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

Type: Observational

Start Date: Apr 2015

open study

Background: - By the time diseases of the retina are detected, serious damage has often already been done. Researchers want to find better ways of viewing the retina. One way called adaptive optics may help detect problems earlier. Objectives: - To study if adaptive optics can help find better ways to diagnose, treat, and manage retinal diseases. Eligibility: - People over age 12 with an eye disease. - Healthy volunteers over age 12. Design: - Participants will be screened with medical history and eye exams. These may include dilating pupils and taking pictures of the eyes. - Participants will have 1 or more study visits. They will have: - Medical and eye history. - Questions about their medications. - Eye exam including pupil dilation. - Adaptive optics imaging. After dilation, participants sit still while looking into an adaptive optics instrument. They look at specific places and images are taken of their retina. - They may also have: - More images. - Perimetry. Participants look into a lens and press a button when they see a light. - Color vision tests. - Electroretinogram. Participants will get numbing eye drops and special contact lenses. A small metal electrode will be put on their forehead. They will look at flashing lights and try not to blink.

Type: Observational

Start Date: Feb 2015

open study

Background: The NCI Surgery Branch has developed an experimental therapy that involves taking white blood cells from patients' tumors, growing them in the laboratory in large numbers, and then giving the cells back to the patient. These cells are called Tumor Infiltrating Lymphocytes, or TIL and we have given this type of treatment to over 200 patients with melanoma. Researchers want to know if TIL shrink s tumors in people with digestive tract, urothelial, breast, or ovarian/endometrial cancers. In this study, we are selecting a specific subset of white blood cells from the tumor that we think are the most effective in fighting tumors and will use only these cells in making the tumor fighting cells. Objective: The purpose of this study is to see if these specifically selected tumor fighting cells can cause digestive tract, urothelial, breast, or ovarian/endometrial tumors to shrink and to see if this treatment is safe. Eligibility: - Adults age 18-72 with upper or lower gastrointestinal, hepatobiliary, genitourinary, breast, ovarian/endometrial cancer, or glioblastoma refractory to standard chemotherapy. Design: Work up stage: Patients will be seen as an outpatient at the NIH clinical Center and undergo a history and physical examination, scans, x-rays, lab tests, and other tests as needed. Surgery: If the patients meet all of the requirements for the study they will undergo surgery to remove a tumor that can be used to grow the TIL product. Leukapheresis: Patients may undergo leukapheresis to obtain additional white blood cells. (Leukapheresis is a common procedure, which removes only the white blood cells from the patient.) Treatment: Once their cells have grown, the patients will be admitted to the hospital for the conditioning chemotherapy, the TIL cells and aldesleukin. They will stay in the hospital for about 4 weeks for the treatment. Follow up: Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1 year as long as their tumors are shrinking. Follow up visits will take up to 2 days.

Type: Interventional

Start Date: Aug 2010

open study

Background: Multiple sclerosis (MS) and progressive multifocal leukoencephalopathy (PML) are disorders that affect the central nervous system (CNS). The CNS includes the brain, spinal cord, and optic nerves. Both diseases can cause muscle weakness and impair vision, speech, and coordination. Researchers are working to better understand how MS and PML affect the CNS. Objective: To test whether an experimental radioactive tracer (minibody) can help positron emission tomography (PET) scans detect certain immune cells in the CNS of people with MS and PML. Eligibility: People aged 18 years and older with MS, other neuroinflammatory diseases with BBB leakage, or PML. Design: Participants will come to the clinic for at least 3 visits over 4 to 6 weeks. Participants will undergo testing. They will have a physical and neurological exam. They will have blood tests and tests of their heart function. They will have a magnetic resonance imaging (MRI) scan of the brain. They may have a spinal tap: Their lower back will be numbed, and a needle will be inserted between the bones of the spine to withdraw fluid from around the spinal cord. Minibody is given through a tube with a needle placed in a vein in the arm. This takes 5 to 10 minutes. Participants will have heart function tests before and after receiving the minibody. Participants may have a PET scan on the day of the Minibody and will return the next day for another PET scan. They will lie on a table that moves through a doughnut-shaped machine. This scan will take about 1 hour. Participants with PML may opt to repeat the minibody infusion and the PET scan within 6 months.

