Clinical Trials

Circadian rhythms influence the efficiency of our metabolism by orchestrating various body functions to appropriate times of the 24 hour day. Chronic circadian rhythm disruption predisposes individuals to metabolic diseases including obesity and type 2 diabetes. Conversely, maintaining a daily rhythm of feeding and fasting cycles sustains a robust circadian rhythm which improves cellular bioenergetics and results in improved metabolism. Time-restricted eating (TRE) is a specific feeding-fasting pattern in which feeding is restricted to 8-12 hours a day.

This NIH NIDDK funded study investigates the impact of TRE (time-restricted eating to 10 hours a day) on optimizing the health of people with metabolic syndrome over a 3 month period. Participants will be randomized to one of two groups - the TRE group or the non-TRE group. All participants will be required to log their food and beverages through a smartphone app throughout the course of the study. In addition, the study will involve 2 DXA scans and 2 muscle biopsies. For this study, we are looking for people who currently have a long or irregular eating window and who meet the criteria for Metabolic Syndrome.

ClinicalTrials.gov Identifier: NCT04057339

Download TIMET Study Flyer (PDF)

Dr. Michael Wilkinson, MD is conducting a research study in collaboration with Drs. Alan Saltiel, PhD and Pam Taub, MD at UCSD, and Dr. Satchidananda Panda, PhD at the Salk Institute to measure the health impact of a dietary intervention known as time restricted eating (TRE) on patients with obesity. Desired participants are age 18 years or older, you have been identified as having obesity, and have a reported 14-hour (or more) eating period each day. The purpose of this study is to see if reducing the number of hours during which you eat each day will help to improve the health of body fat (called adipose tissue), while reducing levels of glucose (sugar) in the blood, improve other markers of metabolic and cardiovascular health (i.e. lipid levels, inflammation markers, etc), and improve body composition (i.e. body weight, percentage of body fat, waist circumference, abdominal fat, etc).

The study is being funded by UCSD/UCLA Diabetes Research Center (DRC) Pilot and Feasibility Grant Program.

ClinicalTrials.gov Identifier: NCT04916730 

The purpose of this study is to see if reducing the number of hours during which one eats each day will help reduce levels of LDL cholesterol and improve other markers of metabolic and cardiovascular health (i.e. blood sugar levels and blood pressure). The study also aims to assess changes in glucose levels (assessed via Hemoglobin A1c, the gold standard in clinical trials of T2D) and cardiovascular health (assessed via LDL or “bad” Cholesterol and Triglycerides) between participants in the Time-Restricted Eating group versus the Standard of Care Group. We will also be examining long-term adherence to TRE and improvements in quality of life.

ClinicalTrials.gov Identifier: NCT05365529

The mechanisms underlying POTS are not well understood. Though heterogeneous in nature, patients often present with symptoms that include fatigue, orthostatic lightheadedness and tachycardia, “brain fog”, shortness of breath, and sleep disruption. The central mediator that links observations in disease entities similar to POTS is energy use and balance driven by mitochondrial health. Mitochondrial dysfunction (i.e. respiration defects, reactive oxygen species (ROS) generation, and structural abnormalities) are hallmarks of currently defined syndromes that resemble POTS symptomatology. Many patients with POTS have underlying immune system dysfunction, which, when treated, may improve the patient’s overall health. Though autoimmunity has been demonstrated in POTS, overall immune dysregulation may be broader and include immune cell exhaustion and persistent inflammatory cytokine responses. Immune dysfunction including cellular exhaustion and persistent inflammation has been linked to mitochondrial function. We hypothesize that imposing consistent feeding-fasting cycles will restore the equilibrium between catabolic and anabolic processes, which will improve glucose homeostasis and cardiometabolic biomarkers, decrease abdominal fat, and enhance mitochondrial function. 

ClinicalTrials.gov Identifier: NCT05409651

The purpose of this study is to see if reducing the number of hours during which one eats each day will help reduce levels of LDL cholesterol and improve other markers of metabolic and cardiovascular health (i.e. blood sugar levels and blood pressure). The study also aims to assess changes in exercise capacity and trimethylamine N-oxide (TMAO) levels in response to Time Restricted Eating (TRE) and Intensive Cardiac Rehabilitation (ICR) versus ICR alone. TMAO is a metabolite, or a substance, produced during digestion and metabolism. Preliminary data illustrates a correlation between high levels of TMAO and higher risk of cardiovascular disease and mortality. We will also be looking at participants' long-term cardiovascular health status after they complete the ICR program.

