DNA Methylation and Vascular Function

NCT ID: NCT03527420

Last Updated: 2025-09-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-11
• Study Completion Date: 2026-08-31

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.

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.

Conditions

Obesity; Vascular Dysfunction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Exercising

12 weeks of aerobic exercise training

Group Type: ACTIVE_COMPARATOR

Exercise training

Intervention Type: OTHER

Twelve weeks of aerobic exercise training

Non-exercising

standard of care

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Exercise training

Twelve weeks of aerobic exercise training

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of Illinois at Chicago

OTHER

Sponsor Role: lead

Responsible Party

Abeer M. Mohamed

Postdoctoral Research Associate

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Abeer Mohamed, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Illinois at Chicago

Locations

University of Illinois at Chicago

Chicago, Illinois, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Abeer Mohamed, MD, PhD

Role: CONTACT

amahmo4@uic.edu

3127539998

Facility Contacts

Abeer M Mohamed, MD, PhD

Role: primary

amahmo4@uic.edu

312-355-8099

Other Identifiers

1K99HL140049-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2017-1125

Identifier Type: -

Identifier Source: org_study_id