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

Background: - Some nerve and muscle disorders that start early in life (before age 25), like some forms of muscular dystrophy, can run in families. However, the genetic causes of these disorders are not known. Also, doctors do not fully understand how symptoms of these disorders change over time. Researchers want to learn more about genetic nerve and muscle disorders that start in childhood by studying affected people and their family members, as well as healthy volunteers. Objectives: - To better understand nerve and muscle disorders that start early in life and run in families. Eligibility: - Individuals at least 4 weeks old with childhood-onset muscular and nerve disorders, including those who have a later onset of a disorder that typically has childhood onset. - Affected and unaffected family members of the individuals with muscular and nerve disorders. - Healthy volunteers at least 4 weeks old with no nerve or muscle disorders. Design: - Participants will be screened with a physical exam and medical history. Genetic information will be collected from blood, saliva, cheek swab, or skin samples. Urine samples may also be collected. - Healthy volunteers and unaffected family members will have imaging studies of the muscles. These studies will include magnetic resonance imaging (MRI) and ultrasound scans. Results will be compared with those from the affected participants. - All participants with nerve and muscle disorders will have multiple tests, including the following: - Imaging studies of the muscles, including ultrasound and MRI scans. - Imaging studies of the bones, such as x-rays and DEXA scans. - Heart and lung function tests. - Eye exams. - Nerve and muscle electrical activity tests and biopsies. - Video and photo image collection of affected muscles. - Speech, language, and swallowing evaluation. - Lumbar puncture to collect spinal fluid for study. - Tests of movement, attention, thinking, and coordination. - Participants with nerve and muscle disorders will return to the Clinical Center every year. They will repeat the tests and studies at these visits.

Type: Observational

Start Date: Mar 2012

open study

Adapt the Regulation of Cues (ROC) treatment program for Latinas to see if it can treat prediabetes and prevent developing of Type 2 Diabetes and reduce weight.

Type: Interventional

Start Date: Mar 2026

open study

This single-arm pilot study evaluates the effects of whole-body electrical muscle stimulation (WB-EMS) exercise on neuromuscular and physical function in adults with neuromuscular disease (NMD). Due to motor unit impairments, NMD patients often cannot tolerate traditional exercise. WB-EMS bypasses voluntary activation limits by directly stimulating muscle contractions. Up to 50 adults with conditions like ALS, SMA, and MG will undergo 20-minute supervised WB-EMS sessions (1-2 times weekly for 4-8 weeks) using the Katalyst system. Outcomes include neural excitability (TMS), motor unit behavior (EMG, NCS), functional tests (walk, balance, strength), and patient-reported fatigue, pain, and quality of life. Strict safety monitoring and exclusion criteria are in place. This study will provide preliminary data on WB-EMS as a potential exercise modality for NMD.

Type: Interventional

Start Date: Mar 2026

open study

The researchers are doing this study to find out whether adding gefitinib, trametinib, disulfiram, and sunitinib to standard chemotherapy is a more effective treatment approach for people with osteosarcoma than standard chemotherapy on its own. The researchers will also look at the safety of adding these drugs to standard chemotherapy. The researchers will also use the additional research biopsies from Cohort 1 participants to learn more about how osteosarcoma survives during chemotherapy.

Type: Interventional

Start Date: Mar 2026

open study

The objective of this project is to develop a behavioral intervention that combines wearable continuous glucose monitoring (CGM) with smartphone feedback and educational video clips generated by artificial intelligence (AI) software to improve glycemic control among individuals with pre-diabetes. The goal is to prevent transition to type 2 diabetes.

Type: Interventional

Start Date: Feb 2026

open study

A repository of biospecimens and detailed phenotypic information collected longitudinally from adults with congenital heart disease and related conditions, with an aim to facilitate future research on biologic mechanisms of underlying disease, compensation and deterioration; biologic correlates of patient experience and functional status; associations between clinical characteristics and various biomarkers; and predictors of clinical outcomes.

