Background: The microbiome is the bacteria and other microorganisms that live inside and on the body. The microbiome is important for our health. Researchers study how the microbiome help people stay healthy. They study how the microbiome affects the body when people get sick. To do this research, they need samples of the microbiome living on the bodies of many people. The purpose of this natural history study is to collect microbiome samples in a repository. These samples will be used for future research. Objective: To collect microbiome samples from the body that can be used for future research. Eligibility: People of any age. Only those older than 3 years will be seen at the NIH clinic. Design: Participants will fill out a questionnaire. Topics will include their medical history and foods they eat. Participants will be asked to give 1 or more of the following: Stool, urine, saliva, vaginal fluid, and breastmilk. These samples can be collected at home and sent to the researchers. Cells from participants cheek, nose, mouth, skin, rectum, and/or vagina. The cells may be collected by rubbing the area with a sterile cotton swab. These procedures can also be done at home. Blood. Blood may be drawn using a needle inserted into a vein in the arm. For young children, blood may be collected by a prick on the heel or finger. Intestinal tissue samples. These may be collected from participants who are having an endoscopy or colonoscopy for other reasons. Skin tissue samples. These may be collected from participants who are having biopsies for other reasons.

Type: Observational

Start Date: Mar 2023

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: - 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

Patients with hepatic steatosis due to alcohol will be offered liver biopsies when they enter a detoxification program. The first biopsy will occur in the first week of admission and the second in the fourth week when the steatosis has resolved. The hepatic transcriptome will be compared,

Type: Observational

Start Date: Aug 2026

open study

Background: The National Cancer Institute, part of the National Institutes of Health, has partnered with nine health care systems across the U.S. to establish the Connect for Cancer Prevention Study. While researchers have made important discoveries, there is more to learn to lower the number of people affected by cancer. By taking part in Connect, participants can help researchers learn how the way we live, our genetics, and our health history may affect cancer risk. Objective: To study and better understand the causes of cancer and to find new ways to prevent it. Eligibility: The study will include 200,000 adults who get their health care from a partner health care system, are between 30 and 70 years old at enrollment, and have never had cancer. People remain eligible to join if they have or once had non-melanoma skin cancer, or a condition that may raise cancer risk (such as ductal carcinoma in situ, or DCIS). Design: Eligible recruits can sign up for Connect online by creating an account on MyConnect using their email address or phone number. After creating an account, they will complete the informed consent process. All information shared through MyConnect is secure to protect participant privacy. After joining the study, participants will be asked to answer online health surveys a few times a year, donate samples of blood, urine, and saliva every two to three years, and safely share access to their electronic health records with Connect. In the future, participants may donate unused samples that are collected at clinical visits, like tissue, stool, or blood, and may mail in samples collected at home. Participants may also share information from personal health trackers, like wearable devices or apps. This information will help researchers study the health and behavior patterns that may affect cancer risk. It takes time to understand the causes of cancer, so Connect will go on for many years. The longer people participate, the more researchers may learn. Participants can leave the study at any time. Learn more about Connect by visiting cancer.gov/connectstudy.

Type: Observational

Start Date: Jul 2021

open study

Background: - Inflammation is how the body reacts to infection or injury. Infections or inflammation in the brain and nerves can be serious. There aren t always good tests to detect this. Researchers want to learn more about how diseases affect the brain and nerves to develop better tests and treatments. Objective: - To learn more about how inflammation and infections hurt the brain and nervous system. Eligibility: - People at least 2 years old with a diagnosis or suspected diagnosis of nervous system infection or inflammation. Design: - For some participants, a clinician outside of NIH will collect blood, tissue, and other samples. These will be sent to NIH and analyzed. - Other participants will have several visits to NIH. Children may not have all these tests. - Participants will have: - Medical history. - Physical and neurological exam. - Blood and urine samples collected. - Saliva collected. They will chew on a piece of sterile cotton for one minute. - Magnetic resonance imaging (MRI) scan. The scanner is a metal cylinder in a strong magnetic field. Participants will lie on a table that slides in and out of the cylinder. Participants will get a contrast agent through an intravenous (IV) catheter during the MRI. A needle will be used to guide a thin plastic tube (catheter) into an arm vein. - Lumbar puncture. Skin will be numbed and a needle will be inserted into the space between the bones in the back. Fluid will be removed. - Some participants may have optional study procedures. These may include eye tests, memory and thinking testing, tests with electrodes on the head, or skin biopsy.

