MitoQ for Peripheral Arterial Disease

Overseen By Holly DeSpiegelaere, BSN RN CCRC

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Nebraska

Disqualifiers: Rest pain, Acute ischemic event, others

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

60 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires that your blood pressure, lipid, and diabetes treatments remain stable for 6 weeks before joining.

Is MitoQ safe for human use?

Research indicates that MitoQ, a mitochondrial-targeted antioxidant, is generally safe in humans. Studies have shown that even at high doses, MitoQ does not increase markers of kidney injury in healthy adults, suggesting it is well-tolerated. ^{1 2 3 4 5}

How does the drug MitoQ differ from other treatments for peripheral arterial disease?

MitoQ is unique because it is a mitochondrial-targeted antioxidant that improves vascular function by enhancing the health of mitochondria in blood vessels, which can lead to better walking capacity and reduced leg pain in patients with peripheral arterial disease. ^{1 6 7 8 9}

What is the purpose of this trial?

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.

Research Team

Iraklis Pipinos, MD

Principal Investigator

University of Nebraska

Eligibility Criteria

This trial is for individuals with peripheral artery disease (PAD) or peripheral vascular disease (PVD), who experience leg pain while walking. Participants should be willing to undergo various assessments, including muscle oxygen tests, walking evaluations, quality of life surveys, ankle pressure measurements, and a needle biopsy.

Inclusion Criteria

I have a history of leg pain when walking.

I have been diagnosed with blocked arteries in my legs.

Exercise-limiting claudication established by history and direct observation during a screening walking test administered by the evaluating vascular surgeon

Exclusion Criteria

I have severe leg pain or tissue loss because of poor blood flow.

My ability to walk is mainly limited by non-claudication issues like joint, nerve, or systemic diseases.

I recently had a blockage in the blood flow to my legs.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a 24-week regimen of oral dosing with MitoQ or placebo

24 weeks

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• MitoQ

Trial Overview The study investigates whether MitoQ supplementation over six months can improve walking ability and daily activity levels in PAD patients with intermittent claudication. It also examines the impact on muscle health and overall quality of life.

Participant Groups

Group I: MitoQ Active Control 6 Interventions

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

Group II: Placebo Placebo Group 6 Interventions

The patients will take two identical caps of matched placebo on empty stomach, each morning

Who Is Running the Clinical Trial?

University of Nebraska

Lead Sponsor

Trials

563

Recruited

1,147,000+

Findings from Research

Acute intake of the mitochondrial-targeted antioxidant MitoQ significantly improved vascular endothelial function and increased superoxide dismutase levels in patients with peripheral artery disease (PAD), based on a study involving 11 participants.

MitoQ also enhanced walking capacity and delayed the onset of claudication, suggesting it may effectively restore mitochondrial function and improve overall leg performance in PAD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute mitochondrial antioxidant intake improves endothelial function, antioxidant enzyme activity, and exercise tolerance in patients with peripheral artery disease. Park, SY., Pekas, EJ., Headid, RJ., et al.[2021]

In a study involving 50 male Wistar rats, the mitochondrial-targeted antioxidant MitoQ significantly improved survival rates (80%) and reduced tumor incidence (by 60% and 40% in different treatment groups) compared to those treated with diethyl nitrosamine (DEN) alone, indicating its potential as a protective agent against liver cancer.

MitoQ treatment also enhanced liver function and mitochondrial enzyme activities while reversing oxidative damage, suggesting that it effectively modulates mitochondrial antioxidant defenses and may serve as a promising chemotherapeutic agent in the context of DEN-induced hepatocellular carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitoquinol mesylate (MITOQ) attenuates diethyl nitrosamine-induced hepatocellular carcinoma through modulation of mitochondrial antioxidant defense systems. Adisa, RA., Sulaimon, LA., Okeke, EG., et al.[2023]

Acute high-dose MitoQ supplementation (100-160 mg) in 32 healthy adults showed no significant changes in urinary biomarkers associated with kidney injury, suggesting it is not nephrotoxic.

The study's results support the safety of MitoQ for further research on its effects related to mitochondrial oxidative stress, as it did not affect kidney function or injury markers in the short term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute High Dose MitoQ Does not Increase Urinary Kidney Injury Markers in Healthy Adults. Linder, BA., Stute, NL., Hutchison, ZJ., et al.[2023]

Mitoquinone (MitoQ(10)) is effectively absorbed in the intestines, with 18-41% of the administered dose accumulating intracellularly, indicating its potential as a treatment for neurodegenerative diseases.

The absorption of MitoQ(10) can be significantly enhanced by the presence of serum proteins like bovine serum albumin, suggesting that its bioavailability may improve in real-life conditions despite some limitations from metabolism and transport proteins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transport and metabolism of MitoQ10, a mitochondria-targeted antioxidant, in Caco-2 cell monolayers. Li, Y., Fawcett, JP., Zhang, H., et al.[2018]

In a study of 6,809 patients who underwent endovascular intervention for peripheral artery disease, those discharged on therapeutic anticoagulation (mostly warfarin) had a higher risk of adverse outcomes, including patency loss, major adverse limb events (MALE), and all-cause mortality.

