Role of Mitochondria-derived Oxidative Stress on Microvascular Endothelial Function in Healthy Non-Hispanic Black and White Adults
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- University of Georgia
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Cutaneous microvascular responses to local heating
Study Overview
Brief Summary
Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide, and the non-Hispanic Black (NHB) population is disproportionately affected. Our research has previously demonstrated that oxidative stress may contribute to reduced vascular function in otherwise healthy NHB adults, potentially predisposing them to the development of hypertension and CVD. This study is designed to examine whether the mitochondria are an important source of oxidative stress-induced vascular dysfunction in healthy NHB adults.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Self-identify as either non-Hispanic Black or non-Hispanic White.
- •Men and women 18-75 years old.
- •Non-hypertensive (systolic blood pressure [SBP]<130 and diastolic blood pressure [DBP] <85 mmHg).
- •Have low density lipoprotein cholesterol <150mg/dl.
- •Have HbA1C <6.0%.
Exclusion Criteria
- •Rash, skin disease, or disorders of pigmentation (e.g., psoriasis, eczema, vitiligo, or other skin inflammatory skin disorders)
- •Known skin allergies to latex or adhesives
- •Smoking and/or use of nicotine-containing products within the past year
- •Use of illegal/recreational drugs
- •Generalized kidney disease
- •Taking chloramphenicol, cholestyramine, medication for seizures, methotrexate, nitrofurantoin, tetracycline, barbiturates, steroids, phenobarbital/phenytoin, orlistat or pyrimethamine
- •Any current medications which could conceivably alter the cardiovascular control or responses
- •Diagnosed or suspected metabolic or cardiovascular disease
- •Current pregnancy or breastfeeding
- •History of skin or other cancers
- •Diagnosed or suspected diabetes (HbA1c ≥6.0)
- •Anybody with narcolepsy or who has been diagnosed with any condition that impairs body temperature regulation.
Arms & Interventions
Placebo, then MitoQ
Participants will be given a single dose of Placebo (matched to 80mg MitoQ) first following an overnight fast. Then they will receive 80mg MitoQ supplement single dose within a minimum of 14 days
Intervention: Placebo (Dietary Supplement)
MitoQ, then Placebo
Participants will be given a single dose of 80mg MitoQ supplement first following an overnight fast. Then they will receive a matched Placebo single dose within a minimum 14 days
Intervention: MitoQ (Dietary Supplement)
MitoQ, then Placebo
Participants will be given a single dose of 80mg MitoQ supplement first following an overnight fast. Then they will receive a matched Placebo single dose within a minimum 14 days
Intervention: Placebo (Dietary Supplement)
MitoQ, then Placebo
Participants will be given a single dose of 80mg MitoQ supplement first following an overnight fast. Then they will receive a matched Placebo single dose within a minimum 14 days
Intervention: MitoTempo (Drug)
MitoQ, then Placebo
Participants will be given a single dose of 80mg MitoQ supplement first following an overnight fast. Then they will receive a matched Placebo single dose within a minimum 14 days
Intervention: Tempol (Drug)
MitoQ, then Placebo
Participants will be given a single dose of 80mg MitoQ supplement first following an overnight fast. Then they will receive a matched Placebo single dose within a minimum 14 days
Intervention: L-NAME (Drug)
MitoQ, then Placebo
Participants will be given a single dose of 80mg MitoQ supplement first following an overnight fast. Then they will receive a matched Placebo single dose within a minimum 14 days
Intervention: SNP - Sodium Nitroprusside (Drug)
Placebo, then MitoQ
Participants will be given a single dose of Placebo (matched to 80mg MitoQ) first following an overnight fast. Then they will receive 80mg MitoQ supplement single dose within a minimum of 14 days
Intervention: MitoQ (Dietary Supplement)
Placebo, then MitoQ
Participants will be given a single dose of Placebo (matched to 80mg MitoQ) first following an overnight fast. Then they will receive 80mg MitoQ supplement single dose within a minimum of 14 days
Intervention: MitoTempo (Drug)
Placebo, then MitoQ
Participants will be given a single dose of Placebo (matched to 80mg MitoQ) first following an overnight fast. Then they will receive 80mg MitoQ supplement single dose within a minimum of 14 days
Intervention: Tempol (Drug)
Placebo, then MitoQ
Participants will be given a single dose of Placebo (matched to 80mg MitoQ) first following an overnight fast. Then they will receive 80mg MitoQ supplement single dose within a minimum of 14 days
Intervention: L-NAME (Drug)
Placebo, then MitoQ
Participants will be given a single dose of Placebo (matched to 80mg MitoQ) first following an overnight fast. Then they will receive 80mg MitoQ supplement single dose within a minimum of 14 days
Intervention: SNP - Sodium Nitroprusside (Drug)
Outcomes
Primary Outcomes
Cutaneous microvascular responses to local heating
Time Frame: 1 hour post intervention
Using intradermal microdialysis, skin blood vessels will be locally treated with a mitochondria-targeted antioxidant (MitoTempo; 1 mM concentration). Nitric oxide (NO)-mediated skin vasodilation will be quantified via local inhibition of endothelial NO synthase during the course of the local skin heating protocol using L-NAME (15 mM concentration). Finally, maximal skin blood flow will be measured by heating the local area of skin to 43 degrees Celsius and locally perfusing sodium nitroprusside (SNP; an NO donor; 28 mM concentration). Two (2) thin fiber optic laser Doppler flowmeter probes and their holders, containing local heaters, will be used to measure skin blood flow.
Mitochondrial ROS production in peripheral blood mononuclear cells (PBMCs)
Time Frame: 1 hour post intervention
Blood will be drawn for isolation of PBMCs and measurement of mitochondrial function and oxidative stress production.
Flow-mediated dilation responses
Time Frame: 1 hour post intervention
FMD measures the health of blood vessels. The ultrasound makes sound waves to measure the size of blood vessels and the speed of the blood during rest and occlusion. The cuff is inflated to 220 mmHg (a commonly-used suprasystolic pressure; i.e., arterial blood flow is completely occluded) for 5 minutes to stop blood flow to and from the forearm.
Secondary Outcomes
No secondary outcomes reported
Investigators
S. Tony Wolf
Assistant Professor
University of Georgia