Type: Observational

Start Date: May 2015

open study

Background: - Researchers are studying types of thyroid cancer that seem to cluster in families. Non-medullary thyroid cancer accounts for the vast majority of all types of thyroid cancer, but little is known about possible genes that may cause the cancer. More research is needed to develop the best ways to screen for familial non-medullary thyroid cancer (FNMTC) so that it can be diagnosed and treated at an early stage. Objectives: - To evaluate the natural history of FNMTC. - To determine the best screening strategy for FNMTC. - To identify genes that may indicate susceptibility to FNMTC. Eligibility: - Individuals at least 7 years of age who have two first-degree relatives (e.g., parents, children, siblings) who have or have had non-medullary thyroid cancer or a documented diagnosis of non-medullary thyroid cancer and one living relative with documented non-medullary thyroid cancer. Design: - Participants will be evaluated by family history pedigree, physical examination, imaging (including possible neck ultrasound and radioactive iodine scans), and laboratory testing. - Participants who agree to have blood or other biological samples collected will be asked to enroll in an additional study to provide the appropriate samples and tissues. - After the initial study evaluation, participants who are not found to have a malignant thyroid tumor will be re-screened every year with non-invasive imaging studies. Participants who are found to have a malignant thyroid tumor will be informed of possible treatment options.

Type: Observational

Start Date: Aug 2010

open study

Background: - Previous studies have shown that people with certain types of brain damage may have particular problems paying attention and processing things that they see. Researchers are interested in comparing how people with brain damage and without brain damage process visual images. Objectives: - To better understand the areas of the brain involved in paying attention to things that are seen. Eligibility: - Individuals at least 18 years of age who either have had damage to one or both sides of specific parts of the brain (e.g., stroke, injury, certain neurosurgery procedures) or are healthy volunteers. Design: - The study involves 4 to 10 visits to the NIH Clinical Center over 1 to 2 years. Each visit will last approximately 2 hours. - Participants will be screened with a medical history and physical examination, and may have the cognitive testing described below during the same visit. - On the first visit and for at least one visit thereafter, participants will have cognitive testing to evaluate thinking and memory. These tests will be either written tests or computer-based tests. - Some participants will qualify for functional magnetic resonance imaging (fMRI) as part of the study. This part will involve a decision-making task that will be performed on a computer during the fMRI scan. Additional scans may be required as directed by the study doctors. - Some randomly selected participants will be asked to have magnetoencephalography (MEG), a procedure to record very small magnetic field changes produced by brain activity. - During the behavioral training, or fMRI or MEG scanning, participants may be monitored with equipment to track eye movements.

Type: Observational

Start Date: Jul 2012

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

Background: Hypereosinophilic syndrome (HES) is a blood disorder that causes high levels of white blood cells called eosinophils. HES can damage the lungs and airways, intestines, skin, and other organs. The current primary treatment for HES can cause serious side effects. Secondary treatments do not work in all people. Objective: To test an approved drug (dupilumab), combined with other drugs, in people with HES. Eligibility: People aged 18 years and older who take drugs (mepolizumab, reslizumab, or benralizumab) to treat HES. Design: Participants will have up to 6 clinic visits and 7 remote visits in up to 48 weeks. Participants will be screened. They will have blood and urine tests. They will have a test of their heart function. They will take surveys about how HES affects their daily life. Some participants may have a bone marrow biopsy: A sample of tissue and fluid from inside a bone will be removed with a large needle. Participants will have other tests specific to their symptoms. For example, those with symptoms affecting their lungs will have breathing tests. Others may have tests that target symptoms in their sinuses, gastrointestinal tract, or skin. Dupilumab is injected under the skin once every 1 or 2 weeks. Dose and timing will vary among participants. They will be taught how to inject themselves at home between clinic visits. They will take dupilumab plus their current medications for 24 weeks. If the drug is helping them, they will continue taking it for another 24 weeks. Participants will have a final visit 12 weeks after their last dose.

