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: In non-alcoholic fatty liver disease (NAFLD), fat accumulates in the liver and can cause damage. Researchers want to learn what causes the damage NAFLD, and to see if a medication can help. Objective: To find out how the liver in people with NAFLD responds to feeding, and how this relates to their response to the drug semaglutide. Eligibility: People with NAFLD and healthy volunteers ages 18 and older Design: Participants will be screened with: Medical history Physical exam Blood tests Imaging: A machine will take pictures of the participant s body. Within 2-8 weeks of enrollment, participants will stay in the clinic for several days. This includes: Blood, urine, heart, and imaging tests For NAFLD participants only: A needle-like device will remove a small biopsy of the liver and fatty tissue. Participants will be alone in a special room for 5 hours. They will breathe through a tube under the nostrils. They will have blood drawn several times. The baseline visit concludes participation for healthy volunteers but NAFLD participants will contine. About 6 weeks after discharge, participants will stay in the clinic again and repeat the tests. They will get their first semaglutide dose by injection. Participants will have visits weeks 1, 2, 4, 8, 12, 16, 20, and 24 of treatment. Visits include blood tests. Participants will inject semaglutide once a week at home. At week 30, participants will stay in the clinic again and repeat the tests. Participants will have a final visit 12 weeks after stopping treatment. This includes blood and urine tests. ...

Type: Interventional

Start Date: Jul 2019

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: Fanconi anemia (FA) is a rare, inherited cancer syndrome. FA causes a range of physical issues. Children with FA may have abnormal features; these may include a small head and eyes and issues with their internal organs. Young adults have a much higher risk of cancer. To screen for these cancers, people with FA may need to pursue many visits with different doctors. This constant need for cancer screening may cause anxiety for people with FA. Objective: To learn more about anxiety related to cancer screenings in people with FA. Eligibility: Adults aged 18 years and older with FA. They must also be enrolled in FACSS. FACSS is a study that screens people with FA for cancer every year. Design: All data gathered for this study will occur during routine FACSS visits. No other visits are needed. An observer will be in the room during participants FACSS visits. The observer and participant will have a polite introduction. After that, the observer will not interact with participants in any way. The observer will note details about the participants, such as: - Body language. - Worries about screening. - Comments that suggest anxiety or depression. - Clinical environment, such as d(SqrRoot)(Copyright)cor and temperature. - Accessibility issues. These can include lights and noises as well as ease of traveling around the clinic center. - Evidence of social support, such as engaging in the FA community. - Challenges they ve had in FACSS. - Their motivation to participate in FACSS. - Relationship dynamics among clinic staff, participants, and their care partners. Data will also be collected from FACSS visit notes dating back to December 2024 and from participants medical records.

Type: Observational

Start Date: Jul 2026

open study

Background: Magnetic resonance imaging (MRI) is a tool for getting pictures of the tissues and organs inside the body. MRI can help diagnose many injuries and diseases. But not all patients are equally likely to receive MRIs. Factors such as race or ethnicity, distance to imaging centers, mobility, and a lower income can limit some people s access to MRIs. A new ultra-low field (ULF) type of MRI, which can be used on a vehicle, may help take imaging scans to more people. But researchers need to know that UFL-MRI works just as well as standard MRIs. Objective: To learn whether UFL-MRI is as good as standard MRI at detecting neurological disorders. Eligibility: People aged 3 years or older who have or show symptoms of neurological disease (such as stroke, cancer, or epilepsy). Healthy adults are also needed. Design: Participants will have 1 or 2 study visits. Adult participants will have a physical exam. They will receive two MRI exams: - Standard MRI. They will lie still on a narrow bed that will move into a large tube. They will wear earplugs to muffle the sounds. - ULF-MRI. They will lie on a stretcher, and only their head will be inside a smaller tube. The noises will be quieter. They will wear earplugs to muffle the sounds. Some adults may receive a contrast agent given through a small tube attached to a needle in the arm. The contrast agent helps the researchers see differences in the body more clearly. This may be done during 1 or both MRIs. Children will have only 1 ULF-MRI. Some participants may be invited to have additional visits for up to 6 months.

