ACTIVE_NOT_RECRUITING

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

Conditions

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

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.

Official Title

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

Quick Facts

Study Start:2021-04-02
Study Completion:2026-12
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:ACTIVE_NOT_RECRUITING

Study ID

NCT04851288

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:60 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:Yes
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * Age 60 years and over
  2. * Ability to provide informed consent
  3. * Willing to accept random assignment to condition
  4. * Body mass index \<40 kg/m2
  5. * Weight stable in the prior 3 months (\<2 kg weight change) and willing to remain weight stable throughout the study
  6. * Free from alcohol dependence or abuse,
  7. * Mini-mental stage examination score ≥21
  1. * Uncontrolled thyroid disease
  2. * Regular vigorous aerobic (\>6 bouts/week, \>60 min/bout at a workload \>6 METS)
  3. * Blood donation within 8 weeks prior to enrolling in the study

Contacts and Locations

Principal Investigator

Douglas R Seals
PRINCIPAL_INVESTIGATOR
University of Colorado, Boulder

Study Locations (Sites)

University of Colorado Boulder
Boulder, Colorado, 80309
United States

Collaborators and Investigators

Sponsor: University of Colorado, Boulder

  • Douglas R Seals, PRINCIPAL_INVESTIGATOR, University of Colorado, Boulder

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-04-02
Study Completion Date2026-12

Study Record Updates

Study Start Date2021-04-02
Study Completion Date2026-12

Terms related to this study

Additional Relevant MeSH Terms

  • Aging