Supervised Exercise Therapy for Peripheral Arterial Disease

(MOMET Trial)

Overseen By Farahnaz Fallahtafti, PhD

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: VA Office of Research and Development

Disqualifiers: Rest pain, Acute ischemic event, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 36

Duration: 12 weeks

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new type of exercise therapy for individuals with peripheral artery disease (PAD), a condition where blocked leg arteries lead to poor blood flow and pain during walking. Researchers aim to determine if this new exercise program, guided by muscle oxygen levels, surpasses the standard exercise therapy. The trial includes two groups: one following the standard exercise routine and another using the new oxygen-guided method. Individuals with PAD who experience regular leg pain when walking and have stable blood pressure and diabetes treatments may be suitable candidates for this study. As an unphased trial, this study allows participants to contribute to innovative research that could enhance exercise therapies for PAD.

Will I have to stop taking my current medications?

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

What prior data suggests that this exercise therapy is safe for patients with peripheral arterial disease?

Research has shown that supervised exercise therapy is generally safe and well-tolerated for people with peripheral artery disease (PAD). Studies indicate that exercise therapy can reduce symptoms like leg pain and improve overall function.

In oxygen-guided supervised exercise, muscle oxygen levels determine exercise intensity. This approach prevents overexertion and reduces pain while still offering the benefits of exercise.

Both methods aim to enhance mobility and quality of life without causing significant negative effects. The goal is to help people safely increase their physical activity, leading to better heart health and a lower risk of complications from PAD. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the supervised exercise therapy for Peripheral Arterial Disease (PAD) because it offers a non-invasive and targeted approach to managing the condition. Unlike standard exercise regimens that rely on general activity levels, this treatment uses a personalized method, tailoring exercise intensity based on the individual's claudication pain or oxygen levels in the muscles. The oxygen-guided exercise approach is particularly promising as it adjusts based on muscle oxygen saturation, potentially allowing patients to exercise more effectively without reaching debilitating pain. This could lead to improved mobility and quality of life for people with PAD, offering a fresh alternative to traditional treatments like medications or surgical interventions.

What evidence suggests that this trial's exercise therapies could be effective for peripheral artery disease?

Research shows that supervised exercise therapy (SET) helps people with peripheral artery disease (PAD). Studies have found that exercise programs enable participants to walk longer and farther before experiencing pain. In this trial, participants will join one of two groups: standard supervised exercise or oxygen-guided supervised exercise. The oxygen-guided approach adjusts based on muscle oxygen levels to prevent fatigue. By stopping exercise before it becomes too uncomfortable, this method maintains muscle function and enhances overall physical activity. These adjustments aim to safely increase physical activity, potentially lowering the risk of heart-related health issues. ^{2 3 5 6 7}

Who Is on the Research Team?

Iraklis I Pipinos, MD

Principal Investigator

Omaha VA Nebraska-Western Iowa Health Care System, Omaha, NE

Are You a Good Fit for This Trial?

This trial is for veterans with Peripheral Arterial Disease (PAD) who can consent, have documented artery blockages in their legs, and experience leg pain when walking. They must be on stable medication regimens for blood pressure, cholesterol, and diabetes. It's not for those with severe PAD causing rest pain or tissue loss, recent ischemic events due to clots or trauma, or walking issues caused by non-PAD conditions.

Inclusion Criteria

Be able to give written, informed consent

My blood pressure, cholesterol, and diabetes treatments have been stable for 6 weeks.

I have been diagnosed with blocked arteries in my legs.

Exclusion Criteria

I recently had a blood clot or injury affecting my leg.

My walking is limited due to conditions not related to leg pain from poor circulation.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo either standard supervised exercise therapy (SET) or oxygen-guided supervised exercise therapy (M-SET) for 12 weeks, with sessions three times per week.

12 weeks

36 sessions (in-person)

Follow-up

Participants are monitored for exercise outcomes, muscle biochemistry, and subject-reported preferences after the intervention.