This study examines the effectiveness of the Heart Exercise And Resistance Training - Peer Lead Activity (HEART-PLAY) intervention to significantly sustain exercise adherence in patients referred for Cardiac Rehabilitation (CR) at the UCSD Step Family Cardiovascular Rehabilitation and Wellness Center. CR Clinic staff and CR patients who meet study inclusion criteria and are willing to serve as peer leaders, will be taught to lead the intervention activities with trained health educators and research staff. The HEART-PLAY program and behavior change will be sustainable because of the presence of peer and staff leadership and because it employs proven strategies from social cognitive theory and ecological models including self-monitoring, feedback, social support, role modeling, and relapse prevention. HEART-PLAY teaches patients how to accumulate meaningful PA across the day and provides a supportive social infrastructure to maintain motivation. Since the aim is to test an augmented CR program that can be widely adopted, the project employs a design that allows for the concurrent testing of both intervention and implementation strategies and outcomes.

Across the five days of the week and the AM and PM clinic sessions, there will be approximately 25 different peer-led groups (clusters) run to obtain complete data on a total of 264 women and men 18+ years old of varied socioeconomic and ethnic backgrounds referred for CR. HEART-PLAY and STANDARD participants will be scheduled to visit the Step Clinic on distinctly different days/times to avoid contamination. Participants in the STANDARD condition will receive the standard of care cardiac rehabilitation, consisting of 36 sessions across 12 weeks of prescribed, supervised exercise sessions, Participants in the HEART-PLAY will receive standard CR and additionally receive pedometers, resistance bands, and the National Institute of Aging (NIA) exercise guide. Patients will further receive counseling from peer health coaches, social support from group education sessions, and supplemental educational materials. After the 12 weeks of prescribed, supervised exercise sessions, HEART-PLAY group participants will continue to receive support from peers and clinic staff with check-in calls, feedback on pedometer goals, and bi-weekly group events including walks and/or resistance band group exercise classes. Pilot data support that the peer-led approach in the clinic setting will be enthusiastically received by patients and significantly increase PA and adherence.

This study is sponsored by the NIH.

ClinicalTrials.gov Identifier: NCT03632018

Diabetic Cardiomyopathy (DbCM) is a common sequelae of diabetes, resulting from diabetes associated metabolic alterations. DbCM is characterized by abnormal cardiac structure and/or performance in the absence of coronary artery disease or hypertensive, valvular or congenital heart disorder. The condition exists in 17-24% of patients with diabetes, with a resulting prevalence of ~77 M patients worldwide (~ 8.0M in North America and ~10.0M in Europe). DbCM is a form of Stage B Heart Failure (SBHF) and is associated with a high risk of progression to overt Stage C Heart Failure (SCHF). Approximately 24% of DbCM patients progress to symptomatic HF or death within 1.5 years and 37% within 5 years. No therapies currently exist to target the metabolic derangement responsible for DbCM or to prevent progression to overt heart failure. 

Hyperactivation of the polyol pathway is a pathogenetic mechanism of DbCM. Aldose Reductase (AR), the first and rate-limiting step in the polyol pathway, is activated by hyperglycemia and catalyzes the conversion of glucose into sorbitol. This induces oxidative stress, up-regulates proinflammatory signals and ultimately causes cell death. AT-001 is a novel investigational Aldose Reductase Inhibitor (ARI) shown to significantly inhibit the production of sorbitol at well tolerated doses in a phase 1-2 clinical study. The ARISE-HF pivotal study is a randomized, placebo-controlled, double blind, global clinical study to investigate the safety and efficacy of two doses of AT-001 (1,000 mg BID and 1,500 mg BID) in 675 patients with DbCM/SBHF at high risk of progression to SCHF.

The study consists of two consecutive parts: Part A and Part B. Part A will evaluate the safety and efficacy of two doses of AT-001 vs placebo. The primary objective of Part A is to demonstrate that AT-001 improves or prevents the decline of functional capacity in patients with Diabetic Cardiomyopathy. Part B is an extension of at least 12 months that will evaluate the safety and efficacy of chronic administration of AT-001 vs placebo in the same patients who had previously been evaluated in Part A. Assessments in Part B will include safety endpoints and exploratory clinical efficacy endpoints, i.e. death and hospitalization due to a cardiac event.

Epicatechin is a bioactive compound naturally found in dark chocolate. The purpose of this study is to gain insight into the side-effects of statin consumption, and assess the ability of epicatechin to counteract or reverse these changes. Dr. Taub's prior research has shown that epicatechin can improve skeletal muscle structure and mitochondrial (cellular component that produces energy) structure.

Participants will take a statin with either placebo or epicatechin daily during the 3-month trial. At the beginning and end of the study, functional and cellular changes will be assessed via exercise testing and a muscle biopsy.

This study is funded by the American Heart Association.

ClinicalTrials.gov Identifier: NCT02490527