Mitochondrial-targeted Antioxidant Supplementation for Improving Age-related Vascular Dysfunction in Humans

NCT ID: NCT04851288

Last Updated: 2025-11-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

112 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-04-02

Study Completion Date

2026-12-31

Brief Summary

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The majority of cardiovascular diseases (CVD) occur in men and women ≥60 years of age. Vascular dysfunction, including endothelial dysfunction, as assessed by reduced endothelium-dependent dilation (EDD), and stiffening of the large elastic arteries (i.e., aortic and carotid artery stiffening), is a major mechanism of increased risk of CVD in older adults. Excess production of ROS (reactive oxygen species) by mitochondria (mtROS) has emerged as a central feature of vascular oxidative stress with aging and driver of age-related vascular dysfunction. As such, identifying novel strategies to decrease mtROS and improve vascular function, to ultimately reduce the risk of age-related CVD, is an important biomedical objective.

MitoQ is a mitochondria-targeted antioxidant that accumulates at the inner mitochondrial membrane where it is optimally positioned to reduce mtROS. Preclinical findings showed that 4 weeks of oral MitoQ supplementation completely restored EDD in old mice, ameliorated mtROS-associated suppression of EDD, and was associated with reduced arterial mtROS, oxidative stress, and improved mitochondrial health. MitoQ therapy also reduced aortic stiffness in old mice. A recent small pilot study of older adults (n=20) found that supplementation with MitoQ was well-tolerated, improved endothelial function, and reduced plasma levels of oxidized low-density lipoprotein, a circulating biomarker of oxidative stress. Consistent with the preclinical findings, preliminary mechanistic assessments in subsets of subjects from the pilot study suggested that improved endothelial function with MitoQ was mediated by reduced endothelial cell mtROS production, associated reductions in tonic mtROS-related suppression of EDD, and improved mitochondrial health, linked in part to changes in circulating factors in the serum induced by chronic MitoQ supplementation. Lastly, MitoQ reduced aortic stiffness in older adults who exhibited age-related aortic stiffening at baseline.

The investigators are conducting a randomized, placebo-controlled, double-blind clinical trial to establish oral MitoQ (20 mg/day; MitoQ, Ltd.) for 3 months vs. placebo (n=56/group) for improving endothelial function in older men and women (≥60 years), and determine the mechanisms by which MitoQ improves endothelial function. The investigators will also assess the effect of MitoQ on aortic stiffness.

Detailed Description

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Conditions

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Aging

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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MitoQ, 20 mg/day

Each MitoQ capsule contains 20 mg of mitoquinol mesylate. Dosage: 20 mg orally per day for 3 months.

Group Type EXPERIMENTAL

MitoQ

Intervention Type DIETARY_SUPPLEMENT

MitoQ is a biochemically modified form of ubiquinol

Placebo

Matched placebo capsules.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DIETARY_SUPPLEMENT

Each placebo capsule contains inert excipient and is identical in appearance

Interventions

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MitoQ

MitoQ is a biochemically modified form of ubiquinol

Intervention Type DIETARY_SUPPLEMENT

Placebo

Each placebo capsule contains inert excipient and is identical in appearance

Intervention Type DIETARY_SUPPLEMENT

Other Intervention Names

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Mitoquinol

Eligibility Criteria

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Inclusion Criteria

* Age 60 years and over
* Ability to provide informed consent
* Willing to accept random assignment to condition
* Body mass index \<40 kg/m2
* Weight stable in the prior 3 months (\<2 kg weight change) and willing to remain weight stable throughout the study
* Free from alcohol dependence or abuse,
* Mini-mental stage examination score ≥21

Exclusion Criteria

* Uncontrolled thyroid disease
* Regular vigorous aerobic (\>6 bouts/week, \>60 min/bout at a workload \>6 METS)
* Blood donation within 8 weeks prior to enrolling in the study
Minimum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute on Aging (NIA)

NIH

Sponsor Role collaborator

University of Colorado, Boulder

OTHER

Sponsor Role lead

Responsible Party

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Douglas Seals

PI

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Douglas R Seals

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Boulder

Locations

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University of Colorado Boulder

Boulder, Colorado, United States

Site Status

Countries

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United States

References

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Murray KO, Berryman-Maciel M, Darvish S, Coppock ME, You Z, Chonchol M, Seals DR, Rossman MJ. Mitochondrial-targeted antioxidant supplementation for improving age-related vascular dysfunction in humans: A study protocol. Front Physiol. 2022 Sep 15;13:980783. doi: 10.3389/fphys.2022.980783. eCollection 2022.

Reference Type DERIVED
PMID: 36187760 (View on PubMed)

Other Identifiers

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R01AG066730

Identifier Type: NIH

Identifier Source: secondary_id

View Link

20-0502

Identifier Type: -

Identifier Source: org_study_id