Background: All childhood cancers are rare, but some are called very rare. Very rare cancers are diagnosed in 2 or fewer out of 1 million people each year. Researchers want to gather data so they can learn more about these very rare cancers. They hope to use the data to develop future treatments. Objective: To gather data for a registry of very rare cancers found in children, teens, and young adults. Eligibility: People aged 1 month to 39 years newly diagnosed (within the past year) with a very rare cancer. Design: Participation will be by phone or email. No clinic visits are required. Researchers will look at the participant s medical records. They will ask for samples of tumor tissue that were already removed. They will use the samples for genetic testing. The results of these tests will be sent to the participant s own doctors. Some participants will be asked for saliva or cheek swab samples. They will receive a kit in the mail. They will spit into a tube or swab the inside of their cheek. They will mail the sample back to the lab. Participants will fill out questionnaires once a year for 5 years. They will answer questions about: Family history, such as other cancers in the family and their income, work, and education. Demographics, such as their gender, nationality, ethnicity, education, and work history. Symptoms and treatment for their cancer. This may include level of pain, and emotional and physical well-being. Participants data will be added to a secure database for other researchers. Their data will be anonymous.

Type: Observational

Start Date: Jul 2026

open study

Background: Lung cancer is the leading cause of cancer-related death worldwide. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Surgery to remove the tumors is the standard treatment for people diagnosed with early stages of NSCLC. Despite complete removal of these tumors, many recur (happen again). An FDA-approved drug combination to treat early-stage NSCLC prior to the surgery is durvalumab plus standard chemotherapy. The FDA approved infusion drug azacytidine [AZA] is used to treat several diseases because it can rapidly kill dividing cells (including cancer cells) but it is not approved for NSCLC. An inhaled (aerosolized) form of AZA is also not approved for NSCLC. However, researchers want to know if an inhaled version of AZA can help improve treatment of people with NSCLC because inhaled AZA goes directly into the lungs with limited absorption into the bloodstream. Objective: To find the safest and most effective dose of inhaled AZA in participants with early-stage non-small cell lung cancer (NSCLC) that can still be removed by surgery. Eligibility: Adults aged 18 and older with operable early-stage NSCLC. Participants will be required to also enroll in NIH protocol 06C0014 which allows for pre- and post-treatment biopsies and bloodwork to be obtained for additional research studies. Design: Participants will be screened. They will have a physical exam with blood tests. Their medical records will be reviewed. They will have imaging scans and tests of their heart and lung functions. Participants will be required to have a tissue sample (biopsy) taken of their tumor prior to receiving study drug and again during surgery after Cycle 3; airway tissue biopsies and collection of collect bronchial (lung) fluid may also be done. Participants will receive the study treatment for 3 cycles. Each cycle is 21 days. They will need to come to the NIH Clinical Center (CC) on days 1-4 of Cycles 1-3. AZA will be given as a drug mist that can be inhaled (like the type of mist in an asthma inhaler) using a nebulizer at the NIH Clinical Center (CC) for 3 days in a row (consecutive days) during the first week of each cycle. The participant will inhale the AZA drug mist for 20 to 30 minutes each time. Participants will also receive durvalumab and a specific 2-drug assigned chemotherapy by intravenous (IV) infusion on day 4 of each cycle. Participants will have a follow-up visit 2 weeks after their last dose of study drugs. Then they will have planned surgery to remove the tumors. Participants will have additional follow-up visits at the NIH CC about 1 and 3 months after the surgery, and then for every 3 months for up to 3 years.

