Background: People with Idiopathic CD4 lymphopenia (ICL) have lower numbers of a type of white blood cell called CD4 cells. White blood cells fight against infections. Low levels of CD4 cells may make a person more likely to get sick. There are no approved treatments for ICL. Researchers think a drug called belimumab may be able to help in specific situations. Objective: To see if belimumab is safe for people with ICL. Eligibility: People ages 18-70 who have ICL and are participating in NIH protocol 09-I-0102 (EPIC) Design: Participants will be screened with: Medical and medication history Physical exam Questionnaire about mental health and depression Blood and urine tests Participants will have a baseline visit. This will include some repeats of the screening tests. They may also have leukapheresis: Blood will be taken from a needle in one arm and passed through a machine that separates out the white blood cells. The rest of the blood will be returned through a needle in the other arm. Participants will receive 8 doses of belimumab through IV: A needle will insert a thin plastic tube into an arm vein. Belimumab will be given through the IV line. The first 3 doses will be given every 2 weeks. The other 5 will be given once every 4 weeks. Participants will have a physical exam and blood and urine tests at each dosing visit. They will be monitored for up to 4 hours after the infusion. Participants will have 3 follow-up visits, at around 8, 16, and 24 weeks after the last dose of belimumab. They will have a physical exam and blood and urine tests. Once they finish this protocol and they will continue to be followed under 09-I-0102 (EPIC study).

Type: Interventional

Start Date: Jan 2020

open study

Background: - Little is known about how the brain changes during childhood and adolescence, how genes affect this process, or how the brains of people with 7q11.23 genetic variation change during this period. Researchers are interested in using magnetic resonance imaging to study how the brain changes in healthy children and children with 7q11.23 genetic variation, including Williams syndrome and 7q11.23 duplication syndrome. Objectives: - To study developmental changes in the brains of healthy children and children who have been diagnosed with Williams syndrome,7q11.23 duplication syndrome, or other 7q11.23 genetic variation. Eligibility: - Healthy children and adolescents between 5 and 17 years of age. - Children and adolescents between 5 and 17 years of age who have been diagnosed with Williams syndrome, 7q11.23 duplication syndrome, or have other 7q11.23 genetic variation. Design: - Participants will have a brief physical examination and tests of memory, attention, concentration, and thinking. Parents will be asked about their child s personality, behavior characteristics, and social interaction and communication skills. - Both participants and their parents may be asked to complete additional questionnaires or take various tests as required for the study. - Participants will have approximately 10 hours of magnetic resonance imaging (MRI) scanning, usually over 4 to 5 days, within a one month period. Some of these tests will require the participants to do specific tasks while inside the MRI scanner. - Participants will be asked to return to the National Institutes of Health clinical center to repeat these procedures every 2 years thereafter until age 18.

Type: Observational

Start Date: Jan 2011

open study

BACKGROUND - This protocol acknowledges that it is in the interest of the NIH and ROB, as well as our participants, to continue to follow those who have been treated with radiotherapy at ROB and are not otherwise eligible for current active research protocols. - It also provides a mechanism for the correlation and interpretation of disparate data for research into the long term side effects and outcomes for a variety of disease entities and treatments, such as combined modality treatment, MoAb, PDT, radiation modifiers, intraoperative radiotherapy, etc. OBJECTIVE -The primary objective of this protocol is to assess the late effects of treatment and the natural history of disease through collection of data from any standard procedures performed as part of follow up care on participants previously treated with radiotherapy. ELIGIBILITY -Participants who received radiation therapy. DESIGN - This is a natural history protocol in which long-term follow up data will be collected from participants who received radiation therapy. - It will be made clear to participants in the consent form, that data collected during their follow-up may be used anonymously for publications concerning the natural history of disease processes and long-term effects of treatment.

