Despite the overwhelming focus on genetic and genomic causes of human disease over the past two decades, it has been estimated that genetics is currently known to explain only 20% and 40% of the etiology of common disease. Thus, it is becoming increasingly apparent that human disease is a consequence of both genetic susceptibility and environmental exposures. Importantly, while individuals cannot change their genetic composition, we do have the ability both personally and as a society, to influence our environment, promoting health and decreasing the risk of disease. The Personalized Environment and Genes Study (PEGS) aims to determine how the environment and gene-environment interactions can inform our understanding of human health and disease. As science has evolved, so too has the science of this project. This evolution was reflected in a change in the title of this project from the Environmental Polymorphisms Registry (EPR) to the Personalized Environment and Genes Study (PEGS) to more accurately reflect the science that can be conducted. PEGS is a unique resource because of the depth of environmental phenotyping which includes extensive information from exposome surveys, as well as whole genome sequencing on a significant number of participants in the cohort. While it is small relative to genomic cohorts, none of these have the extensive environmental data that is present in PEGS. In addition, other cohorts with deep environmental data lack the depth of genomic data that is present in PEGS. Importantly, PEGS has already provided important analytic advances that are of great interest to and can be confirmed in larger cohorts such as All of Us. The Personalized Environment and Genes Study (PEGS) aims to provide a resource for environmental health translational research by examining gene-environment interactions in health and disease. PEGS is an extension of two previous efforts where it began as a pilot study, the Environmental Polymorphisms Study (EPS; IRB# 02E9004) and was approved subsequently as a full protocol titled the Environmental Polymorphisms Registry (EPR) (IRB #04-E-N0053 and transitioned to its current ID# 04-E-0053). The EPR was envisioned as a phenotype-by-genotype registry of participants who had donated DNA samples, and who had agreed to be contacted for follow-up clinical translational studies based on their DNA genotypes. At the time, the only information available was a participant s age, sex, race, and ethnicity. Further phenotyping of a participant and/or any biospecimens obtained were investigated during a follow-up translational clinical study on participants recruited based on their genotype (hence phenotype-by-genotype) and the PEGS was the first recruit-by- genotype study at the NIH. Following a period focused on recruiting approximately 15,000 participants to enable genotyping of rare (approximately 1% minor allele frequency) single nucleotide polymorphisms (SNPs), the PEGS Consortium Project was undertaken in 2010- 2011 to examine, using the DNA of nearly 4,000 participants, approximately 700 SNPs in approximately 80 environmental response genes that work in concert with environmental exposures to elicit a phenotype. Several clinical follow-up studies, genotype-phenotype association studies, and publications have resulted from the PEGS Consortium Project. To expand phenotype information available to researchers, the Health and Exposure Questionnaire was administered between 2013-2014. In 2017, a more detailed Exposome Questionnaire which includes questions relating to the external and internal exposome was administered. This was an important resource through which to integrate exposures with genotype-phenotype association studies. Whole genome sequencing has now been performed on approximately 4700 participants who were reconsented for this purpose, as indicated above. Questionnaire data was fully adjudicated and combined in a robust and searchable database. With the increased power of the data available, the project was renamed as the Personalized Environment and Genes Study (PEGS) and rolled out in Sept. 2021.

Type: Observational

Start Date: May 2010

open study

Head and neck cancers have one of the highest recurrence rates among solid malignancies, and recurrence is strongly correlated with overall survival. Reducing recurrence rates depends, in part, on the surgeon's ability to accurately re-resect areas of positive or close margins during surgery. Currently, margin status is communicated primarily through verbal descriptions between the surgeon and pathologist, which can be imprecise. This challenge is further compounded by the deformable nature of soft tissues, as once the specimen is resected, the shape and size of the specimen change, making it difficult to accurately map the specimen's margins back onto the surgical site. Emerging technologies -such as augmented reality (AR), 3D scanning, and advanced soft tissue modeling- offer promising solutions for improving surgical navigation and precision. Building on these advances, an AR-based surgical navigation system was developed specifically for head and neck tumor resections. The system uses a 3D scanner to generate virtual models of both the resected specimen and the patient's surgical site, as demonstrated in prior work. A soft tissue modeling algorithm is then applied to account for specimen shrinkage and deformation, enabling accurate tracking of positive tumor margins. This guidance information is visualized through an AR headset, which overlays the margin data directly onto the patient's surgical site, providing surgeons with real-time visual guidance during re-resection. In this study, the goal is to evaluate the benefits and usability of this novel navigation software, compared to the standard of care. By assessing surgeon performance and user experience in cadaveric tasks with and without the AR system to identify strengths, limitations, and opportunities for refinement of the system, ultimately advancing surgical precision and improving patient outcomes by reducing recurrence rates.

