Exercise and beetroot juice for improving walking in patients with PAD

Sequential Multiple Assessment Randomized Trial of Exercise for PAD: SMART Exercise for Peripheral Artery Disease: The SMART PAD Trial

This study is testing whether combining treadmill and home exercises with beetroot juice can help older patients with peripheral artery disease walk farther and feel better.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 210 (estimated)
• Ages: 50 Years and up
• Sex: All
• Sponsor: Northwestern University (Academic / other)
• Locations: 3 sites (Chicago, Illinois and 2 other locations)
• Trial ID: NCT06032065 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of supervised treadmill exercise and home-based exercise, combined with nitrate-rich beetroot juice, in improving walking distance for patients with peripheral artery disease (PAD). The study employs a 2 x 2 factorial design to compare these interventions and address barriers to exercise adherence. Participants aged 50 and older with PAD will be enrolled, and their exercise tolerance and walking ability will be assessed. The goal is to determine if these combined approaches can enhance outcomes for patients who struggle with traditional exercise therapies.

Who should consider this trial

Good fit: Ideal candidates for this study are individuals aged 50 and older who have been diagnosed with peripheral artery disease.

Not a fit: Patients with severe limb-threatening ischemia, amputations, or those unable to participate in exercise due to other conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a more accessible and effective treatment option for patients with PAD, improving their walking ability and quality of life.

How similar studies have performed: Previous studies have shown promising results with home-based exercise interventions for PAD, but this specific combination of approaches is novel.

Eligibility criteria

Inclusion Criteria:

First, all participants will be age 50 and older. Second, all participants will have PAD. PAD will be defined as either:

1. An ABI \<= 0.90 at baseline.
2. Vascular lab evidence of PAD (such as a toe brachial pressure less than or equal to 0.70 or an ankle brachial index less than or equal to 0.90), or angiographic evidence of PAD defined as at least 70% stenosis of an artery supplying the lower extremities.
3. An ABI of \>0.90 and \<1.00 who experience a 20% or greater drop in ABI in either leg after the heel-rise test.

Exclusion Criteria:

1. Above- or below-knee amputation
2. Limb-threatening ischemia defined as an ABI \<0.40 with symptoms of rest pain
3. Wheelchair confinement or requiring a walker to ambulate
4. Walking is limited by a condition other than PAD
5. Current foot ulcer on bottom of foot
6. Unwilling to drink beetroot juice
7. Unwilling to accept randomization into either group (home based exercise or supervised exercise)
8. Planning to engage in new walking exercise outside of the study or unwilling to refrain from new walking exercise activity during the trial.
9. Already exercising at a level consistent with exercise intervention.
10. End-stage kidney disease (ESKD) associated with the need for dialysis.
11. Planned major surgery, coronary or leg revascularization during the next six months
12. Major surgery, coronary or leg revascularization or major cardiovascular event in the previous three months
13. Major medical illness including lung disease requiring oxygen, Parkinson's disease, a life-threatening illness with life expectancy less than six months, or cancer requiring treatment in the previous two years. \[NOTE: potential participants may still qualify if they have had treatment for an early stage cancer in the past two years and the prognosis is excellent. Participants who require oxygen only at night may still qualify.\]
14. Mini-Mental Status Examination (MMSE) score \< 23 or dementia. However, if the MMSE is \< 23 and the Principal Investigator evaluation determines that the lower score is related to language barriers or education level, the Principal Investigator has discretion to allow a participant with MMSE \< 23 to participate, as appropriate.
15. Allergy to beetroot juice
16. Currently consuming beetroot juice or oral nitrate or nitrite, or a beetroot supplement, and/or unwilling to avoid these during study participation. Participants currently consuming one cup of beets daily will be asked to discontinue beet ingestion for 30 days before baseline testing and throughout the clinical trial. If the potential participant is unwilling to refrain from daily beet consumption of one cup or more, they will not be eligible for the clinical trial.
17. Unstable angina
18. Abnormal baseline stress test without subsequent clearance for exercise by physician
19. Non-English speaking. The SMART PAD interventions are delivered by interventionists who do not speak non-English languages. The integrity of the clinical trial requires clear and effective communication for data collection and intervention delivery. The trial does not have staff members who are fluent in non-English languages, nor does it have the ability to translate all study materials into other languages.
20. Participation in or completion of a clinical trial in the previous three months. \[NOTE: after completing a stem cell or gene therapy intervention, participants will become eligible after the final study follow-up visit of the stem cell or gene therapy study so long as at least six months have passed since the final intervention administration. After completing a supplement or drug therapy (other than stem cell or gene therapy), participants will be eligible after the final study follow-up visit as long as at least three months have passed since the final intervention of the trial.\] Participants in a study that involved up to three single doses of nitrate-rich beetroot juice administered on separate days may participate if a month has passed since their last dose of nitrate-rich beetroot juice.
21. Visual impairment that limits walking ability.
22. Baseline blood pressure \<100/45.
23. Participation in a supervised treadmill exercise program or cardiac rehabilitation program in previous three months.
24. Using a mouthwash containing chlorhexidine or cetylpyridinium chloride or a mouthwash determined to be bactericidal and unwilling to discontinue.
25. An eGFR value \<30 or potassium \>5.0.
26. History of kidney stones that requires minimized intake of oxalate. Potential participants who need to minimize oxalate intake will be excluded from the trial.
27. In addition to the above criteria, investigator discretion will be used to determine if the trial is unsafe or not a good fit for the potential participant.

Where this trial is running

Chicago, Illinois and 2 other locations

• Northwestern University Feinberg School of Medicine — Chicago, Illinois, United States (Recruiting)
• University of Chicago — Chicago, Illinois, United States (Recruiting)
• University of Minnesota — Minneapolis, Minnesota, United States (Recruiting)

Study contacts

• Study coordinator: Mary McDermott, MD

Conditions Peripheral Arterial Disease; Aging; Peripheral Vascular Diseases; Walking, Difficulty; behavior change; patient reported outcome measure