Type: Observational [Patient Registry]

Start Date: Jul 2021

open study

This phase IV trial studies whether there is a relationship between how a patient is positioned while receiving bacillus Calmette Guerin (BCG) within the bladder (intravesical) and how long BCG stays in the bladder (dwell time) to improve the treatment of non-muscle invasive bladder cancer. For the past 40 years, intravesical BCG has been used for the treatment of non-muscle invasive bladder cancer. An important factor for BCG treatment is the dwell time, which is the period of time a patient can hold the BCG medication in the bladder after it has been given. Normally, patients are instructed during intravesical BCG treatment to avoid emptying the bladder for 2 hours after the BCG is given. However, this may be difficult for some patients who may have limited bladder capacity, restricted movement, or severe urinary symptoms. There have been studies outlining the relationship with increased dwell time and how well the treatment works, but studies on the potential impact of patient positioning or activity on the patient's ability to retain the drug are limited. Researchers hope by studying whether there is a relationship between patient positioning during intravesical BCG treatment and dwell time, they may be able to improve how BCG treatment for non-muscle invasive bladder cancer is given, especially for patients with limited bladder capacity, restricted movement, or severe urinary symptoms.

Type: Interventional

Start Date: Feb 2026

open study

End stage liver disease or cirrhosis is a major cause of mortality in the United States and the world. Other than targeting the underlying cause, such as alcohol cessation and antiviral therapy, very few medical treatments can change the natural history of cirrhosis. Malnutrition is one of the few potentially modifiable factors that have been associated with cirrhosis severity and poor prognosis. The transition metal copper (Cu) is an essential trace metal that must be acquired from diet. Its metabolism is primarily regulated by the liver in its role as a master regulator of nutrients. In 2019, the investigators reported that Cu deficiency defined by below normal serum or liver concentrations occurred in a wide range of liver disorders and was associated with a severe disease phenotype. Improvement in liver function was observed in 2 of the 3 patients who received Cu supplementation. In 2023, the investigators conducted a longitudinal cohort study utilizing clinical, serum and liver explant tissue data from 183 cirrhosis patients. The investigators showed that Cu deficiency was associated with 2-fold higher infection rate and a more than 3-fold increase in the risk of death compared to patients with normal Cu status. These preliminary findings and the well-established importance of Cu in human health prompted the investigators to design the current pilot randomized, placebo-controlled, crossover trial to determine the effect of Cu supplementation on Cu dependent biochemical changes, patient safety and patient reported outcomes in cirrhosis.

Type: Interventional

Start Date: Mar 2026

open study

This study is a prospective cohort study which aims to assess patient satisfaction and preparedness for surgery through two methods of preoperative counseling: standard individual phone calls versus virtual group sessions called Shared Medical Appointments (SMAs). The study will focus on patients undergoing urogynecology prolapse surgeries at Cleveland Clinic. Researchers hypothesize that virtual group counseling will improve patient satisfaction and preparedness compared to individual phone calls. Additionally, the study will evaluate healthcare resource utilization as a secondary outcome. Participants will complete surveys before and after surgery to measure satisfaction and preparedness using validated tools. The study will enroll patients aged 18 and older who can provide informed consent and are scheduled for specific prolapse surgeries. Findings may help improve preoperative counseling practices and enhance patient-centered care.

Type: Observational

Start Date: Mar 2026

open study

Histotripsy is a treatment that uses focused ultrasound waves to break down tissue without surgery. The ultrasound waves meet at a specific spot and turn the tissue into liquid. This study is a prospective observational registry of participants receiving histotripsy. The goal of this study is to gather information about the use of histotripsy to confirm it is safe and effective medical procedure.

Type: Observational [Patient Registry]

Start Date: Jan 2026

open study

This study aims to clarify relations between brain oscillations and two cognitive functions: cognitive control and memory.