Type: Observational

Start Date: Feb 2000

open study

Background: - Researchers at the National Institutes of Health give many tests of hearing and balance. These tests can help detect problems that affect hearing or balance. It is important to know exactly how healthy people perform on each of these tests. This information will indicate when a test result is normal and when a test result shows a problem. Researchers also want to determine the best methods for each test. Objectives: - To test different types of hearing and balance tests, and collect information on normal values for each test. Eligibility: - Healthy volunteers between 5 and 80 years of age. Design: - This study will require a single visit to the National Institutes of Health Clinical Center. It will include both screening tests and study tests of hearing and balance. Sometimes, a second visit may be required if a test is designed to measure the same thing on 2 different days. Each visit will last between 2 and 5 hours, depending on the number of tests scheduled per visit. - Participants will have a physical exam and medical history. They will also have basic tests to check for normal hearing and balance. - Participants may have different hearing tests, including the following: - Auditory Evoked Potentials to study how the ears and brain handle sound information. - Auditory Processing Tests to study how a person processes complex sounds like speech in background noise. - Tests of middle ear and inner ear function. - Participants may have different balance and inner ear tests, including the following: - Balance test on a tilting platform. - Different tests to measure how well the eyes, ears, and brain work together to help maintain balance. - Treatment will not be needed as part of this study.

Type: Observational

Start Date: Sep 2012

open study

Background: Gynecologic conditions are those that are related to the reproductive system. They can be reproductive gland disorders or reproductive system tumors. They can also be inborn anomalies of the reproductive tract. Researchers want to gather data over time from a large group of young people with these conditions. Objective: To create a database about child and teenage gynecologic conditions. Eligibility: Participants of any age with known or suspected pediatric and adolescent gynecologic conditions, and their adult family members Design: Participants will be screened with a review of their medical records. Participants may have a medical history and physical exam. Participants will have blood drawn using a needle. The blood will be used for genetic tests. Participants will have saliva collected. They will spit into a small plastic container. Or their spit will be absorbed from their mouth using a small sponge. The saliva will be used for genetic tests. Participants may have samples collected from their vagina. A small cotton swab will be used to gather the samples. This procedure is optional. If participants have a surgery related to their condition, a small tissue sample will be taken. It will be stored for future research. Participants may complete optional surveys. These surveys ask about their physical and emotional health. They can choose not to answer any of the questions. Researchers will collect medical data from participants standard tests. Such tests may include blood and urine tests, X-rays, nuclear medicine scans, and other tests. Data will also be collected from standard treatments they may receive.

Type: Observational

Start Date: Apr 2021

open study

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

Type: Observational

Start Date: Apr 2015

open study

Background: -Sjogren s Disease (formerly: Sjogrens Syndrome, Sj(SqrRoot)(Delta)gren s syndrome) is a disease that affects about 1-4 million Americans. It is more common in women. It mainly affects the glands that produce saliva and tears, leading to dry eyes and dry mouth. The cause of Sjogren s Disease is unknown, but inflammation plays an important role. The purpose of this study is to learn more about Sjogren s Disease. Objectives: -To better understand how Sjogren s Disease begins and how it affects patients so that we can develop better ways to treat them. Eligibility: - Participants must be 16 years of age or older. - They must have a diagnosis of Sjogren s Disease or have at least two symptoms of Sjogren s Disease. Design: - People taking part in the study will come to the NIH Clinical Center for at least three visits. - During these visits, participants will have a medical history and physical exam. They will have oral and dental assessments, and saliva collection. Lab tests (blood and urine) and dry eye exams will be done. Participants will answer questionnaires and have salivary scintigraphy (adults only unless required for diagnosis). - Other optional tests may also be done. Participants may have to come in for additional visits if they have these optional tests or if their disease changes. - The only treatment provided as part of this study is for medical emergencies or complications that occur while you are at NIH for evaluation.

Type: Observational

Start Date: Jan 2012

open study

Background: Primary immunodeficiency disorders, or PIDs, are diseases that weaken the immune system. This makes it easier for a person to get sick. Some PIDs are mild and may not be diagnosed until later in life. Other kinds are severe and can be identified shortly after birth. Researchers want to learn more about PIDs by comparing data from relatives and healthy volunteers to people with a PID. Objective: To learn more about PIDs, including their genetic causes. Eligibility: People ages 0-90 with a PID or their healthy biological relatives the same ages Healthy volunteers ages 18-75 Design: Participants will be screened with a medical history, physical exam, and HIV blood test. They may have a pregnancy test. Participants may repeat the screening tests. Blood taken at screening will be used for genetic tests and research tests. Participants will be told test results that affect their health. Some blood will be stored for future research. Adult participants with a PID may have a small piece of skin removed. The area will be numbed. A small tool will take a piece of skin about the size of a pencil eraser. Researchers may collect fluid or tissue samples from PID participants regular medical care. They will use them for research tests. Participants with a PID will have 3 follow-up visits over 10 years (for infants, 2 years). Visits will include a physical exam, medical history, and blood draw. Participants with a PID and their relatives will be called once a year for 10 years. They will talk about how they are feeling and if they have developed any new symptoms or illnesses. ...