Type: Observational

Start Date: Mar 2024

open study

Background: Each year, more than 32,000 people in the United States are diagnosed with colorectal cancer that has returned or progressed after treatment and spread to other organs. This is called metastatic colorectal cancer (mCRC). Most people with mCRC survive only about 2 years. Objective: To test the ability of a combination of up to 4 experimental anti-cancer drugs treat mCRC. The names of these drugs are retifanlimab, TriAdeno vaccine, N-803, and SX-682. They are described below. Eligibility: Adults aged 18 years or older with mCRC. Participants must have Design: Participants will be screened. This includes having a physical exam, blood tests, urine tests, and imaging tests. If signed on to the study, participants will have 2 tumor biopsies. One when starting the study and once about 8 weeks after bring on the study. Participants will receive $500 for each biopsy. Participants will be treated with either 3 or 4 drugs and will receive a detailed calendar explaining when each drug is given. Retifanlimab is given every 4 weeks through an IV (an IV is tube attached to a needle inserted into a vein in the arm). N-803 is injected under the skin on the abdomen every 4 weeks. TriAdeno vaccine is injected under the skin of the upper arm or thigh once a month for 3 doses and then once every 3 months. Some participants will also receive a 4th drug. SX-682 is a pill taken by mouth. Participants will take this drug 2 times a day at home for about 3 weeks of each month. Study treatment will continue up to 2 years. Follow-up phone calls/emails may continue for 3 more years.

Type: Interventional

Start Date: Mar 2024

open study

Background: People who have had an allogeneic hematopoietic stem cell transplant (HCT), cellular therapy (CT), or gene therapy (GT) 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, CT, or GT. 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, CT, or GT. To collect data, blood, and tissue samples to learn about late complications after HCT, CT, or GT. Eligibility: Adults age 18 and older who will undergo HCT or underwent HCT, Cellular Therapy (CT), or Gene Therapy (GT) and are surviving one year or more from the date of therapy. 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: - Malignant mesothelioma is a malignancy arising from the mesothelial cells of the pleura, peritoneum, pericardium, or tunica vaginalis. - Mesothelioma accounts for 0.10% of deaths annually in the United States. Malignant pleural mesothelioma is the most common of these, comprising of 80% of the cases with an annual incidence of about 2,500 in the United States. - The median survival from diagnosis of pleural mesothelioma is approximately 12 months. The majority of patients present with stage III or IV disease with 85-90% of patients considered unresectable at diagnosis. - Peritoneal mesothelioma has a better prognosis than pleural mesothelioma; nevertheless, patients undergoing therapy for peritoneal mesothelioma have few well-studied treatment options due in large part to the rarity of the disease. - In addition to mesothelioma, mesothelin is highly expressed in several cancers, including pancreatic, biliary adenocarcinomas, gastric and ovarian cancers; mesothelin is also expressed in a significantly larger proportion of thymic carcinoma than thymoma. Objectives: -To allow sample acquisition for use in the study of mesothelioma. Eligibility: - All participants age greater than or equal to 2 years with malignant mesothelioma OR - All participants greater than or equal to 18 years with thymic carcinoma, pancreatic or biliary adenocarcinoma or lung, gastric or ovarian cancers or other solid tumor known to express mesothelin - Must be able and willing to provide informed consent if 18 or over; parent or guardian must be able and willing to provide consent for patients under the age of 18 Design: - Up to 1000 subjects will be enrolled. - Patients will be followed to determine the course of disease and to record any treatment received for mesothelioma. - Patients will undergo sampling of blood, urine, tumor and abnormal body fluids for tissue banking. - Studies which may be performed on banked material include genetic and genomic studies, establishment of cell cultures and immunologic studies.

