We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
ClinicalTrials.gov Menu

DNA Methylation and Vascular Function

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03527420
Recruitment Status : Recruiting
First Posted : May 17, 2018
Last Update Posted : June 10, 2021
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Abeer M. Mohamed, University of Illinois at Chicago

Brief Summary:
The main objective is to examine DNA hypomethylation as an underlying mechanism for the increased production of inflammatory cytokines and the impaired vascular function in obese individuals and as a potential target for nonpharmacological preventive/therapeutic interventions such as aerobic exercise.

Condition or disease Intervention/treatment Phase
Obesity Vascular Dysfunction Other: Exercise training Not Applicable

Detailed Description:
The long-term goal of this study is to identify valid targets and strategies for the prevention and treatment of obesity-related cardiovascular disease. Obesity is characterized by a large accumulation of fat tissues that secrete numerous inflammatory mediators (called adipocytokines), generating a systemic inflammatory state. These adipocytokines induce vascular dysfunction which is the initial step towards developing cardiovascular disease. Obesity is affected by environmental factors such as diet and physical activity. These factors induce epigenetic changes, which are changes that affect gene expression without altering the DNA sequence. One of these epigenetic modifications is the reduction in DNA methylation (referred to as hypomethylation) resulting in subsequent increases in gene expression. Preliminary data of the current study showed that the extracted DNA from fat tissues of obese subjects is hypomethylated compared to non-obese controls. DNA hypomethylation correlated significantly with higher expression of adipocytokines and impaired vasodilation in obese subjects. Therefore, the main hypothesis in this study is that the increase in adipocytokine expression in obese adults is mediated by DNA hypomethylation and that DNA hypomethylation is a promising target to prevent obesity-associated inflammation and vascular dysfunction. The flexible modifiable nature of DNA methylation makes it a perfect target for lifestyle interventions such as physical activity and weight loss. Thus, the investigators propose that aerobic exercise training and weight loss following Bariatric surgery will reverse DNA hypomethylation and improve vascular function in obese subjects. This hypothesis will be tested by (1) Investigating abnormal DNA methylation patterns of adipocytokines in fat tissues from obese adults between the age of 18 and 50 compared to non-obese subjects; (2) Test the effectiveness of 12-week aerobic exercise training on reversing DNA hypomethylation and improving vascular function in obese adults; and (3) Examine the effectiveness of weight loss surgery on DNA methylation and vascular function. The proposed studies will improve the understanding of the epigenetic underpinning of obesity-related vascular dysfunction, identify novel therapeutic targets for improving vascular function in obese adults, and provide an evidence for the positive effects of aerobic exercise training and weight loss on the prevention and treatment of obesity-associated cardiovascular disease. These studies will have a positive impact on improving the prevention and therapeutic management of obesity-related cardiovascular morbidities that affect millions of people worldwide.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: DNA Methylation and Vascular Function in Obesity: Role of Exercise and Weight Loss
Actual Study Start Date : October 11, 2019
Estimated Primary Completion Date : June 30, 2022
Estimated Study Completion Date : August 31, 2022

Arm Intervention/treatment
Active Comparator: Exercising
12 weeks of aerobic exercise training
Other: Exercise training
Twelve weeks of aerobic exercise training

No Intervention: Non-exercising
standard of care

Primary Outcome Measures :
  1. DNA methylation status of adipocytokines in obese individuals [ Time Frame: Month 24-30 ]
    DNA methylation of 20 preselected adipocytokines using "Amplicon sequencing-based methylation profiling" will be measured in fat tissue collected from obese individuals who are scheduled for bariatric surgery before and after 12 weeks of aerobic exercise training.

Secondary Outcome Measures :
  1. Vascular health biomarkers in obese individuals before and after exercise training [ Time Frame: Month 24-30 ]
    Serum or plasma levels (pg/ml) of biomarkers of vascular function such as endothelin-1, cyclic guanosine monophosphate (cGMP), and endothelial cell adhesion molecules (soluble intracellular adhesion molecules, soluble vascular cell adhesion molecules, soluble platelet and endothelial cell adhesion molecules, soluble E-selectin, and soluble P-selectin).

  2. Flow induced dilation [ Time Frame: Month 1-20 ]
    Measuring reactivity of brachial artery and isolated arterioles from adipose tissues

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Gender identity
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • BMI ≥ 35 kg/m2
  • Between ages 18-50 years
  • Not pregnant
  • Approved for a bariatric surgery

Exclusion Criteria:

  • To avoid confounding from other inflammatory conditions individuals with current cancer, heart, kidney or liver disease, gallbladder disease or acute or chronic inflammatory diseases (including rheumatoid arthritis, lupus and other autoimmune diseases and genetic diseases) will be excluded
  • Pregnant women will be excluded, as they will not be eligible for bariatric surgery
  • Current smokers
  • Currently abusing alcohol or drugs

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03527420

Layout table for location contacts
Contact: Abeer Mohamed, MD, PhD 3127539998 amahmo4@uic.edu

Layout table for location information
United States, Illinois
University of Illinois at Chicago Recruiting
Chicago, Illinois, United States, 60612
Contact: Abeer M Mohamed, MD, PhD    312-355-8099    amahmo4@uic.edu   
Sponsors and Collaborators
University of Illinois at Chicago
National Heart, Lung, and Blood Institute (NHLBI)
Layout table for investigator information
Principal Investigator: Abeer Mohamed, MD, PhD University of Illinois at Chicago
Layout table for additonal information
Responsible Party: Abeer M. Mohamed, Postdoctoral Research Associate, University of Illinois at Chicago
ClinicalTrials.gov Identifier: NCT03527420    
Other Study ID Numbers: 2017-1125
1K99HL140049-01 ( U.S. NIH Grant/Contract )
First Posted: May 17, 2018    Key Record Dates
Last Update Posted: June 10, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All data obtained will be shared with the public openly via publication in the most rigorous, visible and appropriate scientific journals possible. Data will be published as soon as it is reasonable to do so (i.e., sufficient data generated to warrant a suitable paper). Supplemental data for each published paper will be made available in one location on the laboratory webpage of the applicant and her mentor. The applicant and other investigators are open to collaboration with outside groups as well when there is mutual interest in this approach. In accordance to the NIH public access requirement (Section 218), we will submit to the National Library of Medicine's PubMed Central an electronic version of our final peer-reviewed manuscripts upon acceptance for publication to be made public no later than 12 months after the official date of publication. We will make every effort to keep findings of this research project widely available and accessible to the research community.
Supporting Materials: Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Month 30-36

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Abeer M. Mohamed, University of Illinois at Chicago:
DNA methylation
Weight loss
Adipose tissue
Additional relevant MeSH terms:
Layout table for MeSH terms
Nutrition Disorders
Body Weight