Effects of an Antioxidant Supplement on Blood Vessel Health

Role of Mitochondria-derived Oxidative Stress on Microvascular Endothelial Function in Healthy Non-Hispanic Black and White Adults

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 Overview

• Status: Recruiting
• Conditions: Healthy
• Intervention / Treatment: Dietary supplement: MitoQ; Dietary supplement: Placebo; Drug: MitoTempo; Drug: Tempol; Drug: L-NAME; Drug: SNP - Sodium Nitroprusside

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: S. Tony Wolf; Phone Number: 706-542-4378; Email: stwolf@uga.edu
• Study Contact Backup: Name: Melissa Gorejena; Email: mgorejena@uga.edu

Study Locations

• United States
  • Georgia
    • Athens, Georgia, United States, 30602
      • Recruiting
      • Ramsey Student Center, University of Georgia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Dietary supplement: MitoQ; MitoQ supplement is composed of mitoquinol mesylate, which is a synthetic analog of coenzyme Q10; Dietary supplement: Placebo; MitoQ matched Placebo; Drug: MitoTempo; During each experimental visit, intradermal microdialysis will be used to locally infuse MitoTempo (a mitochondria-specific superoxide dismutase mimetic) into the cutaneous microvasculature in the ventral aspect of the left forearm.; Drug: Tempol; During each experimental visit, intradermal microdialysis will be used to locally infuse Tempol (a superoxide dismutase mimetic) into the cutaneous microvasculature in the ventral aspect of the left forearm.; Drug: L-NAME; During each experimental visit, L-NAME (nitric oxide synthase inhibitor) will be perfused through microdialysis fibers for quantification of nitric oxide-mediated vasodilation.; Drug: SNP - Sodium Nitroprusside; At the end of each experimental visit, SNP will be perfused through microdialysis fibers to elicit a maximal vasodilation response.
Experimental: 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	Dietary supplement: MitoQ; MitoQ supplement is composed of mitoquinol mesylate, which is a synthetic analog of coenzyme Q10; Dietary supplement: Placebo; MitoQ matched Placebo; Drug: MitoTempo; During each experimental visit, intradermal microdialysis will be used to locally infuse MitoTempo (a mitochondria-specific superoxide dismutase mimetic) into the cutaneous microvasculature in the ventral aspect of the left forearm.; Drug: Tempol; During each experimental visit, intradermal microdialysis will be used to locally infuse Tempol (a superoxide dismutase mimetic) into the cutaneous microvasculature in the ventral aspect of the left forearm.; Drug: L-NAME; During each experimental visit, L-NAME (nitric oxide synthase inhibitor) will be perfused through microdialysis fibers for quantification of nitric oxide-mediated vasodilation.; Drug: SNP - Sodium Nitroprusside; At the end of each experimental visit, SNP will be perfused through microdialysis fibers to elicit a maximal vasodilation response.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cutaneous microvascular responses to local heating	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.	1 hour post intervention
Flow-mediated dilation responses	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.	1 hour post intervention
Mitochondrial ROS production in peripheral blood mononuclear cells (PBMCs)	Blood will be drawn for isolation of PBMCs and measurement of mitochondrial function and oxidative stress production.	1 hour post intervention

Collaborators and Investigators

• Sponsor: University of Georgia

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2024
• Primary Completion (Estimated): March 31, 2030
• Study Completion (Estimated): March 31, 2030

Study Registration Dates

• First Submitted: May 16, 2024
• First Submitted That Met QC Criteria: May 16, 2024
• First Posted (Actual): May 22, 2024

Study Record Updates

• Last Update Posted (Estimated): December 9, 2024
• Last Update Submitted That Met QC Criteria: December 4, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Cardiovascular disease; Hypertension; Endothelial function; Nitric oxide; Vascular dysfunction
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antioxidants; Protective Agents; Protein Synthesis Inhibitors; Vasodilator Agents; Neuroprotective Agents; Antihypertensive Agents; Radiation-Protective Agents; Nitric Oxide Donors; Tempol; Nitroprusside
• Other Study ID Numbers: PROJECT00009286

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes