Researchers intend on diagnosing and treating certain inborn errors of metabolism. By doing this researchers hope to expand their knowledge about these disorders and provide access to patients of interest for research, teaching, and clinical experience. Patients participating in this study will be examined and treated on an out patient basis, if practical. However, patients requiring specialized tests or treatments will be admitted to the NIH Clinical Center as necessary. Researchers will use only accepted medical procedures in diagnosing (medical history, physical examinations, X-ray studies, eye examinations, blood tests, and urine tests) and treating the patients involved in this study. Additional tests may be required on a case to case basis. Many patients seen in this study will go on to be enrolled in a specific disease-related research study.<TAB>

Type: Observational

Start Date: Sep 1978

open study

This is a non-ablative (partial) stem cell transplant for patients with severe sickle cell disease or beta-thalassemia requiring red cell transfusions. The intensity of the transplant is slightly increased from our previous transplant regimens. The goal is to aim for higher percentage of donor cells to stably remain in the recipients long term.

Type: Interventional

Start Date: Jul 2026

open study

Background: Many tasks people do every day require a series of individual movements. Control over these movements is called motor skills. But even highly skilled people can make mistakes. Researchers have found that they can predict when a person will make a mistake 0.1 second before it happens. Now, they want to find out if they can increase that time up to 1 second-long enough to warn the person and prevent the mistake. Objective: To see if motor skill errors can be detected up to 1 second before they occur. Eligibility: Right-handed healthy adults aged 18 to 35. Design: Participants will have 2 to 5 study visits. Each visit will be 1 to 2 hours. They will have a physical and neurological exam. They will have 1 or 2 magnetic resonance imaging (MRI) scans. They will lie on a table that slides into a large cylinder. The MRI uses strong magnets to capture images of the inside of the body, including the brain. They will have another scan, called magnetoencephalography (MEG). Small metal disks attached to wires will be taped to their head. Participants will sit in a padded chair with their head inside of a helmet. The helmet will not cover their eyes or face. Participants will perform a series of typing tasks on a keyboard. They will have short breaks between each round. Their head movements will be tracked, and their eye and finger movements will be videotaped.

Type: Observational

Start Date: Jun 2026

open study

Background: Androgen effects in humans are usually (but not always) mediated by the androgen receptor which is coded for by the androgen receptor gene (AR gene). Androgen Insensitivity Syndrome (AIS) is a rare condition in which the body cannot sense the male hormones in the blood or tissue. Both women and men can be affected by AIS. Researchers want to learn more about the health of people with AIS over time. With a natural history study in individuals with AIS, data and tests may provide information regarding health risks (including the risks and benefits of gonadectomy and best ways to monitor for tumor) and optimal management of individuals with AIS as well as elucidate the role of the androgen receptor in human health. This study does not involve any interventions and we can provide clinical care while collecting data. Objective: The objective of this natural history study is to describe and define a comprehensive phenotype (characteristic) of patients with AIS based on confirmed androgen receptor (AR) gene difference. We will evaluate hormones, bone density and markers, cardiovascular and metabolic parameters, as well as quality of life and tumor formation risk and evaluation. The purpose is to obtain a better understanding of the overall health issues that people with AIS may have through the study procedures listed. Eligibility: People ages 8-99 with AIS and their adult relatives Design: Participants will go through a series of study procedures for data and specimen collection. This will be done to understand how AIS affects individuals since the androgen receptor is found in many tissues in the body including skin, bone, muscle, and the neurologic, immune and metabolic systems. All tests will be performed by skilled and trained study professionals. Participants will be screened with: Medical history Physical exam Medical record review Lab tests. Participants will have physical exams. Their body measurements will be taken. They will have blood and urine tests. They will have electrocardiograms to check heart health. They may complete questionnaires. They may have an Oral Glucose Tolerance Test. Participants may have x-rays and HRpQCT scans taken of the hand, wrist, and other bones. Participants will have body scans to measure bone thickness. Participants will have magnetic resonance imaging (MRI) or sonogram of the pelvis. For MRI, they may get a contrast agent via intravenous (IV) catheter. Adult participants may have the following: MR elastography. It uses MRI and low-frequency vibrations to map stiffness of body tissues. MR spectroscopy. It uses MRI to take pictures of chemicals in the liver and body fat. Cardiac computed tomography scan. It uses x-rays to make pictures of the heart. Participants may get a contrast agent via IV. Optional genital exam. Optional one-time vaginal swab. Participants will have visits every 1-2 years. Participation lasts indefinitely. Adult relatives will also be invited to participate but will have only 1 visit. It will include some of the above tests.

