DNA Methylation and Vascular Function

Obesity Clinical Trial

Official title:

DNA Methylation and Vascular Function in Obesity: Role of Exercise and Weight Loss

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03527420
• Other study ID #: 2017-1125
• Secondary ID: 1K99HL140049-01
• Status: Recruiting
• Phase: N/A
• Start date: October 11, 2019
• Est. completion date: August 31, 2024

Study information

• Verified date: May 2023
• Source: University of Illinois at Chicago
• Contact: Abeer Mohamed, MD, PhD
• Phone: 3127539998
• Email: amahmo4[@]uic.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: August 31, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Obesity
• Vascular Dysfunction

Intervention

Other:
• Exercise training
Twelve weeks of aerobic exercise training

Locations

Country	Name	City	State
United States	University of Illinois at Chicago	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
University of Illinois at Chicago	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	DNA methylation status of adipocytokines in obese individuals	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.	Month 24-30
Secondary	Vascular health biomarkers in obese individuals before and after exercise training	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).	Month 24-30
Secondary	Flow induced dilation	Measuring reactivity of brachial artery and isolated arterioles from adipose tissues	Month 1-20