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

NCT04851288 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 20-0502R01AG066730
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Aging

Outcome Measures

Primary Outcomes (1)

• Change from baseline in endothelial function at 3 months

  Brachial artery flow-mediated dilation

  3 months

Secondary Outcomes (2)

• Change from baseline in suppression of endothelial function by mitochondrial oxidative stress at 3 months

  3 months

• Change from baseline in aortic stiffness at 3 months

  3 months

Other Outcomes (10)

• Change from baseline in serum exposure-induced endothelial cell reactive oxygen species production at 3 months

  3 months

• Change from baseline in endothelial cell markers of oxidative stress and mitochondrial health from baseline at 3 months

  3 months

• Change from baseline in carotid artery stiffness at 3 months

  3 months

Study Arms (2)

MitoQ, 20 mg/day

EXPERIMENTAL

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

Dietary Supplement: MitoQ

Placebo

PLACEBO COMPARATOR

Matched placebo capsules.

Dietary Supplement: Placebo

Interventions

MitoQ DIETARY_SUPPLEMENT

MitoQ is a biochemically modified form of ubiquinol

Also known as: Mitoquinol

MitoQ, 20 mg/day

Placebo DIETARY_SUPPLEMENT

Each placebo capsule contains inert excipient and is identical in appearance

Placebo

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Colorado, Boulder: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

University of Colorado Boulder

Boulder, Colorado, 80309, United States

Location

Related Publications (2)

• Oh ES, Opoku G, Darvish S, Craighead DH, Ostrow A, Rossman MJ, Steele CN, Struemph T, You Z, Seals DR, Chonchol M, Nowak KL. Sex Differences in Dementia and Mild Cognitive Impairment in Nondialysis CKD. Clin J Am Soc Nephrol. 2025 Nov 20. doi: 10.2215/CJN.0000000922. Online ahead of print. No abstract available.

  PMID: 41264372 DERIVED

• 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.

  PMID: 36187760 DERIVED

MeSH Terms

Interventions

mitoquinone; mitoquinol

Study Officials

• Douglas R Seals

  University of Colorado, Boulder

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 7, 2021
• First Posted: April 20, 2021
• Study Start: April 2, 2021
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: November 12, 2025

Record last verified: 2025-11

Locations

US (1)