Type: Interventional

Start Date: Jul 2026

open study

Background: Medical advances have improved survival rates for many cancers and other illnesses. This means that more people are coping with the long-term effects of these treatments. Some treatments can cause female infertility. Ovarian tissue cryopreservation (OTC) may help. Before undergoing a treatment that may damage their fertility, patients may opt to freeze a sample of ovarian tissue. The tissue contains immature egg cells. When thawed, the tissue can be reimplanted. This procedure can help women become pregnant. Objective: This natural history study will create a databank of ovarian tissue. The NIH will provide OTC as a clinical service. The NIH will also request a portion of the tissue to use for research. Eligibility: Females aged 4 to 35 who opt to have OTC before receiving cancer treatment. Design: Participants will be screened. Their existing medical records will be reviewed. They will be asked if they want to donate a portion of their ovarian tissue for research. No more than 20% of the tissue collected will be taken for research. Some other tissues that would otherwise be discarded will also be kept. Medical data from each participant may also be collected and stored in the database. This data may include results of routine blood tests, imaging tests, and other information. The data will be coded for privacy. Participants will answer a questionnaire. They will be asked about their fertility treatment and general health. The survey takes about 30 minutes. They will repeat the questionnaire once a year for 30 years.

Type: Observational

Start Date: Jul 2022

open study

Background: Multiple sclerosis (MS) is a disease that damages the central nervous system (brain and spinal cord). This leads to increased physical disability over time. The disease is lifelong once it begins. Researchers want to learn more about MS s stages and follow them until a person s death. Objective: To understand how the physical and clinical signs of MS relate to its changes over time. Eligibility: Adults age 18 or older with MS or a disease of the brain and spinal cord that may act like MS. Design: Participants will have a medical history and a complete neurological exam. They may have timed tests of neurological function, such as a 25-foot walk and a 9-hole peg test. Participants will have multi-day visits about once a year. Participants will have blood drawn. Participants may have a brain magnetic resonance imaging (MRI) scan. They may also have an MRI of the spinal cord. They may get a contrast agent (dye) injected into a tube in an arm vein. During the MRI, participants will lie on a table that slides in and out of a metal cylinder. Participants will have the thickness of their retina measured using optical coherence tomography. A camera on top of a table uses lasers. Participants will look through a lens and follow instructions. Eye drops may be used to dilate the pupils. Participants will chew on a piece of sterile cotton for 1 minute to collect saliva. Participants agree to have an autopsy at the time of their death and to donate some of their organs to research, such as the brain and spinal cord.

Type: Observational

Start Date: Apr 2016

open study

Background: - Chromatin is is the structural building block of a chromosome. It is found inside the nucleus of the cell and consists of a complex of DNA and protein. - Cancers of the lung, pleura (lung lining) and esophagus show profound changes in chromatin structure that may affect the course of disease in patients. - A better understanding of these diseases and the genetic changes associated with them may be helpful in developing new treatments for them. Objectives: - To evaluate people with cancer of the lung, pleura or esophagus for participation in NCI clinical trials. - To obtain biopsies (small pieces of tissue) from tumor, normal tissue and blood samples to learn more about the cellular changes in blood and tissue in tumors of the lung, esophagus and pleura and surrounding structures in the chest. Eligibility: Patients 2 years of age and older with cancer of the lung, esophagus, pleura, mediastinum or chest wall, or cancers of other origin that have invaded the lung. Note: Patients >= 2 years of age and under 18 years of age may only participate in research sample collection. Design: - Up to 1310 patients may be included in this study. - Patients undergo standard tests for evaluating the stage of their disease and for determining eligibility for an NCI investigational treatment study. - All patients undergo bronchoscopy and bronchoalveolar lavage ("washing" with salt water) to assess their tumor and collect a sample of normal tissue. Patients whose tumor is located on the outside portion of the lung may also undergo thoracoscopy to obtain a tumor sample. For bronchoscopy and bronchoalveolar lavage a tube with a light is passed through the nose or mouth into the lungs to examine the airways. Salt water is injected through the tube and then withdrawn to obtain cells for laboratory studies. For the thoracoscopy a small tube with a light is put through a small hole in the chest to obtain the tumor sample. Both procedures are usually done under general anesthesia. The tissue is examined to identify cell characteristics of people who respond to certain therapies and to identify markers on the surface of the tissue that may be useful in future research and treatment. - Blood and urine samples are collected from patients. - Patients who are eligible for a treatment study at NCI are offered participation in the study. - Patients for whom standard surgery, radiation or chemotherapy is more appropriate may receive treatment at NCI or with their own physician. - Patients who receive treatment at NCI return for follow-up examinations 4 weeks after discharge and then every 2 to 4 months depending on the nature of their cancer.

