Impacts of Mitochondrial-targeted Antioxidant on Peripheral Artery Disease Patients

March 12, 2025 updated by: University of Nebraska

Impacts of Mitochondrial-targeted Antioxidant on Leg Function, Leg Blood Flow and Skeletal Muscle Mitochondrial Function in Peripheral Artery Disease Patients

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
14

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Nebraska
      • Omaha, Nebraska, United States, 68182
        • University of Nebraska - Omaha

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.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

46 years to 81 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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.
Dietary supplement: 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.
Experimental: 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.
Dietary supplement: 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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Endothelial Function
Time Frame: 2 days
Flow-mediated dilation will be used to measure vasodilation in the brachial artery, and blood flow in the femoral and popliteal arteries. This is measured in percents. Scale range is approximately 8-12% for healthy populations. A higher value represents a better outcome.
2 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Skeletal Muscle Oxygenation
Time Frame: 2 days
Near-infrared spectroscopy will be used to measure leg muscle oxygenation. Measures of oxygenation are measured in percents. Scale range is ~70-90% in healthy populations. A higher value represents a better outcome.
2 days
Walking Function
Time Frame: 2 days (1 day for MitoQ and 1 day for Placebo)
Subject will walk on a treadmill starting at a speed of 2.0 mph for two minutes with 0% incline. Every two minutes the treadmill incline will increase by 2% up to a maximum of 14%. The subject will be asked to walk until they feel pain in there legs, at which point the test will stop. This is measured in meters (distance) and seconds (time). Scale range is ~800 meters and 840 for healthy populations. A higher value represents a better outcome. This assessment occurred on two separate days (one for each intervention).
2 days (1 day for MitoQ and 1 day for Placebo)
Oxidative Stress
Time Frame: 2 days
Blood draws will be taken to measure oxidative stress markers in the blood. This is measured in units per milliliter (U/mL). Measures of oxidative stress are approximately 70-80 U/mL in healthy populations. A lower value represents a better outcome.
2 days
Autonomic Nervous System Activity
Time Frame: 2 days
Autonomic nervous system function will be measured non-invasively using heart rate variability via the head-up tilt test. Raw R-R interval data will be converted to time frequency domain with the wavelet transform across the frequency intervals 0.04-0.15 Hz (low-frequency, (LF)) and 0.15-0.4 Hz (high-frequency, HF). Units for both will be expressed as ms^2. Final outcome measure will be the ratio of LF/HF, which is a unitless ratio to indicate sympathetic-to-parasympathetic nervous system function.
2 days
Microvascular Function
Time Frame: 2 days
Microvascular function will be assessed using near-infrared spectroscopy. NIRS measurements were taken continuously throughout the entire protocol at a sampling rate of 10 Hz. Hemoglobin and myoglobin possess indistinguishable spectral characteristics in the NIRS signal; therefore, the signal is considered to be primarily derived from Hb. The signals were analyzed according to a modified Beer- Lambert's law, and a constant differential path length factor was not used due to the assumption that constant optical scattering of the photons has been demonstrated to affect alterations in NIRS signals. Data were expressed as relative changes with respect to baseline as a percentage (TOI). Tissue reoxygenation was estimated by calculating the initial slope of TOI recovery, which has been used as an index of microvascular function.
2 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Nebraska

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Song-Young Park, PhD, University of Nebraska

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 Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 5, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 17, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 17, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 13, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 13, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 24, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 1, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 12, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 0086-18-FB

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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