design: Participants will be screened with medical history and medical records. Participants will have one visit that will take 3-4 hours. This will include: Medical and family history Eye exam: This includes the pupil being dilated. Electroretinography: A small electrode is taped to the forehead. Participants sit in the dark with their eyes patched for 30 minutes. Then numbing drops and contact lenses are put in the eyes. They will watch flashing lights. Blood tests Saliva sample: They will spit into a container or have the inside of their cheek swabbed. Genetic testing will be done on participants blood or saliva. Participants may meet with the researchers to discuss their genetic tests.

Type: Observational

Start Date: Oct 2016

open study

Background: - Skin disease can have many causes. It can have widespread consequences, and in rare cases can lead to death. Researchers want to determine the causes of various types of skin diseases and find a way to treat them. Objectives: - To determine the causes of various skin diseases and find ways to treat them. Eligibility: - People ages 2 and older who have: - A skin disease or at risk of developing a skin disease OR - A family member of persons with a skin disease - Healthy volunteers ages 2 and older Design: - Participants will be screened under a separate protocol. - Participants may take a survey about how their skin condition affects their quality of life. - Participants will have a medical history and a physical exam including a detailed skin exam. Pictures will be taken of their skin to document any skin disease. - Participants will have specimens collected. This may include: - Several teaspoons of blood taken at each visit - Stool samples - Nail and body fluid (like saliva) samples - Cheek swabs. The inside of the cheek will be scraped for about a minute in each direction to collect cells. - Collection of skin samples with: - A swab (like a Q-tip) - Gently scraping skin to remove the outer layers of cells - Applying and removing 1-inch pieces of tape - Participants may have up to 4 skin biopsies in 12 months, with 4 separate biopsies taken each time. - An area of skin will be numbed with an injection. - A piece of skin the size of a pencil eraser will be removed using a small instrument. - A flat scar usually develops at the biopsy site.

Type: Observational

Start Date: Jun 2015

open study

Background: People who have had an allogeneic hematopoietic stem cell transplant (HCT) have bone marrow or an immune system that is damaged. They get stem cells from a donor who is a relative. Researchers want to study stem cell donors and recipients to learn about the long-term effects of HCT. They want to learn how the stem cells change and how to improve their ability to fight cancer. Objective: To provide long-term follow-up care for people who underwent or will undergo HCT. To collect data, blood, and tissue samples to learn about late complications after HCT. Eligibility: Adults age 18 and older who will undergo HCT or underwent HCT and are surviving one year or more from the date of HCT. The stem cell donors for these recipients are also needed. Design: Recipients will have 1 visit each year. They will have a physical exam. They will answer questions about their medical history and health. They will receive screening and surveillance testing. They will complete brief questionnaires. Recipients will have blood tests. They may have tissue biopsies or specimens (such as tissue in their cheek or skin or bone marrow biopsy). Recipients will give their current address and phone number, and the same data for one or two other people, who can get in contact with them. After the first visit at the clinic, some recipients may see a doctor close to home to get the necessary information and send it to NIH. Donors will come to the clinic for 1 visit. They will answer questions about their medical history. Blood samples will be taken.

Type: Observational

Start Date: Apr 2017

open study

Background: After an allogeneic hematopoietic stem cell transplant (HSCT), the donor genome is found in the recipient s circulation and tissues. Post-HSCT recipients may receive a medication in which the dosing needs to be adjusted based on genetic variation. While genes in donor genome may influence dosing and administration of some agents, the majority of established gene-drug pairs in pharmacogenetics are related to expression of metabolic or transporting enzymes located in recipients tissues, often the liver. Determining which genetic variants influence drug disposition in HSCT recipients is complicated by chimerism in samples that are routinely collected for determining genotype. However, chimerism in tissues is poorly studied in this patient population. Objectives: To determine the most reliable host genomic source for pharmacogenetic testing in participants that have received allogeneic HSCT. Eligibility: People ages 18 years and older who are enrolled on a clinical trial at the NIH Clinical Center under which they will donate or receive an allogeneic HSCT. Design: DNA is collected prior to HSCT and for two years after HSCT. Blood will be collected and skin fibroblast cell lines will be established prior to HSCT to serve as a reference genome. Blood, buccal cells, skin, and hair will be monitored for the development of mixed chimerism via detection of short tandem repeats. Liver biopsies will be collected from participants undergoing hepatic surgery. Pharmacoscan arrays will be conducted to determine which samples are useful for pharmacogenetic testing in participants who receive allogeneic HSCT. A probe drug cocktail will be administered pre- and post-HSCT to determine if transplantation alters the metabolic phenotype of liver enzymes. ...

