MitoQ Treatment of Claudication: Myofiber and Micro-vessel Pathology

In our research, we are delving into whether taking MitoQ for six months can improve the symptoms and function of people diagnosed with peripheral artery disease, especially those who suffer from leg pain while walking, known as intermittent claudication. We will be checking if MitoQ helps people with claudication walk better, be more active every day, feel better about their lives, and if it enhances the health of their leg muscles.

Study Overview

• Status: Recruiting
• Conditions: Peripheral Arterial Disease
• Intervention / Treatment: Diagnostic test: Walking assessment; Other: QOL Survey; Diagnostic test: Ankle pressure at rest and after stress; Diagnostic test: Muscle Oxygen; Diagnostic test: Serum MitoQ Level; Procedure: Needle Biopsy

Detailed Description

This study will investigate whether taking MitoQ for six months can improve the walking ability, daily activity levels, and quality of life of people with claudication (leg pain) caused by peripheral artery disease (PAD). We'll also look at how MitoQ affects their calf muscles.

Here's what we'll be checking:

Muscle health: We'll examine muscle tissue samples under a microscope to see if MitoQ improves muscle health and function.

Body chemistry: We'll check blood tests to see if MitoQ affects overall health markers.

Mitochondrial health: We'll see if MitoQ reduces damage to mitochondria (the cell's powerhouses) and helps the body get rid of damaged ones. We'll also see if it improves how well mitochondria function.

Blood flow: We'll measure blood flow in the legs and see if MitoQ improves the function of tiny blood vessels in the calf muscles.

In short, we want to see if MitoQ can improve various aspects of health in people with claudication and PAD, and if these improvements are linked to better functioning mitochondria in their muscles.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Holly DeSpiegelaere, BSN RN CCRC; Phone Number: 402-995-4171; Email: Holly.DeSpiegelaere@va.gov

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68105
      • Recruiting
      • VA Medical Center
      • Contact: Holly DeSpiegelaere; Phone Number: 402-995-4171; Email: Holly.DeSpiegelaere@va.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. a positive history of chronic claudication
2. exercise-limiting claudication established by history and direct observation during a screening walking test administered by the evaluating vascular surgeon
3. documented lower extremity arterial occlusive disease based on ankle/brachial index measurements and/or arterial imaging
4. stable blood pressure, lipid and diabetes regimens and risk factor control for 6 weeks.

Exclusion Criteria:

1. rest pain or tissue loss due to PAD (Fontaine stage III and IV)
2. acute lower extremity ischemic event
3. walking capacity significantly and primarily limited by conditions other than claudication including leg (joint/musculoskeletal, neurologic) and systemic (heart, lung disease) pathology.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: MitoQ; Participants will be placed on a 24-week regimen of oral dosing with MitoQ. The patients will take two 20 mg caps of MitoQ on empty stomach, each morning	Diagnostic test: Walking assessment; Participating patients will undergo the following evaluations at baseline and after six months of treatment with MitoQ or placebo: Assessment of walking impairment: Evaluation of treadmill maximum walking distances, six-minute walking distance, and daily physical activity (average steps taken daily); Other: QOL Survey; Assessment of quality of life: Survey of Quality of life with the Walking Impairment Questionnaire and Short Form 36; Diagnostic test: Ankle pressure at rest and after stress; Assessment of leg hemodynamics: Evaluation of post-occlusive ankle pressure and ankle/brachial index; Diagnostic test: Muscle Oxygen; Evaluation of calf muscle heme oxygen saturation; Diagnostic test: Serum MitoQ Level; Evaluation of serum concentrations of MitoQ; Procedure: Needle Biopsy; Needle biopsy of the calf muscle
Placebo Comparator: Placebo; The patients will take two identical caps of matched placebo on empty stomach, each morning	Diagnostic test: Walking assessment; Participating patients will undergo the following evaluations at baseline and after six months of treatment with MitoQ or placebo: Assessment of walking impairment: Evaluation of treadmill maximum walking distances, six-minute walking distance, and daily physical activity (average steps taken daily); Other: QOL Survey; Assessment of quality of life: Survey of Quality of life with the Walking Impairment Questionnaire and Short Form 36; Diagnostic test: Ankle pressure at rest and after stress; Assessment of leg hemodynamics: Evaluation of post-occlusive ankle pressure and ankle/brachial index; Diagnostic test: Muscle Oxygen; Evaluation of calf muscle heme oxygen saturation; Diagnostic test: Serum MitoQ Level; Evaluation of serum concentrations of MitoQ; Procedure: Needle Biopsy; Needle biopsy of the calf muscle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Walking Impairment: maximum treadmill distance	Evaluation of maximum walking distance on treadmill until participant chooses to stop due to pain in his legs.	Before and After 6 months of treatment with MitoQ or placebo