Type: Observational

Start Date: May 2018

open study

Study description: This is a natural history study that will evaluate any patient with enzyme or DNA confirmed GM1 or GM2 gangliosidosis, sialidosis or galactosialidosis. Patients may be evaluated every 6 months for infantile onset disease, yearly for juvenile onset and approximately every two years for adult-onset disease as long as they are clinically stable to travel. Data will be evaluated serially for each patient, and cross-sectionally for patients of similar ages and genotypes. Genotype-phenotype correlations will be made where possible although these are rare disorders and the majority of the patients are compound heterozygotes. Objectives: To study the natural history and progression of neurodegeneration in individuals with glycosphingolipid storage disorders (GSL), GM1 and GM2 gangliosidosis, and glycoprotein (GP) disorders including sialidosis and galactosialidosis using clinical evaluation of patients and patient/parent surveys. To develop sensitive tools for monitoring disease progression. To identify biological markers in blood, cerebrospinal fluid, and urine that correlate with disease severity and progression and can be used as outcome measures for future clinical trials. To further understand and characterize the mechanisms of neurodegeneration in GSL and GP storage disorders across the spectrum of disease beginning with ganglioside storage in fetal life. Endpoints: Exploring the natural history of Lysosomal Storage Diseases and Glycoprotein Disorders Study Population: Patients with enzyme or DNA confirmed GM1 or GM2 gangliosidosis, sialidosis or galactosialidosis. Accrual ceiling is 200 participants. No exclusions based on age, gender, demographic group, or demographic location. Patients included in our study are those that are seen at the NIH Clinical Center, subjects that have only sent in blood samples, as well as those who complete the questionnaire or provided head circumference measures. ...

Type: Observational

Start Date: Feb 2002

open study

Background: The right amount of fats in the blood (cholesterol and triglycerides) are a key part of a healthy organism. Too much or too little of these fats may manifest as diseases (dyslipidemia). There are many causes for these abnormalities, but some are genetically determined and we would like to better understand the progression of these conditions over time. Objective: This natural history study aims to learn more about dyslipidemias; how they change over time; and how they respond to therapy. We also want to develop new diagnosis methods for these conditions. With the knowledge we will acquire we hope to provide new insights, new approaches and improve the overall health of these patients. Eligibility: Individuals aged 10 years and older, residing both within and outside the United States, who have or are suspected of having a disorder that causes changes in the levels of fats in their blood (genetic dyslipidemias). Design: Participants residing within and outside the United States will be screened. Their medical records may be reviewed. They may talk to researchers about their medical history by phone, telehealth, or in person. All study visits are optional. Participants may visit the NIH up to 15 times per year, if needed. Each visit may include a physical exam and blood tests. Participants may also have an electrocardiogram (EKG). The EKG measures the electrical activity when the heart beats. In some cases, participants may remain in the study for up to 20 years.

