Recruiting
Phase 2

Exercise & Nitric Oxide

Sponsor:

Northwestern University

Code:

NCT06657976

Conditions

Peripheral Artery Disease

Exercise

Intermittent Claudication

Nitric Oxide

Eligibility Criteria

Sex: All

Age: 50+

Healthy Volunteers: Not accepted

Interventions

Supervised Treadmill Exercise

Attention Control

Nitrate-Rich Beetroot Juice + supervised exercise therapy

Placebo + supervised exercise therapy

Study Details

Brief summary:

RESIST PAD is a randomized trial of 200 PAD patients to establish: 1) whether a 12-week exercise intervention significantly increases Δ nitrite at 12-week follow-up, compared to control; 2) whether exercise "responders" have greater Δ nitrite increases compared to "non-responders"; 3) among non-responders, whether supplementing exercise with nitrate-rich beetroot juice between weeks 13-24 increases Δ nitrite and improves 6-minute walk at 24-week follow-up.

Conditions

Peripheral Artery Disease

Exercise

Intermittent Claudication

Nitric Oxide

Study ID

NCT06657976

Start date

Jan 23, 2025

Status verified date

Jul, 2026

Completion date

Oct 1, 2029

Anticipated

Primary completion date

Jul 1, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 50+

Healthy Volunteers: Not accepted

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 14 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. History of kidney stones that requires minimized intake of oxalate. Potential participants who need to minimize oxalate intake will be excluded from the trial.
26. 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.

Study Design

Enrollment

200 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Supervised Treadmill Exercise

This group will be participating in supervised treadmill exercise for 12 weeks. Participants will walk for exercise on a treadmill 3 times per week at a center while supervised by healthcare personnel.

sham comparator: Attention Control Group

This group will attend weekly one-hour educational sessions either on Zoom or in-person for 12 weeks. These sessions are on topics of interest to the typical PAD patient and may be led by study staff, physicians, or other health care workers.

experimental: Exercise Supplementation with Nitrate-Rich Beetroot Juice

This group for "non-responders" will receive supervised exercise supplementation with nitrate-rich beetroot juice for an additional 12 weeks.

placebo comparator: Exercise Supplementation with Placebo Beetroot Juice

This group for "non-responders" will received supervised exercise supplementation with placebo beetroot juice for the additional 12 weeks.

Interventions

Supervised Treadmill Exercise

This is a 12 week intervention where participants will walk for exercise 3 times a week on a treadmill at a center while being supervised by healthcare personnel.

Attention Control

This group will attend weekly one-hour educational sessions either on Zoom or in-person for 12 weeks. These sessions are on topics of interest to the typical PAD patient and may be led by study staff, physicians, or other health care workers.

Nitrate-Rich Beetroot Juice + supervised exercise therapy

Participants randomized to this group will drink nitrate-rich beetroot juice while engaged in supervised exercise.

Placebo + supervised exercise therapy

Participants randomized to this group will drink placebo while engaged in supervised exercise.

Primary outcome measure

  • Delta nitrite [ Time Frame: Baseline to 12-week follow-up ]
  • Six-minute walk [ Time Frame: From 12-weeks to 24-week follow-up ]

Central Contacts and Locations

Central contacts

Locations

Northwestern University Feinberg School of Medicine

Recruiting

Chicago, Illinois, United States, 60611

Contacts

Principal Investigator:

Mary M McDermott, MD

More Information

Sponsor

Northwestern University

Last update posted

Jul 27, 2026

Last verified

Jul, 2026

Keywords

  • Peripheral artery disease
  • Claudication
  • Walking difficulty

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Northwestern University on 2026-07-27.