Type: Interventional

Start Date: Oct 2023

open study

Background: Researchers want to better understand pain by studying people with and without different kinds of pain. To do this, researchers will expose people to pleasant and unpleasant sensations. They will ask them questions about their pain. Researchers also want to see if these people are eligible for other research studies at the National Center for Complementary and Integrative Health. Objectives: To study the experience of pain. Also to find people eligible to join other NIH studies. Eligibility: People 12 years and older with and without pain disorders. Design: Participants will be screened by phone. Participants will have one required visit lasting about 2 hours. This may include: - Medical history - Physical exam - Questionnaires about themselves and their pain experience - Blood and urine tests - MRI: They will lie on a table that slides into a cylinder. They will feel different sensations while completing tasks on a computer. This lasts 15 minutes to 2 hours. - Quantitative sensory testing: They will be exposed to different pictures, sounds, tastes, and smells. They will also be exposed to pleasant and unpleasant sensations. These could include: - Burning, itching, or cold sensations - Pinpricks - Pressure and pinches - Electrocardiogram: Stickers on the chest record heart activity. - Straps placed around the chest to measure breathing. - Small sensors on the fingers or palms to measure pulse and sweating. Participants may have up to 12 other outpatient study visits. Participants may be recorded at the visits.

Type: Observational

Start Date: Jul 2016

open study

The goal of this clinical trial is to investigate biomarkers of non-IgE-mediated immediate hypersensitivity reactions during infusion of intravenous vancomycin. The main question it aims to answer is: • Identifying novel biomarkers in blood that occur during infusion reaction Participants will: - Have allergy skin testing for vancomycin - Receive an infusion of vancomycin

Type: Interventional

Start Date: May 2026

open study

The goal of this observational study is to compare the outcomes of transcatheter edge-to-edge repair (TEER) versus surgical mitral valve repair for degenerative mitral regurgitation (DMR) over the long term. The study aims to: 1. Evaluate the effectiveness and safety of TEER versus surgery in patients with DMR over long term. 2. Investigate the predictors of left ventricular dysfunction and clinical outcomes using advanced imaging techniques, such as cardiac MRI 3. Assess patient-reported recovery and quality of life outcomes using validated tools. The study focuses on improving care strategies for patients with DMR, particularly those at higher surgical risk, by identifying optimal treatment approaches and predictors of recovery.

Type: Observational

Start Date: Feb 2025

open study

This multi-site clinical trial will generate data on the efficacy of tirzepatide for smoking cessation and associated outcomes (e.g., post-cessation weight gain) in treatment-seeking people who smoke (PWS) with overweight or obesity. A sample of 300 treatment-seeking people who smoke with body mass index of 25 kg/m2 or greater will be recruited from four geographic sites (University of Southern California, Yale University, University of Chicago, and University of Colorado Anschutz Medical Campus) to participate in a parallel-arm, dose-escalating, placebo-controlled trial. Participants will attend weekly clinic visits to receive subcutaneous tirzepatide or placebo over 16 weeks (Visit Weeks 1-16), followed by follow-up visits at Week 17 and Week 27. Medication will be prescribed according to the standard dose titration schedule for the first 16 weeks of treatment (initial dose: 2.5mg/week; final dose: 10mg/week). All participants will also receive nicotine patches.

Type: Interventional

Start Date: May 2026

open study

The purpose of the study is to discover at least two distinct Musculoskeletal pain subtypes. These types are caused by different brain-and-immune system signals that affect how the body feels pain, and they are also shaped by a person's biology, psychology, and social environment. Aim 1. We want to sort adolescents and young adults with long lasting muscle and bone pain into two different groups. To do this, we will look at participants' childhood medical histories, past treatments, when their pain started, the sex they were assigned at birth, what their pain feels like now, tests of how their body senses pain, and immune system markers found in their blood. We think we will find at least two different types of chronic pain groups, plus one group of patients who had a higher risk for pain (because of a rheumatic disease or past surgery) but never developed long term pain. Aim 2. We want to find out if certain patterns of inflammation in the body change how nerve cells react to pain. Aim 3: We want to understand how different biological, psychological, and social factors are connected to the chronic pain groups we identified. We think we will find certain mental, behavioral, and social risks-as well as protective factors-that help explain why some people develop long-lasting pain and others do not. We expect these factors to play different roles in each pain group, including the group that does not develop chronic pain.

Type: Observational [Patient Registry]

Start Date: Aug 2026

open study

This study aims to provide mechanistic insights into how group drumming as a music-based intervention (MBI) affects pain responses and nociceptive function in individuals with Alzheimer's Disease (AD), mild dementia or mild cognitive impairment (MCI). Heart rate (HR), heart rate variability (HRV), and brain activity will be measured during communal drumming with their dyadic partners and others. Brain activity, blood pressure, cognitive abilities, blood hormone levels, and static and dynamic pain will also be measured during sessions pre and post the 8-week community drum circle. Investigators will leverage various measurement techniques including, but not limited to, electroencephalography (EEG), quantitative sensory testing (QST), behavioral, surveys, and physiological monitoring to study the impact of group drumming on pain and brain activity in AD and inter-dyad synchrony.