Type: Observational

Start Date: Feb 2026

open study

This phase II trial studies how well pirtobrutinib works in treating elderly patients with chronic lymphocytic leukemia (CLL). Bruton tyrosine kinase (BTK) inhibitors such as ibrutinib, acalabrutinib, and zanubrutinib work by blocking the action of the BTK protein that signals cancer cells to multiply. These are very effective, tolerable, and commonly used to treat people with CLL, but they may lead to drug resistance over time. Pirtobrutinib, also a BTK inhibitor, may work better in treating elderly patients with CLL.

Type: Interventional

Start Date: Aug 2026

open study

This clinical trial studies statewide optimization of lung cancer screening (LCS) in Kentucky using the Quality Implementation of Lung Screening (QUILS™) System. Data from the Kentucky Cancer Registry shows that LCS implementation has contributed to a rapid decline in late-stage lung cancer diagnosis at twice the national average. Further, the declines are more than three times the national average decline in Kentucky's Central Appalachian region. Kentucky-based multilevel initiatives are needed to expand and accelerate this leading role and extend the LCS opportunity to more Kentuckians who are at increased risk of lung cancer. This trial may be able to accelerate optimal high-quality implementation of LCS utilizing the QUILS™ System and reduce the burden of lung cancer by assisting lung cancer screening programs located throughout Kentucky in implementing best practices in lung cancer screening by integrating the QUILS™ System domains and elements into their screening programs.

Type: Interventional

Start Date: Apr 2025

open study

The goal of this National Institutes of Health (NIH) Stage 1a study is to develop and pilot test a research- and community-informed financial counseling and advocacy (FCA) intervention for dementia family caregivers in early and middle adulthood. The main question it aims to answer is: Is a research- and community-informed financial counseling and advocacy intervention usable, feasible and acceptable for dementia family caregivers in early and middle adulthood? Participants will engage in a four-week single group financial counseling and advocacy intervention and complete pre- and post-intervention measures addressing financial well-being, caregiver strain, workplace productivity, and flourishing along with usability, acceptability, and feasibility measures.

Type: Interventional

Start Date: Apr 2026

open study

The goal of this study is to investigate the effects of a non-invasive, low intensity focused ultrasound (LIFU) stimulation on seizure frequency and the epileptogenic network in drug-resistant epilepsy. LIFU uses focused sound waves to modulate deep brain regions and to enable changes in brain network activity. Encephalography (EEG) and behavioral tasks will also be used to study how LIFU affects brain activity.

Type: Interventional

Start Date: Jul 2025

open study

This study investigates the impact of ∆9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on recognition memory in healthy, regular cannabis users. Participants complete the same recognition memory task after self-administering one of two different strains of cannabis flower one day and while not intoxicated another day. Event-related potentials (ERPs) are measured via electroencephalogram (EEG) during the recognition memory task. Blood is collected to quantify THC and CBD exposure. Participants also complete self-report measures of medical history, sleep quality, subjective cognitive function, physical activity, psychological functioning, substance use, and acute drug effects.

Type: Observational

Start Date: Dec 2025

open study

In this experiment, subjects will view a cross pattern on the screen and be asked to focus their eyes on it. The cross pattern will look like it is moving towards and away from the eye in a back-and-forth motion. As the subjects focus their eyes on the shapes, we will measure the focus of their eyes using a device called a wavefront sensor. This device uses infrared light to measure the optical properties of the eye in real time. Our goal is to find out how well the eye focuses before and after viewing images on a screen up close (25cm). Since many people spend a lot of time looking at a computer screen while at work or at school, it is important to understand how this affects the eye's ability to focus.