Type: Observational

Start Date: Sep 2013

open study

Background: - The immune system is made up of special cells, tissues, and organs that fight infections. Problems with this system may lead to frequent, severe, or unusual fungal infections. These infections are often difficult to treat. Researchers want to collect blood and tissue samples from people who have unusual, persistent or severe fungal infections or immune problems that increase the risk of these infections. Objectives: - To collect medical information and samples for a long-term study of people with immune system problems that lead to fungal infections. Eligibility: - People with a history of fungal infections caused by immune system problems. - Parents, children, and siblings of this group. - Healthy volunteers not related to the first two groups. Design: - This long-term study may last for up to 25 years. Those in the study may need to provide new information about every 6 months. The procedures for each person may vary with the particular diagnosis and the extent of fungal infection. Healthy volunteers may have only one or two visits. - At the first visit, those in the study will have a full medical history and physical exam. They will also provide blood. - Research procedures may include the following: - Saliva, urine or stool testing - Mouthwash collection for DNA testing - Collection of cheek cells, nail clippings, or vaginal fluid - Tests of leftover tissue or body fluid from previous medical procedures - Skin or oral mucous membrane biopsy - Collection of white blood cells - Followup visits will involve a physical exam and updated medical history. Blood, saliva, urine, or nail clipping samples may be taken for ongoing studies. Any additional tests or exams required by the study doctors may also be done. - Participants may withdraw from the study pool at any time.

Type: Observational

Start Date: Nov 2012

open study

Background: - Bronchiectasis is a disease characterized by airways that are inflamed, abnormally dilated, and chronically infected. Individuals with bronchiectasis have a history of chronic and recurring respiratory infections. Depending on the underlying cause, these infections may involve the entire respiratory tract, resulting in sinus, ear, and lung disease. - Bronchiectasis continues to be a significant problem in developing countries and in specific groups of individuals, particularly in people who have cystic fibrosis. Although treatments are available or under development for bronchiectasis related to cystic fibrosis, many of the disease-specific treatments may not be effective for bronchiectasis not related to cystic fibrosis. Objectives: - To study the natural history of bronchiectasis to identify inherited and immune factors that may explain why certain individuals have chronic recurring infections. Eligibility: - Individuals 5 years of age and older who have an established diagnosis of bronchiectasis or a history of chronic/recurring respiratory infections. - Direct family members (e.g., parents, siblings, children) of patients in the study may also be asked to participate. Design: - Potential participants will be screened with an initial clinic evaluation and full medical history, as well as a general quality of life and respiratory symptom questionnaire. - The following standard procedures may be done as part of the study: air sampling from the nose; imaging studies, which may include an x-ray or computed tomography (CT), lung function tests; and collection of samples of blood, urine, and sputum (phlegm or mucus). Other tests may be performed as required by the researchers, and will be explained to patients as needed. - Both patients and relatives (if asked to participate) will provide the following samples: blood or buccal (cheek swab) cells for genetic testing, sputum, and urine. - To prevent infections and potential disease progression, patients may receive standard medical care and treatment for bronchiectasis and related infections during this protocol.

Type: Observational

Start Date: Aug 2009

open study

Background: Sickle cell disease (SCD) is an inherited blood disorder. The disease affects the ability of red blood cells to carry oxygen. Research has shown that curcumin, a natural compound found in turmeric, can improve the health of red blood cells in people with SCD. But the body cannot absorb curcumin well when it is taken by mouth. Researchers want to know if a skin gel (VAS-101) can help the body better absorb curcumin. VAS-101 contains curcumin, which comes from turmeric. Objective: To test VAS-101 in people with stable SCD. Eligibility: People aged 18 to 70 years with stable SCD. Design: People who want to join the study will be screened with physical exam with blood tests to see if they are eligible. If they qualify, they can enroll in the study. Participants will have up to 15 clinic visits over about 14 weeks. Some may need to stay overnight in the hospital for up to 2 days to make it easier to collect blood samples after the gel is applied. For 6 weeks, a special gel called VAS-101 will be put on the forearms in the clinic two times a week. Staff will rub the gel into the skin for at least 30 seconds using a soft toothbrush. The area stays uncovered for at least 10 minutes, then is covered with a bandage or sleeve. After 24 hours, the dressing can be removed and the skin can be washed. Some visits will include blood tests and other exams. On three visits, a test called near infrared spectroscopy (NIRS) will be done. For this test, probes are placed on the skin to measure blood flow, oxygen levels, and the makeup of skin and muscle. A blood pressure cuff is used to squeeze the arm for up to 5 minutes. The last clinic visit will happen about 4 weeks after the final gel application....