Type: Observational

Start Date: Mar 2026

open study

Background: Childhood-onset essential hypertension (COEH) is high blood pressure that develops in children and teens. High blood pressure is a major risk factor for heart disease. COEH is more likely to be caused by changes in genes rather than by factors like stress or diet. Researchers want to learn more about how changes in genes relate to COEH. They hope to use that information to develop better treatments for children with high blood pressure. Objective: This natural history study will look for genes and gene changes that may lead to COEH. Eligibility: People aged 2 years and older with COEH or who had COEH when they were children. Healthy relatives of those with COEH are also needed. Design: Participants will have one clinic visit per year for up to 10 years. All participants will have a physical exam. They will provide samples of blood and urine. At their first visit, they will have a swab (like a Q-tip) rubbed between their gums and cheeks. They may agree to having a skin biopsy; a piece of skin about the size of a pencil eraser will be removed. Affected participants aged 2 to 17 years old will have additional tests: - They will have sensors placed on their skin to look at their blood vessels and see how blood is moving in their bodies. - They will lie or stand while a machine measures the amount of fat and muscle in their bodies. - They will have an ultrasound; a wand will be rubbed against their skin to take pictures of their kidneys. Other things are optional for all participants: - They may have photographs taken of their bodies. - They may have tests of their heart function. - They may have different types of imaging scans....

Type: Observational

Start Date: May 2025

open study

This study will evaluate subjects with adult- and childhood-onset myositis to learn more about their cause and the immune system changes and medical problems associated with them. Myositis is an inflammatory muscle disease that can damage muscles and other organs, resulting in significant disability. Children or adults with polymyositis or dermatomyositis or a related condition may be evaluated under this study. Healthy children or adults will also be enrolled as "controls," for comparison of test results. All patients will undergo a complete history (including completing some questionnaires) and physical examination, review of medical records, and blood and urine tests. Patients may then choose to participate in an additional 1- to 5-day evaluation, which will include some or all of the following diagnostic, treatment or research procedures: 1. Standardized muscle strength testing, range of motion of joints and walking (gait) analysis by a physiotherapist; completion of a questionnaire regarding ability to perform daily tasks 2. Skin assessment, possibly including photographs of lesions and a skin biopsy (removal of a small skin sample under local anesthetic) 3. Magnetic resonance imaging (scans that use magnetic fields to visualize tissues) of leg muscles 4. Swallowing studies, including a physical examination and questionnaire on swallowing ability, studies of tongue strength, and ultrasound imaging during swallowing, and possibly, a modified barium swallow 5. Voice and speech assessment, possibly including computerized voice analysis and laryngoscopy-analysis of the larynx (voice box) using a small rigid scope with a camera placed in the mouth to view and record vocal cord function 6. Pulmonary function tests (measurement of air moved into and out of the lungs, using a breathing machine) to evaluate lung function and, possibly, chest X-ray 7. Electrocardiogram (measurement of the electrical activity of the heart) and, possibly, echocardiogram (ultrasound imaging of the heart) 8. Endocrine evaluation 9. Eye examination, in patients with vision loss or other eye symptoms 10. Nutrition assessment to evaluate muscle mass and muscle wasting, including tape measurements or bioelectric impedance testing, a painless procedure in which wires are attached to the extremities with a sticky paste. 11. Muscle ultrasound. 12. Electromyography (record of the electrical activity of muscles) 13. Muscle or skin biopsy (removal of a small piece of muscle tissue for microscopic examination) All patients may have only a one-time evaluation or may return for one follow-up evaluations (either the 1-day or 3- to 5-day evaluation) over a 1-year period. Healthy children will undergo a medical history and brief physical examination; blood and urine tests; speech and swallowing studies including questionnaires and physical examination, tongue strength, and ultrasound study; and bioelectric impedance testing. Children 8 to 18 years old may also have exercise testing.

