- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03527420
DNA Methylation and Vascular Function
May 3, 2023 updated by: Abeer M. Mohamed, University of Illinois at Chicago
DNA Methylation and Vascular Function in Obesity: Role of Exercise and Weight Loss
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.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Anticipated)
80
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Abeer Mohamed, MD, PhD
- Phone Number: 3127539998
- Email: amahmo4@uic.edu
Study Locations
-
-
Illinois
-
Chicago, Illinois, United States, 60612
- Recruiting
- University of Illinois at Chicago
-
Contact:
- Abeer M Mohamed, MD, PhD
- Phone Number: 312-355-8099
- Email: amahmo4@uic.edu
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 50 years (Adult)
Accepts Healthy Volunteers
Yes
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Exercising
12 weeks of aerobic exercise training
|
Twelve weeks of aerobic exercise training
|
No Intervention: Non-exercising
standard of care
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Month 24-30
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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).
|
Month 24-30
|
Flow induced dilation
Time Frame: Month 1-20
|
Measuring reactivity of brachial artery and isolated arterioles from adipose tissues
|
Month 1-20
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Abeer Mohamed, MD, PhD, University of Illinois at Chicago
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
October 11, 2019
Primary Completion (Anticipated)
June 30, 2024
Study Completion (Anticipated)
August 31, 2024
Study Registration Dates
First Submitted
May 3, 2018
First Submitted That Met QC Criteria
May 15, 2018
First Posted (Actual)
May 17, 2018
Study Record Updates
Last Update Posted (Estimate)
May 4, 2023
Last Update Submitted That Met QC Criteria
May 3, 2023
Last Verified
May 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2017-1125
- 1K99HL140049-01 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD 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.
IPD Sharing Time Frame
Month 30-36
IPD Sharing Supporting Information Type
- SAP
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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