Type: Interventional

Start Date: Jul 2026

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: - Researchers who are studying hairy cell leukemia, and how the disease compares with other disorders, are interested in obtaining additional samples from leukemia patients and healthy volunteers. The investigators are particularly interested in samples from individuals who have diseases that can be treated with a new type of drug called immunotoxin, in which an antibody carrying a toxin binds to a cancer cell and allows the toxin to kill the cell. Objectives: - To collect a variety of clinical samples, including blood, urine, lymph samples, and other tissues, in order to study the samples and develop new treatments for leukemia. Eligibility: - Individuals 18 years of age and older who have been diagnosed with leukemia or other kinds of blood and lymphatic system cancers, or who are healthy volunteers. Design: - Individuals who have leukemia will be asked to provide blood, bone marrow, urine, and tumor tissue samples as requested by the researchers. Healthy volunteers will provide only blood and urine samples. - No treatment will be given as part of this protocol.

Type: Observational

Start Date: Mar 2010

open study

Methylmalonic acidemia (MMA), one of the most common inborn errors of organic acid metabolism, is heterogeneous in etiology and clinical manifestations. Affected patients with cblA, cblB and mut classes of MMA are medically fragile and can suffer from complications such as metabolic stroke or infarction of the basal ganglia, pancreatitis, end stage renal failure, growth impairment, osteoporosis, and developmental delay. The frequency of these complications and their precipitants remain undefined. Furthermore, current treatment protocol outcomes have continued to demonstrate substantial morbidity and mortality in the patient population. Increasingly, solid organ transplantation (liver, and/or kidney) has been used to treat patients. Disordered transport and intracellular metabolism of vitamin B12 produces a distinct group of disorders that feature methylmalonic acidemia as well as (hyper)homocysteinemia. These conditions are named after the corresponding cellular complementation class - (cblC, cblD, cblF, cblJ and cblX) - and are also heterogenous, clinically and biochemically. The genetic disorders underlying cblE and cblG feature an isolated impairment of the activity of methionine synthase, a critical enzyme involved in the conversion of homocysteine to methionine and these disorders feature (hyper)homocysteinemia. Lastly, a group of patients can have increased methylmalonic acid and/or homocysteine in the blood or urine caused by variant(s) in recently identified (ACSF3) and unknown genes. In this protocol, we will clinically evaluate patients with methylmalonic acidemia and cobalamin metabolic defects. Routine inpatient admissions will last up to 4-5 days and involve urine collection, blood drawing, ophthalmological examination, radiological procedures, MRI/MRS, skin biopsies in some, and developmental testing. In a subset of patients who have or will receive renal, hepato- or hepato-renal transplants or have an unusual variant or clinical course and have MMA, a lumbar puncture to examine CSF metabolites will be performed. In this small group of patients, CSF metabolite monitoring may be used to adjust therapy. The study objectives will be to further delineate the spectrum of phenotypes and characterize the natural history of these enzymopathies, query for genotype/enzymatic/phenotype correlations, search for new genetic causes of methylmalonic acidemia and/or homocysteinemia, identify new disease biomarkers and define clinical outcome parameters for future clinical trials. The population will consist of participants previously evaluated at NIH, physician referrals, and families directed to the study from clinicaltrials.gov as well as the Organic Acidemia Association, Homocystinuria Network America and other national and international support groups. Most participants will be evaluated only at the NIH Clinical Center. However, if the NIH team decides that a patient under the age of 2 years is a candidate subject for this research protocol, that patient may enroll at the Children's National Medical Center (CNMC) site, pending approval by Dr Chapman, the Principal Investigator of the CNMC location Individuals may also enroll in the tissue collection only part of the study at the UPMC Children's Hospital of Pittsburgh or share medical history and clinical data via telemedicine visits remotely. Outcome measures will largely be descriptive and encompass correlations between clinical, biochemical and molecular parameters....

