The Mito-Frail Trial: Effects of MitoQ on Vasodilation, Mobility and Cognitive Performance in Frail Older Adults

NCT ID: NCT06027554

Last Updated: 2026-01-09

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-10-07
• Study Completion Date: 2028-02-01

Brief Summary

The goal of this clinical trial is to test the effects of MitoQ supplementation in older adults and frail older adults with physical dysfunction and/or cognitive dysfunction. The main question[s] it aims to answer are:

• To compare vascular function, oxidative stress levels, and physical and cognitive function among older adults and frail older adults with physical and cognitive dysfunction
• To determine whether MitoQ supplementation has the potential to improve vascular function in central and cerebral vessels
• To determine whether MitoQ supplementation can enhance physical and cognitive capabilities.

Detailed Description

Chronic diseases and associated declines in physical and cognitive performance contribute greatly to lost independence with aging. In addition to a lack of effective interventions other than exercise to address either problem, few studies have examined strategies for targeting both conditions in frail individuals who may experience difficulties with both walking and memory. Use of geroscience-guided therapies permits us to target mechanisms shared by aging with chronic conditions for which aging represents a major risk factor. Thus, instead of focusing on one single disease at a time, it may be possible to delay the onset and progression of disability involving multiple functional domains.

Gait speed is predictive of mobility, morbidity, and mortality in older adults. Vasoreactivity is a critical cerebrovascular control mechanism used to maintain brain perfusion during metabolic demands such as walking. In contrast to healthy older adults, middle cerebral artery blood flow velocities fail to increase proportionally in response to walking speed in slow walkers. Thus, abnormalities in vasoreactivity and perfusion adaptation to metabolic demands may reflect and contribute to declines in gait speed.

Mild cognitive impairment (MCI), an intermediate condition between normal cognitive performance and dementia, significantly increases the risk of transitioning dementia caused by Alzheimer's disease (AD). Moreover, changes in physical and cognitive function frequently co-exist in the same individual and influence each other.

In the absence of other effective therapies, modifiable cardiovascular risk factors (e.g., hypertension, atherosclerosis, cerebral hypoperfusion) represent opportunities to prevent declines in physical and cognitive function by targeting the vascular endothelium and vasodilation.

Physiological reactive oxygen species (ROS) levels play critical roles in cerebral vasculature, which can contribute to the regulation of brain perfusion through their action in vascular tone control. Of the many potential cellular sources of ROS in the vasculature, mitochondria are the major source in endothelium regulation of vascular homeostasis and are associated with aging and cardiovascular disease. Specifically, mitochondrialtargeted antioxidant, MitoQ, improves vascular endothelial function by reducing mitochondrial ROS (mtROS) in older adults and animal models.

Investigators have recently shown that MitoQ, a mitochondria-targeted antioxidant known to improve endothelial function and Nitric Oxide (NO) bioavailability, also restore impaired flow-mediated vasodilation in frail older adults, enhancing gait speed. In the Mito-Frail study, investigators will explore the hypothesis that MitoQ attenuates aging-related declines in flow-mediated vasodilation involving both peripheral and cerebral blood vessels. At the same time, investigators will obtain feasibility and pilot data involving measures of physical mobility and cognitive performance that may help us design and power a future clinical trial. Thus, this study will seek to develop strategies for preventing or slowing the progression of Alzheimer's Disease and the vascular contribution to dementia.

Therefore, Aim 1 will assess peripheral and cerebral NO bioavailability and mitochondrial reactive oxygen species (mtROS) levels in older adults who are healthy, others who are frail with slow walking speed and those who meet criteria for mild cognitive impairment (MCI). Aim 2 will determine whether MitoQ supplementation can enhance NO bioavailability and improve declines in flow-mediated vasodilation central and cerebral vessels.

Moreover, this study will also generate physical performance and cognitive data needed to design and power a future clinical trial focused on these functional outcomes.

Conditions

Frailty; Mild Cognitive Impairment; Aging

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Placebo capsule

Gelatin capsules

Group Type: PLACEBO_COMPARATOR

Placebo capsule

Intervention Type: DIETARY_SUPPLEMENT

Placebo capsule taken every day for 12 weeks.

MitoQ capsule

Capsules containing mitoquinone mesylate (MitoQ, 5 mg/capsule) totaling 20 mg taken every day for 12 weeks.

Group Type: EXPERIMENTAL

Mitoquinone Mesylate

Intervention Type: DRUG

MitoQ given 20 mg per day for 12 weeks.

Interventions

Mitoquinone Mesylate

MitoQ given 20 mg per day for 12 weeks.

Intervention Type: DRUG

Placebo capsule

Placebo capsule taken every day for 12 weeks.

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

• men and women aged 65-80 with a slow gait speed (0.4m/s based on a 4m walk) and/or mild cognitive impairment.
• good cardiovascular health (not taking any blood pressure/flow/metabolism altering medications)

Exclusion Criteria

• A vaccination in past two weeks
• Recent acute infection three weeks prior to enrollment
• Known immunodeficiency (including HIV infection, primary immunodeficiency, any history of chemotherapy or radiotherapy
• Use of medicines during past 6 months known to alter immune response such as high- dose corticosteroids
• Severe autoimmune disease requiring biological therapy
• Major severe illness and/or Hospitalization in past 3 months
• On warfarin or other medications that are considered a blood thinner
• Recent fall or other conditions that will impair ability to complete and/or interpret mobility performance test
• Known bleeding disorder
• Any conditions that would impair the function to perform grip strength test
• include advanced neurological disease, severe co-morbid disease, terminal illness with reduced life expectancy, severe disability, unintentional weight loss in last 12 months and participation in another study.
• Diabetes patients requiring insulin (For reducing the risk that participants will have hypoglycemic episodes when fasting for study visits)
• Baseline ECG QTc >450 ms in men and QTc >460 ms in women
• Prior diagnosis of ventricular arrhythmia (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes)

• Minimum Eligible Age: 65 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

University of Connecticut

OTHER

Sponsor Role: collaborator

UConn Health

OTHER

Sponsor Role: lead

Responsible Party

Oh Sung Kwon

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Oh Sung Kwon, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Connecticut

Locations

UConn Health

Farmington, Connecticut, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Oh Sung Kwon, PhD

Role: CONTACT

ohsung.kwon@uconn.edu

860-486-1120

Facility Contacts

George Kuchel, MD

Role: primary

kuchel@uchc.edu

860-679-6796

Other Identifiers

1K01AG080164-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

AG220138

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

23-132S-1

Identifier Type: -

Identifier Source: org_study_id