Exercise and Nitric Oxide Effects in Peripheral Artery Disease

Response to Exercise and Nitric Oxide in Peripheral Artery Disease: The RESIST PAD Trial

This study is testing if a 12-week exercise program can boost nitric oxide levels in people with Peripheral Artery Disease and whether drinking beetroot juice can help those who don't see improvements from exercise.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 200 (estimated)
• Ages: 50 Years and up
• Sex: All
• Sponsor: Northwestern University (Academic / other)
• Locations: 2 sites (Chicago, Illinois and 1 other locations)
• Trial ID: NCT06657976 on ClinicalTrials.gov

What this trial studies

This trial investigates the effects of a 12-week supervised exercise program on nitric oxide levels in patients with Peripheral Artery Disease (PAD). It aims to determine if exercise increases nitrite levels and whether some patients respond better than others. Additionally, for those who do not respond to exercise, the study will assess if supplementing with nitrate-rich beetroot juice can enhance results. The trial will involve 200 participants and will measure outcomes at 12 and 24 weeks.

Who should consider this trial

Good fit: Ideal candidates are individuals diagnosed with Peripheral Artery Disease who meet specific criteria regarding ankle-brachial index measurements.

Not a fit: Patients with severe limb ischemia, amputations, or those whose walking difficulties are due to conditions other than PAD may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could improve walking ability and quality of life for patients with Peripheral Artery Disease.

How similar studies have performed: Previous studies have shown promising results with exercise interventions in PAD, but the specific combination of exercise and nitrate supplementation is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. An ABI less than or equal to 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 more than 0.90 and less than 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 less than 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. Failure to complete study-run
7. Unwilling to accept randomization into either group (supervised exercise or attention control)
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, using investigator discretion.
10. End-stage kidney disease (ESKD) that is treated with hemodialysis.
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 less than 23 or dementia. If the MMSE is less than 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 less than 23 to participate, as appropriate. Dementia with sufficient impairment to prevent full engagement in all aspects of the trial will be an exclusion per the investigator's discretion.
15. Allergy to beetroot juice
16. Currently consuming beetroot juice, oral nitrate or nitrite, or a beetroot supplement and/or unwilling to avoid beetroot juice during the study. Participants will be asked to discontinue these items for 30 days before baseline testing and throughout the clinical trial. If the potential participant is unwilling to refrain from taking these items, they will not be eligible for the clinical trial.
17. Currently consuming one cup or more of beets daily. Participants will be asked to discontinue beet ingestion of one cup or more of beets 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 for 30 days before the trial and during the trial, they will not be eligible for the clinical trial.
18. Unstable angina
19. Abnormal baseline stress test without subsequent clearance for exercise by physician
20. Non-English speaking. The RESIST 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.
21. 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.
22. Visual impairment that limits walking ability.
23. Baseline blood pressure less than 100/45.
24. Participation in a supervised treadmill exercise program in previous three months or planning to begin a supervised treadmill exercise program in the next six months.
25. 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 1 other locations

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

Study contacts

• Study coordinator: Mary M McDermott, MD

Conditions Peripheral Artery Disease; Exercise; Intermittent Claudication; Nitric Oxide; Peripheral artery disease; Claudication; Walking difficulty