4 weeks

Open-label extension (optional)

Participants may opt into continuation of exercise therapy long-term if proven beneficial.

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Supervised Exercise Therapy

Trial Overview The study tests a new supervised exercise program guided by muscle oxygen levels against the standard exercise therapy for PAD patients. The goal is to see if this new method helps increase physical activity without harming muscle structure and function while reducing heart-related risks.

How Is the Trial Designed?

Group I: Oxygen guided supervised exercise Experimental Treatment 1 Intervention

Modified-SET parameters will be determined from resting StO2 during 10 minutes of sitting. The StO2 threshold will be set at 15% lower than baseline StO2 levels. After warm-up, the subjects will walk until they reach the StO2 threshold. The subjects will be instructed to stop walking once they reach the threshold and to rest until the StO2 level returns to the baseline level. Then, subjects will be instructed to begin walking again and this cycle will be repeated for 50 total minutes. The threshold was selected to be above the 31% drop associated with claudication onset time. If subjects experience pain earlier than the 15% drop, the threshold will be progressively decreased by 5%, as needed. Subjects will repeat this for up to 50 minutes (including walking and rest). Walking speed and treadmill incline will be adjusted to allow for 5-10 minutes of walking before reaching the threshold. Subjects will complete 3 sessions/week for 12 weeks.

Group II: Standard supervised exercise Active Control 1 Intervention

After the warmup, subjects will walk until claudication pain becomes severe and needs to stop. Then subjects will rest until claudication pain subsides. Afterwards, subjects will walk again, repeating the cycle for up to 50 minutes (including walking and rest). Walking speed and treadmill incline will be adjusted during the SET session to allow individuals with PAD to walk for 5-10 minutes before claudication symptoms arise. Time at each speed and incline, along with rest times will be recorded during each exercise session. Subjects will complete 3 sessions/week for 12 weeks.

Supervised Exercise Therapy is already approved in United States, European Union for the following indications:

Approved in United States as Supervised Exercise Therapy for:

• Peripheral Artery Disease (PAD)
• Claudication

Approved in European Union as Supervised Exercise Therapy for:

• Peripheral Artery Disease (PAD)
• Claudication

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

University of Nebraska

Collaborator

Trials

563

Recruited

1,147,000+

Published Research Related to This Trial

Supervised exercise training is an effective first-line therapy for patients with peripheral arterial disease (PAD), significantly improving pain-free walking distance and overall quality of life.

In addition to alleviating symptoms of claudication, supervised exercise training can enhance cardiovascular health and potentially lower the risk of serious events like heart attacks and strokes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of exercise training in peripheral arterial disease. Milani, RV., Lavie, CJ.[2007]

A survey of 84 vascular surgeons in the UK revealed that only 24% had access to supervised exercise programs for patients with intermittent claudication, despite strong recommendations for such programs from major clinical guidelines.

The study highlights a significant gap between evidence-based recommendations and actual practice, with 72% of respondents citing lack of resources as a barrier to implementing supervised exercise, which is known to improve patient outcomes and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Supervised exercise for intermittent claudication - an under-utilised tool. Shalhoub, J., Hamish, M., Davies, AH.[2022]

A randomized controlled trial showed that both long-term home exercise programs (HEP) and short-term supervised exercise therapy transitioning to HEP significantly improved peak walking time (PWT) in participants with peripheral artery disease, with PWT increasing from 408 meters to 814 meters in the HEP group and from 457 meters to 818 meters in the SET/HEP group over 18 months.

Both exercise interventions also enhanced exercise time-to-minimum calf muscle oxygen saturation (StO2), indicating improved muscle oxygenation during activity, which was correlated with the improvements in PWT, highlighting the effectiveness of structured exercise in managing symptoms of peripheral artery disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Long-Term Home Exercise in Participants With Peripheral Artery Disease. Gardner, AW., Montgomery, PS., Wang, M., et al.[2023]

In a study of 47 patients with peripheral artery disease (PAD), six months of supervised exercise therapy significantly improved walking distances, quality of life, and maximal plantar flexor strength, despite no significant change in the ankle-brachial index (ABI).