Type: Interventional

Start Date: Feb 2025

open study

Background: During a transplant, blood stem cells from one person are given to someone else. The cells grow into the different cells that make up the immune system. This can cure people with certain immunodeficiencies. But transplant has many risks and complications. Objective: To see if stem cell transplant can be successfully performed in people with primary immunodeficiency disease and cure them. Eligibility: People ages 4-69 for whom a primary immunodeficiency (PID) or Primary Immune Regulatory Disorder (PIRD), has caused significant health problems and either standard management has not worked or there are no standard management options, along with their donors Design: Donors will be screened under protocol 01-C-0129. They will donate blood or bone marrow. Participants will be screened with: Medical history Physical exam Blood, urine, and heart tests CT or PET scans Before transplant, participants will have dental and eye exams. They will have a bone marrow biopsy. For this, a needle will be inserted through the skin into the pelvis to remove marrow. Participants will be hospitalized before their transplant. They will have a central catheter put into a vein in their chest or neck. They will get medications through the catheter to prevent complications. Participants will get stem cells through the catheter. They will stay in the hospital for at least 4 weeks. They will give blood, urine, bone marrow, and stool samples. They may need blood transfusions. They may need more scans. They will take more medications. Participants will have visits on days 30, 60, 100, 180, and 360, and 24 months after the transplant. Then they will have visits once a year for about 5 years

Type: Interventional

Start Date: Sep 2020

open study

Objective The current proposal investigates behavioral, psychophysiological, and social processes that may help explain biases and disparate outcomes in pain. Health disparities, or health outcomes that adversely affect disadvantaged populations, are pervasive and apparent in many diseases and symptoms, including pain. Pain is the number one reason individuals seek medical treatment. Health disparities in pain encompass both differences in pain experience and treatment for pain. For instance, research indicates that Black individuals report increased pain and have reduced pain tolerance relative to White individuals, yet doctors are less likely to treat minority patients pain and underestimate their pain experience. This project aims to address this systemic discrepancy by focusing on interpersonal processes that may contribute to these disparities, including socially-relevant responses to pain (i.e. pain expression) and pain assessment (e.g. visual attention). The proposed research aims to determine whether the study of pain expressions and their assessment can yield insights on how social factors shape pain and its treatment. Further, we test the efficacy of potential interventions designed to improve accuracy and reduce biases in pain assessment. If successful, this work will form the foundation of a new research program that will link the field of pain research with the field of social neuroscience, and forge new insights on the critical problem of health disparities in pain. Study population We will accrue up to 700 total healthy volunteers to target 240 completers Design Our overall aim is to understand how social factors influence the assessment and management of pain, and to gain insight into psychosocial processes that may underlie health disparities in pain. We propose a series of studies designed to test these links. First, we will measure pain perception and physiological responses to painful stimuli in a diverse group of individuals to test for sociocultural and biological influences on pain and pain-related responses. In subsequent studies, new participants ("perceivers") will view images of these initial participants ("targets") and will provide estimates of 'targets' pain experience. We will measure a) whether perceivers can accurately estimate 'targets' pain experience; b) whether accuracy differs as a function of similarity between target and perceiver (ingroup vs outgroup); and c) whether individuals can improve accuracy through feedback. Outcome measures Primary outcome measures for all experiments will be decisions about pain (experienced by self or other) measured with visual analogue scales, reaction time, and/or categorical judgments (pain/no pain). We will also measure physiological responses (e.g., facial muscle response, skin conductance, pupil dilation) and brain responses using functional magnetic resonance imaging (fMRI) as secondary outcome measures. We will test whether pain and pain-related responses varies as a function of sociocultural/demographic factors (e.g. race, ethnicity, sex) and whether accuracy in assessing others' pain is influenced by group similarity (i.e. ingroup vs. outgroup) and training (e.g. performance-related feedback)....

