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).
None
History of leg amputation, not including toe and partial foot amputation
Active gangrene
Active limb threatening ischemia
Already exercising at a level consistent with exercise intervention, using investigator discretion.
Factorial
Home Based Exercise
BehavioralThis 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
DrugParticipants will drink one shot of nitrate rich beet-root juice twice daily for six months.
Attention Control
BehavioralParticipants 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
DrugParticipants will drink one shot of placebo beetroot without nitrate juice twice daily for six months.
Six-Minute Walk Distance 6-month change
Distance walked in six minutes
Walking Impairment Questionnaire (WIQ) Distance Score 6-month change
Patient reported ability to walk long distances. Score Range 0-100, 100 is best.
Walking Impairment Questionnaire (WIQ) Distance Score 12-month change
Patient reported ability to walk long distances. Score Range 0-100, 100 is best.
PROMIS Mobility Questionnaire Score 6-month change
Patient report of mobility in daily living. Score range is from zero to infinity and a higher score means a better outcome.
PROMIS Mobility Questionnaire Score 12-month change
Patient report of mobility in daily living. Score range is from zero to infinity and a higher score means a better outcome.
Six-Minute Walk Distance
Change in six-minute walk distance 24 hours after the final study beverage
Plasma Nitrite Levels
Change in plasma nitrite levels in the blood at 6-month follow-up
BH4/BH2 6-month change
Change in BH4/BH2 ratio
Progression of PAD
Determine whether home-based walking exercise, compared to attention control prevents progression of PAD, defined by any new lower extremity revascularization, acute limb ischemia, or amputation of either lower extremity between baseline and 12-month follow-up.
Click on the lead sponsor to view all of their trials.
Northwestern University
Lead sponsor
Rancho Research Institute, Inc.
Collaborator
University of Chicago
Collaborator
Wake Forest University
Collaborator
University of Pittsburgh Medical Center
Collaborator
Emory University
Collaborator
University of Arizona
Collaborator
Dartmouth-Hitchcock Medical Center
Collaborator
Henry Ford Health + Michigan State University Health Sciences
Collaborator