Type: Observational

Start Date: Jun 1995

open study

Background: Allergic and inflammatory conditions have been increasing over the years. Many factors may play a role in this. Every day, people are exposed to pollution and chemicals in our foods, clothing, and all of the cleaning, hygiene, and other products we use. Studies have suggested there may be links between these environmental exposures and allergic and inflammatory illnesses. Researchers want to know more about how these exposures affect our health. Objective: To learn how everyday exposure to common substances affects people s health. Eligibility: Healthy people aged 18 to 80 years. Design: Participants will have 2 stays in the hospital. Each stay will last 7 days, and the stays will be spaced 4 to 6 weeks apart. During both stays, participants will remain confined to their room. They will eat only food from the menu, and they will use only provided products for personal care. (They may bring their own electronic devices, such as their phone and computer.) One stay will be in a pure room. Participants will breathe filtered air, eat unprocessed foods, and use personal care products with fewer chemicals. One stay will be in a room that allows exposure to common environmental chemicals. Some participants will be limited to only 1 type of exposure: chemicals thought to affect only skin, gut, or respiratory health. Some participants will be exposed to all 3 types. Participants will undergo testing. Blood, skin cell, urine, mouth swabs, and stool samples will be taken. They will have lung tests, smell tests, and tests that measure the health of their skin. These tests will be repeated in outpatient visits 2 weeks after each hospital stay....

Type: Interventional

Start Date: Apr 2026

open study

Background: Allogeneic blood or marrow transplant is when stem cells are taken from one person s blood or bone marrow and given to another person. Researchers think this may help people with immune system problems. Objective: To see if allogeneic blood or bone marrow transplant is safe and effective in treating people with primary immunodeficiencies. Eligibility: Donors: Healthy people ages 4 or older Recipients: People ages 4-75 with a primary immunodeficiency that may be treated with allogeneic blood or marrow transplant Design: Participants will be screened with medical history, physical exam, and blood tests. Participants will have urine tests, EKG, and chest x-ray. Donors will have: Bone marrow harvest: With anesthesia, marrow is taken by a needle in the hipbone. OR Blood collection: They will have several drug injections over 5-7 days. Blood is taken by IV in one arm, circulates through a machine to remove stem cells, and returned by IV in the other arm. Possible vein assessment or pre-anesthesia evaluation Recipients will have: Lung test, heart tests, radiology scans, CT scans, and dental exam Possible tissue biopsies or lumbar puncture Bone marrow and a small piece of bone removed by needle in the hipbone. Chemotherapy 1-2 weeks before transplant day Donor stem cell donation through a catheter put into a vein in the chest or neck Several-week hospital stay. They will take medications and may need blood transfusions and additional procedures. After discharge, recipients will: Remain near the clinic for about 3 months. They will have weekly visits and may require hospital readmission. Have multiple follow-up visits to the clinic in the first 6 months, and less frequently for at least 5 years.

Type: Interventional

Start Date: Nov 2015

open study

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

Type: Interventional

Start Date: Dec 2025

open study

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

Type: Interventional

Start Date: Oct 2025

open study

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

Type: Interventional

Start Date: Feb 2023

open study

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

Type: Interventional

Start Date: Jan 2023

open study

The study will allow researchers to obtain blood, plasma, DNA, and RNA for genetic studies of insulin. There will be a focus on the causes of insulin resistance and diabetes mellitus. Insulin is a hormone found in the body that controls the level of sugar in the blood. Insulin resistance refers to conditions like diabetes when insulin does not work properly. In this study researchers would like to compare patients with diabetes and other forms of insulin resistance to normal individuals. The study will investigate how insulin attaches to cells. Researchers will take 4 to 6 ounces (100-150 ml) of blood from adult patients and may request up to 12 ounces (one unit) of blood if necessary. Skin samples may be taken for a biopsy if further genetic testing is necessary. In addition some patients may be asked not to eat for up to 72 hours prior to testing....