Type: Observational

Start Date: Nov 2005

open study

Background: Less toxic and more effective treatments are needed for cancers caused by viruses. These cancers include Hodgkin and non-Hodgkin lymphoma, hepatocellular carcinoma, head and neck cancer, nasopharyngeal carcinoma, gastric cancer, anal cancer, cervical cancer, vaginal cancer, vulvar cancer, penile cancer, Merkel cell carcinoma, Kaposi sarcoma, and leiomyosarcoma. Researchers want to see if a combination of drugs can help. Objective: To find a safe dose of pomalidomide plus nivolumab in people with cancers caused by viruses. Eligibility: Adults ages 18 or older who have cancers caused by Epstein Barr virus (EBV), human herpes virus 8/Kaposi sarcoma herpesvirus (HHV8/KSHV), human papilloma virus (HPV), hepatitis B or C virus (HBV/HCV), and Merkel cell polyomavirus (MCPyV) that have not responded to previous treatments or have relapsed, or in adults who do not want to have surgery because of disfigurement or other risks. Adults who have HIV with any CD4 T cell count are eligible. Design: Participants will be screened with blood and urine tests, scans, and heart tests. They will have a physical exam. Their ability to perform normal daily activities will be assessed. They may have a tumor biopsy. Treatment will be given in 28-day cycles. Participants will take pomalidomide as a tablet by mouth for 21 days of each cycle, for up to 24 cycles. They will get nivolumab by intravenous infusion once each cycle. They will take an aspirin each day until 30 days after their last dose of the study drugs. Participants will keep a pill diary. They will bring it to their study visit at the end of each cycle. At these visits, some screening tests will be repeated. Participants with Kaposi sarcoma will have pictures taken of their lesions. Participants will give blood and saliva samples for research. They may have optional anal and/or cervical swabs. They may have optional biopsies. Participants will have a follow-up visit 30 days after they stop taking the study drugs, then every month for 100 days. Some screening tests will be repeated. Then they may by contacted by phone every 3 months for 9 months, and then every 6 months thereafter.

Type: Interventional

Start Date: Dec 2021

open study

Objective: To screen and create a list of adult volunteers in good health for participation in research studies conducted at the National Institutes of Health (NIH) in Bethesda, Maryland. Develop a normative set of structural and functional brain MRI scans that are linked to healthy research volunteer characteristics. Maximize scientific impact of data from volunteers by broadly sharing with other researchers. Study Population: Adult males and females in general good health who are 18 years of age and older. Design: Adult individuals who are interested in participating in NIMH IRP clinical studies as a healthy research volunteer can directly visit or be directed to visit the study website where they will first consent electronically and then complete a set of online self-report measures. Items may include: demographic information, mental health symptoms, disability status, substance use patterns, handedness and clinical/family history. Individuals who are flagged based on predetermined responses to survey items will be further screened by a member of the study clinical team. If found to be ineligible for the study because of a clinically significant or unstable medical or mental health condition, these individuals will be referred back to the community and/or given information about NIMH clinical studies for which they may be eligible. Respondents with no flags or who pass through additional screening will be scheduled for an in-person assessment. During the outpatient appointment and after in-person informed consent, participants will receive a brief clinical interview to screen for current medical and mental conditions, and risk for self-harm. They will complete assessments of psychological, emotional, physiologic, biological and cognitive functioning. Participants will undergo a physical exam and be asked to provide blood and urine samples for routine clinical labs. Participants can separately consent for an optional baseline brain magnetic resonance imaging (MRI) scan and an optional magnetoencephalography (MEG) exam. All consent forms will explicitly inform participants that if enrolled in the study, their de-identified data will be broadly and publicly shared through NIH-approved data repositories. Participants in this recruitment and characterization study will then be placed on a list of healthy research volunteers from which other NIMH IRP studies may recruit according to the inclusion and exclusion criteria in their respective IRB-approved protocols. Outcome Measures: Outcome measures may include demographic data, mental and medical history and symptoms, results of psychological, emotional, physiologic, biological, and cognitive testing, physical exam and MRI findings....