Type: Interventional

Start Date: Jun 2026

open study

The goal of this clinical trial is to learn if low-dose atropine eye drops work to reduce excessive watery eyes (epiphora) in adults. It will also learn about the safety of the eye drops. The main questions it aims to answer are: Do the eye drops reduce how often participants have watery eyes? What medical problems do participants have when taking the eye drops? Researchers will compare two strengths of the eye drops (0.005% and 0.01%) to see whether one works better than the other and whether the lower strength works as well as the higher one. Participants will: - Use the assigned eye drops in the affected eye(s) for one week - Visit the clinic twice for checkups and eye tests - Receive a follow-up phone call about two weeks after starting, to check on any symptoms

Type: Interventional

Start Date: Jun 2026

open study

Father-child pairs (N=200; children ages 12-36 months) will be randomized to FIND-F or a waitlist control group. Assessments comparing the two groups will occur at baseline, end of program, and 6 months post-program. Our aims include: Aim 1: Evaluate the main impacts of FIND-F on the primary program target (fathers' supportive parenting) and related child and parent outcomes. Aim 2. Identify mechanisms of FIND-F's intervention effects. Aim 3. Examine variation by select child, father, and program measures.

Type: Interventional

Start Date: Jun 2026

open study

The goal of this clinical trial is to learn if a dietary supplement called Miricell works to improve cellular health and signs of healthy aging in adults. It will also learn about the safety of Miricell. The main questions it aims to answer are: - Does Miricell improve markers of autophagy, which is the body's natural process for recycling damaged cells? - Does Miricell support brain health, metabolic health, and visible signs of aging? - What medical problems, if any, do participants experience while taking Miricell? Researchers will compare Miricell to a placebo (a look-alike capsule that contains no active ingredients) to see if Miricell works better to support healthy aging. Participants will: - Take either one Miricell capsule or a placebo every day for 12 weeks with a morning meal. - Visit the research clinic four times over the course of the study for checkups and tests. - Complete memory and thinking tests, track their daily physical activity, and give blood samples to measure health changes.

Type: Interventional

Start Date: Jan 2026

open study

With this study, it is expected to learn more about preterm babies on breathing support with nasal continuous positive airway pressure (nCPAP). To gain more information on how much oxygen is actually delivered to the baby from the nCPAP machine.

Type: Interventional

Start Date: Apr 2026

open study

This pilot study aims to evaluate the feasibility and preliminary efficacy of a wearable rhythmic auditory stimulation system, MedRhythms, for improving gait parameters in patients with motor incomplete SCI. Up to 15 participants aged 18 years or older with non-progressive SCI will be enrolled. Participants will complete supervised gait training using the MedRhythms device twice weekly during regularly scheduled physical therapy sessions over a six-week period. The device uses shoe-mounted sensors and headphones to deliver real-time individualized rhythmic auditory cues based on the user's gait pattern. Primary outcome measures include change in walking speed assessed with the 10-Meter Walk Test. Secondary outcomes include walking endurance measured by the 6-Minute Walk Test, gait parameters obtained through GAITRite analysis, and participant-reported outcomes including the Walking Index for Spinal Cord Injury II (WISCI II) and the SCI Quality of Life Satisfaction with Social Roles and Activities measure. Outcomes will be assessed at baseline, post-intervention (6 weeks), and follow-up (12 weeks). Findings from this study will provide preliminary data on the feasibility and potential clinical impact of rhythmic auditory stimulation as an adjunctive gait rehabilitation strategy for individuals with incomplete SCI.

