SMART Exercise for Peripheral Arterial Disease

(SMART PAD Trial)

Recruiting at 3 trial locations

Overseen By Mary McDermott, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Northwestern University

Must not be taking: Oral nitrates, Beetroot supplements

Disqualifiers: Amputation, Wheelchair, Foot ulcer, ESKD, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 27

Duration: 12 weeks

210 Participants Needed

Trial Summary

What is the purpose of this trial?

Supervised exercise therapy (SET), consisting of treadmill exercise conducted three times weekly at a center while supervised by healthcare personnel, is first line therapy for people disabled by lower extremity peripheral artery disease (PAD). However, travelling three times/week to a center for SET is burdensome. Compared to SET, home-based exercise is more accessible and less burdensome. Yet, evidence-based guidelines recommend SET over home-based exercise for PAD. Walking exercise is first line therapy to improve walking distance for PAD, but it does not eliminate ischemic leg symptoms in most people with PAD. The investigators' work and that of others showed that nitrate-rich beetroot juice, which increases plasma nitrite, limb perfusion, and skeletal muscle function, significantly improved exercise tolerance and reduced non-response to exercise in people with and without PAD. The investigators will use a 2 x 2 factorial design to address two major barriers to achieving benefits from exercise therapy for PAD: First, guideline recommendations for supervised exercise therapy (SET) as first line therapy for PAD. Second, the inability of exercise therapy to eliminate PAD-related disability in most people with PAD. Participants will be randomized to one of four groups for 12 weeks: Supervised treadmill exercise + nitrate rich beetroot juice; supervised treadmill exercise + placebo, home-based walking exercise + nitrate rich beetroot juice, home-based walking exercise + placebo.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must avoid beetroot juice, oral nitrate or nitrite, and certain mouthwashes during the study. If you consume one cup of beets daily, you will need to stop for 30 days before starting the trial.

What data supports the effectiveness of the treatment SMART Exercise for Peripheral Arterial Disease?

Supervised exercise therapy (SET) is shown to improve walking ability and quality of life in patients with peripheral artery disease (PAD). Home-based exercise programs, which can be delivered through smartphones, may help increase access to these benefits, especially in areas with limited resources. ^{1 2 3 4 5}

Is home-based or supervised exercise therapy safe for people with peripheral arterial disease?

Supervised exercise therapy (SET) and home-based exercise programs (HEPs) have been studied for safety in people with peripheral arterial disease (PAD). A pilot study found that both treadmill walking and total body recumbent stepping in SET were safe, with few adverse events reported. These findings suggest that these exercise therapies are generally safe for people with PAD. ^{1 2 3 6 7}

How is the SMART Exercise treatment for peripheral arterial disease different from other treatments?

The SMART Exercise treatment is unique because it combines home-based exercise with smartphone technology, making it more accessible for patients who may not have easy access to supervised exercise programs. This approach allows patients to engage in exercise therapy from home, potentially improving adherence and outcomes in low-resource settings. ^{1 2 8 9 10}

Eligibility Criteria

This trial is for individuals over 50 with Peripheral Arterial Disease (PAD), evidenced by specific tests. They must not have severe limb ischemia, amputations, or be wheelchair-bound. Participants should not already be highly active or have major health issues like end-stage kidney disease, recent surgeries, certain cancers, unstable angina, or dementia.

Inclusion Criteria

I have been diagnosed with PAD through tests or symptoms.

I am 50 years old or older.

Exclusion Criteria

I do not have a major illness like lung disease needing oxygen, Parkinson's, a life-threatening condition expected to end my life within six months, or cancer treated in the last two years.

I am not willing to stop consuming beetroot products during the study.

My vision problems make it hard for me to walk.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to one of four groups for 12 weeks: Supervised treadmill exercise + nitrate rich beetroot juice; supervised treadmill exercise + placebo, home-based walking exercise + nitrate rich beetroot juice, home-based walking exercise + placebo.

