Background: Congenital myasthenic syndromes (CMSs) are a group of inherited disorders that affect how the nerves communicate with muscles. These can cause many problems that affect how people can move and use their bodies. Objective: This is a natural history study to learn more about how CMSs affect the body and cause changes over time. Eligibility: People aged 6 months or older with a CMS. The study will focus on DOK7- and COLQ-related CMSs, as well as other forms. Design: Participants will have up to 7 visits in 5 years. At each visit, participants will undergo many tests, including: Physical exam with blood and urine tests. Tests of their heart and lung function. Exams of the eyes, lungs, muscles, and nerves. These will be done with different specialists. Exams of the arms and hands and of body use and movements. These will also be done with specialists. Photos and videos may be taken. Muscle ultrasound. Participants will lie still as a wand is rubbed over their skin. Magnetic resonance imaging (MRI) scans. Participants will lie still on a bed that slides partway into a large tube. A parent or other person may remain in the room, too. The scan will take 60 minutes. Electromyography (EMG). Participants will lie still or may be asked to move around. A machine will measure the electrical activity in their muscles. An activity monitor may be placed on the participant s wrist, ankle, or hip for up to 2 weeks. The monitor is about the size of a wristwatch. A sample of skin may be removed....

Type: Observational

Start Date: May 2025

open study

Dermatomyositis (DM) is a rare autoimmune disease that causes muscle weakness, skin rashes, and other symptoms. Researchers think both genetic and environmental factors play a role in this disease. They want to find out more about how diet and lifestyle choices affect people with DM/JDM. Objective: To see if omega-3 fatty acid supplements from fish oil, combined with a healthy diet, can help people with DM/JDM. Eligibility: Adults 18-60 years old, who live in the United States, can read English, and access Internet to complete questionnaires can participate. Design: Participants will have 5 or 6 inpatient visits. For 5 visits they may need to stay in the Clinical Center for up to 5 days. Participants will be screened. They will have a physical exam with blood, urine and stool tests. They will have tests of their heart and lung function. Their muscle strength will be measured. They may have an imaging scan of their thighs and pelvis. They will complete online questionnaires about their health and lifestyle. They may complete two optional skin biopsies. Participants will take 4 small capsules by mouth twice a day for up to 6 months. The capsules will contain omega-3 fatty acids from fish oil or a placebo. The placebo looks just like the regular capsule but contains no active ingredients. Participants will not know which capsules they are taking. They will follow a healthy diet based on the General Healthy Eating Pattern. Participants will receive dietary coaching and will have virtual check-ins throughout the study. For two 7-day periods, they will wear a watch-like device to track their daily activity and sleep patterns. Participants may opt to remain in the study for an additional 12 weeks. All will receive the fish oil supplements during this stage.

Type: Interventional

Start Date: Jul 2026

open study

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

Type: Observational

Start Date: Mar 2023

open study

Background: A movement disorder is a condition that causes a person s body to move in ways that are not normal. There are different types. Some disorders cause movements people can t control, such as tics or shaking. Some cause reduced or slow movements. Movement disorders can cause disability in people. Sometimes members of the same family will have the same disorder. Researchers want to learn more about how people develop these disorders. This research could lead to better treatments. Objective: This natural history study will collect data on people with different types of movement disorders. It will also collect data on their family members. The data will support further research. Eligibility: Children and adults aged 2 years and older who have a movement disorder. Family members of people with movement disorders are also needed. Design: Participants will undergo screening. They will have a physical exam. Researchers will look at their existing medical images. Any photographs or videos of their movements will also be reviewed. Most participants will come to the NIH clinic for only 1 visit. They will answer questions about their condition. They will have normal tests used to diagnose their condition. They may have blood tests and different types of imaging scans. They may have tests to see how well their nerves function. The tests used will depend on the type of disorder they have. Family members will have some of the same tests as people with disorders. Participants will not receive any new treatments. Some participants may be asked to return for a follow-up visit. Up to 4000 people may participate.