Type: Interventional

Start Date: May 2018

open study

Study Description: Heart and lung transplants can save lives, but long-term success is often limited by organ rejection that is hard to detect early. This study is testing a new, non-invasive blood test that looks for small pieces of DNA from the donor organ in the patient s blood. We believe higher levels of this donor DNA may signal early rejection before damage becomes permanent. Hypothesis: We believe that measuring donor-derived DNA in the blood can help detect early signs of rejection and improve outcomes for transplant patients. The study also collects genetic and biological samples to explore why some people are more at risk of complications after transplant. This may help guide future research and treatments. Who Can Join the Study: People receiving a heart or lung transplant (or both), age 14 and older People who are within three months of their transplant People who can understand and agree to take part in the study Participants will be asked to provide blood and other samples, and some of these will be used in lab research to explore new ideas about how and why transplant rejection happens. This research could lead to better ways to monitor and treat patients after a heart or lung transplant - and help improve long-term survival and quality of life....

Type: Observational

Start Date: Jun 2015

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: The way the brain processes rewards and punishments may play a role in some disorders of the nervous system. People with chronic overlapping pain conditions (such as myalgic encephalomyelitis/chronic fatigue syndrome [ME/CFS]) may have heightened responses to unpleasant, punishing sensations. Some of these conditions may also cause heightened responses to effort; this is an unpleasant sensation felt during physical and mental exertion. Objective: To learn more about how the brain processes different unpleasant sensations. Eligibility: People aged 18 to 50 years with ME/CFS. Healthy volunteers are also needed. Design: Participants will have 3 visits in 1 to 5 weeks. Visit 1: Participants may have a neurologic exam. They will have a mock magnetic resonance imaging (MRI) scan. They will lie on a bed in a wooden tube while they practice 2 tasks: Thermal pain rating: A device that creates mild to moderate heat will be placed on one leg. Physical effort rating: Participants will squeeze a plastic bar with different levels of force. Visit 2: Participants will have a real MRI scan. They will lie on a table that slides into a large tube. Visit 3: Participants will have another MRI scan. They will repeat the thermal pain and physical effort tasks while in the scanner. Sensors will be placed on 1 arm to measure how the muscles function as they squeeze the bar. Their heart rate will be tested: They will hold their finger against a camera lens for 1 minute. They will do 2 other tasks: 1 requires repeatedly pressing a key on a keyboard, and the other requires squeezing a bar.

Type: Interventional

Start Date: Apr 2025

open study

Background: Pyrimidine and purine metabolism disorders (DPPMs) affect how the body metabolizes chemicals called pyrimidines and purines. DPPMs can cause dysfunctions throughout the body, especially in the brain, blood, kidneys, and immune system. People with DPPMs might have no symptoms, mild symptoms, or they may have severe, chronic symptoms, that can be fatal. DPPMs are not well understood, and researchers want to learn more about what causes them and how to treat them. Objective: To learn more about factors that affect DPPMs by comparing test results from affected, uaffected family members, and healthy people. Eligibility: Three types of participants are needed: people aged 1 month and older with DPPMs; their family members who do not have DPPMs; and healthy volunteers. Design: Participants with DPPMs will come to the clinic once a year; some may be asked to come more often. At each visit, all affected participants will have a physical exam and give samples of blood, urine, saliva, and stool. Depending on their symptoms, they may also have other procedures, such as: Swabs of their skin and inside the mouth. Tests of their heart, kidney, brain, and nerve function. Questionnaires about what they eat. Dental exams, and exams of their hearing and vision. Tests of their learning ability. Monitoring of their physical activity. Imaging scans. Photographs of their face and body. These tests may be spread over up to 7 days. Affected participants may remain in the study indefinitely if they wish to. Healthy volunteers and family members will have 1 study visit. They will have a physical exam and may be asked to give blood, urine, saliva, and stool samples.