Type: Interventional

Start Date: Jun 2026

open study

Upper limb essential tremor (UL ET) is a movement disorder characterized by postural and/or kinetic tremor. It can cause difficulty with everyday tasks such as writing, pouring, and eating. This study will assess if AGN-151607-DP is safe and effective by assessing adverse events and change in disease activity in adult participants with UL ET. AGN-151607-DP is an investigational drug being developed to treat UL ET. Participants will be randomly placed in treatment groups to receive either AGN151607-DP or matching placebo. Approximately 94 adult participants with upper limb essential tremor will be enrolled in approximately 40 sites in the United States/Canada. Participants will receive intramuscular injections of AGN-151607-DP or matching placebo. Duration of the study is approximately 72 weeks. The effect of the treatment will be checked by completion of questionnaires and side effects will be monitored by medical assessments.

Type: Interventional

Start Date: Jun 2026

open study

The Period Pills Study is a prospective observational study among people who decide to use a combination of mifepristone and misoprostol for menstrual regulation.

Type: Interventional

Start Date: Jun 2026

open study

The researchers are doing this study to find out whether ELI-002 7P in combination with mFOLFIRINOX, with or without tislelizumab, is a safe treatment approach in people who have pancreatic ductal adenocarcinoma (PDAC) with a KRAS mutation. In addition, the researchers are doing this study to find out whether the study treatment is effective against PDAC.

Type: Interventional

Start Date: Jun 2026

open study

The Health Ahead Comparative Effectiveness Study is a pragmatic, parallel-arm interventional platform that systematically compares successive changes to preventive health screening - each isolated as a single variable against current practice - on the path toward a fully automated screening system deployable in any environment, including the most isolated and resource-limited communities. Each comparison is evaluated with a common set of engagement, behavior-change, experience, cost, and longitudinal outcome measures, allowing results to accumulate on a consistent yardstick across the life of the platform. The first comparison evaluates static versus interactive personalized health report delivery. Subsequent pre-planned comparisons, added by protocol amendment, evaluate mobile community versus fixed laboratory screening; and a hybrid medical-droid plus human-delivery model versus human-only screening. All participants are simultaneously enrolled in the 100-Year Human Aging Study and the Human Observatory Study, contributing individual longitudinal and population-level causal inference data through those protocols.

Type: Interventional

Start Date: Jun 2026

open study

Participants in this study will have already been enrolled in another research study: Combining Stellate Ganglion Block with Prolonged Exposure for PTSD, NCT05889741. The investigators are using a Sleep Profiler, EEG headband to monitor a participants brainwaves while they sleep to see what effects the Stellate Ganglion Block injection has on their sleep. Participants will wear the headband for 3 nights before the injection and then 3 nights after the injection. Participants will also complete self-report questionnaires regarding their sleep prior to the injection and following the injection. Approximately 40 participants will be included in this study. This study is a nested observational study whereby participants in the parent study who elect to participate will have their sleep assessed using the EEG headband device and self-reported sleep measures performed.

Type: Observational

Start Date: Jun 2026

open study

The purpose of this study is to evaluate the disease-drug-drug interaction (DDDI) potential of afimkibart (also known as RO7790121). This will be assessed by the characterization of the pharmacokinetics (PK) of cytochrome P450 (CYP) enzyme substrates alone and after administration of afimkibart in participants with moderately to severely active ulcerative colitis (UC).

Type: Interventional

Start Date: Jun 2026

open study

This study evaluates how useful and acceptable the components of the "Couples Coping Together Against Cancer", referred to as "The Program", are to the participants with cancer.

Type: Observational

Start Date: Jul 2024

open study

The goal of this clinical trial is to develop and test an app designed to reduce suicide risk and improve emotional well-being in adolescents. The study will test if the app's daily check ins and recommended mood boosting skills will improve the adolescent's overall mood and suicidality. The main question it aims to answer is: • Is the app practical and acceptable to use daily? In the study, adolescents will: - Participate in a focus group with other adolescents and provide feedback on the app itself (design, ease of use, etc.). - Complete surveys and assessments on their mood, thoughts, and experiences. - Complete assessments about their app experience. In the study, the legal guardian of the adolescent will: - Participate in a focus group with other adolescents and provide feedback on the app itself (design, ease of use, etc.). - Complete assessments about their app experience.