Type: Observational

Start Date: Oct 2022

open study

Background: Some genetic diseases put increase the risk of heart and blood diseases, which are the number one cause of death and disability in the U.S. Researchers want to study diseases of the heart and/or blood vessels. They want to collect data and specimens from affected people, their family members, and healthy people. Objective: To study diseases of the heart and/or blood vessels. Eligibility: People age 2 and older who may have genetic disease affecting the heart and/or blood vessels Their relatives Healthy volunteers Design: Participants will be screened with a medical history, physical exams, and imaging tests. Participants may have a few visits or visits for 2 weeks or more. This will depend on their age and disease status. Visits may include: Photographs of the face and body Heart tests Samples taken of blood, urine, saliva, skin, and/or tissue Scans. For some, a dye may be injected into a vein. A six-minute walk test Lung tests. For some, participants will blow into a tube. For others, they will breathe in a gas from a mask, have a small injection, then have a scan. Stress tests while walking on a treadmill or riding a stationary bike Ultrasound of veins and arteries Devices outside the body testing the stiffness and function of arteries Eye exam and eye tests. For some, a dye may be injected in a vein. Blood pressure tests Measurements of blood flow under the skin and in the arms and fingernail blood vessels Devices outside the body testing flexibility of the blood vessels and skin, and skin temperature

Type: Observational

Start Date: Jul 2018

open study

Background: Prostate cancer is one of the most common cancers for men in the U.S. There are some new ways to take pictures of the cancer. There are also new ways to use image-guided biopsy and therapy. These could help manage prostate cancer. Researchers want to study how imaging can provide a profile of prostate cancer. They want to collect data to make diagnosis and treatments better. Objectives: To gather data about the radiological and clinical course of prostate cancer. To study imaging-based biomarkers of prostate cancer. Eligibility: Men ages 18 and older with diagnosed or suspected prostate cancer Design: Participants will give permission for researchers to use their medical history and records. Their data will be reviewed, collected, and analyzed. These include results of their tests and scans. Sponsoring Institution: National Cancer Institute

Type: Observational

Start Date: Feb 2018

open study

Background: - The third molars (wisdom teeth) normally grow in during late adolescence or early adulthood. Many people need or choose to have these teeth removed with oral surgery. Normally, the removed teeth and tissue are thrown away as medical waste. However, oral health researchers want to collect the teeth and tissue for research. They also want to encourage dentists at the National Institutes of Health to improve their skills in oral surgery. This study will collect the teeth and tissue of people who need to have oral surgery to remove their wisdom teeth. Objectives: - To provide continued dental skills training for dentists at the National Institutes of Health. - To collect teeth and tissue samples following wisdom tooth removal surgery. Eligibility: - Individuals between 16 and 50 who need to have their wisdom teeth removed. Design: - This study will involve a minimum of three visits. There will be a screening visit, a surgery visit, and at least one follow-up visit. - Participants will be screened with a physical exam and medical history. A full dental exam with x-rays will be given to evaluate the need for surgery. - At the second visit, participants will have oral surgery to remove their wisdom teeth. The teeth and tissue removed during the surgery will be collected for study. - Participants will receive drugs to control the pain after surgery. They will also be able to contact a dentist if there are any problems. - Between 7 and 21 days after surgery, participants will have a followup visit to check the healing. If they are having no problems, this will be the last visit. If there are any postsurgery issues, they will be scheduled for additional visits as needed.

