Recruiting
Phase 3

Home-Based Exercise & Nitrate

Sponsor:

Northwestern University

Code:

NCT06686121

Conditions

Peripheral Artery Disease

Intermittent Claudication

Peripheral Vascular Disease

Mobility Limitation

Revascularization

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Home Based Exercise

Nitrate Rich Beetroot Juice

Attention Control

Placebo Beetroot Juice Without Nitrate

Study Details

Brief summary:

Lower extremity revascularization combined with supervised exercise significantly improves walking performance compared to revascularization alone in people who have PAD without limb threatening ischemia. However, supervised exercise is inaccessible or burdensome for most PAD patients. Investigators hypothesize that home-based exercise combined with lower extremity revascularization will significantly improve walking performance compared to revascularization alone in patients with PAD undergoing revascularization for disabling PAD.

Investigators further hypothesize that inorganic nitrate, a major source of nitric oxide (NO) abundant in beetroot juice, will improve walking performance after lower extremity revascularization, compared to placebo. In preclinical models, NO inhibits inflammation, neointimal hyperplasia, thrombosis, and vascular smooth muscle cell migration at sites of revascularization. NO increases angiogenesis and perfusion, repairs skeletal muscle damaged by ischemia, and stimulates mitochondrial activity.

In a randomized clinical trial with a 2 x 2 factorial design, the trial will test the following two primary hypotheses in 386 patients randomized within three months of a successful lower extremity revascularization for disabling PAD: First, that home-based exercise combined with lower extremity revascularization will improve six-minute walk distance more than revascularization alone at 6-month follow-up (Primary Aim #1). Second, that nitrate-rich beetroot juice combined with lower extremity revascularization will improve six-minute walk, compared to placebo combined with revascularization at 6-month follow-up (Primary Aim #2).

Conditions

Peripheral Artery Disease

Intermittent Claudication

Peripheral Vascular Disease

Mobility Limitation

Revascularization

Study ID

NCT06686121

Start date

Aug 4, 2025

Status verified date

Aug, 2025

Completion date

Aug 1, 2032

Anticipated

Primary completion date

Feb 1, 2032

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

Successful lower extremity revascularization for disabling PAD performed at least 30 days before baseline testing and between 30 and 100 days before randomization.

Exclusion Criteria:

1. History of leg amputation, not including toe and partial foot amputation
2. Active gangrene
3. Active limb threatening ischemia
4. Already exercising at a level consistent with exercise intervention, using investigator discretion.
5. Unstable angina
6. Unwilling to drink study beverages
7. Unwilling to adhere to the interventions and complete follow-up testing
8. Currently taking sildenafil, tadalafil, or related drugs.
9. Unwilling to accept randomization into either group (home-based exercise or attention control)
10. 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.
11. History of kidney stones that requires minimized intake of oxalate. Potential participants who need to minimize oxalate intake will be excluded from the trial.
12. Baseline blood pressure <100/45.
13. Wheelchair confinement or requiring a walker to ambulate
14. Walking is limited by a condition other than PAD
15. Current foot ulcer
16. Planned major surgery, coronary revascularization, or lower extremity revascularization during the next 12 months
17. Major medical illness including lung disease requiring oxygen, Parkinson's disease, or a life-threatening illness with life expectancy less than six months.
18. Allergy to beetroot juice
19. Currently consuming one cup or more of beets daily. Participants will be asked to decrease beet consumption to less than one cup of beets per day for 14 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.
20. Participation in or completion of a clinical trial in the previous three months, using investigator discretion for trials that may not impact study participation or outcome measures of the IMPACT PAD Trial.
21. Visual impairment that limits walking ability.
22. Unable to communicate in English, unless the participant communicates in Spanish and is enrolled at a site that can deliver the intervention in Spanish. All sites with a Spanish speaking coordinator and interventionist will be able to enroll Spanish-speaking participants. While investigators aim to be as inclusive as possible, resources are not available to allow inclusion of people speaking languages that are not Spanish or English.
23. Using a mouthwash containing chlorhexidine or cetylpyridinium chloride or a mouthwash determined to be bactericidal and unwilling to discontinue.
24. Planning to begin a supervised treadmill exercise program in the next 12 months.
25. Heart attack or stroke in previous three months prior to baseline testing.
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

386 participants

Anticipated

Allocation

Randomized

Intervention Model

Factorial

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Home based exercise + nitrate rich beetroot juice

This group will be participating in home based exercise and drinking nitrate rich beetroot juice for six months.

placebo comparator: Home-based exercise + placebo

This group will be participating in home based exercise and drinking placebo beetroot juice with nitrate removed for six months.

experimental: Attention control + nitrate-rich beetroot juice

This group will be participating in attention control and drinking nitrate rich beetroot juice for six months.

placebo comparator: Attention control + placebo

This group will be participating in attention control and drinking placebo beetroot juice with nitrate removed for six months.

Interventions

Home Based Exercise

This is a six month intervention where participants will walk at home for exercise with guidance from a study coach. They will attend two to four weekly meetings with the coach at the clinical site in the first 4 weeks following randomization, followed by once weekly telephone coaching calls for the remainder of the six-month intervention

Nitrate Rich Beetroot Juice

Participants will drink one shot of nitrate rich beet-root juice twice daily for six months.

Attention Control

Participants will be asked to participate in weekly meetings with the coach in the attention control group for weeks 1-26. A staff member will present a topic from the National Institute on Aging "age pages" relevant to health, such as cancer screening or blood pressure treatment. Calls will last approximately 5-15 minutes and will focus on educational topics such as diabetes, healthy eating, and Medicare Part D.

Placebo Beetroot Juice Without Nitrate

Participants will drink one shot of placebo beetroot without nitrate juice twice daily for six months.

Primary outcome measure

  • Six-Minute Walk Distance 6-month change [ Time Frame: Baseline to 6-month follow-up ]

Central Contacts and Locations

Central contacts

Locations

Rancho Research Institute

Recruiting

Downey, California, United States, 90242

Northwestern University Feinberg School of Medicine

Recruiting

Chicago, Illinois, United States, 60611

Contacts

Principal Investigator:

Mary M McDermott, MD

University of Chicago

Recruiting

Chicago, Illinois, United States, 60637

Contacts

Tamar Polonsky, MD

773-702-6153

More Information

Sponsor

Northwestern University

Last update posted

Aug 26, 2025

Last verified

Aug, 2025

Keywords

  • Behavior Change
  • Patient Reported Outcome Measures
  • Mobility
  • Revascularization
  • Peripheral artery disease
  • Intermittent claudication
  • 6-minute walk
  • Oxidative stress

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 2025-08-26.