Type: Observational

Start Date: Feb 1976

open study

Background: People who join a study in the Developmental Therapeutics Clinic (DTC) have tests. These include blood draws and biopsies. Researchers collect data from these samples. Some people take part in more than one study at the DTC. At this time, data are connected only with one single study. Researchers want to access people s medical records. This will allow them to link the research data from all their studies they have or will take part in. Researchers also want to collect medical data about their diagnosis and treatment history. This will allow them to see how their cancer reacted to different drugs over time. Objective: To enter people into a master protocol to connect research sample and treatment data across DTC studies. Eligibility: People ages 18 and older who are being evaluated or treated for cancer in the DTC Design: Participants will allow researchers to look at all the data from their research samples. This includes those from their current, past, and any future NIH studies. Participants will allow researchers to access some of their medical data. This includes age, diagnosis, treatment history, and response to treatment. Participants will provide no new samples. ...

Type: Observational

Start Date: Aug 2017

open study

Objective: The objective of this study is to identify genetic causes of inherited eye conditions through whole exome or whole genome sequencing (referred to as exome sequencing and genome sequencing in the remainder of the document). This includes identifying mutations in known genes or novel genes for recognized conditions, as well as identifying mutations in novel genes for previously uncharacterized genetic conditions involving the eye. Study Population: We plan to recruit 2,000 participants, to include both participants with an eye condition under study and unaffected family members. Ideally unaffected family members will be parents of an affected participant. Design: Participants will be self-referred or referred by an outside clinician. They will preferably be evaluated at the National Institutes of Health (NIH), but the option to participate offsite will be offered. Participants evaluated onsite will be recruited through other pre-existing NIH protocols, such as the National Eye Institute (NEI) Screening protocol (08-EI-0102), the NEI Ocular Natural History protocol (16-EI-0134), the Genetics of Inherited Eye Disease protocol (15-EI-0128), and the Pathogenesis and Genetics of Microphthalmia, Anophthalmia and Uveal Coloboma (MAC) protocol (13-EI-0049). Offsite participants will be screened via phone or secure videoconference, and records will be requested for evaluation of affected participants. Both affected and unaffected eligible participants will undergo genetic counseling and will provide a blood sample and/or saliva sample for exome or genome sequencing. Biological relationships will be confirmed prior to exome or genome sequencing. Sequence data will be analyzed for primary variants and secondary findings, unless participants choose to opt-out of secondary analysis and reporting. All sequence variants deemed clinically relevant will be validated in a Clinical Laboratory Improvement Amendment (CLIA)-certified laboratory. The results will be returned to the participant in-person, secure videoconference, or by telephone. Outcome Measures: This is an etiologic study that will generate molecular information about previously-recognized conditions for which participants did not have a molecular diagnosis, as well as molecular information for previously uncharacterized conditions involving the eye.

Type: Observational

Start Date: Aug 2014

open study

Background: - Plaquenil (hydroxychloroquine) is an anti-inflammatory drug that is used to treat some autoimmune diseases such as lupus and rheumatoid arthritis. This drug can damage the retina by causing a condition called Plaquenil-induced retinal toxicity, which may lead to vision loss. However, most people taking Plaquenil do not develop this problem. Researchers are interested in studying whether differences in a person's genes explain why some people develop Plaquenil-induced retinal toxicity while others do not. Objectives: - To investigate possible correlations between certain genes or genetic mutations and Plaquenil-induced retinal toxicity. Eligibility: - Individuals at least 18 years of age who have previously used Plaquenil. - History of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), or Sjogren's syndrome. - Both individuals who have and have not developed Plaquenil-induced retinal toxicity will be eligible for this study. Design: - The study requires five annual outpatient visits to the NIH Clinical Center. - Participants will provide a personal and family medical history, and will have a full eye examination. - Participants will also provide blood samples for genetic analysis, including whole exome and whole genome sequencing. - No treatment will be provided as part of this protocol.