Type: Observational

Start Date: Jun 2013

open study

This study will allow National Eye Institute (NEI) doctors the opportunity to examine people with eye disease, whether the diagnosis is known or not, to determine if they are eligible for other NEI research studies. No treatment is offered in this study. People of all ages with various eye conditions, including genetic conditions, eye movement disorders, inflammatory eye diseases, retinal diseases and external eye diseases, may be eligible for this study. Participants undergo various tests and procedures to diagnose or evaluate their eye disease. The procedures may include the following: - Personal and family medical history - Physical examination and blood tests, including genetic testing. - Eye examination with dilation to measure visual acuity and eye pressure and to examine the front and back parts of the eye. - Questionnaire about vision and daily activities. - Conjunctival swab or lacrimal bland biopsy, or both: A sample of cells from the eyes is collected by swabbing the surface of the eye or by surgically removing a small sample of the surface of the eye or tear gland. - Electroretinogram to examine retinal function: The subject sits in the dark with his or her eyes patched for 30 minutes. The patches are removed, the surface of the eyes is numbed, and contact lenses that can sense signals from the retina are placed on the eyes. The subject then watches flashing lights. - Fluorescein angiography to examine the blood vessels in the eye: A dye is injected into a vein in the arm. The dye travels through the veins to the blood vessels in the eyes. A camera takes pictures of the dye as it flows through the blood vessels. - Optical coherence tomography to measure retinal thickness: A machine used to examine the eyes produces cross-sectional pictures of the retina. - Microperimetry to test how sensitive different parts of the retina are to changing levels of light. The subject sits in front of a computer and presses a button when he or she sees a light on the screen. - Oculography to record eye movements: Eye movements are measured by contact lenses or goggles that the subject wears while watching a series of spots on a computer screen.

Type: Observational

Start Date: Aug 2008

open study

This study will explore the causes of rheumatic diseases and why many of them affect certain minority communities more severely. Rheumatic diseases may cause joint pain, stiffness or swelling. Some can involve bones, muscles, tendons or ligaments. Some cause abnormalities of the immune system-the body s defense against disease. Some rheumatic diseases are painful or deforming and some can be life threatening. Information obtained from this study will be used to learn about the disparities in rheumatic disease in the minority community and to design further, more targeted, research studies to address this issue. Patients with known or suspected rheumatic disease 18 years of age or older may be eligible for this study. Candidates will undergo a medical history and physical examination to confirm the diagnosis of rheumatic disease and determine what is needed for evaluation and treatment. Participants will receive standard medical care for rheumatic disease and arthritis. No experimental treatments, medications or procedures will be included in this study. Procedures may include routine blood tests for blood chemistries, cell counts, and antibodies commonly found in patients with rheumatic disease; a urine test for proteins and cells; and X-rays and other imaging tests to check for abnormalities in the lungs or other organs. All medical information will be kept confidential. Patients who are found to be eligible for other current NIH research studies will be offered an opportunity to participate in these studies.

Type: Observational

Start Date: Oct 2001

open study

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

Type: Interventional

Start Date: Jul 2026

open study

Background: Chronic lymphocytic leukemia (CLL),small lymphocytic lymphoma (SLL) and B-cell acute lymphoblastic leukemia or lymphoma (ALL) are blood cancers that affect certain white blood cells. Advanced forms of these diseases are difficult to treat. CD19 is a protein often found on the surfaces of these cancer cells. Researchers can modify a person's own immune cells (T cells) to target CD19. When these modified T cells are returned to the body-a treatment called anti-CD19 chimeric antigen receptor (CAR) T cell therapy-they may help kill cancer cells. Objective: To test anti-CD19 CAR T cell therapy in people with CLL or SLL and ALL. Eligibility: People aged 18 years and older with CLL or SLL and ALL that has not been controlled with standard drugs. Design: Participants will be screened. They will have imaging scans and tests of their heart function. If a sample of tissue from their tumor is not available, a new one may be taken; the sample will be tested for CD19. Participants will receive a drug to reduce the leukemia cells in their blood. Then they will undergo apheresis: Blood will be taken from the body through a needle. The blood will pass through a machine that separates out the T cells. The remaining blood will be returned to the body through a different needle. The collected T cells will be gene edited to make them attack cells with CD19. Participants will take drugs to prepare them for treatment for 3 days. These drugs will start 5 days before the treatment. Then their own modified CAR T cells will be returned to their bloodstream. Participants will stay in the hospital for at least 9 days after the treatment. Follow-up visits will continue for 5 years.

