Impacts of Mitochondrial-targeted Antioxidant on Peripheral Artery Disease Patients

NCT ID: NCT03506633

Last Updated: 2025-04-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-05
• Study Completion Date: 2022-01-17

Brief Summary

Peripheral artery disease (PAD) is a common cardiovascular disease, in which narrowed arteries reduce blood flow to the limbs, causing pain, immobility and in some cases amputation or death. PAD patients have shown higher levels of systemic and skeletal muscle inflammation due to the impaired oxygen transfer capacity of these blood vessels. This attenuated oxygen transfer capacity causes hypoxic conditions in the skeletal muscle and results in mitochondrial dysfunction and elevated reactive oxygen species (ROS). These harmful byproducts of cell metabolism are the major cause of intermittent claudication, defined as pain in the legs that results in significant functional limitations. One potential defensive mechanism to these negative consequences may be having higher antioxidant capacity, which would improve blood vessel vasodilatory function, enabling more blood to transfer to the skeletal muscles. Therefore, the purpose of this project is to examine the impact of mitochondrial targeted antioxidant (MitoQ) intake on oxygen transfer capacity of blood vessels, skeletal muscle mitochondrial function, leg function, and claudication in participants with PAD. Blood vessel oxygen transfer capacity in the leg will be assessed in the femoral and popliteal arteries. Skeletal muscle mitochondrial function and ROS levels will be analyzed in human skeletal muscle via near infrared spectroscopy and through blood samples. Leg function will be assessed by walking on a force platform embedded treadmill and claudication times will be assessed with the Gardner maximal walking distance treadmill test.

Detailed Description

Peripheral artery disease (PAD) is a common cardiovascular disease, in which narrowed arteries reduce blood flow to the limbs, causing pain, immobility and in some cases amputation or death. Previous studies reported that atherosclerotic lesions are distributed non-uniformly in the leg arteries, and the resulting impaired blood flow, and concomitant reduced oxygen delivery to skeletal muscle results in the pathophysiology of PAD. PAD patients have shown higher levels of systemic and skeletal muscle inflammation due to the impaired oxygen transfer capacity of these blood vessels. This attenuated oxygen transfer capacity causes hypoxic conditions in the skeletal muscle and results in mitochondrial dysfunction and elevated reactive oxygen species (ROS). These harmful byproducts of cell metabolism are the major cause of intermittent claudication, defined as pain in the legs that results in significant functional limitations.

One potential defensive mechanism to these negative consequences may be having higher antioxidant capacity, which would improve blood vessel vasodilatory function, enabling more blood to transfer to the skeletal muscles. MitoQ, a derivative of CoQ10, is a commercial antioxidant that counteracts this oxidative stress within the mitochondria. High ROS levels have been positively correlated with reduced Nitric oxide (NO) bioavailability, which limits the ability of the blood vessels to dilate, thereby increasing the occlusion that leads to claudication in PAD patients. MitoQ should reduce these ROS levels and increase vasodilatory function. However, the influence of MitoQ intake on leg blood flow, ROS production, claudication and leg function has not yet been investigated in this disease population.

Therefore, the purpose of this project is to examine the impact of mitochondrial targeted antioxidant (MitoQ) intake on oxygen transfer capacity of blood vessels, skeletal muscle mitochondrial function, leg function, and claudication in participants with PAD. Blood vessel oxygen transfer capacity in the leg will be assessed in the femoral and popliteal arteries. Skeletal muscle mitochondrial function and ROS levels will be analyzed in human skeletal muscle via near infrared spectroscopy and through blood samples. Leg function will be assessed by walking on a force platform embedded treadmill and claudication times will be assessed with the Gardner maximal walking distance treadmill test.

Conditions

Peripheral Arterial Disease; Peripheral Artery Disease

Study Design

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

Study Groups

MitoQ-Placebo

Participants will be tested on two different days, first day will be baseline and MitoQ and second day will be Placebo. Testing will take place forty-minutes after MitoQ/placebo intake. There will be a 2-week washout between testing days.

Group Type: EXPERIMENTAL

MitoQ

Intervention Type: DIETARY_SUPPLEMENT

A mitochondrial-targeting antioxidant "MitoQ" or a placebo will be given to each participant in a crossover, double-blinded design and measures of leg function and leg blood flow will be measured.

Placebo-MitoQ

Participants will be tested on two different days, first day will be baseline and Placebo and second day will be MitoQ. Testing will take place forty-minutes after placebo/MitoQ intake. There will be a 2-week washout between testing days.

Group Type: EXPERIMENTAL

MitoQ

Intervention Type: DIETARY_SUPPLEMENT

A mitochondrial-targeting antioxidant "MitoQ" or a placebo will be given to each participant in a crossover, double-blinded design and measures of leg function and leg blood flow will be measured.

Interventions

MitoQ

A mitochondrial-targeting antioxidant "MitoQ" or a placebo will be given to each participant in a crossover, double-blinded design and measures of leg function and leg blood flow will be measured.

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

• Able to give written, informed consent
• Demonstrated positive history of chronic claudication
• History of exercise limiting claudication
• Ankle/brachial index < 0.90 at rest
• Stable blood pressure regimen, stable lipid regimen, stable diabetes regimen and risk factor control for 6 weeks prior to study entry
• 50-85 years old

Exclusion Criteria

• Resting pain or tissue loss due to Peripheral artery disease (PAD), Fontaine stage III and IV
• Acute lower extremity ischemic event secondary to thromboembolic disease or acute trauma
• Walking capacity limited by conditions other than claudication including leg (joint/musculoskeletal, neurologic) and systemic (heart, lung disease) pathology

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Nebraska

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Song-Young Park, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Nebraska

Locations

University of Nebraska - Omaha

Omaha, Nebraska, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

0086-18-FB

Identifier Type: -

Identifier Source: org_study_id