12 weeks

3 visits per week (in-person for supervised groups)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Measured at baseline and 24-week follow-up

Treatment Details

Interventions

• Home-Based Exercise
• Nitrate-rich beetroot Juice
• Supervised Treadmill Exercise

Trial Overview The study compares four approaches to improve walking in PAD: supervised treadmill exercise with beetroot juice; the same exercise with a placebo; home-based walking with beetroot juice; and home-based walking with a placebo. The goal is to find out which combination is most effective for reducing PAD-related disability.

Participant Groups

Group I: Supervised treadmill exercise + nitrate rich beetroot juice Experimental Treatment 2 Interventions

This group will be participating in Supervised Treadmill Exercise and drinking nitrate rich beetroot juice for 12 weeks.

Group II: Home-based walking exercise + nitrate rich beetroot juice Experimental Treatment 2 Interventions

This group will be participating in Home-Based Exercise and drinking nitrate rich beetroot juice for 12 weeks.

Group III: Home-based walking exercise + placebo Placebo Group 1 Intervention

This group will be participating in Home-Based Exercise and drinking placebo beetroot juice with nitrated removed for 12 weeks.

Group IV: Supervised treadmill exercise + placebo Placebo Group 1 Intervention

This group will be participating in Supervised Treadmill Exercise and drinking placebo beetroot juice with nitrate removed for 12 weeks.

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

Findings from Research

The Smart Step pilot trial is exploring the feasibility of smartphone-enabled home-based exercise therapy (HBET) for patients with symptomatic peripheral arterial disease (PAD), with a focus on improving walking distance over 12 weeks.

With 15 participants enrolled so far, the study aims to demonstrate that HBET can increase accessibility to exercise rehabilitation, potentially offering a more convenient alternative to traditional supervised exercise therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and design of a smartphone-enabled, home-based exercise program in patients with symptomatic peripheral arterial disease: The smart step randomized trial. Harzand, A., Vakili, AA., Alrohaibani, A., et al.[2023]

Only 30.4% of vascular surgeons reported access to supervised exercise programs (SEPs) for managing peripheral arterial disease (PAD), highlighting a significant accessibility issue.

Structured home-based exercise programs (HEPs) were found to be effective alternatives, significantly improving functional capacity and quality of life compared to standard advice, although SEPs were superior in some cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Availability of supervised exercise programs and the role of structured home-based exercise in peripheral arterial disease. Makris, GC., Lattimer, CR., Lavida, A., et al.[2018]

A 12-week supervised exercise therapy (SET) program for patients with mild to moderate peripheral artery disease (PAD) significantly improved walking capacity, as evidenced by a 32.1 meter increase in the 6-minute walk test among 93 participants.

The study suggests that non-treadmill walking modalities, such as total body recumbent stepping, can be effectively incorporated into SET programs, although no significant differences in outcomes were found between different exercise modalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Effectiveness of a Supervised Exercise Therapy Program for Treatment of Peripheral Artery Disease: A Translational Study. Salisbury, DL., Brown, R., Elgersma, K., et al.[2023]

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]

Supervised exercise therapy (SET) significantly improves walking ability, functional status, and quality of life for patients with lower-extremity peripheral artery disease (PAD), addressing their greater functional impairments compared to those without PAD.

The 2017 National Coverage Determination by the Centers for Medicare & Medicaid Services provides a framework for implementing SET programs for PAD patients, including referral processes, coverage criteria, and guidance on transitioning to home-based exercise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implementation of Supervised Exercise Therapy for Patients With Symptomatic Peripheral Artery Disease: A Science Advisory From the American Heart Association. Treat-Jacobson, D., McDermott, MM., Beckman, JA., et al.[2020]

In a study of 210 participants with peripheral artery disease (PAD), a 6-month supervised exercise therapy (SET) program significantly reduced systolic blood pressure by 12 mm Hg, pulse pressure by 9 mm Hg, and heart rate by 7 beats per minute during exercise compared to a control group.