Type: Observational

Start Date: Jan 2025

open study

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

Type: Interventional

Start Date: Mar 2026

open study

Background: Small cell carcinoma of the bladder (SCCB) and other high-grade neuroendocrine tumors (HGNET) of the urinary tract are rare but aggressive cancers. Average survival for people diagnosed with SCCB or HGNET is about 1 year. Lurbinectedin and avelumab are drugs that are approved to treat other cancers. Researchers want to see if these drugs can help people with SCCB or HGNET. Objective: To test lurbinectedin with or without avelumab in people with SCCB or HGNET. Eligibility: Adults aged 18 years and older with SCBB or HGNET that returned and spread after treatment. Design: Participants will be screened. They will have a physical exam. They will have blood tests and imaging scans. They may need to have a new biopsy: A small needle will be used to collect a tissue sample from the tumor. Both study drugs are given through a tube attached to a needle inserted into a vein. If participants have already received a drug like avelumab they will receive only lurbinectedin. If patients have not been previously treated with a drug like avelumab they will receive both lurbinectedin and avelumab. All participants will receive their treatment once every 3 weeks for up to 10 years. They will also receive other drugs to relieve adverse effects. Biopsies, blood tests, and imaging scans will be repeated during some study visits. Participants may also have urine tests and tests of their heart function. Participants may remain in the study as long as the treatment is helping them. If they stop treatment, they will have safety visits 14, 30, and 90 days after their last dose. Additional follow-up visits will continue 5 to 10 years.

Type: Interventional

Start Date: Jun 2024

open study

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

Type: Interventional

Start Date: Jan 2024

open study

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

Type: Interventional

Start Date: Jan 2025

open study

Background: In the U.S., over 6.5 million people have heart failure. Researchers want to develop new testing methods for cardiovascular problems using magnetic resonance imaging (MRI) to improve the clinical diagnosis and management of people with heart failure. Objective: To develop and test new methods for imaging the heart and blood vessels using MRI. Eligibility: People ages 18 years and older who are having an MRI of their heart or blood vessels. Healthy volunteers are also needed. Design: Participants will be screened with a medical history. Participants will have a physical exam and blood tests. They will have an electrocardiogram (ECG) to measure the heart s electrical activity. Then they will have their scheduled MRI scan. The MRI scanner is a large, hollow tube. Participants will lie on a table that moves in and out of the tube. During the MRI, they may have contrast dye injected through an intravenous line inserted into their arm or hand. ECG may be used to monitor their heartbeat or coordinate pictures with their heartbeat. A flexible belt may be used to monitor their breathing. A finger probe may be used to track their heart rate and/or oxygenation level. Their blood pressure may be measured. Pictures may be taken of their blood vessels, heart, and lungs before, during, and after they get medicine to increase blood flow. They may lie flat and pedal a stress bicycle to increase their heart rate. Participation will last for 5 years. During that time, participants may receive a yearly survey about their health. They may be contacted for an optional follow-up MRI within 2 years of their MRI.

Type: Observational

Start Date: Apr 2024

open study

Background: Some children/adolescents who have had a stem cell transplant live with chronic graft-versus-host-disease (cGVHD). cGVHD is a side effect of the transplant that can cause multiple bothersome symptoms and negatively affect a child/adolescent squality of daily life. The questionnaires that measure thesymptoms caused by cGVHD are designed for adults. Children/adolescents may not describe their symptoms in the same way. The goal of this research is to improve the way we measure how bothersome these symptoms are for children/adolescents living with cGVHD. Objective: To develop a questionnaire (The Pediatric cGHVD Symptom Scale) for children/adolescents living with cGVHD to identify the symptoms they are experiencing and describe how bothersome those symptoms are to them. An additional goal is to design a parent/guardian companion questionnaire that can be used to capture the symptom experiences of very young children who may not be able to complete a questionnaire. Eligibility: Children/adolescents ages 5-17 who are receiving treatment for cGVHD after a stem cell transplant, and their parent/guardian.. Design: This study consists of 2 projects. Children/adolescents with cGVHD and their parent/guardianparticipants will be grouped by the child/adolescent s age: 5-7, 8-12, and 13-17. In project 1, participants will complete an age-appropriate questionnaire about cGVHD symptoms. The questionnaire will ask about the child/adolescent s physical functioning and emotional well-being. The parent/guardian will out fill out a companion questionnaire online. The child/adolescent will then review their completed questionnaire during an interview with a researcher and will be asked whether the questions about their symptoms were difficult to understand. The parent/guardian and child/adolescent will then be interviewed together to further explore their responses to the questionnaires. Interviews will be done in person, by phone, and online. . Based on what is learned through these interviews, the wording of the questionnaire will be improved for better comprehension and ease of response. In project 2, participants will complete this revised questionnairefor their age group along with some other questionnaires that ask about quality of life. Both the child/adolescent and parent/guardian will fill out the questionnaires online at three separate time points. In both projects, children/adolescents with cGVHD and their parent/guardian participants will be grouped by the child/adolescent s age: 5-7, 8-12, and 13-17. ...