Type: Observational

Start Date: Jun 2004

open study

Background: About 5 million adults in the United States have age-related brain disorders. These include Alzheimer disease (AD), mild cognitive impairment (MCI), and other dementias. The number of people with these disorders will likely increase as the population ages and life span increases. Inflammation is thought to play a role in AD and MCI. Researchers want to know if an enzyme called PDE4B increases inflammation in people with AD or MCI. Objective: To test whether medical imaging using a new radiotracer ([18F]PF-06445974) can measure PDE4B in the brains of people with AD or MCI. Eligibility: People aged 50 years and older with AD or MCI. Healthy volunteers are also needed. Design: Participants will have up to 5 clinic visits with 3 imaging scans of the brain. They will have be screened. They will have a physical exam with blood tests. This will include tests of their heart and nerve function, including memory. Participants will have 2 positron emission tomography (PET) scans. One will use a standard radiotracer. The other will use the study radiotracer. They will receive each tracer through a tube attached to a needle inserted into a vein. During the scan with the study tracer, participants will have a second tube inserted into a vein in the wrist; this tube will be used to draw blood during the scan. Participants will lie on a bed that slides into a doughnut-shaped machine. These visits will take about 6 hours each. Participants will have 1 magnetic resonance imaging (MRI) scan. They will lie on a bed that slides into a cylinder. This visit will take up to 2 hours....

Type: Interventional

Start Date: Jul 2026

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: SARS-CoV-2 is the virus that causes COVID-19. Some people who recover from COVID-19 have long-term symptoms that affect the brain. These include headaches; loss of taste and smell; sleep problems; thinking problems; depression; and anxiety. Researchers want to know if a tracer (a substance that is injected into a person s body before an imaging scan) can help identify inflammation in people with these brain disorders. Objective: To see if a radioactive tracer ([11C]PS13) can highlight brain inflammation in those who had COVID-19 but still have symptoms that affect the brain. Eligibility: Adults aged 18 to 70 years with post COVID-19 brain disorders who are enrolled in protocol 000089 or 000711. Healthy volunteers are also needed. Design: Participants will have up to 5 clinic visits. Participants will be screened. They will have blood tests and a test of their heart function. They will have imaging scans: Magnetic resonance imaging (MRI): They will lie on a table that slides into a metal tube. Pictures will be taken of the brain. Positron emission tomography (PET): A needle attached to a thin tube will be inserted into a vein in the arm. The tracer will be injected through the tube. Another needle attached to a thin tube will be inserted into the wrist or inside of the elbow of the other arm to draw blood. They will lie still on a bed while a machine captures images of their brain. The scan will last about 2 hours. Study involvement is 11 to 14 weeks....

Type: Interventional

Start Date: Jun 2025

open study

Background: The lymphatic system is a network of vessels that carry a clear fluid called lymph through the body. Problems in the lymphatic system can cause pain, fluid buildup, and issues with immunity. There is much researchers do not understand about lymphatic anomalies. In this natural history study, they will collect data from a lot of people over a long time. Objective: To better understand why lymphatic anomalies develop. The goal is to improve future treatments. Eligibility: People aged 0 days and older with a suspected or confirmed lymphatic anomaly. Their unaffected parents or siblings aged 7 years or older are also needed. Design: Participants may remain in the study indefinitely. Affected participants may be evaluated every 10 months to 2 years. Some participants will be seen over telemedicine. Others will be seen at the NIH Clinical Center for 2-5 days. All participants will have a physical exam. They may provide specimens including blood, saliva, hair follicles, stool, skin, and other tissues. Samples may be used for genetic testing. Participants may undergo other tests depending on their medical conditions. The NIH Clinical Center visit may include: Heart tests include placing stickers on the chest to measure electrical activity and using sound waves to capture pictures of the heart. A lung test measures the muscle strength in the chest. Participants will blow into a tube. Photographs may be taken of participants faces and other features. Imaging scans will take pictures of the inside of the body. One scan will measure bone density. One type of scan tracks how lymph fluid moves through the body. Participants will be under anesthesia, and they will be injected with a dye.