The improvements in cardiovascular health metrics (blood pressure and heart rate) were associated with better walking performance, indicating that SET not only enhances walking ability but also positively impacts cardiovascular health in individuals with PAD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of supervised exercise therapy on blood pressure and heart rate during exercise, and associations with improved walking performance in peripheral artery disease: Results of a randomized clinical trial. Slysz, JT., Tian, L., Zhao, L., et al.[2021]

In a pilot study involving 19 participants over 12 weeks, total body recumbent stepping (TBRS) was found to be a feasible and safe alternative to treadmill walking (TM) for supervised exercise therapy in patients with peripheral artery disease (PAD).

Both exercise modalities showed similar improvements in 6-minute walk distance, indicating that TBRS could be as effective as TM, but larger studies are needed to confirm these preliminary findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Total body recumbent stepping vs treadmill walking in supervised exercise therapy: A pilot study. Salisbury, DL., Swanson, K., Brown, RJ., et al.[2022]

The Ti-To program, which involved structured home-based walking sessions and monthly check-ups, significantly improved perceived claudication and functional parameters in patients with peripheral arterial disease (PAD) compared to the traditional free walking exercise program.

Patients in the Ti-To group experienced better hemodynamic improvements, including lower resting heart rates and better ankle-brachial index scores, indicating enhanced cardiovascular health alongside improved walking ability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Training rather than walking: the test in -train out program for home-based rehabilitation in peripheral arteriopathy. Manfredini, F., Malagoni, AM., Mascoli, F., et al.[2019]

A randomized controlled trial involving 194 patients with peripheral artery disease (PAD) showed that a home-based walking exercise program significantly improved walking endurance, with participants increasing their 6-minute walk distance by an average of 53.5 meters compared to a control group.

The intervention also led to improvements in treadmill walking time, overall physical activity, and patient-reported walking ability, suggesting that this program can be an effective alternative for patients with PAD who cannot attend supervised exercise sessions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Home-based walking exercise intervention in peripheral artery disease: a randomized clinical trial. McDermott, MM., Liu, K., Guralnik, JM., et al.[2022]

Exercise therapy significantly improves ambulatory outcomes and reduces leg symptoms in patients with peripheral artery disease (PAD), enhancing their functional independence and quality of life.

The review emphasizes the importance of detailed exercise prescriptions in future trials to better quantify the total exercise dose, which could lead to more effective treatment strategies for PAD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise rehabilitation for peripheral artery disease: An exercise physiology perspective with special emphasis on the emerging trend of home-based exercise. Gardner, AW.[2022]

References

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

Rationale and design of a smartphone-enabled, home-based exercise program in patients with symptomatic peripheral arterial disease: The smart step randomized trial. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Availability of supervised exercise programs and the role of structured home-based exercise in peripheral arterial disease. [2018]

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

Clinical Effectiveness of a Supervised Exercise Therapy Program for Treatment of Peripheral Artery Disease: A Translational Study. [2023]

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

Claudicating patients with peripheral artery disease have meaningful improvement in walking speed after supervised exercise therapy. [2022]

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

Implementation of Supervised Exercise Therapy for Patients With Symptomatic Peripheral Artery Disease: A Science Advisory From the American Heart Association. [2020]

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

Effects of supervised exercise therapy on blood pressure and heart rate during exercise, and associations with improved walking performance in peripheral artery disease: Results of a randomized clinical trial. [2021]

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

Total body recumbent stepping vs treadmill walking in supervised exercise therapy: A pilot study. [2022]

8. Japan pubmed.ncbi.nlm.nih.gov

Training rather than walking: the test in -train out program for home-based rehabilitation in peripheral arteriopathy. [2019]

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

Home-based walking exercise intervention in peripheral artery disease: a randomized clinical trial. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Exercise rehabilitation for peripheral artery disease: An exercise physiology perspective with special emphasis on the emerging trend of home-based exercise. [2022]