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

Phase 2

Recruiting

• Conditions: Aging
• Interventions: Dietary Supplement: MitoQ; Dietary Supplement: Placebo

• Registration Number: NCT04851288
• Lead Sponsor: University of Colorado, Boulder

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-04-02
• Study First Submitted: 2021-04-07
• Study First Submitted QC: 2021-04-16
• Study First Posted: 2021-04-20
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-13
• Last Update Posted: 2024-02-15
• Primary Completion: 2025-08
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 112

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MitoQ, 20 mg/day	MitoQ	Each MitoQ capsule contains 20 mg of mitoquinol mesylate. Dosage: 20 mg orally per day for 3 months.
Placebo	Placebo	Matched placebo capsules.

Primary Outcome Measures

Name	Time	Method
Change from baseline in endothelial function at 3 months	3 months	Brachial artery flow-mediated dilation

Secondary Outcome Measures

Name	Time	Method
Change from baseline in suppression of endothelial function by mitochondrial oxidative stress at 3 months	3 months	Change in brachial artery flow-mediated dilation with acute, supratherapeutic MitoQ (160mg)
Change from baseline in aortic stiffness at 3 months	3 months	Carotid-femoral pulse wave velocity

Trial Locations

Locations (1)

University of Colorado Boulder; 🇺🇸 Boulder, Colorado, United States