Type: Observational

Start Date: Mar 2023

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: Children with attention deficit hyperactivity disorder (ADHD) often have cognitive problems. It may be hard for them to control their behaviors, concentrate for long periods, or make decisions. This can affect their education, friendships, and daily life. Virtual reality-based games may help improve cognitive skills in children with ADHD. It may also help change how the brain functions. Objective: To see if virtual reality-based games help improve thinking skills and brain function in children with ADHD. Eligibility: Children aged 8 to 16 years with ADHD. Design: We will first do a pilot study, meaning that everyone will receive the games. If this is successful, we will then conduct a randomized controlled trial, meaning that some participants will be randomly assigned to the full version of the games and some will be randomly assigned to a limited version. Participants will be screened. Their physical and mental health, medical and family history, and intellectual and emotional development will be evaluated. They will have tests of their mood, memory, attention, thinking, and behavior. Blood or saliva may be collected. Participants may have an MRI scan of the brain. Participants will receive a set of virtual reality games. The set includes 4 different games all played using a virtual reality headset. The participant will play the games for 20 minutes 5 days a week for 4 weeks. The parent or caregiver will start each game using an iPad. Each of the games is designed to help the participant practice specific cognitive skills. These include inhibition control, processing speed, temporal information processing, and working memory. Participants will have interviews each week. They will answer questions about motion sickness, eye strain, headache, and any other side effects, as well as number of game sessions played. Blood or saliva tests and the MRI may be repeated after the last game session. For the pilot, participants will have a final interview at the study end. For the full trial, a 1-month follow-up visit will be done by telehealth.

Type: Interventional

Start Date: Mar 2024

open study

Background: One way to treat liver cancer is to deliver chemotherapy drugs only to the liver (and not to the whole body). Researchers want to see if adding the drug PDS01ADC can improve the treatment. The drug triggers the immune system to fight cancer.<TAB> Objective: To see if treatment with HAIPs to deliver liver-directed FUDR and Dexamethasone chemotherapy in combination with PDS01ADC is effective for certain cancers. Eligibility: People aged 18 and older who have cancer of the bile ducts that is only in the liver, or colorectal cancer that has spread to the liver, or cancer of the adrenal glands that has spread to the liver, who are also receiving or planning to receive standard systemic chemotherapy for their disease. Design: Participants will be screened with: Medical history Physical exam Blood tests Pregnancy test (if needed) Tumor biopsy (if needed) Electrocardiogram Computed tomography (CT) scans Participants will have an abdominal operation. A catheter will be placed into an artery that feeds blood to the liver. The catheter will then be attached to the HAIP. The HAIP will lay under the skin on the left side of the abdomen. All participants will have liver-directed FUDR and Dexamethasone chemotherapy drugs or heparin with saline infused into the HAIP every 2 weeks. PDS01ADC will be injected under the skin every 4 weeks. They will receive this treatment until their cancer gets worse or they have bad side effects. Participants will also receive standard systemic chemotherapy for their disease, assigned based on diagnosis, through an IV by their medical oncologist (at NIH or by a local provider) every 2 weeks. Participants will have 2 study visits at NIH each month. They will have CT scans every 8 weeks. At visits, they will repeat some screening tests. Participants will have a follow-up visit 1 month after treatment ends. Then they will be contacted every 6 months for 5 years.