Type: Observational

Start Date: Dec 2023

open study

Background: Lipodystrophy (LD) syndromes are a group of rare disorders that affect how a person s body can store and use fat tissue. Many people with LDs become severely insulin resistant. Some people are insulin resistant because of a variant in the insulin receptor gene. Insulin resistance causes many health problems. Objective: To learn if blocking the effects of growth hormone in the body will help people with severe insulin resistance. Eligibility: Adults aged 18 to 65 years with either a known variant in the insulin receptor gene or with a diagnosis of partial LD. Design: Participants will have 2 hospital stays, about 1 month apart. Each stay will be 3 or 4 nights. During each hospital stay, participants will have many tests. They will have a physical exam with blood tests. They will have all of their urine collected for a 24-hour period. They will have scans to measure their muscle, bone, and fat tissues. They will have tests to measure metabolism and insulin sensitivity. They may have an optional biopsy of fat tissue. During the first hospital visit, participants will learn how to give themselves shots of a drug (pegvisomant) that blocks growth hormone. The drug is injected under the skin. Participants will continue to give themselves these shots once a day at home. After the first hospital visit, participants will talk on the phone with members of the study team once each week. After 2 weeks they will have blood drawn for tests. Participants will stop the shots after the second hospital visit.

Type: Interventional

Start Date: Jan 2023

open study

Background: Some people with the same disorder on a genetic level have more complications than others. Researchers want to look for a link between the PKLR gene and sickle cell disease (SCD) symptoms. The PKLR gene helps create a protein, called pyruvate kinase that is essential in normal functioning of the red blood cell. Differences in the PKLR gene, called genetic variants, may cause some changes in the pyruvate kinase protein and other proteins, that can affect functioning of the red blood cell adding to the effect of SCD. Researchers can study these differences by looking at DNA (the material that determines inherited characteristics). Objective: To study how the PKLR gene affects sickle cell disease. Eligibility: Adults ages 18-80 of African descent. They may have sickle cell disease or not. They must not have had a transfusion recently or have a known deficiency of pyruvate kinase. They cannot be pregnant. Design: Participants will be screened with questions. Participants will have blood drawn by needle in an arm vein. The blood will be genetically tested. Not much is known about how genes affect SCD, so the test results will not be shared with participants or their doctors. ...

Type: Observational

Start Date: Oct 2018

open study

Background: Neurofibromatosis 1 (NF1) is a disease that causes tumors to grow along the nerves. These include plexiform neurofibromas (pNF) and cutaneous neurofibromas (cNF). Both pNF and cNF can be visible to other people. These tumors can affect a person s appearance and quality of life. Researchers want to be able to assess changes in appearance before and after treatment for NF1 tumors. Objective: To see if two questionnaires can help assess people's ratings about the appearance of their pNF and cNF tumors. Eligibility: People aged 8 years and older with pNF and people 12 years and older either with cNF or both pNF and cNF. Adult caregivers of children with pNF and cNF are also needed. Design: Participants will complete questionnaires on paper or by phone, computer, or tablet. They will answer questions about how they look, how they feel, and how they feel about the way they look. Participants will meet in at least 1 remote focus group or individual interview. The meeting will last about 1 hour. Each group will include 3 to 5 people, organized by age: 8 to 11 years, 12 to 17 years, 18 to 29 years, and over 30 years. Adult caregivers will meet in a group with other caregivers. They will discuss their NF1 symptoms; how their tumors look; how they feel about the way their tumors look; and their daily activities. They will give their opinions about 2 questionnaires about appearance. The group and individual meetings will be audio-recorded and transcribed. Information that can reveal individual identities will be removed.