Type: Interventional

Start Date: Sep 2024

open study

Background: Runt-related transcription factor 1 (RUNX1) gene regulates the formation of blood cells. People with mutations of this gene may bleed or bruise easily; they are also at higher risk of getting cancers of the blood, bone marrow, and lymph nodes. Objective: The purpose of the study includes determining which dose of imatinib is best for people with pathogenic or likely pathogenic RUNX1 mutations without blood cancers, and to determine whether there are any changes in platelet function and inflammatory markers. Eligibility: Adults aged 18 and older with RUNX1 mutations. Healthy people without this mutation, including family members of affected participants, are also needed. Design: Participants with the RUNX1 mutation will be screened. They will have a physical exam with blood tests. They will have a test of their heart function. They may need a new bone marrow biopsy if they haven't had one in the past year. Imatinib is a tablet taken by mouth once a day, every day, at home. Affected participants in different parts of the study will take imatinib for either 28 days or up to 84 days. They will fill out questionnaires about how they are feeling. For the first part of the study, participants will have blood tests every 2 weeks, either at home or at the NIH, while they are taking the imatinib. They will have a follow up visit, at home or at the NIH, when they are done taking imatinib on Day 28. Participants on the second part of the study will come to NIH on days 1 and days 84. They will have blood tests every 2 weeks (at home or the NIH) while they are taking imatinib. They may opt to have a bone marrow biopsy repeated after they finish their course of imatinib. Participants will have a follow-up visit (at home or the NIH) 30 days after they stop taking imatinib. Participants who do not have the RUNX1 mutation will have 1 clinic visit. They will have blood tests. They will fill out questionnaires. They may opt to have a bone marrow biopsy.

Type: Interventional

Start Date: Dec 2023

open study

Background: Myelodysplastic syndromes (MDS) are disorders of blood stem cells that can develop into blood cancers. Treatment options are limited. To find better treatments, researchers need to better understand how MDS develops. To do that, they must be able to compare biospecimens from people with the disease to those of healthy people. Objective: This study will create a database of biospecimens collected from healthy volunteers. Eligibility: Healthy people aged 18 and older. Design: Participants will be screened. They will have a physical exam with blood and urine tests. Up to 5 types of samples will be collected on 1 or more days within 1 month of screening: Blood: Blood will be drawn by inserting a needle into a vein. Saliva: Participants will scrape the insides of their cheeks with a brush. Stool: Participants will be given a container to collect stool at home. They will use a prepaid envelope to mail in the sample. Bone marrow: A sample of the soft tissue inside the bones will be drawn out. The area to be biopsied, usually the lower back, will be numbed. A needle will be inserted through a small cut to remove the sample. Participants' pain will be monitored; additional numbing medicine may be used. Skin: A piece of skin about 1/6 of an inch across will be cut away. Stitches may be used to close the wound. Participants will return to the clinic to have the stitches removed. Participants do not have to provide all of the samples listed. They will give each sample only once.

Type: Observational

Start Date: Jan 2023

open study

Background: Transcranial magnetic stimulation (TMS) is form of non-invasive brain stimulation. It is approved to treat depression. TMS may help decrease drug craving. It is important to understand how TMS affects the brain. Such a better understanding would help to design ways to treat drug addiction. Objectives: To learn how TMS affects the brain when it stimulates an area in the front of the brain. Also, to see how the stimulation affects the area stimulated and other connected areas. Eligibility: Healthy, right-handed adults ages 18-60 who are non-drug users. Design: Participants will be screened under protocol 06-DA-N415. Participants will have at least 3 visits. The first visit will last about 3 hours. All other visits will last up to 6 hours. Participants cannot use drugs or alcohol at least 24 hours before a visit. They cannot have more than half a cup of a caffeinated drink at least 12 hours before a visit. Each visit will include a brief medical history update, urine test for drugs and pregnancy (if female), a breath test for alcohol and smoking, and questionnaires. Participants will have a TMS orientation visit. A wire coil will be placed on the head. An electrical current will pass through the coil to create a magnetic pulse that stimulates the brain. The other visits will include 2 sessions of TMS-MRI. Participants will lie on a table that slides into a cylinder. The TMS coil and the MRI coil will be placed over the head. Pictures will be taken of the brain with and without stimulation. Participants will complete a questionnaire about how they feel before and after each TMS session and in a follow-up call 1-3 days after their last session.