Type: Interventional

Start Date: Oct 2022

open study

This study will investigate how genetic and environmental factors contribute to the development of melanoma, a type of skin cancer, and related conditions. Individuals >=4 weeks with a personal or family history of melanoma or atypical spitzoid/Spitz tumor may be eligible for this study. Participants will: - Fill out one or two questionnaires about their personal and family medical history. - Provide written consent for researchers to review their medical records and pathology materials related to their care and those of deceased relatives with melanomas, tumors, cancer, or other related illnesses for whom they are the next-of-kin or legally authorized representative. - Donate a blood or cheek cell sample to be used for genetic studies. (The blood sample is collected through a needle in an arm vein. The cheek cell sample is obtained either by gently brushing the inside of the mouth with a soft brush or by swishing a tablespoon of mouthwash and then spitting it into a container.) - Undergo a skin biopsy (removal of a small piece of skin tissue) for genetic study. For this procedure, the area of skin to be removed is numbed with a local anesthetic and a 1/4-inch piece of skin is excised with a cookie cutter-like instrument. The wound is then covered with a band-aid. Participants may be asked to travel to the NIH Clinical Center for evaluation, including a medical history, physical examination, and some of the following procedures: - Full body skin examination to evaluate the type and number of moles and document any evidence of sun damage to the skin. The examination involves all the skin from the scalp to the bottoms of the feet. After the examination, a medical photographer will photograph the skin, with close-ups of skin lesions marked by the examiner. If there are parts of the skin the participant does not want examined or photographed, he or she can tell the examiner. - Blood draw of about 120 milliliters (4 ounces) or less - Skin biopsy - Cheek cell sample - X-rays, ultrasound and magnetic resonance imaging (MRI) studies to detect tumors or changes in tumors or other types of changes in specific tissues. MRI is a diagnostic test that uses strong magnetic fields and radiowaves to examine body tissues. The subject lies on a table that is moved into a large tunnel-like machine (the scanner) for about 45 minutes to 1 hour. When the tests are finished, a doctor will discuss the results with the participant and the need, if any, for clinical follow-up....

Type: Observational

Start Date: Jul 2002

open study

The goal of this clinical trial is to determine if perfusion index (PI) can reliably predict changes in systolic blood pressure (SBP) in persons with spinal cord injury (SCI) during a cool temperature challenge. Participants with SCI can be 18-75 years of age, male or female, neurological level of injury C4-T12, ASIA Impairment Scale (AIS: A or B: motor complete) or gender and healthy age-matched able-bodied (AB) controls. The main question this study aims to answer is: can PI reliably predict change in SBP during a cool temperature challenge? We hypothesize that PI can be used as a biomarker of SBP in persons with SCI. Researchers will compare the relationship of 1) changes in PI and SBP and 2) relationship of changes in other vital signs to SBP, during the cool temperature challenge. The researchers aim to determine if PI can be used as a biomarker of SBP in persons with SCI during a cool temperature challenge (experimental group/arm). Able-bodied controls (control group/arm) will receive the same intervention (cool challenge) as the experimental group. During the study, participants will be asked to wear only shorts and a T-shirt so that their skin can be exposed to the warm and cool temperatures of the 2 rooms. We will put put on non-invasive sensors (taped or attached on the surface of your body) to measure PI, BP, and other vital signs. We will record these measurements while you are seated in a wheelchair for 10 minutes in a warm room and up to 90 minutes in a cool room.

Type: Interventional

Start Date: Jul 2026

open study

The investigators propose to implement and evaluate the effectiveness of the peer-led CARE Intervention designed to mitigate health differences among rural and low-income communities in Texas. This intervention leverages the expertise of Community Health Workers (CHWs) to empower rural and low-income communities, improving health outcomes through outreach, education, counseling, and social support.

Type: Interventional

Start Date: Jun 2026

open study

This study will evaluate the safety and effects, good or bad of faricimab (Vabysmo®), a drug that is approved by the U.S. Food and Drug Administration (FDA) for other retinal conditions, but its use is considered investigational when used specifically for choroidal neovascularization (CNV) related to presumed ocular histoplasmosis (POHS)

Type: Interventional

Start Date: Jul 2026

open study