Type: Observational

Start Date: Apr 2021

open study

Background: There are many endocrine and metabolic-related conditions. Two well-known disorders include diabetes and thyroid disease. Some of these diseases are caused by a change in genes. Researchers want to identify the genes involved in these disorders. They hope this will help them learn more about these diseases. Objectives: To learn more about conditions that affect the hormone-secreting glands (endocrine glands) in adults. To train doctors to diagnose and treat people with endocrine or metabolic conditions. Eligibility: Adults age 18 years and older with a known or suspected endocrine disorder. Relatives ages 18 years and older. Doctors will review all requests and available medical records to determine final eligibility for the protocol. Design: Participants will have a medical history and physical exam. Most participants will have 1 visit, and may have follow up visits if necessary. They may have tests, surgery, or other procedures to help diagnose or treat their condition. These could include: - Blood, urine, and saliva tests - Imaging tests. These may include X-ray, ultrasound, or scans. - Sleep study - Medical photographs - Visits with other specialists at NIH Participants will provide blood, urine, saliva, or tissue samples. Some of these samples may be stored in the freezer for future studies. Participants may be asked to participate in genetic testing. They will give a blood or saliva sample for this.

Type: Observational

Start Date: Jul 2016

open study

Background: - Lab studies help researchers better understand cancer biology. This information may lead to new methods for diagnosing or treating cancer. To develop these studies, researchers want to collect samples from people with cancer or precancer conditions of the lymph system. These conditions include multiple myeloma, different types of lymphoma, and adult leukemia/lymphoma. The samples collected will include blood, urine, bone marrow, and tumor and skin tissue. Objectives: - To collect tissue samples to study different types of lymph cancer. Eligibility: - Individuals at least 18 years of age who have a lymphoid cancer or precancer condition. Design: - Participants will be screened with a physical exam and medical history. - Different samples will be collected for study. Blood samples will be collected at the initial testing. More blood samples will be collected at different treatment points. Other liquid samples include urine, bone marrow, and any abnormal fluid. Tumor tissue and skin tissue biopsies will also be collected for study. - Treatment will not be provided as part of this study.

Type: Observational

Start Date: Sep 2012

open study

This study will evaluate patients with abnormal immune function that results in recurrent or unusual infections or chronic inflammation. This may include inherited conditions, such as X-linked severe combined immunodeficiency (XSCID), chronic granulomatous disease (CGD), and leukocyte adhesion deficiency (LAD), or conditions resulting from outside factors, such as graft-versus-host disease (GVHD). The information from this study will be used to establish the pattern and pace of change of the disease and to help develop new treatments. The period of observation and study following enrollment in this study may be for up to one year. In addition these studies may provide the medical information needed to determine eligibility for enrollment in other clinical study protocols and more prolonged follow up. Patients of any age with abnormal immune function who have recurrent or unusual infections, whose blood tests show evidence of immune dysfunction, or who have GVHD, XSCID, CGD or LAD may be eligible for this study. Patients' parents, siblings, grandparents, children, aunts, uncles and first cousins of any age also may be included. Healthy normal volunteers between 18 and 85 years of age are recruited as controls. Normal volunteers undergo a physical examination and provide blood, saliva, and urine samples for immune function studies. Patients' family members provide a medical history, have a physical examination, and give blood and urine samples, and possibly a saliva sample. The samples are used for genetic and routine laboratory studies. Investigators may request tissue samples, such as biopsy specimens, previously removed for medical reasons to be sent to NIH for study. Patients undergo the following tests and procedures: 1. Medical history and physical examination. 2. Blood and urine tests, including analysis for genes involved in immune disorders. 3. Buccal smear (in some patients) for genetic studies. This involves scraping the lining of the mouth near the cheek. 4. Specialized tests to evaluate specific conditions in patients who have an immune disorder that might affect lung function, gum infections or eye problems. These may include chest x-ray, CT scan, breathing function test, dental, eye, and hearing examinations. 5. Follow-up visits of patients with immune problems may occur at 6 months and at one year after the first visit (or more frequently if medically required) to include: - Medical history update - Physical examination - Follow-up on abnormal test results and medical treatments initiated at NIH - Collection of blood, saliva, urine, or wound drainage samples for repeat immune function studies - Tissue study of specimens removed for medical reasons at other institutions besides NIH