Type: Interventional

Start Date: Mar 2026

open study

The purpose of this study is to learn how exercise and physical activity during pregnancy and after pregnancy may affect the composition of breastmilk. Certain changes in breast milk after exercise may have an impact on how infants use energy. Understanding this process may improve public health recommendations for exercise during and after pregnancy. This study can help investigators learn more about how maternal exercise patterns may affect body growth and obesity risk in infants who are breastfed. This research may help identify how different factors can influence healthy weight and early development in infants.

Type: Interventional

Start Date: Dec 2025

open study

This is a Phase 1, two-part, multicenter study to evaluate ELA026 in participants ≥18 years old with relapsed/refractory TCM following any line of prior therapy who are eligible for investigational treatments.

Type: Interventional

Start Date: Feb 2026

open study

Cyclic vomiting syndrome (CVS) is a fairly common disorder characterized by relentless episodes of vomiting followed by return to baseline health.The majority of children with CVS have concurrent severe abdominal pain and migraine-features, causing significant disability during the attacks. There are very few non-drug treatment options for CVS. Many patients are treated with antidepressants that are often ineffective and may cause serious side effects. Emergency room visits and hospitalizations for patients with CVS is extremely high and the syndrome has an immense impact on quality of life. Safe and effective, non-pharmacological therapies for children with CVS are greatly needed. Nausea, vomiting and gastrointestinal pain is modulated by the vagus nerve, an important regulator of the autonomic nervous system. The vagus communicates signals between the gastrointestinal tract and the central nervous system. Many studies indicate that vagal nerve stimulation is effective for various pain and vomiting conditions. Recent studies show that vagus nerve signaling is impaired in children with CVS. Researchers have demonstrated safety and efficacy of auricular percutaneous electrical nerve field stimulation (PENFS) targeting the vagus nerve in a small study of children with CVS. The aim of the current study is to investigate the effects of non-invasive PENFS on CVS episode frequency, duration and severity compared to a sham device in a randomized clinical trial.

Type: Interventional

Start Date: Feb 2026

open study

- The purpose of the study is to improve care for patients with high cholesterol. - If you choose to join the study, you will be asked to answer a phone call from study personnel. They will help you coordinate follow up appointments, review your medications and lab with you, and answer any questions you have about your medications. You will also continue to be seen by a clinical pharmacy team member. Your cholesterol medications may change to better lower your cholesterol. We will collect information about your visits, medicines, and cholesterol levels for 6 months. - If you choose not to participate, you will receive the same information and treatment at your next scheduled visit. You will receive the same care regardless of choosing to participate in the study. - Participation might involve a very low risk of some loss of privacy. There is low risk that someone outside the research study could see information about you. - A possible benefit is lower cholesterol. - Taking part in this research study is your choice. You do not have to participate, and you can stop at any time without any penalty.

Type: Observational [Patient Registry]

Start Date: Jan 2026

open study

The purpose of this study is to assess the pharmacokinetics (PK), safety and tolerability of different oral formulations of AZD5004, and to evaluate the effect of food on these formulations in healthy participants.

Type: Interventional

Start Date: Mar 2026

open study

This study will examine how two important brain circuits - one involving the subthalamic nucleus (STN) and one involving the ventral intermediate nucleus of the thalamus (VIM) - contribute to learning and producing speech sequences. Participants will include two groups: 1. individuals with Parkinson's disease who have deep brain stimulation (DBS) devices targeting the STN and 2. individuals with essential tremor who have DBS devices targeting the VIM. Participants will complete speech tasks involving the learning and repetition of novel sound sequences. During some parts of the study, DBS stimulation will be temporarily turned on or off in a controlled research setting. This will allow researchers to examine how stimulation affects both the learning of new speech sequences and the production of previously learned sequences. All STN participants and most VIM participants will also be equipped with a cutting-edge DBS system, the Percept PC, which will enable the recording of deep brain activity during the tasks. The results of this study will improve our understanding of how different brain circuits support speech learning and production. In particular, this study will help to differentiate the roles of the STN and VIM in learning the ordering of speech sounds within a syllable from learning of speech sequences containing multiple syllables. This knowledge may help guide future approaches to optimizing DBS settings to improve both movement and speech outcomes in individuals with neurological disorders, as well as provide greater general insight into how these brain structures contribute to speech production and learning.