Type: Observational

Start Date: Oct 2019

open study

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

Type: Interventional

Start Date: Feb 2019

open study

Background: When children have severe irritability and temper outbursts, they can be so cranky or angry that it leads to problems at home, in school, and with friends. This is called Disruptive Mood Dysregulation Disorder (DMDD) and there have been no psychological treatments developed specifically for children with this problem. Researchers think two forms of therapy, Cognitive Behavioral Therapy (CBT) and Interpretation Bias Training (IBT), might help children with DMDD. Objective: To test two whether IBT and CBT can decrease severe irritability in children and youth. Eligibility: Children 8-17 years old with DMDD. Their symptoms must have started before age 10. Design: Participants will be screened with a review of their symptoms. Parents and participants will answer questions. Participants can do only one or both of these treatments if they wish. Those who wish to do both will start with IBT. Participants who do CBT will have 12-16 weekly meetings of research talk therapy. A parent will participate in part of the sessions. Participants will talk about what makes them irritable and how it affects them. They may be put in situations that might make them annoyed or irritable. Participants will rate how intense their irritability is. Parents and participants will complete rating scales, questionnaires, and interviews. Participants will do practice activities at home. Participants doing IBT will have up to 14 sessions over 10 weeks. Participants will view 15 faces, one at a time, on a computer. They will choose if the face looks happy or angry on a computer. Sometimes the computer gives feedback. Participants will complete some sessions at the NIH and some at home. Participants and parents answer questions about their progress.

Type: Observational

Start Date: Nov 2015

open study

This study is designed to establish a population of patients with Lyme disease for evaluation, treatment and follow-up to learn more about the infection. Patients with active Lyme disease may be eligible for this study. Participants will have a medical history and physical examination and diagnostic evaluations as appropriate to their individual condition. Laboratory tests may include routing blood and urine tests, X-rays, or other imaging studies, body fluid or tissue cultures, skin biopsy and tests for allergic or immune responses. Treatment will include only medications approved by the Food and Drug Administration, given according to accepted dose schedules and ways of taking the medicines. All diagnostic tests and treatments will be according to standard medical practice for the disease. No experimental procedures will be offered under this protocol. Patients will be followed as needed for evaluation and treatment of their condition. In general, they will be asked to return at the end of therapy, then 3, 6 and 12 months later, and then every 6 to 12 months. More frequent visits may be required or less frequent visits may be allowed, depending on the individual s condition. Participants may be asked to undergo the following additional procedures for research purposes: - Extra blood draws to study Lyme disease and other inflammatory conditions. Blood will be drawn from arm veins. The total amount drawn during any 6-week period will not exceed 450 cc (30 tablespoons) for adults and 7 cc (1/2 tablespoon) per kilogram (2.2 pounds) of body weight for children under 18 years of age. - Leukapheresis to collect large numbers of white blood cells. Whole blood is collected through a needle in an arm vein, similar to donating blood. The blood circulates through a machine that separates it into its components, and the white cells are removed. The rest of the blood is returned to the body through the same needle. Only adults 18 years of age and older will be asked to undergo leukapheresis.

