SMART Exercise for Peripheral Arterial Disease

(SMART PAD Trial)

Recruiting in Palo Alto (17 mi)

+3 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Northwestern University

Must not be taking: Oral nitrates, Beetroot supplements

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

Pivotal Trial (Near Approval)

Prior Safety Data

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.

Trial 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 (Behavioral Intervention)
• Nitrate-rich beetroot Juice (Dietary Supplement)
• Supervised Treadmill Exercise (Behavioral Intervention)

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.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of Minnesota Minneapolis, MN

Northwestern University Feinberg School of Medicine Chicago, IL

University of Chicago Chicago, IL

University of Virginia Charlottesville, VA

Who Is Running the Clinical Trial?

Northwestern University Lead Sponsor

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] Supervised exercise therapy (SET) is recommended in patients with symptomatic peripheral arterial disease (PAD) as first-line therapy, although patient adoption remains low. Home-based exercise therapy (HBET) delivered through smartphones may expand access. The feasibility of such programs, especially in low-resource settings, remains unknown.

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] The effectiveness of supervised exercise programs (SEPs) for the management of peripheral arterial disease (PAD) can be hampered by low accessibility and poor compliance. The current international availability and use of SEPs was evaluated and the evidence on alternative approaches such as structured, home-based exercise programs (HEPs) was reviewed. METHODS-MATERIALS: International survey on SEP availability among vascular surgeons using an online questionnaire. A systematic review on structured-HEPs effectiveness was also performed.

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] National guidelines for the treatment and management of symptomatic peripheral artery disease (PAD) recommend supervised exercise therapy (SET) as a first line of therapy. However, it is unknown how these expert opinion-based SET guidelines work in clinical practice as SET programs become established following the 2017 Centers for Medicare & Medicaid Services coverage announcement. The purpose of this prospective, nonrandomized translational study was to evaluate the clinical effectiveness of a SET program and specifically walking exercise modalities that did not incorporate a treadmill (TM).

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] Supervised exercise therapy (SET) is a first-line treatment for patients with peripheral artery disease (PAD). The efficacy of SET is most commonly expressed by significant statistical improvement of parameters that do not clarify how each individual patient will benefit from SET. This study examined the minimal clinically important difference (MCID) in walking speed in claudicating patients with PAD after SET.

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] Patients with lower-extremity peripheral artery disease (PAD) have greater functional impairment, faster functional decline, increased rates of mobility loss, and poorer quality of life than people without PAD. Supervised exercise therapy (SET) improves walking ability, overall functional status, and health-related quality of life in patients with symptomatic PAD. In 2017, the Centers for Medicare & Medicaid Services released a National Coverage Determination (CAG-00449N) for SET programs for patients with symptomatic PAD. This advisory provides a practical guide for delivering SET programs to patients with PAD according to Centers for Medicare & Medicaid Services criteria. It summarizes the Centers for Medicare & Medicaid Services process and requirements for referral and coverage of SET and provides guidance on how to implement SET for patients with PAD, including the SET protocol, options for outcome measurement, and transition to home-based exercise. This advisory is based on the guidelines established by the Centers for Medicare & Medicaid Services for Medicare beneficiaries in the United States and is intended to assist clinicians and administrators who are implementing SET programs for patients with PAD.

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] Supervised exercise therapy (SET) improves walking ability in people with peripheral artery disease (PAD). However, the effects of SET on cardiovascular health in PAD remain unclear. Using data from a randomized clinical trial, this post hoc analyses investigated the effects of a 6-month SET intervention, compared with a control group, on changes in blood pressure (BP) and heart rate (HR) during a graded treadmill exercise test in people with PAD.

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

Total body recumbent stepping vs treadmill walking in supervised exercise therapy: A pilot study. [2022] Background: Treadmill walking is the most commonly recommended exercise modality in supervised exercise therapy (SET) for peripheral artery disease (PAD); however, other modalities may be equally effective and more tolerable for patients. The primary aim of this single-blind, randomized pilot study was to compare the feasibility, safety, and preliminary efficacy of a treadmill walking (TM) versus a total body recumbent stepping (TBRS) exercise program for treatment of PAD (i.e., "Stepper Study").. Methods: Participants (n = 19) enrolled in a 12-week SET program and were randomized to either a TM (n = 9) or TBRS (n = 10) exercise group that followed current SET exercise guidelines. Feasibility, safety, and efficacy outcomes were assessed. Results: SET attendance was 86% and 71%, respectively, for TBRS and TM groups (p = 0.07). Session exercise dose (metabolic equivalents of task [MET] minutes) (mean [SD]) for TM was 117.6 [27.4] compared to 144.7 [28.7] in the TBRS group (p = 0.08). Study-related adverse events were nine in 236 training hours and three in 180 training hours for the TBRS and TM groups, respectively. There were no significant differences between groups for improvement in 6-minute walk distance (mean [SD]) (TM: 133.2 ft [53.5] vs TBRS: 154.8 ft [49.8]; p = 0.77) after adjusting for baseline 6-minute walk distance. Conclusion: This is the first randomized study comparing TBRS to TM exercise in SET using current SET guidelines. This pilot study showed that TBRS is a feasible and safe exercise modality in SET. This study provides preliminary efficacy of the use of TBRS exercise in SET programs following current guidelines. Larger studies should be conducted to confirm these findings.

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] Exercise training reduces walking disability in peripheral arterial disease (PAD). This non-randomized study evaluates the effects on walking ability and hemodynamic parameters of a novel approach to home-based rehabilitation, the test in -train out program (Ti-To), compared with the traditional home-based free walking exercise (Tr-E).

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

Home-based walking exercise intervention in peripheral artery disease: a randomized clinical trial. [2022] Clinical practice guidelines state there is insufficient evidence to support advising patients with peripheral artery disease (PAD) to participate in a home-based walking exercise program.

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] Peripheral artery disease (PAD) is a significant medical concern that is highly prevalent, costly, and deadly. Additionally, patients with PAD have significant impairments in functional independence and health-related quality of life due to leg symptoms and ambulatory dysfunction. Exercise therapy is a primary treatment for patients with PAD, as ambulatory outcome measures improve following a program of exercise rehabilitation. This review describes the outcomes that improve with exercise, the potential mechanisms for improved leg symptoms, key exercise program considerations for training patients with PAD with walking-based exercise, other exercise modalities that have been utilised, the use of on-site supervised exercise programs, and a major focus on historical and contemporary trials on conducting home-based, minimally supervised exercise program to treat PAD. The review concludes with recommendations for future exercise trials, with particular emphasis on reported greater details of the exercise prescription to more accurately quantify the total exercise dose of the program.