Peripheral Arterial Disease
Conditions
Brief summary
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.
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.
Interventions
DIAGNOSTIC_TESTWalking 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)
OTHERQOL Survey
Assessment of quality of life: Survey of Quality of life with the Walking Impairment Questionnaire and Short Form 36
DIAGNOSTIC_TESTAnkle pressure at rest and after stress
Assessment of leg hemodynamics: Evaluation of post-occlusive ankle pressure and ankle/brachial index
DIAGNOSTIC_TESTMuscle Oxygen
Evaluation of calf muscle heme oxygen saturation
DIAGNOSTIC_TESTSerum MitoQ Level
Evaluation of serum concentrations of MitoQ
PROCEDURENeedle Biopsy
Needle biopsy of the calf muscle
Sponsors
University of Nebraska
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind, randomized, placebo-controlled trial with two parallel arms.
Intervention model description
Patients with peripheral artery disease and claudication will participate in a double-blind, randomized, placebo-controlled trial with two parallel arms. Patients will be randomized 2:1 to receive either a daily oral dose of 40 mg MitoQ or matched placebo for six months.
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Walking Impairment: maximum treadmill distance | Before and After 6 months of treatment with MitoQ or placebo | Evaluation of maximum walking distance on treadmill until participant chooses to stop due to pain in his legs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Walking Impairment: 6 minute distance | Before and after 6 months of treatment with MitoQ or placebo | Evaluation of maximum walking distance the participant can walk over 6 minutes in hallway. |
| Walking Impairment: initial claudication treadmill distance | Before and after 6 months of treatment with MitoQ or placebo | Evaluation of walking distance on treadmill until participant starts experiencing claudication pain in his legs. |
| Walking Impairment: daily physical activity | Before and after 6 months of treatment with MitoQ or placebo | Measurement of average steps taken daily using a pedometer |
| Walking Impairment Questionnaire | Before and after 6 months of treatment with MitoQ or placebo | 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. |
| Walking Impairment Short Form-36 | Before and after 6 months of treatment with MitoQ or placebo | 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. |
| Leg hemodynamics ankle/brachial index at rest and after stress | Before and after 6 months of treatment with MitoQ or placebo | 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. |
| Leg hemodynamics muscle heme-oxygen (StO2) | Before and after 6 months of treatment with MitoQ or placebo | 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. |
| Calf muscle cell damage | Before and after 6 months of treatment with MitoQ or placebo | 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. |
| Calf muscle mitochondria function and damage | Before and after 6 months of treatment with MitoQ or placebo | 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. |
| Calf muscle fibrosis | Before and after 6 months of treatment with MitoQ or placebo | 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. |
| Calf muscle blood vessel health | Before and after 6 months of treatment with MitoQ or placebo | 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. |
| Calf muscle inflammation | Before and after 6 months of treatment with MitoQ or placebo | 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. |
| Level of MitoQ in the blood and the muscle | After 6 months of treatment with MitoQ or placebo | 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. |
Countries
United States
Contacts
CONTACTHolly DeSpiegelaere, BSN RN CCRC
PRINCIPAL_INVESTIGATORIraklis Pipinos, MD
University of Nebraska
Outcome results
None listed