Type: Observational

Start Date: Nov 2017

open study

Background: Genes are the basic units of heredity. When genes are changed, certain cells don t work like they should. Researchers want to try to better understand the genetic conditions that are linked with inherited eye diseases. Objective: To try to identify the genes linked to the development of inherited eye diseases. Eligibility: People ages 4 and older who have or have a family member with an inherited eye disease Design: Participants will be screened with medical history and medical records. Participants will have one visit that will take 3-4 hours. This will include: Medical and family history Eye exam: This includes the pupil being dilated. Electroretinography: A small electrode is taped to the forehead. Participants sit in the dark with their eyes patched for 30 minutes. Then numbing drops and contact lenses are put in the eyes. They will watch flashing lights. Blood tests Saliva sample: They will spit into a container or have the inside of their cheek swabbed. Genetic testing will be done on participants blood or saliva. Participants may meet with the researchers to discuss their genetic tests.

Type: Observational

Start Date: Oct 2016

open study

Background: - Deep brain stimulation (DBS) is an approved surgery for certain movement disorders, like Parkinson's disease, that do not respond well to other treatments. DBS uses a battery-powered device called a neurostimulator (like a pacemaker) that is placed under the skin in the chest. It is used to stimulate the areas of the brain that affect movement. Stimulating these areas helps to block the nerve signals that cause abnormal movements. Researchers also want to record the brain function of people with movement disorders during the surgery. Objectives: - To study how DBS surgery affects Parkinson s disease, dystonia, and tremor. - To obtain information on brain and nerve cell function during DBS surgery. Eligibility: - People at least 18 years of age who have movement disorders, like Parkinson's disease, essential tremor, and dystonia. Design: - Researchers will screen patients with physical and neurological exams to decide whether they can have the surgery. Patients will also have a medical history, blood tests, imaging studies, and other tests. Before the surgery, participants will practice movement and memory tests. - During surgery, the stimulator will be placed to provide the right amount of stimulation for the brain. Patients will perform the movement and memory tests that they practiced earlier. - After surgery, participants will recover in the hospital. They will have a followup visit within 4 weeks to turn on and adjust the stimulator. The stimulator has to be programmed and adjusted over weeks to months to find the best settings. - Participants will return for followup visits at 1, 2, and 3 months after surgery. Researchers will test their movement, memory, and general quality of life. Each visit will last about 2 hours.

Type: Interventional

Start Date: Aug 2011

open study

This will be a multicenter registry-based study to evaluate safety and efficacy of GLP-1RA and SGLTi therapies in adjunct to insulin in adults with type 1 diabetes (T1D) over 1 year. This study will enroll participants who have been prescribed adjunct therapy as part of usual care.

Type: Observational [Patient Registry]

Start Date: Mar 2026

open study

A study to evaluate the effect of over- the- counter (OTC) lubricating eye drops on tolerability, symptoms and visual outcomes in patients with dry eye disease (DED)

Type: Interventional

Start Date: Jun 2026

open study

About 6.5 million adults in the United States who are 65 or older have dementia. While the exact cause of dementia is not known, it may be due to changes in the brain. Further, risk may be higher when the brain does not respond to insulin. Indeed, brain insulin resistance has emerged as a pathologic factor affecting memory, executive function as well as systemic glucose control. Regular aerobic exercise may help reduce the risk of dementia by increased blood flow to the brain and help the brain respond better to insulin. In addition, giving insulin through a nose spray (called intranasal insulin) may also help with thinking and memory. However, it is unknown if using both exercise and intranasal insulin is best for the brain.

