NCT04087655 · Florida State University
Microvascular Dysfunction in Obesity
What this study is about
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.
View original scientific description
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.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- 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.
Exclusion criteria
- 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
- Tallahassee, Florida
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Dec 11, 2025 · Source of record for eligibility and locations