Type: Interventional

Start Date: Sep 2018

open study

Background: - About 17 million adults had an alcohol use disorder in 2012. Researchers want to follow people that have alcohol problems and want treatment, as well as those who do not want treatment and healthy volunteers. They also want to gather information on people with and without alcohol problems, including information on genes and biological processes in the body.. This will help them better understand, prevent, and treat alcohol problems. Objective: -To look at a broad range of traits in people who are healthy people and people with alcohol problems. To study them for potential eligibility for other research protocols conducted at the NIH Clinical Center. Eligibility: - Adults age 18 and older. - Not being pregnant or imprisoned. Design: - Participants will have a physical exam. They will answer questions about their health and alcohol and drug use. They will have an electrocardiogram to check their heart. They will have blood, urine, and breath alcohol tests. - Participants without alcohol problems, or who have them but do not want treatment, can sign the second consent for screening and research. - Participants that have alcohol problems and want treatment will be treated at the NIH Clinical Center. They will be offered to sign the second consent at a later time. - Participants may join an inpatient treatment and detox program. It could last up to 6 weeks. Or they may join an outpatient program. Some may do both. - After discharge, participants may be called and asked questions about their drinking and health. - If participants sign the second consent, they: - will complete paper- and computer-based questionnaires. - will give blood samples. - may have a brain scan using magnetic resonance imaging. They will lie on a table that slides in and out of a cylinder that takes pictures. The machine makes loud noises. They will get earplugs.

Type: Observational

Start Date: Jan 2015

open study

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

Type: Observational

Start Date: Sep 2013

open study

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

Type: Observational

Start Date: Aug 2009

open study

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

Type: Interventional

Start Date: Apr 2026

open study

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

Type: Interventional

Start Date: Jul 2026

open study

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

Type: Interventional

Start Date: Jun 2025

open study

Background: Mood disorders, such as bipolar disorder, can have serious effects on a person s life. People with bipolar disorder are more likely to have heart disease and abuse substances. In this natural history study, researchers would like to learn more about the connection between exercise and mental health in people with and without mood disorders. Objective: To better understand relationships among physical activity, sleep, and mental health. Eligibility: People aged 8 to 60 years with a history of a mood disorder. Healthy spouses and relatives with no mood disorders are also needed. Design: Participants will be in the study up to 2 years. For up to 20 days in a row, at 4 times during the study, participants will: Complete an electronic diary on their smartphone. Participants will answer questions about their mood, health, sleep, and daily activities. Wear an activity monitor, like a wristwatch, that records how much they move. Wear a light sensor, as a necklace, to record the amount of light in their environment. Some participants will do additional tests. Twice during the study, for 3 days in a row, they will: Wear monitors to record their temperature, heart rate, and sleep. Provide saliva samples. Complete cognitive tasks on their smartphone. Participants will visit the NIH clinic 2 times. They will have a physical exam, with blood and urine tests. They will wear a heart monitor. They will ride a stationary bike for 30 minutes. They may have an imaging scan. Some participants will stay overnight. They will go to sleep wearing a cap to measure their brain activity.

Type: Observational

Start Date: Nov 2023

open study

Background: The current standard treatment of prostate cancer is either surgery or radiation. Typically, this includes either the removal or radiation of the whole prostate gland. Many people now seek out focal therapy options to decrease the side effects of treatment. Until now, several forms of physical destruction with heat (thermal ablation), cold (cryotherapy), sound waves (HIFU), laser (FLA), and electrical energy (IRE). A new type of radiation (SBRT) may be an effective way to cure men of early-stage prostate cancer with fewer side effects than standard treatments. Objective: To see how people with untreated localized prostate cancer will respond to focal therapy with SBRT. Eligibility: People aged 18 years and older with untreated localized prostate cancer (prostate cancer which has not spread outside of the prostate gland). Design: - Participants will undergo screening including blood tests, an MRI, a PSMA PET/CT (18F-DCFPyL), and a biopsy. - Small, non-radioactive, gold seeds about the size of a grain of rice will be placed in and/or around the tumor to help target the radiation treatment. - Radiation (SBRT) will occur in 2 separate sessions about 1 week apart. No sedation is used, these sessions are painless. Each session will take about 1-2 hours. Participants can go home afterwards. - Follow-up will continue for 2 years with repeat scans (MRI and PSMA PET/CT) and blood (PSA) tests. - After two years, a biopsy will be done to understand the impact of this new treatment on prostate cancer.