Type: Interventional

Start Date: Aug 2026

open study

Dystrophin associated heart dysfunction is a leading cause of death in patients with Duchenne and Becker Muscular dystrophy (DMD/BMD) and Duchenne and Becker muscular dystrophy carriers (MDC); however, the evolution of heart dysfunction is not well-understood. The central objectives of this proposal are to elucidate this evolution of heart dysfunction and identify measures from cardiac MRI images that can predict death or significant heart disease in patients with DMD/BMD/MDC. This study will create a large clinical and cardiac MRI registry of dystrophin associated heart dysfunction, will utilize advanced image analysis techniques, including deep learning neural networks, to comprehensively evaluate every patient, and will create a risk toolkit accessible to clinicians around the world; this proposal has the potential to improve the quality of life in patients with dystrophin associated heart dysfunction by allowing for earlier and more intensive therapy in patients with severe disease and by identifying surrogate outcome measures for use in therapeutic trials.

Type: Observational [Patient Registry]

Start Date: Jan 2025

open study

The primary purpose of this study is to evaluate the efficacy of ublituximab in adult participants with MG responding to treatment with efgartigimod.

Type: Interventional

Start Date: Jul 2026

open study

The sequential trial compares recovery and mHealth engagement outcomes among Black participants who participated in the mHealth intervention uMAT-R or uMAT-R + enhanced community engagement. The mHealth intervention seeks to support people in various stages of recovery who are also seeking other forms of substance use treatment. Participants are recruited from community-based substance use treatment facilities and recovery services. Participants must be adults who have or are currently using opioids and/or stimulants.

Type: Interventional

Start Date: Aug 2025

open study

The purpose of this project is to determine the impact of hydration education on participant knowledge and water intake for residents in the independent living unit at Cornwall Manor. Therefore, we aim to look at the impact of education as a tool to improve overall hydration among the geriatric population.

Type: Interventional

Start Date: May 2026

open study

The purpose of this study is to evaluate patient navigation programs designed to reduce barriers to cancer screening and improve healthcare experiences for adults living in Chicago. Participants will be asked to complete two surveys: the first survey shortly after the participants join the study and a second survey after 1 year. Participants will be joining one of three patient navigation programs, assigned at random. The investigators expect the participants to be in this patient navigation program for 12 months, followed by a 1-month window to complete the final survey.

Type: Interventional

Start Date: Jun 2026

open study

This is a prospective, randomized controlled trial evaluating the effect of a hemostatic agent on tract-related bleeding during percutaneous nephrolithotomy (PCNL). Patients undergoing standardized PCNL will be randomized to receive either application of a hemostatic agent or no agent during tract closure, following uniform balloon occlusion, complete aspiration, and irrigation-free endoscopic assessment. The researchers hypothesize that adjunctive hemostatic agent use reduces perioperative hemoglobin decline compared with balloon tamponade alone and improves tract-related hemostasis outcomes.

Type: Interventional

Start Date: Jul 2026

open study

People with hereditary hemorrhagic telangiectasia (HHT) often experience frequent and severe nosebleeds that can disrupt daily life and lead to anemia, medical procedures, and reduced quality of life. This study is testing a new nasal ointment called TOR-582, which contains sirolimus, to determine whether it can be used safely when applied inside the nose. Adults with HHT and frequent nosebleeds will be invited to participate. Participants will first complete one week of observation without treatment, followed by up to 12 weeks of applying the study ointment inside each nostril twice daily. Different participants will receive different strengths of the ointment so researchers can identify the safest dose. During the study, participants will attend study visits, complete questionnaires about their nosebleeds and quality of life, keep a daily nosebleed diary, undergo nasal examinations, and have blood tests to monitor safety and medication levels. The information gained from this study will help determine whether this topical treatment can be safely studied further and will support the development of a new, less invasive option for managing nosebleeds in people with HHT.