Type: Observational

Start Date: Aug 2010

open study

This study will examine rare congenital disorders that involve malformations and abnormal growth. It will focus on patients with Proteus syndrome, whose physical features are characterized by overgrowth, benign tumors of fatty tissue or blood vessels, asymmetric arms or legs, and large feet with very thick soles. The study will explore the genetic and biochemical cause and course of the disease, the changes in symptoms over time, and the effects of the disease on patients. Patients with Proteus syndrome may be eligible for this study. Study candidates will have a medical history and physical examination, including X-rays and possibly other imaging tests, such as computerized tomography (CT), magnetic resonance imaging (MRI) and ultrasound. Other tests and examinations may be done if needed. Those enrolled in the study may be interviewed or complete questionnaires, or both, about how their disease affects them. Patients will provide a small blood sample for research....

Type: Observational

Start Date: Apr 1994

open study

Background: People with familial partial lipodystrophy (FPLD) do not store fat in the body normally. This can lead to serious illnesses such as diabetes and heart disease. To learn more about FPLD, researchers want to compare the fat tissue in people with this disease to the fat tissue of healthy people. Objective: To collect and analyze samples of fat tissue in people with and without FPLD. Eligibility: People aged 18 to 65 years with FPLD. Healthy adults are also needed. Design: Participants will be screened. They will have a physical exam. The size and shape of their body will be measured. They will have an imaging scan to measure their bones, muscle, and fat. Participants will be given heavy water to drink at home. The water contains a tracer to help measure the fat in their blood. They will drink 1 vial 3 times a day. After drinking the water for 9 days, participants will come to the clinic for a 3-day stay. They will eat only foods provided by the hospital; the foods will contain tracers. A needle will be inserted into a vein in the arm; participants will receive infusions of other tracers through this needle into their blood; this needle will also be used to draw blood samples for testing. On their third day in the clinic, participants will have biopsies: Small samples of fat will be removed from under the skin on the belly and thigh. Participants may return for a follow-up visit 8 days after leaving the clinic. Blood draws and fat tissue biopsies will be repeated.

Type: Observational

Start Date: Jan 2024

open study

Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder characterized in its classical form by oculocutaneous albinism, a bleeding diathesis, recurrent infection due to abnormal neutrophil and natural killer cell function, and eventual progression to a lymphohistiocytic infiltration known as the accelerated phase . Death often occurs within the first decade as a result of infection or the development of the accelerated phase; bone marrow transplantation is curative except for the late occurrence of neurological deterioration. The basic defect is unknown, although it probably involves abnormal fusion or trafficking of intracellular vesicles. Patients with classical CHS have their disease due to mutations in the LYST gene, but mildly affected individuals have been reported whose genetic defect has not been defined. It is likely that these variants of CHS have abnormalities in proteins involved in the pathways responsible for vesicle fusion. Since the full clinical spectrum of CHS and its variants has not been characterized, and the underlying defects remain enigmatic, we plan to evaluate this group of patients clinically, biochemically, and molecularly, and perform cell biological studies on their fibroblasts, melanocytes, and transformed lymphoblasts. Routine admissions will be 5 days and may occur every two years, or required by changes in clinical symptomatology.

Type: Observational

Start Date: Sep 2002

open study

Background: Anakinra is a drug used to treat people with certain diseases that affect their immune systems. Sometimes anakinra can cause proteins under the skin to clump together. These clumps are called amyloidosis; they can spread to other organs. The only way to diagnose amyloidosis is to remove a piece of tissue (biopsy). Researchers want to find a way to locate amyloidosis in internal organs using positron emission tomography (PET)/computed tomography (CT). Objective: To test a new tracer used during PET/CT scans in people with amyloidosis. A tracer is a radioactive dye injected into the body. Eligibility: Adults aged 18 years or older with amyloidosis from anakinra injections. They must be enrolled in NIH protocol 17-I-0016. Design: Participants will come to the clinic once every 6 months for 2 years. Each visit will be 1 day. They will have a PET/CT scan with the new tracer at each visit: The tracer will be given through a tube attached to a needle inserted into a vein. The PET/CT scanner is a machine shaped like a doughnut. Participants will lie still on a padded table. The table will move in and out of the machine. The scan takes about 1 hour. Radiation from the tracer will remain in the body for 24 hours after each scan. Participants will need to follow rules to avoid exposing pets and other people. Participants will collect a 24-hour urine sample before each visit. They will also have blood tests and a physical exam at each visit. Participants will receive a follow-up phone call about 1 week after each visit.