The therapy also enhanced gait biomechanics, particularly in torque and power generation at the ankle and hip, indicating that supervised exercise can effectively improve mobility and function in claudicating patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Supervised walking exercise therapy improves gait biomechanics in patients with peripheral artery disease. Schieber, MN., Pipinos, II., Johanning, JM., et al.[2021]

In a study of 63 patients with peripheral artery disease (PAD) undergoing a 6-month supervised exercise therapy (SET) program, an increase in walking speed of 0.03 m/s or greater was identified as the minimal clinically important difference (MCID), indicating meaningful improvement in walking ability.

The study established specific thresholds for small and substantial improvements in walking speed, which can help clinicians set realistic goals and assess progress in claudicating patients with PAD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Claudicating patients with peripheral artery disease have meaningful improvement in walking speed after supervised exercise therapy. Rahman, H., Pipinos, II., Johanning, JM., et al.[2022]

A supervised exercise therapy (SET) program for patients with intermittent claudication showed a 20% improvement in walking distance, increasing from an average of 298.5 meters to 360 meters, based on a study involving 155 patients over nearly two years.

The program is cost-effective compared to traditional physiotherapy and is designed to be accessible, with efforts made to increase participation through additional classes and venues, demonstrating the potential for successful implementation of community-based health interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implementation of a supervised exercise therapy programme. Murgitroyd, E., Fraser, S., Hebson, A., et al.[2020]

Supervised exercise therapy (SET) has been effectively integrated into cardiopulmonary rehabilitation programs over a 3-year period, demonstrating its potential to improve walking distance for patients with symptomatic peripheral artery disease (PAD).

The recent decision by the Centers for Medicare and Medicaid to cover SET could significantly enhance its adoption in clinical practice, providing a structured approach for rehabilitation therapists to implement SET in their programs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience Implementing Supervised Exercise Therapy for Peripheral Artery Disease. Salisbury, DL., Whipple, MO., Burt, M., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10562863/

Exercise Therapy in the Management of Peripheral Arterial ... The EXITPAD trial revealed that supervised ET significantly improved walking distance and QoL as compared with unsupervised ET. A systemic review of multiple ...

2. cms.gov cms.gov/medicare-coverage-database/view/ncacal-decision-memo.aspx?proposed=N&NCAId=287

NCA - Supervised Exercise Therapy (SET) for Symptomatic ... The authors concluded that exercise programs clearly improve walking time and distance for people who were considered able to participate in exercise programs, ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3061490/

Exercise Rehabilitation in Peripheral Artery Disease Exercise therapy combined with comprehensive secondary prevention has the potential to benefit patients with PAD by preserving or improving functional capacity.

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06003855/oxygen-guided-supervised-exercise-therapy

Oxygen-guided Supervised Exercise Therapy This project aims to establish the feasibility and acceptability of a muscle oxygen-guided supervised exercise program for patients with PAD.

5. ahajournals.org ahajournals.org/doi/10.1161/CIR.0000000000000623

Optimal Exercise Programs for Patients With Peripheral ... 6 months of unsupervised intermittent walking exercise was demonstrated to improve time walked to onset of pain and peak walking time (PWT).

6. reporter.nih.gov reporter.nih.gov/project-details/8685367

Reuse of ZD4054 for patients with symptomatic PAD The study will seek to confirm the safety and tolerability of 10mg of ZD4054 in patients with intermittent claudication (Rutherford II or III and, in parallel, ...

7. research.va.gov research.va.gov/about/funded_research/proj-details-FY2025.cfm?pid=781269

Oxygen-guided supervised exercise therapy in peripheral ... Funded Project Details - FY2025 ; Title: Oxygen-guided supervised exercise therapy in peripheral artery disease. ; Principal Investigator: Iraklis I. Pipinos.