Type: Interventional

Start Date: Jun 2026

open study

This is a phase 2b, multicenter, randomized, double-blind, placebo-controlled study.

Type: Interventional

Start Date: May 2026

open study

The proposed research aims to investigate the use of speech amplification devices as a potential treatment option for people with Parkinson's disease and related disorders who exhibit hypophonia, a voice disorder that affects over half of those with Parkinson's disease. By characterizing the acoustic and perceptual effects of speech amplification and identifying ways to optimize outcomes through talker- and device-specific enhancements, this project seeks to develop personalized, evidence-based treatment options for hypophonia. The current proposal will move this effort forward by systematically eliciting and modifying speech amplification device output that leverage both behavioral and technological approaches.

Type: Interventional

Start Date: Mar 2024

open study

The following experiment will be conducted with 15 chronic stroke survivors and 15 control subjects. Subjects will perform hand movements in the virtual reality environment using a head-mounted display. Quest's onboard cameras allow real-time tracking of hand motion, estimating joint angles of the finger and the thumb. For each feedback manipulation condition (i.e., movement amplification or reduction), the estimated joint angles will be multiplied by a factor greater than 1 (amplification) or a factor smaller than 1 (reduction). Then the newly-estimated hand posture will be displayed in the VR environment. Subjects will be randomly assigned into two groups (A and B), who will receive the assistance in a different order. Subjects will perform finger extension under three conditions: no sensory modulation, movement visual feedback (VF) amplification, and movement VF reduction (error augmentation), while their movement muscle activation patterns are recorded.

Type: Interventional

Start Date: Oct 2025

open study

NYC Public Schools is testing offering soy milk alongside dairy milk on the lunch line for all students during the month of May at select school sites to understand: - Whether students choose and drink soy milk - Whether offering soy milk can reduce milk waste - The potential environmental, nutrition, and cost impacts

Type: Observational

Start Date: May 2026

open study

This study examines the effects of e-cigarette (EC) flavors among adults with opioid use disorder (OUD) receiving buprenorphine treatment who currently use e-cigarettes. Participants will smell and rate 11 EC flavors based on appeal, sensory characteristics, and likelihood of future use. Researchers will examine how different flavor profiles influence the appeal and reinforcing effects of ECs in this population. The goal is to identify EC flavors that may enhance the acceptability of ECs as a potential harm-reduction strategy among adults with OUD receiving buprenorphine treatment.

Type: Observational

Start Date: Nov 2025

open study

This is a first-in-human Phase 1 study evaluating the safety and tolerability of C.001 in patients with retinal diseases involving degeneration of the retinal pigment epithelium. Participants will receive a single administration of C.001 delivered by subretinal injection. The study will evaluate three dose levels in a sequential manner. The primary objective is to assess the safety of C.001 over a 3-month period following administration. Participants will be followed for up to 12 months to further evaluate safety and explore changes in visual function and retinal structure.

Type: Interventional

Start Date: Apr 2026

open study

A Phase 3 Double-blind, Placebo-controlled Study (Part A) with an Open-label Extension (Part B) Evaluating DT120 Compared to Placebo in Major Depressive Disorder - Ascend

Type: Interventional

Start Date: May 2026

open study

This is a device study (while the device has been patented and cleared by the FDA, the indication of the use for Erectile Dysfunction has been yet approve). EXSTACY is a study to collect information on which patients who have trouble getting or keeping an erection rigid enough for sex (sometimes known as Erectile Dysfunction or ED) benefit from light intensity shockwave therapy (LI-SWT). LI-SWT is a form of energy transfer to the penis that has been shown to help some men with ED in studies over the past decade. This study will collect information about patients prior to treatment to determine what predicts a good outcome. The investigators hope that this information will help decide which patients are likely to benefit from LI-SWT and which patients should consider other treatments for ED.

Type: Interventional

Start Date: Sep 2024

open study

Single arm- subject treated with Tegoprubart and everolimus. The purpose of this research is to gather information on the safety and effectiveness of investigational regimen containing 2 experimental components: - An investigational drug called Tegoprubart and - Human pancreatic islet cells Both Tegoprubart and human pancreatic islet cells are considered investigational because they are not approved for use in the United States by the Food and Drug Administration (FDA). Participation in this research will last about 5 years. Assess safety, tolerability, and efficacy of transplanted islet cells and immunomodulation with Tegoprubart in combination with anti-thymocyte globulin (ATG), etanercept and with everolimus in adults with brittle T1D and chronic kidney disease (stage 2-3a).