Type: Interventional

Start Date: Feb 2026

open study

This is a 16 week pilot study of the impact of a nutritionist led ketogenic diet (Ren-Nu) supplemented with the medical food KetoCitra on autosomal dominant polycystic kidney disease.

Type: Interventional

Start Date: Feb 2026

open study

The goal of this single blinded clinical trial is to investigate blood flow restriction (BFR) for rehabilitation of patients after ankle ligament reconstruction surgery. Outcome measures will be compared between the standard of care (SoC) and BFR groups at the end of the study intervention. Following standard surgical procedures, both groups will undergo physical therapy by a certified physical therapist for a minimum of 6 weeks. The SOC group will receive standard physical therapy without use of BFR. The BFR group will receive physical therapy with BFR. Outcome measures of interest will be taken at the start of physical therapy (time 0) and at the end of physical therapy (minimum of 6 weeks of PT) for both groups. Outcome measures of interest include: - muscle atrophy; - ankle function; - fatigability/manual muscle testing; - pain scores; - cardiovascular effects (heart rate, blood pressure).

Type: Interventional

Start Date: Mar 2026

open study

The goal of this observational clinical study is to learn if DeepMSI AI detects age-related macular degeneration (AMD) biomarkers with sensitivity and specificity equivalent to experienced clinicians in adults over 40 years old. The main questions it aims to answer are: - Does DeepMSI AI detect AMD biomarkers with sensitivity equivalent to experienced clinicians? - Does DeepMSI AI detect AMD biomarkers with specificity equivalent to experienced clinicians? Participants' eyes will be imaged by MSI-120 and their images will be analyzed for AMD biomarkers by both DeepMSI AI and retina specialists independently. Researchers will compare retina image analysis from DeepMSI AI with ground truth (clinicians' interpretations) to see if AI achieves equivalency in sensitivity and specificity.

Type: Observational [Patient Registry]

Start Date: Feb 2026

open study

This first-in-human study is designed to evaluate the safety, tolerability, pharmacokinetics, anti-drug antibodies, and neutralizing activity of MDX2301 administered by intravenous (IV), intramuscular (IM), or subcutaneous (SC) routes in healthy adults and adults at higher risk for severe COVID-19. Participants will receive single IV, IM, and SC doses of MDX2301 or placebo and a repeat IM or SC dose approximately 3 months apart of MDX2301 or placebo.

Type: Interventional

Start Date: Mar 2026

open study

The purpose of this study is to find better ways to help support families in their hopes during cancer treatment. Primary Objective - To characterize themes related to how patients and parents/caregivers narrate their experience of 'hope' when receiving cancer therapy on a phase 1/2 clinical trial, with a focus on whether, why, when, and how patients' and caregivers' hopes adapt to changing circumstances. - To engage patients, caregivers, and clinicians in focus groups to identify strengths, weaknesses, opportunities, and threats to hope during phase 1/2 clinical trial participation and facilitate the co-design of a stakeholder-driven supportive intervention related to hope based on focus group recommendations. Secondary Objective - To describe health care provider perspectives on patient and family hope and goal-care concordance in the context of phase 1/2 clinical trials.

Type: Observational

Start Date: Mar 2026

open study

The overall objective of this study is to implement a sustainable oncology legal navigation program that will provide direct legal navigation services to help patients and caregivers overcome legal barriers to care in order to reduce cancer-related financial toxicity (FT) and improve health-related quality of life (QOL) among patients/caregivers.

Type: Interventional

Start Date: Mar 2025

open study

This will be a 3-visit, single-site, randomized, single-masked, bilateral wear, non-dispensing, crossover study which will evaluate visual performance with different magnitudes of scatter.

Type: Interventional

Start Date: Feb 2026

open study