Microvascular Dysfunction in Obesity

Recruiting now · Not applicable

Conditions studied: Obesity, Endothelial Dysfunction

In brief

Impaired endothelial function is observed in disease states related to obesity, such as atherosclerosis, coronary artery disease, and diabetes. Reactive oxygen species (ROS) production and resultant oxidative stress contribute to the development of these obesity-related diseases. The enzyme NADPH-oxidase is a major source of oxidative stress within the vasculature, and has been linked with the Metabolic Syndrome. In the investigator's previously funded studies, the investigators demonstrated for the first time that: 1) in vivo ROS were elevated in skeletal muscle of obese as compared to lean or overweight human subjects, 2) perfusion of the NADPH-oxidase inhibitor apocynin locally into muscle normalized ROS levels and reversed local microvascular endothelial dysfunction in the obese individuals, and 3) aerobic exercise training was effective at attenuating in vivo hydrogen peroxide production and reversing microvascular endothelial dysfunction in the obese individuals. The investigators will investigate in this R15 renewal application the mechanism of exercise training-induced alterations in ROS production and action on endothelial dysfunction in obesity using our newly developed microdialysis methodology of monitoring ROS production, in combination with analysis of muscle biopsy samples obtained before and after our previously tested 8-week intervention of aerobic interval exercise training. The objectives of this study are to determine the impact of in vivo NADPH oxidase activity on endothelial function in obese individuals, and to determine the mechanism of training-induced improvements in endothelial function. The investigator's unique microdialysis methodology will allow monitoring of microvascular/endothelial function and ROS generation, as well as the administration of pharmacological agents directly into muscle. The central hypothesis is that it is upregulation of both mitochondrial ROS and NADPH oxidase-derived ROS that results in endothelial dysfunction in obesity, and that exercise training down-regulates mitochondrial-derived ROS, and NADPH oxidase 4, thereby improving endothelial function. The aims of this proposal are to: 1) determine the contributions of mitochondrial ROS and specific NADPH oxidase isoforms to the NADPH oxidase dependent endothelial dysfunction in skeletal muscle of obese individuals; 2) determine the mechanism of ROS reduction and improved endothelial function resulting from an 8-week aerobic interval training program.

Key facts

Study ID: NCT04087655
Run by: Florida State University
People needed: 25
Starts: 2019-11-20
Expected to finish: 2027-05-31
Last updated by the study team: 2025-12-11

Who can join

Age: 18 and older, up to 45. Sex: any. Healthy volunteers: accepted.

You may qualify if…

There will be no restrictions with regard to race, sex, or socioeconomic status.
Women will be premenopausal
Women will be on combined estrogen/progestin hormonal contraceptive therapy (oral pill, transdermal patch or vaginal ring).
Sedentary obese individuals will have been weight stable for the preceding 6 months.
Sedentary obese individuals will have the Metabolic Syndrome as defined according to the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III).
Individuals with the Metabolic Syndrome will have at least three of the following:
Central obesity as measured by waist circumference (men >40 inches; women >35 inches);
Fasting blood triglycerides > 150 mg/dL;
Blood HDL cholesterol in men<40 mg/dL and women <50 mg/dL;
Blood pressure > 130/85 mmHg; 5) Fasting blood glucose > 110 mg/dL, and (not per ATP III) a 2-hour GTT glucose of 140-200 mg/dl.

You may not qualify if…

Subjects participating in purposeful endurance exercise training (>20 min/day, >1 day/week) will be excluded.
Pre-menopausal female subjects must not be pregnant or lactating, and must have had regular menstrual cycles for the past year.
Individuals taking medications that may affect central or peripheral circulation,
Individuals on nonsteroidal anti-inflammatory agents or serotonin reuptake inhibitors,
Individuals who smoke or chew tobacco,
Individuals with diabetes (fasting blood glucose >125 mg/dL),
hypertension >160/95 mmHg
Individuals with congestive heart failure, angina, or peripheral vascular disease. --Individuals with ECG evidence of serious arrhythmias and/or acute myocardial ischemia reflected in ST-segment depression of 1 mm or greater at rest or during exercise.
Individuals with chronic infections, paralysis due to stroke, advanced Parkinson's Disease, severe rheumatoid arthritis or other serious orthopedic problems that would prevent performance of the exercise training tasks will be excluded.
Individuals taking antioxidant, herbal or vitamin supplementation for at least 2 weeks prior to investigation.
Individuals ingesting caffeine the day of the experiment.
Individuals whose weight changes by more than 5% during the training program.
Individuals whose exercise adherence is below 90% of the exercise sessions or total exercise time.

Where it is running

Florida State University — Tallahassee, Florida, United States (enrolling)

Full record on ClinicalTrials.gov

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