Type: Observational

Start Date: Sep 2005

open study

Background: Diseases related to the immune system, blood clots, and blood vessels can affect every part of the body. These diseases are now known to be interrelated: People who have strokes, blood clots in their legs, or autoimmune disease, for example, are at greater risk of complications in the heart, brain, and other organs. Researchers want to learn more about how these diseases start, how they change over time, and how they affect different organs. Objective: To learn more about how inflammation and diseases of the blood vessels start and how they change over time. Eligibility: People aged 5 years and older with a disease related to blood clots, the immune system, or blood vessels. Healthy relatives of people with these diseases and unrelated healthy volunteers are also needed. Design: Participants will have a baseline visit: They will provide a medical history, physical exam and blood test. All other tests and procedures are optional; these may be spread over more than 1 day: Tests of heart and lung function. Fill in a family tree form. Imaging scans Treadmill or bike stress tests and a 6-minute walk test. Tests of blood pressure and the flow of blood through vessels. Photos of the face and body. Eye exams, with photos taken of the retina. Saliva and urine samples. Biopsies (tissues samples) of the skin and fat. Tests of thinking and mental function. Evaluations by other medical specialists. Participants may opt to return for repeat testing for up to 90 months (7.5 years). Some visits may be done by telehealth.

Type: Observational

Start Date: Nov 2024

open study

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

Type: Observational

Start Date: Nov 2001

open study

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

Type: Interventional

Start Date: Mar 2025

open study

Background: Sickle cell disease (SCD) is a genetic disease that causes the body to produce abnormal ( sickled ) red blood cells. SCD can cause anemia and life-threatening complications in the lungs, heart, kidney, and nerves. People with SCD are also at increased risk of forming blood clots in the veins and lungs, but the standard treatments for these clots can cause increased bleeding in people with SCD. Better treatments are needed. Objective: To test a drug (fostamatinib) in people with SCD. Eligibility: People aged 18 to 65 with SCD. Design: Participants will have 6 clinic visits over 12 weeks. Each visit will be 2 to 3 hours. Participants will be screened. They will have a physical exam with blood tests. They will tell the researchers about the medications they take. Fostamatinib is a tablet taken by mouth. Participants will take the drug at home, twice a day, for up to 6 weeks. Participants will have a clinic visit every 2 weeks while they are taking the drug. At each visit they will have a physical exam with blood tests. They will talk about any side effects the drug may be causing. If they are tolerating the drug well after the first 2 weeks, they may begin taking a higher dose. Participants will have a final visit 4 weeks after they stop taking the drug. They will have a physical exam and blood tests; they will be checked for any side effects of the drug.

Type: Interventional

Start Date: Dec 2024

open study

Background: - Li-Fraumeni syndrome (LFS) is a genetic condition that increases the risk for some types of cancer. LFS may lead to cancer of the bone or connective tissue, breast, and brain. It may also increase the risk for certain types of leukemia and other cancers. The only known cause of LFS is a change (called a mutation ) in a gene known as TP53. However, not all people with LFS have a TP53 mutation. Researchers want to study other possible genetic causes of LFS, and factors that may increase or decrease cancer risk in people with the syndrome. Objectives: - To learn more about the types of cancers that occur in individuals with LFS. - To study the role of the TP53 gene in the development of cancer. - To look for other possible genes that cause LFS - To study the effect of LFS diagnosis on families. - To determine if environmental factors or other genes can change a person s cancer risk associated with LFS. Eligibility: - Individuals with a family or personal medical history of cancers consistent with LFS. - Individuals with a family or personal medical history of cancers that does not meet the diagnosis of LFS, but the history is suggestive for LFS (meets the diagnosis for the so-called Li-Fraumeni like syndrome) - Individuals with certain rare cancers - Individuals with a family or personal history of a TP53 gene mutation, with or without related cancer(s). Design: - Participants will fill out a medical history questionnaire and a family history questionnaire. - Blood samples will be collected for DNA and for storage. Cheek cell samples may be collected if blood cannot be obtained for DNA. Participants can choose to have or not have cancer screening with blood tests, imaging studies, and other exams. - Participants will complete questionnaires about their worries about cancer, stress levels, and coping strategies. Diet and physical activity questionnaires will also be given. Other psychological tests may be given as needed. - Participants will be monitored for several years, with regular followup visits to the National Institutes of Health, if indicated. Any changes in health or cancer status will be recorded.