Type: Interventional

Start Date: Apr 2026

open study

The goal of this clinical trial is to learn if a community health worker led intervention that helps facilitate palliative care works to treat newly-diagnostic pancreatic cancer. It will also help understand the impact of this intervention on people who are caregivers for patients with pancreatic cancer. The main questions it aims to answer are: Does the community health worker improve symptoms and quality of life in patients with pancreatic cancer? Does the community health worker improve the burden of caregiving and quality of life in family caregivers? Researchers will compare drug ABC to a control (where patients get the care that patients with pancreatic cancer receive including access to handouts and videos that the investigators provide patients by national organizations) to see if the intervention works to help patients with pancreatic cancer. Participants will: Meet with study staff several times over 3 months and complete surveys about their experience and symptoms Patients assigned with the community health worker will meet with them in person or video.

Type: Interventional

Start Date: Sep 2025

open study

The goal of this clinical study is to evaluate the efficacy and safety of the Ultra device for the treatment of hair regrowth by assessing the improvement of hair density and hair shaft diameter.

Type: Interventional

Start Date: Feb 2026

open study

This study investigates integrated epigenetic and epitranscriptomic features of appendiceal cancer using archived tumor tissue specimens from the same patient cohort. The study includes DNA methylation profiling and m6A epitranscriptomic profiling to define molecular subtypes, evaluate associations with clinicopathologic features, and develop molecular risk scores for prognostic stratification. The primary goal is to determine whether DNA methylation- and m6A-based molecular features can complement conventional histopathologic grading and improve risk stratification.

Type: Observational

Start Date: May 2026

open study

The goal of this clinical study is to evaluate the safety and preliminary efficacy of an investigational umbilical cord blood-derived stem cell and exosome infusion in adults with chronic lower back pain associated with degenerative spine disease. The primary questions this study aims to answer are whether the investigational infusion is safe and well tolerated and whether treatment may reduce pain and improve physical function and quality of life. Researchers will compare the investigational infusion to a placebo (saline solution) to evaluate potential treatment effects in participants with chronic mechanical lower back pain. Participants will receive either the investigational infusion or placebo intravenously during a study visit, complete pain, disability, and quality-of-life assessments, undergo magnetic resonance imaging (MRI) and laboratory testing, and attend follow-up evaluations over a 6-month period. Participants initially assigned to placebo may later receive the investigational treatment during an open-label crossover phase of the study.

Type: Interventional

Start Date: May 2026

open study

The Expanded Access Program will provide access to avexitide for people with post-bariatric hypoglycemia (PBH) following Roux-en-Y gastric bypass (RYGB) who meet the eligibility criteria for this program. The safety of avexitide and patient treatment experience will be monitored during this program.

Type: Expanded Access

open study

The NATURAL Study is a prospective, observational, pragmatic study of RNA biomarkers of infections to aid in the diagnosis of abdominal pain. Summary of Research Study: Hypothesis: A genomic-derived panel of 6 RNA biomarkers present in stabilized whole blood will provide diagnostic information about the presence of bacterial, biofilm, and viral infections in the abdomen. We hypothesize that biomarkers will be more than 90% sensitive with a high (>90%) negative predictive value for IAI. Research Design: The project design is a prospective, pragmatic, observational study. The NATURAL Study will be sponsored by True Bearing Diagnostics, Inc., and performed at 5 or more academic medical centers. Patients with suspected intra-abdominal infections (IAIs), such as appendicitis, diverticulitis, acute cholecystitis, pancreatitis, peritonitis, pyelonephritis, and abscess are candidates for this study. This is a broad category of patients that are defined by the suspicion of an internal abdominal infection, usually involving some type of advanced imaging analysis, such as CT scan or ultrasound. All participants will be consented for this observational, minimal-risk study prior to venipuncture. Ultimately, The NATURAL Study will determine the positive agreement (~sensitivity) and negative agreement (~specificity) of the TruNAV RNA biomarkers in relation to the clinical diagnosis of the presence or absence of an IAI, based on CT scans and/or surgical confirmation, the current standard of care for diagnosis of IAI. Objective: To validate a novel RNA fingerprint in ED patients with suspected IAIs. The NATURAL Study is designed to determine the accuracy of novel RNA biomarkers for diagnosis of IAI in patients suspected of having IAI. Subgroup analysis will analyse RNA biomarker for multiple types of actual and suspected IAIs (appendicitis, diverticulitis, acute cholecystitis, pancreatitis, peritonitis, pyelonephritis, and abscess.) Subjects: Approximately 1,000 ED patients presenting with abdominal pain that are candidates to receive CT or other confirmatory diagnostics will be enrolled.

Type: Observational

Start Date: Apr 2026

open study