Type: Observational

Start Date: Apr 2025

open study

Background: RASopathies are a group of genetic diseases that affect a child s development. They cause physical, cognitive, and behavioral symptoms. Caring for a child with a RASopathy can be stressful. Acceptance and Commitment Therapy (ACT) is a therapy that helps people become more aware and accepting of difficult thoughts and feelings. ACT has been found to be helpful for parents with high parenting stress. Objective: To find out if Acceptance and Commitment Therapy (ACT) can help caregivers of children with a RASopathy better cope with parenting stress. Eligibility: People aged 18 years or older who care for a child (younger than 18 years) with a RASopathy. The child must live with the caregiver at least 50% of the time. Design: The study is fully remote. Participants need a mobile device that can play audio and video and connect to the internet. They can borrow an iPod if needed. Participants will download a free app called MetricWire. They will use this app to watch videos and answer questions. The first 8 participants will be in a pilot study. They will receive the ACT intervention starting the first week after they begin the study. After the pilot study, we will start a new phase called the randomized trial. In this phase, participants will have a 50-50 chance of being in the group that will start the intervention right away or the group that will start the intervention after about 2 months. Participants will fill out surveys on 5 random days each week. These surveys have 7 questions and take about 2 minutes. They will also fill out 3 longer questionnaires: once before ACT begins, once just after the 8-week study period, and once about 3 months later. Questions will cover topics including: Parenting stress Life satisfaction Self-compassion Uncomfortable feelings and thoughts Mindfulness Participants will take part in an 8-week ACT intervention. They will have one 75-minute session with an ACT coach in the first week. Participants will watch 9- to 17-minute videos each week. The videos talk about how to practice ACT techniques to cope with parenting stress. Participants will have 20- to 30-minute coaching sessions in weeks 3 and 6. The coach will help them practice exercises and work through any problems.

Type: Interventional

Start Date: Jan 2024

open study

Background: Rare tumors of the genitourinary (GU) tract can appear in the kidney, bladder, ureters, and penis. Rare tumors are difficult to study because there are not enough people to conduct large trials for new treatments. Two drugs-sacituzumab govitecan (SG) and atezolizumab-are each approved to treat other cancers. Researchers want to find out if the two drugs used together can help people with GU. Objective: To test SG, either alone or combined with atezolizumab, in people with rare GU tumors. Eligibility: Adults aged 18 years and older with rare GU tumors. These may include high grade neuroendocrine carcinomas; squamous cell carcinoma of the bladder; primary adenocarcinoma of the bladder; renal medullary carcinoma; or squamous cell carcinoma of the penis. Design: Participants will be screened. They will have a physical exam with blood and urine tests. They will have tests of heart function. They will have imaging scans. They may need a biopsy: A small needle will be used to remove a sample of tissue from the tumor. Both SG and atezolizumab are given through a tube attached to a needle inserted into a vein in the arm. All participants will receive SG on days 1 and 8 of each 21-day treatment cycle. Some participants will also receive atezolizumab on day 1 of each cycle. Blood and urine tests, imaging scans, and other exams will be repeated during study visits. Treatment may continue for up to 5 years. Follow-up visits will continue for 5 more years.

