The Influence of Mitochondrial-Derived Reactive Oxygen Species on Racial Disparities in Neurovascular Function

NCT04334135 | Recruiting DMC

• 1 other identifier: AU IRB#20-105
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Black individuals are at increased cardiovascular disease risk. The central goal of the study is to determine if mitochondrial reactive oxygen species influence blood vessel function and nervous system regulation of blood pressure differentially in black, compared to white individuals. These findings may help to explain a potential mechanism that contributes to racial disparities in blood pressure and cardiovascular disease risk. A secondary goal is to determine if mitochondrial reactive oxygen species improves blood pressure and vascular function in individuals with elevated blood pressure and stage 1 hypertension.

Conditions

Racial Disparities; Blood Pressure; Cardiovascular Risk Factor; Renal Function

Keywords

blood pressure; hypertension; cardiovascular health; renal function; health disparities

Outcome Measures

Primary Outcomes (6)

• Changes in flow-mediated dilation (FMD)

  Flow-mediated vasodilation will be assessed using continuous measures of brachial artery diameter and velocity via duplex Doppler ultrasound (Hitachi Arietta 70). The brachial artery will be imaged in the longitudinal plane proximal to the medial epicondyle using a high-frequency (6-12 MHz) linear-array probe. The ultrasound probe will be stabilized using a custom-built clamp. Shear rate (sec-1) will be calculated as \[(blood flow velocity (cm\*s-1) \*4)/blood vessel diameter (mm)\] The image will be recorded throughout a 60-s baseline, a 300-s ischemic stimulus (250 mmHg), and 180 seconds post deflation. FMD will be expressed as % dilation (final diameter-baseline diameter/baseline diameter x 100) and also normalized to the shear stimulus. Allometric scaling will be used if appropriate, including if there are baseline differences in artery diameter by race or condition.

  Before and one hour after supplementation or placebo

• Changes in indices of arterial stiffness

  The investigators will use the SphygmoCor XCEL system to assess pulse wave analysis (PWA) and pulse wave velocity (PWV). A high-fidelity strain-gauge transducer is used to obtain the pressure waveform at the carotid and radial pulse. Distances from the carotid artery sampling site to the femoral artery (upper leg instrumented with a thigh cuff for oscillometric sphygmomanometry), and from the carotid artery to the suprasternal notch will be recorded. The investigators will also assess forward and reflective wave magnitudes. PWV will be expressed as cm/s and PWA will be expressed as % (calculated as augmentation pressure divided by the pulse pressure).

  Before and one hour after supplementation or placebo

• Changes in muscle sympathetic nerve activity (MSNA) and sympathetic transduction

  The investigators will directly record MSNA using an active tungsten microelectrode inserted into a nerve near the fibular head or popliteal fossa using standard microneurography techniques. The raw signal will be amplified, band-pass filtered, rectified, and integrated using a nerve traffic analyzer. The presence of MSNA will be confirmed by a pulse-synchronous signal that responds to an end-expiratory breath-hold and stimulation of muscle (tendon tapping), but not skin afferents (gentle skin stroke and/or startle stimulus). MSNA will be expressed as bursts per minute and per 100 cardiac cycles. Further, the investigators will measure common femoral artery blood flow using ultrasound and mean arterial pressure using photoplethysmography. This will allow determination of sympathetic transduction (the vasoconstrictor and pressor effects of MSNA) expressed as changes in blood pressure (mmHg) or changes in vascular conductance (ml blood flow/mmHg).

  Before and one hour after supplementation or placebo

• Changes in blood pressure reactivity

  The investigators will measure systolic and diastolic pressure using photoplethysmography at the finger. Systolic and diastolic blood pressure will be assessed at rest and during handgrip exercise. Blood pressure reactivity will be expressed as a change in pressure (mmHg) from baseline to a predetermined time during the stressor (e.g., minute one average and minute two average).

  Before and one hour after supplementation or placebo

• Changes in circulating reactive oxygen species

  We will use electron paramagnetic resonance to measure reactive oxygen species (spectra units) in whole blood samples treated with a spin probe.