Type: Interventional

Start Date: Jul 2026

open study

The goal of this study is to evaluate the tooth whitening efficacy of Oil Pulling oral rinse compared to a competitor's whitening mouthwash and a water-based mouthwash (placebo). Each participant will use one of three mouthwashes: GuruNanda Oil Pulling oral rinse (test), Competitor's mouthwash (positive), Water-based oral rinse (placebo). All mouthwashes will be used once daily last thing before bed at night. Data will be collected on tooth shade evaluated on the anterior teeth.

Type: Interventional

Start Date: May 2026

open study

Just-In-Time Adaptive Interventions (JITAIs) offer a framework for delivering personalized behavioral support using time-varying data to optimize the timing and type of intervention content. This project will develop the foundational components of a JITAI tailored to adults with chronic pain and either MS or SCI by drawing on symptom self-management content from existing programs (PainGuide, MyMSToolkit, and MySCIToolkit). Intervention content and delivery parameters will be refined through stakeholder engagement via structured interviews to ensure relevance, acceptability, and feasibility.

Type: Observational

Start Date: May 2026

open study

The primary objective is to determine if the use of the colonoscopy surveillance recommendations algorithm increases the accuracy of surveillance timing recommendations compared to traditional methods. The secondary objective is to assess the time required to make surveillance recommendations with and without the algorithm, determine the efficiency gains (the average time saved per recommendation), and evaluate the opportunity cost (the financial value of the time saved).

Type: Observational

Start Date: Mar 2026

open study

The MILES Study is a longitudinal, mixed-methods investigation of urinary biomarkers, energy balance, and lifestyle modifications in diverse women during early breast cancer treatment. The study's overarching goal is to assess dietary quality and physical activity changes over time using reliable, scalable tools suitable for clinical or population settings, supporting newly diagnosed patients in adopting and maintaining healthy behaviors through treatment and survivorship.

Type: Interventional

Start Date: Jan 2026

open study

The goal of this clinical trial is to find out if vitamin D supplements help healthy adults maintain their cognitive and simple physical task performance and emotional state during highly stressful situations. The main question it aims to answer is: - Does vitamin D help maintain cognitive and physical task performance and emotional state during highly stressful situations? Researchers will compare vitamin D to placebo (a look-alike tablet that contains no active ingredients) to see if vitamin D better maintain cognitive and physical task performance and emotional state during highly stressful situations. Participants will: - Take vitamin D or placebo tablets daily for 8 weeks. - Perform cognitive and simple physical tasks and rate their emotional state under highly stressful situations. - Wear a stress belt that delivers mild electric shocks 1 - 5 times while participants are performing laboratory tasks. - Wear a wristwatch-shaped activity monitor for 9 weeks. - Visit the laboratory 5 times.

Type: Interventional

Start Date: Jun 2026

open study

Female life stages including premenopausal, perimenopausal, postmenopausal, are characterized by changing concentrations and patterns of hormones. The premenopause stage represents the reproductive years with normal menstrual cycles lasting between 21-35 days. The perimenopause stage is the beginning of the menopause transition and can last up to 10 years. During this transition, menstrual cycles become longer and irregular in length (7 days or longer). After 12 consecutive months with no period, the transition is complete into the postmenopause stage. Hormones that change across the lifespan are known to influence systems that regulate thirst, fluid balance, and sodium balance. Yet, fluid balance across life stages remains poorly understood, with no direct comparisons across all three life stages. The purpose of this study is to evaluate the effect of female life stage on rehydration with water and electrolyte solution after overnight fast and fluid restriction

Type: Interventional

Start Date: Jun 2026

open study