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Walking Impairment: 6 minute distance	Evaluation of maximum walking distance the participant can walk over 6 minutes in hallway.	Before and after 6 months of treatment with MitoQ or placebo
Walking Impairment: initial claudication treadmill distance	Evaluation of walking distance on treadmill until participant starts experiencing claudication pain in his legs.	Before and after 6 months of treatment with MitoQ or placebo
Walking Impairment: daily physical activity	Measurement of average steps taken daily using a pedometer	Before and after 6 months of treatment with MitoQ or placebo
Walking Impairment Questionnaire	Walking Impairment Questionnaire: There are 14 questions across three categories of walking distance, walking speed and stair climbing. The WIQ is graded on a scale of 0-4; 0 represents no difficulty; 4 represents inability to walk. 0 score represents no difficulty, 1 score is slight difficulty, 2 score is some difficulty, 3 score is much difficulty, 4 score is unable to complete the task in question.	Before and after 6 months of treatment with MitoQ or placebo
Walking Impairment Short Form-36	Walking Impairment Short Form-36 - (The Short Form 36 Health Survey Questionnaire) has 8 scale (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health) that measures quality of life. The SF-36 scoring ranges from 0-100. Higher scores indicate better health; lower scores indicate more disability.	Before and after 6 months of treatment with MitoQ or placebo
Leg hemodynamics ankle/brachial index at rest and after stress	Evaluation of ankle/brachial index at rest and after stress. The ankle-brachial index test compares the blood pressure measured at the ankle with the blood pressure measured at the arm. A care provider measures your blood pressure in both arms and both ankles. This is done using an inflatable cuff and a hand-held ultrasound device. The device uses sound waves to detect blood flow and allows the pulse in the ankle arteries to be heard after the cuff is deflated. The test will be done first with you resting and then under stress. The stress will be produced by a blood pressure cuff placed around the lower thigh and the cuff being inflated to block blood flow to your calf and foot for five minutes.The cuff is then deflated, allowing blood to flow back into the leg.	Before and after 6 months of treatment with MitoQ or placebo
Leg hemodynamics muscle heme-oxygen (StO2)	Evaluation of the level of oxygen in your calf muscle at rest and during during exercise. StO2 is measured with a wireless, probe placed on the skin of your calf.	Before and after 6 months of treatment with MitoQ or placebo
Calf muscle cell damage	In the small tissue sample (biopsy) from your calf muscle we will look at the damage of the muscle cells by oxidative stress and the way the shape and size of the cells changes. This will be measured with quantitative widefield fluorescence microscopy.	Before and after 6 months of treatment with MitoQ or placebo
Calf muscle mitochondria function and damage	In the small tissue sample (biopsy) from your calf muscle we will look at the function and possible damage of the mitochondria in your muscle cells. Mitochondria are the powerhouses of your cells. We'll see if they're working properly or damaged.This will be measured with high-resolution respirometry, quantitative widefield fluorescence microscopy, 2-dimensional gel electrophoresis and mass spectrometry.	Before and after 6 months of treatment with MitoQ or placebo
Calf muscle fibrosis	In the small tissue sample (biopsy) from your calf muscle we will look at the amount of scarring (fibrosis) and measure if there is there any scar tissue buildup in the muscle.This will be measured with high-resolution respirometry, quantitative widefield fluorescence microscopy and with multiSpectral wide-field microscopy.	Before and after 6 months of treatment with MitoQ or placebo
Calf muscle inflammation	In the small tissue sample (biopsy) from your calf muscle we will measure the inflammation present in the muscle.This will be measured with quantitative widefield fluorescence microscopy and enzyme-linked immunosorbent assay.	Before and after 6 months of treatment with MitoQ or placebo
Calf muscle blood vessel health	In the small tissue sample (biopsy) from your calf muscle we will check how well the tiny blood vessels inside your muscle are working and if they are damaged and how much.This will be measured with videomicroscopy of calf muscle micro-vessel vasomotor function, high-resolution respirometry and quantitative widefield fluorescence microscopy.	Before and after 6 months of treatment with MitoQ or placebo
Level of MitoQ in the blood and the muscle	In the blood sample and the muscle sample we will collect from you we will check the level of MitoQ. This will be measured with mass spectrometry.	After 6 months of treatment with MitoQ or placebo

Collaborators and Investigators

• Sponsor: University of Nebraska
• Investigators: Principal Investigator: Iraklis Pipinos, MD, University of Nebraska

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2023
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: April 17, 2024
• First Submitted That Met QC Criteria: May 7, 2024
• First Posted (Actual): May 10, 2024

Study Record Updates

• Last Update Posted (Actual): May 10, 2024
• Last Update Submitted That Met QC Criteria: May 7, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Peripheral Arterial Disease; Peripheral Vascular Diseases
• Other Study ID Numbers: 0053-23-EP

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