Type: Interventional

Start Date: Oct 2023

open study

Background: - Recent advances in cancer research have led to new therapies to treat the disease. It is important to continue these advances and discover new ones. To do that, researchers need tissue samples from solid tumors. This study will collect such samples from people already scheduled to have a procedure at the National Institutes of Health Clinical Center (NIHCC). Objectives: - To collect tissue samples for use in studying new ways to treat tumors. Eligibility: - Adults 18 years and older, with a precancerous or cancerous solid tumor who are scheduled to have surgery or a biopsy at the NIHCC. - Children under the age of 18 but who are older than 2 years of age are eligible to be enrolled on the research sample collection portion of this study if they will have a biopsy or surgery as part of their medical care. Design: - Before their procedure, participants will have a small blood sample taken. - Some participants will undergo leukapheresis. In this procedure, blood is removed through a tube in one arm and circulated through a machine that removes white blood cells. The blood, minus the white blood cells, is returned through a tube in the other arm. The procedure takes 3-4 hours. - For all participants, during the surgery or biopsy, pieces of the tumor and pieces of normal tissue near it will be removed for this study. The rest of the tumor or precancerous growth will be sent to a lab for analysis. - Participants will return to the clinic about 6 weeks after the operation for a routine checkup. Some may have to return for additional follow-up.

Type: Observational

Start Date: Jul 2013

open study

Background: - Stem cell transplants from related donors (allogenic stem cell transplants) can be used to treat individuals with certain kinds of severe blood diseases or cancers, such as severe anemia. Allogenic stem cell transplants encourage the growth of new bone marrow to replace that of the recipient. Because stem cell transplants can have serious complications, researchers are interested in developing new approaches to stem cell transplants that will reduce the likelihood of these complications. - By reducing the number of white blood cells included in the blood taken during the stem cell collection process, and replacing them with a smaller amount of white blood cells collected prior to stem cell donation, the stem cell transplant may be less likely to cause severe complications for the recipient. Researchers are investigating whether altering the stem cell transplant donation procedure in this manner will improve the likelihood of a successful stem cell transplant with fewer complications. Objectives: - To evaluate a new method of stem cell transplantation that may reduce the possibly of severe side effects or transplant rejection in the recipient. Eligibility: - Recipient: Individuals between 4 and 80 years of age who have been diagnosed with a blood disease that can be treated with allogenic stem cell transplants. - Donor: Individuals between 4 and 80 years of age who are related to the recipient and are eligible to donate blood. OR unrelated donors found through the National Marrow Donor Program. Design: - All participants will be screened with a physical examination and medical history. - DONORS: - Donors will undergo an initial apheresis procedure to donate white blood cells. - After the initial donation, donors will receive injections of filgrastim to release bone marrow cells into the blood. - After 5 days of filgrastim injections, donors will have apheresis again to donate stem cells that are present in the blood. - RECIPIENTS: - Recipients will provide an initial donation of white blood cells to be used for research purposes only. - From 7 days before the stem cell transplant, participants will be admitted to the inpatient unit of the National Institutes of Health Clinical Center and will receive regular doses of cyclophosphamide, fludarabine, and anti-thymocyte globulin to suppress their immune system and prepare for the transplant. - After the initial chemotherapy, participants will receive the donated white blood cells and stem cells as a single infusion. - After the stem cell and white blood cell transplant, participants will have regular doses of cyclosporine and methotrexate to prevent rejection of the donor cells. Participants will have three doses of methotrexate within the week after the transplant, but will continue to take cyclosporine for up to 4 months after the transplant. - Participants will remain in inpatient care for up to 1 month after the transplant, and will be followed with regular visits for up to 3 years with periodic visits thereafter to evaluate the success of the transplant and any side effects.

Type: Interventional

Start Date: Dec 2010

open study

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

Type: Interventional

Start Date: Dec 2025

open study