Type: Interventional

Start Date: Jun 2026

open study

This study evaluates whether a home-based telerehabilitation program (tele-CPASS) is as effective as an in-person rehabilitation program (CPASS) for improving arm and hand function after stroke. Stroke often leads to long-term difficulty using the affected arm in daily activities, and access to in-person therapy can be limited. This study aims to determine whether therapy delivered remotely can provide similar benefits to standard in-clinic care. Participants who recently experienced a stroke will be randomly assigned to receive 20 hours of upper extremity rehabilitation therapy either in person or through a telehealth platform. Both groups will receive the same type and amount of therapy focused on practicing meaningful, patient-selected daily activities. Participants will complete assessments before treatment, immediately after treatment, and at 6 and 12 months to measure recovery of arm function, real-world arm use, and participation in daily life. The results of this study will help determine whether telerehabilitation can improve access to effective stroke recovery interventions while maintaining clinical effectiveness comparable to in-person therapy.

Type: Interventional

Start Date: Sep 2025

open study

The objective of this randomized controlled trial is to examine the efficacy of a new intervention to prevent postpartum smoking relapse and related health consequences through breastfeeding promotion. After the pre-test, ex-smokers who are still abstinent from smoking will be randomized into either the breastfeeding intervention or the attention placebo control group. The outcomes are postpartum smoking relapse, breastfeeding practices, and maternal and child health.

Type: Interventional

Start Date: Jan 2026

open study

The purpose of this study is to learn about the safety of a new study medicine called PF-08103402 in healthy adults (do not have disease) and or in adults with mild-to-moderate asthma. This is the first time the study medicine is being given to people. For Parts A, B, C, D and F, the study is seeking participants who: - Are healthy (do not have disease) males or females who can no longer have children, - Are 18 to 65 years old, - Have a body mass index (BMI) of 16 to 32 kilograms per meter squared and a body weight of more than 50 kilograms (110 pounds). Body mass index is a way to measure body fat by using a person's height and weight For Part A (optional group or cohort 3: Japanese participants only): - A body weight of more than 45 kilograms (100 pounds). - Have 4 biological Japanese grandparents who were born in Japan. For Part E only: - Adults with a documented history of asthma (confirmed by a doctor) for at least 12 months before entering the study. - Have a body mass index (BMI) of 16 to 35 kilograms per meter squared and a total body weight of more than 50 kilograms (110 pounds). The study has six parts: Part A, Part B, Part C, Part D, Part E and Part F. The study medicine will be taken as a suspension or tablet by mouth 1 time a day (except in Parts B and E where it will be taken 1 time a day for 14 days) at the study clinic. The study will help understand: - how the body processes the study medicine in healthy participants (Parts A and B), - how much of the study medicine gets into the bloodstream and if food affects the amount of study medicine in the blood in healthy participants (Part C), - how the study medicine is broken down and leaves the body in healthy participants (Optional Part D), - how the study medicine is processed in adults with mild-to-moderate asthma (Optional Part E), - if taking the study medicine together with another medicine affects how each medicine is processed by the body in healthy participants (Optional Part F). Participants will take part in the study for about 10 weeks (Parts A and F), 12 weeks (Part B), 9 weeks (Parts C and D), and 16 weeks (Part E). During this time, they will have 2 study visits at the study clinic and up to 28 overnight stays (Part A), 18 overnight stays (Parts B and E), 10 overnight stays (Part C), 11 overnight stays (Part D), and 16 overnight stays (Part F). The study team will also call participants 1 time over the phone at the end of the study to assess how they are doing. Study measurements will be taken by body examination, monitoring side effects, blood and urine tests, heart tests (ECG), vital signs (blood pressure and pulse), questionnaires (Parts C and E), stool samples (Part D only), and breathing tests (Part E only).

Type: Interventional

Start Date: Jun 2026

open study

To compare the safety, effectiveness, and preventive benefits of a medical device (X92001483) against Nix Cream Rinse (1% Permethrin) in people with head lice

Type: Interventional

Start Date: May 2026

open study