NCT04851288

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

Active, enrolled Phase 2 Last updated 7 November 2025

What this trial tests

Phase 2 trial testing MitoQ in Aging in 112 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

2 April 2021

Primary endpoint
1 December 2025

1 December 2026

Quick facts

Lead sponsor	University of Colorado, Boulder
Phase	Phase 2
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	other
Enrollment	112
Start date	2 April 2021
Primary completion	1 December 2025
Estimated completion	1 December 2026
Sites	1 location across United States

Drugs / interventions tested

• MitoQ — full drug profile →
• Placebo

Conditions studied

• Aging — all drugs for Aging →

Sponsor

University of Colorado, Boulder

Who can join

60 and older, any sex, with Aging. Healthy volunteers can join.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Change from baseline in endothelial function at 3 months
  Time frame: 3 months
  Brachial artery flow-mediated dilation

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Mitochondrial dysfunction: mechanisms and advances in therapy.
   Zong Y, Li H, Liao P, Chen L, et al · · 2024 · cited 614× · PMID 38744846 · DOI 10.1038/s41392-024-01839-8
2. Aging, aerobic exercise, and cardiovascular health: Barriers, alternative strategies and future directions.
   Murray KO, Mahoney SA, Venkatasubramanian R, Seals DR, et al · · 2023 · cited 32× · PMID 36731386 · DOI 10.1016/j.exger.2023.112105
3. Multifaceted functions of Drp1 in hypoxia/ischemia-induced mitochondrial quality imbalance: from regulatory mechanism to targeted therapeutic strategy.
   Hao S, Huang H, Ma RY, Zeng X, et al · · 2023 · cited 28× · PMID 37833768 · DOI 10.1186/s40779-023-00482-8
4. Mitochondrial-targeted antioxidant supplementation for improving age-related vascular dysfunction in humans: A study protocol.
   Murray KO, Berryman-Maciel M, Darvish S, Coppock ME, et al · · 2022 · cited 24× · PMID 36187760 · DOI 10.3389/fphys.2022.980783
5. Promoting healthy cardiovascular aging: emerging topics.
   Clayton ZS, Craighead DH, Darvish S, Coppock M, et al · · 2022 · cited 19× · PMID 36337728 · DOI 10.20517/jca.2022.27
6. LKB1-SIK2 loss drives uveal melanoma proliferation and hypersensitivity to SLC8A1 and ROS inhibition.
   Proteau S, Krossa I, Husser C, Guéguinou M, et al · · 2023 · cited 14× · PMID 37966164 · DOI 10.15252/emmm.202317719
7. From Physiology to Pathology: The Role of Mitochondria in Acute Kidney Injuries and Chronic Kidney Diseases.
   Zhang L, Miao M, Xu X, Bai M, et al · · 2023 · cited 14× · PMID 37901706 · DOI 10.1159/000530485
8. The Therapeutic Strategies Targeting Mitochondrial Metabolism in Cardiovascular Disease.
   Huang X, Zeng Z, Li S, Xie Y, et al · · 2022 · cited 14× · PMID 36559254 · DOI 10.3390/pharmaceutics14122760