Type: Observational

Start Date: Jan 2012

open study

The purpose of this study is to assess the safety and effectiveness (usefulness) of an investigational technique used to repair the mitral valve for patients with mitral regurgitation due to a defective valve leaflet. This procedure is called trans-ventricular off-pump mitral valve repair (TRANSOM) and it repairs the mitral valve by replacing some of the cords that support the mitral valve. This type of repair is minimally-invasive since it is performed through a small incision and avoids making a breast-bone-splitting incision.

Type: Interventional

Start Date: Jun 2026

open study

The goal of this clinical trial is to learn if AT673 contributes to additional weight loss and glycemic control when given with semaglutide in participants with overweight/obesity and type 2 diabetes. The main questions it aims to answer are: - To compare the effect on body weight of two doses of AT673 once-weekly versus matched placebo when concurrently administered with semaglutide once-weekly - To evaluate the effect of AT673 on glycated hemoglobin (HbA1c) - To compare the safety and tolerability of AT673 versus matched placebo when concurrently administered with semaglutide

Type: Interventional

Start Date: Jun 2026

open study

The purpose of this study is to present social media posts with varying combinations of flavor types and mentions of stealth use, to adolescents and determine whether these message characteristics increase adolescents' perceptions of these products and susceptibility to using these products.

Type: Interventional

Start Date: Jul 2025

open study

The purpose of the study is to test different categories of ankle foot orthoses (AFOs) with patients who have had lower limb salvage, reconstruction or other problems impacting limb function.

Type: Interventional

Start Date: Jul 2026

open study

This study explores the acute effects of neurodynamics, an intervention commonly used by physical therapist to improve nerve mobility and decrease pain, on the strength and muscular endurance in the athletic population. This study aims to find if these interventions can maintain or promote strength and endurance in the hamstrings. The studies results will help physical therapist better prescribe exercise and hands-on treatment for hamstring and sciatic nerve related conditions and injuries.

Type: Interventional

Start Date: Jun 2026

open study

The present study investigates the feasibility of a support pillow for use after spinal surgical procedures, and more particularly, to protect the midline region of the back following spinal surgery. Existing cushioning pillows do not accommodate the anatomy of the human back nor the requirements of isolating a vertical spinal incision. For example, donut-style or ring-shaped pillows are designed for entirely different purposes, such as hemorrhoidal relief, and cannot provide the desired spinal relief. As a result, there is no suitable, dedicated support structure that allows a patient to rest on their back while eliminating pressure on the surgical site. Accordingly, there is a need for a device that permits postoperative spinal surgery patients to sit or lie in a supine or reclined position without the surgical incision contacting or being compressed by any supporting surface.

Type: Interventional

Start Date: Jul 2026

open study

This study is the first to assess the impact of lower extremity orthoses on gait and balance in individuals with CA. By investigating how orthoses influence mobility and stability, this research will provide critical data to inform clinical guidelines, improve patient care, and support evidence-based orthotic prescriptions for individuals with CA.

Type: Interventional

Start Date: Nov 2025

open study

There is increasing interest in using GLP-1 Receptor Agonist (GLP-1 RA) medications after pregnancy. This study is designed to determine if these medications affect breastmilk production or the nutritional makeup of breastmilk. The main questions the study will address are: - Does GLP-1 RA-induced weight loss increase or decrease breastmilk production? - Does GLP-1 RA-induced weight loss affect the nutritional composition of milk, including milk fat content? Researchers will assess milk production rates before and after mothers begin taking injected GLP-1 RA medications to decrease their body weight. Weight loss will be confirmed with 7-day body weight averages. Participants will: - Weigh themselves and report measurements daily. - Participate in 2-3 morning study visits over approx. 2.5-4.5 months (approx. 3-3.5hrs each). During each visit, participants will: - Use a study provided breastpump to express milk 3 times hourly for measurement of hourly milk production. - Provide 1-3 oz of milk for further study. - Answer questions about breastfeeding patterns.

