RECRUITING

Improving Mobility After Revascularization in Peripheral Artery Disease

Description

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).

Study Overview

Study Details

Study overview

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).

IMProving Mobility After revasCularizaTion in Peripheral Artery Disease: The IMPACT PAD Trial

Improving Mobility After Revascularization in Peripheral Artery Disease

Condition
Peripheral Artery Disease
Intervention / Treatment

-

Contacts and Locations

Tucson

University of Arizona, Tucson, Arizona, United States, 85724

Downey

Rancho Research Institute, Downey, California, United States, 90242

Atlanta

Emory University School of Medicine, Atlanta, Georgia, United States, 30307

Chicago

Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States, 60611

Chicago

University of Chicago, Chicago, Illinois, United States, 60637

Lebanon

Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire, United States, 03766

Pittsburgh

University of Pittsburgh, Pittsburgh, Pennsylvania, United States, 15213

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility 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.

Ages Eligible for Study

18 Years to

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

No

Collaborators and Investigators

Northwestern University,

Study Record Dates

2032-08-01