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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to make exercise therapy for peripheral artery disease (PAD) more accessible and effective. It tests whether combining exercise—either supervised treadmill workouts or home-based walking—with nitrate-rich beetroot juice (a dietary supplement) can improve walking ability and reduce leg pain more effectively than current methods. Participants will be divided into four groups to compare these treatments. The trial seeks individuals aged 50 and older who have PAD, experience walking difficulties related to PAD, and are open to trying beetroot juice as part of the treatment. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the treatments in this trial have been safe in past studies. Supervised treadmill exercise, a common treatment for peripheral artery disease (PAD), has undergone extensive research. While it can sometimes reveal hidden heart issues, such as new chest pain, it is generally safe. Many individuals experience improved walking ability and a better quality of life.

Home-based exercise is another method to manage PAD. Studies have shown it can increase walking endurance and is generally safe for people with PAD. This option offers more flexibility and convenience since it can be done at home.

Nitrate-rich beetroot juice, included in this trial, has been studied for its benefits in PAD. It is usually well-tolerated and can improve blood flow and exercise performance. Research confirms it is safe for most people and might even support heart health.

Overall, these treatments have demonstrated safety and could benefit those with PAD. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for Peripheral Arterial Disease (PAD) because they combine exercise with dietary interventions that might enhance blood flow. Unlike standard treatments that often focus solely on medications or procedures to improve circulation, these trial regimens incorporate nitrate-rich beetroot juice. This juice is believed to boost nitric oxide levels in the blood, potentially improving vascular health and exercise performance. By pairing either home-based walking or supervised treadmill exercise with beetroot juice, the trial explores a natural, non-invasive way to enhance the benefits of physical activity for people with PAD.

What evidence suggests that this trial's treatments could be effective for PAD?

Research shows that supervised treadmill exercise, a treatment in this trial, can significantly improve walking distance for people with peripheral artery disease (PAD). Studies indicate that engaging in this exercise for more than six weeks leads to noticeable improvements in walking ability. Another treatment option in this trial is home-based walking exercise, which also helps increase the duration PAD patients can walk and remain active. Early research suggests that drinking nitrate-rich beetroot juice, tested in combination with both exercise types in this trial, might improve blood flow and enhance exercise performance. This could enable people with PAD to exercise with less pain and for longer periods. Together, these treatments aim to alleviate the walking difficulties often faced by those with PAD. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6007977/

Home-Based Walking Exercise Intervention in Peripheral ... The primary outcome was 6-month change in 6-minute walk performance. Secondary outcomes included 6-month change in treadmill walking, physical activity, the ...

2. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/1707722

Home-Based Walking Exercise Intervention in Peripheral ... A home-based walking exercise program significantly improved walking endurance, physical activity, and patient-perceived walking endurance and speed in PAD ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39755577

Effectiveness of home-based walking exercise for patients ... Home-based exercise interventions for patients with PAD and IC were beneficial in improving pain-free walking distance and maximal walking distance.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04749732

Home-based Exercise Therapy for Patients With PAD Patients with peripheral arterial disease (PAD) have a severe impairment of functional ability, namely in walking distance due to muscle ischemia defined as ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02462824

Patient Centered Home Exercise Program for Peripheral ... The purpose of this study is to determine the effects of a home-based exercise intervention on walking ability in people with peripheral artery disease.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39423932/

Safety and efficacy of home-based walking exercise for ... Among people with PAD, home-based exercise improved 6MW by at least 20 meters in 54.9% of people. Older age, female sex, Black race, ...

7. bmjopen.bmj.com bmjopen.bmj.com/content/14/3/e080071

Comparison of home-based rehabilitation and a centre ... This will be the first clinical trial to investigate the effectiveness of a home-based exercise programme for individuals with peripheral arterial disease (PAD) ...