Type: Observational

Start Date: Jul 2026

open study

The goal of this clinical trial is to test the MedMemos Intervention with parents and children who have received a bone marrow transplant. The main study questions are: - Is the MedMemos intervention acceptable to patients and families? - Is the MedMemos intervention feasible for patients, families, and healthcare providers? - Does MedMemos help patients and families take their medications better? Participants will be asked to complete surveys, attend 4 intervention sessions, and use an electronic box or pill bottle to store their medications in.

Type: Interventional

Start Date: May 2026

open study

Regular physical activity is associated with numerous health benefits, yet many young adults do not achieve recommended levels of physical activity. Exercise snacking, which involves performing brief bouts of physical activity throughout the day, may provide a practical alternative to traditional exercise programs by making physical activity easier to incorporate into daily routines. This randomized controlled trial will evaluate whether a 12-week exercise snacking intervention improves physical activity levels, aerobic fitness, cardiometabolic health, and psychological well-being in insufficiently active young adults. Participants will be randomly assigned to either an exercise snacking intervention or a usual behavior control group. Assessments will be completed at baseline, after the 12-week intervention, and after an additional 12-week follow-up period to determine whether any changes are maintained after the intervention ends. The study will measure physical activity using wearable activity monitors and assess aerobic fitness, body composition, blood pressure, blood lipids, glucose, exercise motivation, affective responses to exercise, and mental well-being. The findings will help determine whether exercise snacking is an effective and sustainable strategy for improving health in young adults and may inform future physical activity recommendations and interventions

Type: Interventional

Start Date: Aug 2026

open study

This study is a Phase 3, multi-center, randomized, 6-week, double-blind, placebo-controlled, parallel-group trial to assess the efficacy and safety of solriamfetol in children aged 6 to <12 years with ADHD.

Type: Interventional

Start Date: Jul 2026

open study

The purpose of this study is to investigate the potential benefits of an online yoga module for patients with gastroparesis. Specifically, the study aims to: 1. Evaluate the Impact of Yoga Practices: Examine whether practicing yoga, including pranayama (breathing techniques), mindfulness meditation, and guided relaxation, can help reduce symptoms of gastroparesis, such as nausea, vomiting, bloating, and abdominal pain. 2. Assess Psychological Factors: Determine if the yoga intervention can improve associated psychological factors, including mental well-being, sleep quality, and overall quality of life for individuals with gastroparesis. 3. Provide Evidence-Based Insights: Contribute to the evidence base on the effectiveness of non-pharmacological treatments like yoga in managing gastroparesis, which may offer an additional, accessible management option for patients.

Type: Interventional

Start Date: Jul 2026

open study

This study examines whether participating in poetry workshops can improve emotional well-being among patients with chronic digestive symptoms. Many individuals with long-standing digestive conditions experience distress, anxiety, isolation, and difficulty expressing their emotions in clinical settings. These emotional challenges can negatively affect daily life, relationships, and overall health. Poetry writing offers a creative and supportive way for participants to explore their feelings, express their experiences, and build emotional resilience. It also allows individuals to focus on aspects of their identity beyond their illness. The purpose of this research is to evaluate whether poetry workshops can reduce anxiety, lessen feelings of isolation, and strengthen participants' sense of community and well being. 1. Why is this study being done? The purpose of this research study is to offer a creative outlet for patients to explore their identity and story, build resilience, and seek hope. This study is being done because we understand that the psychological discomfort that can come upon hearing a diagnosis can lead to increased anxiety levels, negatively impacting a patient's well-being and relationships. Often healthcare practitioners may merely view a patient through the lens of their diagnosis, neglecting other aspects of their identity and humanity. Through reading various poems, crafting their own poems, and sharing their work with their peers, we hope the workshops offer a comforting opportunity for the participants to explore their identities and creativity.

Type: Interventional

Start Date: Jul 2026

open study