Specifically, patients on anticoagulation had a 41% increased risk of patency loss, a 39% increased risk of MALE, and a 24% increased risk of all-cause mortality compared to those not on anticoagulation, suggesting that anticoagulation may not be beneficial post-intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Anticoagulation and Major Adverse Limb Events After Index Peripheral Endovascular Intervention. Ramkumar, N., Goodney, PP., Creager, MA., et al.[2023]

The Peripheral Artery Questionnaire (PAQ) is a reliable and valid tool for measuring health status in patients with peripheral arterial disease, showing strong internal consistency with a Cronbach alpha of 0.80 to 0.94 across its 7 domains.

The PAQ demonstrated significant responsiveness to clinical improvement after revascularization, with score changes ranging from 13.7 to 41.9 points (P < 0.001), making it a sensitive measure for assessing treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The peripheral artery questionnaire: a new disease-specific health status measure for patients with peripheral arterial disease. Spertus, J., Jones, P., Poler, S., et al.[2022]

In a study of 3194 patients with peripheral arterial disease (PAD) who underwent revascularization, the minimum important difference for health-related quality of life (HRQoL) as measured by the VascuQoL-6 (VQ-6) was found to be between 1.7 to 2.2 scale steps for patients with intermittent claudication and 1.9 scale steps for those with critical limb ischemia after one year.

The study established that a substantial clinical benefit, indicated by VQ-6 scores, occurs at thresholds of 3.5 scale steps for intermittent claudication patients and 4.5 scale steps for critical limb ischemia patients, providing valuable benchmarks for evaluating treatment outcomes in clinical practice and research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of Minimum Important Difference and Substantial Clinical Benefit with the Vascular Quality of Life Questionnaire-6 when Evaluating Revascularisation Procedures in Peripheral Arterial Disease. Nordanstig, J., Pettersson, M., Morgan, M., et al.[2022]

In the OMEGA-PAD I Trial involving 80 patients with peripheral artery disease, high-dose fish oil supplementation did not significantly improve endothelial function compared to placebo, indicating that it may not be effective for this specific outcome.

However, fish oil supplementation did lead to a significant reduction in triglycerides and an increase in omega-3 fatty acids in the blood, suggesting potential benefits in lipid profiles and inflammation management for patients with PAD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-Term, High-Dose Fish Oil Supplementation Increases the Production of Omega-3 Fatty Acid-Derived Mediators in Patients With Peripheral Artery Disease (the OMEGA-PAD I Trial). Grenon, SM., Owens, CD., Nosova, EV., et al.[2018]

A study involving 171 patients with peripheral arterial disease (PAD) showed that both invasive and conservative treatments significantly improved self-reported health status and quality of life after one year, as measured by the VascuQoL-6 (VQ-6) instrument.

Patients who underwent invasive interventions (like surgery) reported greater improvements in quality of life compared to those receiving conservative treatments, with 56% of the invasive group showing a significant improvement in VQ-6 scores compared to 36% in the conservative group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Self-reported health status and disease-specific quality of life one year after treatment for peripheral arterial disease in clinical practice. Larsen, ASF., Reiersen, AT., Nådland, IH., et al.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

Acute mitochondrial antioxidant intake improves endothelial function, antioxidant enzyme activity, and exercise tolerance in patients with peripheral artery disease. [2021]

2. Singapore pubmed.ncbi.nlm.nih.gov

Mitoquinol mesylate (MITOQ) attenuates diethyl nitrosamine-induced hepatocellular carcinoma through modulation of mitochondrial antioxidant defense systems. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Acute High Dose MitoQ Does not Increase Urinary Kidney Injury Markers in Healthy Adults. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Transport and metabolism of MitoQ10, a mitochondria-targeted antioxidant, in Caco-2 cell monolayers. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Association of Anticoagulation and Major Adverse Limb Events After Index Peripheral Endovascular Intervention. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

The peripheral artery questionnaire: a new disease-specific health status measure for patients with peripheral arterial disease. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Assessment of Minimum Important Difference and Substantial Clinical Benefit with the Vascular Quality of Life Questionnaire-6 when Evaluating Revascularisation Procedures in Peripheral Arterial Disease. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Short-Term, High-Dose Fish Oil Supplementation Increases the Production of Omega-3 Fatty Acid-Derived Mediators in Patients With Peripheral Artery Disease (the OMEGA-PAD I Trial). [2018]

9. England pubmed.ncbi.nlm.nih.gov

Self-reported health status and disease-specific quality of life one year after treatment for peripheral arterial disease in clinical practice. [2020]