Type: Interventional

Start Date: Sep 2025

open study

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

Type: Interventional

Start Date: Jan 2024

open study

Background: Less toxic and more effective treatments are needed for cancers caused by viruses. These cancers include Hodgkin and non-Hodgkin lymphoma, hepatocellular carcinoma, head and neck cancer, nasopharyngeal carcinoma, gastric cancer, anal cancer, cervical cancer, vaginal cancer, vulvar cancer, penile cancer, Merkel cell carcinoma, Kaposi sarcoma, and leiomyosarcoma. Researchers want to see if a combination of drugs can help. Objective: To find a safe dose of pomalidomide plus nivolumab in people with cancers caused by viruses. Eligibility: Adults ages 18 or older who have cancers caused by Epstein Barr virus (EBV), human herpes virus 8/Kaposi sarcoma herpesvirus (HHV8/KSHV), human papilloma virus (HPV), hepatitis B or C virus (HBV/HCV), and Merkel cell polyomavirus (MCPyV) that have not responded to previous treatments or have relapsed, or in adults who do not want to have surgery because of disfigurement or other risks. Adults who have HIV with any CD4 T cell count are eligible. Design: Participants will be screened with blood and urine tests, scans, and heart tests. They will have a physical exam. Their ability to perform normal daily activities will be assessed. They may have a tumor biopsy. Treatment will be given in 28-day cycles. Participants will take pomalidomide as a tablet by mouth for 21 days of each cycle, for up to 24 cycles. They will get nivolumab by intravenous infusion once each cycle. They will take an aspirin each day until 30 days after their last dose of the study drugs. Participants will keep a pill diary. They will bring it to their study visit at the end of each cycle. At these visits, some screening tests will be repeated. Participants with Kaposi sarcoma will have pictures taken of their lesions. Participants will give blood and saliva samples for research. They may have optional anal and/or cervical swabs. They may have optional biopsies. Participants will have a follow-up visit 30 days after they stop taking the study drugs, then every month for 100 days. Some screening tests will be repeated. Then they may by contacted by phone every 3 months for 9 months, and then every 6 months thereafter.

Type: Interventional

Start Date: Dec 2021

open study

Background: Primary sclerosing cholangitis is a rare chronic liver disease. It affects the bile ducts of the liver. It can result in bile duct infections, cirrhosis, cancer, and end stage liver disease. Researchers want to learn more about this disease. Objective: To understand the biological causes of primary sclerosing cholangitis. Eligibility: Adults age 18 and older who have primary sclerosing cholangitis. Design: Participants will be screened with a medical history, physical exam, and blood tests. Participants will give blood, saliva, urine, and stool samples. They will have nasal swabs. They will complete surveys. Participants will get an intravenous (IV) catheter. A plastic tube is inserted into an arm vein. Participants will have a colonoscopy. A tube with a video camera at the end is inserted into the rectum. Participants will have an upper endoscopy. A scope with a light and camera at its tip is used to look inside the upper digestive tract. Participants will have a liver biopsy, entering through the chest wall or a neck vein. Blood is drawn from a blood vessel that carries blood to the liver. A liver tissue sample is taken. Participants will have magnetic resonance imaging or spectroscopy. They will get a contrast agent through an IV. Participants may have an optional bone marrow aspiration. A large needle is inserted into the hip to withdraw marrow. Participants will have a liver ultrasound. Participants will complete a 3-day food diary. They will have a nutrition assessment. Participants may give contact details for people who live with them, to also take part in this study. Participation will last for 12 months.

Type: Observational

Start Date: Mar 2023

open study