  Before and one hour after supplementation or placebo

• Changes in blood biomarkers of nitric oxide bioavailability

  The investigators will measure nitric oxide metabolites (nitrate and nitrite nanomolar concentration).

  Before and one hour after supplementation or placebo

Secondary Outcomes (7)

• Objective sleep duration and quality

  Baseline (pre-intervention)

• Subjective sleep duration and quality

  Baseline (pre-intervention)

• Physical activity

  Baseline (pre-intervention)

• Cardiorespiratory fitness

  Baseline (pre-intervention)

• Mental health - social anxiety

  Baseline (pre-intervention)

Study Arms (2)

MitoQ

EXPERIMENTAL

Participants will have sympathetic nerve activity, vascular function, blood pressure and blood samples (from intravenous catheters) assessed before and after acute MitoQ supplementation (80 - 160mg).

Dietary Supplement: MitoQ

Placebo

PLACEBO COMPARATOR

Participants will have sympathetic nerve activity, vascular function, blood pressure and blood samples (from intravenous catheters) assessed before and after a placebo matched in appearance to the MitoQ.

Dietary Supplement: MitoQ

Interventions

MitoQ DIETARY_SUPPLEMENT

Four to eight 20mg capsules (depending on body mass)

MitoQ; Placebo

Eligibility Criteria

• Age: 19 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Are between the ages of 19-75.
• Have blood pressure no higher than 150/90 mmHg.
• Have a BMI below 35 Kg/m2 (otherwise healthy)
• Free from metabolic disease (diabetes or renal disease), pulmonary disorders (e.g., COPD \& cystic fibrosis), and cardiovascular disease (peripheral vascular, cardiac, or cerebrovascular).
• Do not have any precluding medical issues that prevent participants from exercising (i.e., cardiovascular issues, or muscle/joint issues including painful arthritis) or giving blood (e.g., blood thinners).
• Are not currently smoking, using smokeless tobacco, nor smoked within the past 12 months.

You may not qualify if:

• Known allergy to MitoQ
• High blood pressure - greater the 150/90 mmHg
• Low blood pressure - less than 90/50 mmHg
• History of cardiovascular disease
• History of cancer
• History of diabetes
• History of kidney disease
• Obesity (BMI \> 30 kg/m2)
• Smoking or tobacco use
• Current pregnancy
• Nursing mothers
• Communication barriers

Sponsors & Collaborators

• Auburn University: lead

Study Sites (1)

Kinesiology Building

Auburn, Alabama, 36849, United States

RECRUITING

Related Publications (1)

• Culver MN, Linder BA, Lyons DE, Hutchison ZJ, Garrett CL, McNeil JN, Robinson AT. Do not sleep on vitamin D: vitamin D is associated with sleep variability in apparently healthy adults. Am J Physiol Regul Integr Comp Physiol. 2025 Mar 1;328(3):R262-R273. doi: 10.1152/ajpregu.00168.2024. Epub 2025 Jan 28.

  PMID: 39873709 DERIVED

MeSH Terms

Conditions

Hypertension

Interventions

mitoquinone

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Central Study Contacts

Austin T Robinson, PhD

CONTACT

334 844 1619; atr0026@auburn.edu

Zachary J Hutchison, MS

CONTACT

zzh0026@auburn.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The member of the study team performing data analysis will be blinded when performing data analysis and unblinded after final statistical analysis
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: The intervention is to provide subjects with either a mitochondrial antioxidant, MitoQ (no more than 160 mg) and a placebo (dextrin and silica), in a randomized order.

Study Record Dates

• First Submitted: April 2, 2020
• First Posted: April 6, 2020
• Study Start: October 2, 2020
• Primary Completion: July 31, 2025
• Study Completion: August 31, 2025
• Last Updated: May 29, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: One year after completion of trial, indefinitely
• Access Criteria: A formal plan identifying the intended use of the data and proper completion of a DMDA and MTA (if needed) with Auburn University and the study PI.

Locations

US (1)