Effects of an Antioxidant Supplement on Blood Vessel Health

NCT06424756 | Recruiting Phase 2 FDA Drug

• 1 other identifier: PROJECT00009286
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

Vascular dysfunction; Cardiovascular disease; Hypertension; Nitric oxide; Endothelial function

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (2)

MitoQ, then Placebo

EXPERIMENTAL

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; Dietary Supplement: Placebo; Drug: MitoTempo; Drug: Tempol; Drug: L-NAME; Drug: SNP - Sodium Nitroprusside

Placebo, then MitoQ

EXPERIMENTAL

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; Dietary Supplement: Placebo; Drug: MitoTempo; Drug: Tempol; Drug: L-NAME; Drug: SNP - Sodium Nitroprusside

Interventions

MitoQ DIETARY_SUPPLEMENT

MitoQ supplement is composed of mitoquinol mesylate, which is a synthetic analog of coenzyme Q10

MitoQ, then Placebo; Placebo, then MitoQ

Placebo DIETARY_SUPPLEMENT

MitoQ matched Placebo

MitoQ, then Placebo; Placebo, then MitoQ

MitoTempo DRUG

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.

MitoQ, then Placebo; Placebo, then MitoQ

Tempol DRUG

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.

MitoQ, then Placebo; Placebo, then MitoQ

L-NAME DRUG

During each experimental visit, L-NAME (nitric oxide synthase inhibitor) will be perfused through microdialysis fibers for quantification of nitric oxide-mediated vasodilation.

MitoQ, then Placebo; Placebo, then MitoQ

SNP - Sodium Nitroprusside DRUG

At the end of each experimental visit, SNP will be perfused through microdialysis fibers to elicit a maximal vasodilation response.

MitoQ, then Placebo; Placebo, then MitoQ

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Georgia: lead

Study Sites (1)

Ramsey Student Center, University of Georgia

Athens, Georgia, 30602, United States

RECRUITING

MeSH Terms

Conditions

Cardiovascular Diseases; Hypertension

Interventions

mitoquinone; MitoTEMPO; tempol; NG-Nitroarginine Methyl Ester

Condition Hierarchy (Ancestors)

Vascular Diseases

Intervention Hierarchy (Ancestors)

Arginine; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino

Central Study Contacts

S. Tony Wolf

CONTACT

706-542-4378; stwolf@uga.edu

Melissa Gorejena

CONTACT

mgorejena@uga.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: For the experimental visits, participants will receive an antioxidant supplement in capsule form or a matching placebo pill in a randomized, double-blinded, crossover fashion. During each visit, participants will be given a single dose of the treatment to which they are randomized upon arrival at the laboratory (i.e., either 80 mg MitoQ or placebo will be administered on Visit 3, and the other treatment will be given on Visit 4). Peak concentrations of the antioxidant (MitoQ) occur after approximately 1 hour, allowing for appropriate time to prepare the participant for the experimental procedures.

Study Record Dates

• First Submitted: May 16, 2024
• First Posted: May 22, 2024
• Study Start: July 1, 2024
• Primary Completion (Estimated): March 31, 2030
• Study Completion (Estimated): March 31, 2030
• Last Updated: December 9, 2024

Record last verified: 2024-12

Locations

US (1)