Type: Interventional

Start Date: Aug 2024

open study

Background: Many cancers of the testicles and urinary tract are rare diseases; these are diseases that affect less than 200,000 people in the United States. It can be hard to study treatments for these diseases. One combination of drugs-enfortumab vedotin (EV) and pembrolizumab-has already been approved to treat some urinary cancers. Researchers want to see if they can help people with other types of testicle and urinary cancers. Objective: To test EV, with or without pembrolizumab, in patients with rarer cancers of the testicles or urinary tract. Eligibility: People aged 18 and older with rarer cancers of the testicles or urinary tract. Design: Participants will be screened. They will have a physical exam with blood and urine tests. Their ability to perform normal daily activities will be tested. They will have exams of their skin and eyes. They will have imaging scans. A biopsy may be needed: A sample of tissue will be removed from the tumor. The study drugs are both given through a tube attached to a needle inserted into a vein in the arm. Some participants will receive treatments 3 times during 28-week cycles; others will receive treatments 2 times during 21-day cycles. All participants may continue to receive treatments for up to 5 years. Imaging scans and other tests will be repeated. Participants who stop taking the drugs will have follow-up visits every 3 to 4 weeks until the disease gets worse. They will have imaging scans and blood tests. After that, follow-up visits will continue by phone every 3 months for up to 5 years after study therapy is finished.

Type: Interventional

Start Date: Jan 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: Metastasis is the spread of cancer from one organ to a nonadjacent organ. It causes 90% of cancer deaths. No treatment specifically prevents or reduces metastasis. Researchers hope a new drug can help. It stops cancer cells from growing and spreading further and possibly shrink cancer lesions in distant organs. Objective: To find a safe dose of metarrestin and to see if this dose shrinks tumors. Eligibility: Adults age 18 and older with pancreatic cancer, breast cancer, or a solid tumor that has not been cured by standard therapies. Also, children age 12-17 with a solid tumor (other than a muscle tumor) with no standard therapy options. Design: Participants will be screened with: - blood tests - physical exam - documentation of disease confirmation or tumor biopsy - electrocardiogram to evaluate the heart - review of their medicines and their ability to do their normal activities Participants will take metarrestin by mouth until they cannot tolerate it or stop to benefit from it. They will keep a medicine diary. Participants will visit the Clinical Center. During the first month there are two brief hospital stays required with visits weekly or every other week thereafter. They will repeat some of the screening tests. They will fill out questionnaires. They will have tests of their cognitive function. They will have an electroencephalogram to record brain activity. They will have a computed tomography (CT) scan or magnetic resonance imaging (MRI). A CT is a series of X-rays of the body. An MRI uses magnets and radio waves to take pictures of the body. Adult participants may have tumor biopsies. Participants will have a follow-up visit 30 days after treatment ends. Then they will have follow-up phone calls or emails every 6 months for the rest of their life or until the study ends.

Type: Interventional

Start Date: Oct 2020

open study

Background: Neurodegenerative disorders can lead to problems in movement or memory. Some can cause abnormal proteins to build up in brain cells. Researchers want to understand whether these diseases have related causes or risk factors. Objective: To test people with movement or thinking and memory problems to see if they are eligible for research studies. Eligibility: People ages 18 and older with a neurodegenerative disorder associated with accumulation of TDP-43 or Tau proteins Design: Participants will have a screening visit. This may take place over 2-3 days. Tests include: Medical history Physical exam Questions about behavior and mood Tests of memory, attention, concentration, and thinking Movement measurement. The speed at which participants can stand up from a chair, tap their finger and foot, and walk a short distance will be measured. Some movements will be videotaped. They will be videotaped while they speak and read a paragraph. Blood tests. This might include genetic testing. Lung and breathing tests MRI. They will lie on a table that slides into a cylinder that takes pictures of the body. Some participants will get a dye through IV. Electromyography. A thin needle will be inserted into the muscles to measure electrical signals. Nerve tests. Small electrodes on the skin record muscle and nerve activity. A small piece of skin may be removed. A skin or blood sample may be taken to create stem cells. Optional lumbar puncture. A needle will be inserted into the space between the bones of the back to collect fluid. If participants are not eligible for current studies, they may be contacted in the future.

Type: Observational

Start Date: Oct 2017

open study