Type: Observational

Start Date: Jan 2002

open study

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

Type: Observational

Start Date: Jun 1992

open study

This protocol is designed to evaluate selected patients with documented recurrent or unusual infections and their family members for clinical and laboratory correlates of immune abnormalities. It allows long term follow up of patients with host defense defects and permits the periodic study of their blood, urine, saliva, skin, stool and vaginal specimens or wound drainage from such patients or their family members for medically indicated purposes and research studies related to understanding the genetic and biochemical bases of these diseases. This protocol may help provide patients and materials for the development of therapies for these diseases. This study will: 1. Determine the biochemical and genetic causes of inherited immune diseases affecting phagocytes (white blood cells that defend against bacterial and fungal infections) 2. Try to develop better ways to diagnose and treat patients with these diseases, and to prevent, diagnose and treat their infections Patients and family members may undergo the following procedures: - A personal and family medical history, physical examination and other procedures, which may include various blood tests; urinalysis; saliva collection; imaging studies such as chest X-ray, computed tomography (CT) or magnetic resonance imaging (MRI); and lung function studies, dental examination or eye examinations, if medically indicated. - Patients who have draining wounds will have fluid collected from these wounds for biochemical study. - Tissues removed as part of medical care, such as pieces of lung, liver, or teeth, or biopsies of these tissues will be studied. - Patients who have an immune problem that investigators wish to study further will be asked to return to NIH for follow-up visits at irregular intervals, but at least every 6 months. The visits will include an updated medical history, examination directed at the particular medical problem related to the immune disorder, follow-up of abnormal tests or treatment, and collection of blood, saliva, urine, or wound fluid for study. - Patients may have genetic testing and must be willing to have specimens stored for future research. - Family members will have a medical history, saliva or urine collection, and chest X-ray or other imaging study, if medically indicated. - Normal volunteers who have had tissue biopsies or pieces of tissue removed as part of medical care, such as pieces of lung, liver, or teeth, will have these tissues studied. - NIH does not cover the cost of the initial screening visit for travel or lodging. A financial assessment may determine if the patient is eligible for financial assistance. This study does not enroll children under the age of 2. - Patients will be asked to obtain their medical records, previous test results, or imaging studies prior to the first visit.

Type: Observational

Start Date: Sep 1993

open study

Background: Prostate cancer may return after treatment in 30,000 to 50,000 people each year. There is no clear best way to treat these people. Better treatments are needed. Objective: To test a study drug (enzalutamide), both alone and combined with a second drug (PDS01ADC), in people with prostate cancer that returned after treatment. Eligibility: People aged 18 years and older with prostate cancer that returned after treatment. Design: Participants will be screened. They will have a physical exam, with blood tests. All their urine will be collected for 24 hours. They will have imaging scans of their chest, abdomen, pelvis, and bones. Their ability to perform everyday activities will be assessed. They may opt to give a stool sample. Participants will be treated in 4-week cycles. Enzalutamide is a pill taken by mouth once a day, every day. All participants will be given a supply of this drug to take at home. PDS01ADC is injected under the skin once a month, on the first day of each cycle. Half of the participants will receive both drugs. All participants will visit the clinic once a month. Each visit should last no more than 8 hours. Blood and urine tests will be repeated. All participants will receive the study treatment for 3 cycles. Some participants may need 3 more cycles of treatment with enzalutamide only. This re-treatment can be done only once. Participants will have a follow-up visit 1 month after they finish treatment. After that, they will have visits every 6 weeks for up to 5 years. Imaging scans and blood tests will be repeated. ...

Type: Interventional

Start Date: Apr 2024

open study

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

Type: Observational

Start Date: Sep 2022

open study

Background: When people see and hear, the brain changes signals from the eyes and ears into perceptions and thoughts. No one fully understands how this happens. Researchers want to explore how healthy brains process sights and sounds. Objectives: To explore how people understand what they see and hear when the brain processes sights and sounds. Eligibility: Participants aged 13-65 who have at least 20/40 vision in at least one eye and do not use a hearing aid. Design: Some participants will take tests online anonymously. They will do computer tasks related to colors and behavior. In-person participants will be screened with medical history and physical exam. They will complete questionnaires and vision and hearing tests. Participants will plan how many testing sessions they will have and when. Sessions last 2-5 hours. They may include: - Magnetic Resonance Imaging: Magnets and radio waves to take pictures of the brain. Participants will lie on a table that slides in and out of a tube. They will do a task during the scan. - Magnetoencephalography: Records magnetic field changes from brain activity. Participants will sit or lie down. A cone will be lowered onto their head. They may do a task during the test. - Electromyography: Electrodes attached to the skin will measure the electrical activity of muscles. - Electroencephalogram: Electrodes on the scalp will record brain waves. - Electrocardiography: Electrodes on the chest will record heart electrical activity. - Tests of memory, attention, thinking, vision, and hearing. - Eye Tracking: Cameras will follow participants eye movements. They may wear a cap with infrared cameras in front of their eyes. During the sessions, participants vital signs may be monitored.

Type: Observational

Start Date: Mar 2019

open study

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

Type: Observational

Start Date: Jul 2015

open study