Improving Mobility After Revascularization in Peripheral Artery Disease

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

Interventions

BEHAVIORAL

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

DRUG

Nitrate Rich Beetroot Juice

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

BEHAVIORAL

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.

DRUG

Placebo Beetroot Juice Without Nitrate

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

Sponsors & Collaborators

• Rancho Research Institute

  collaborator UNKNOWN

• University of Chicago

  collaborator OTHER

• Wake Forest University

  collaborator OTHER

• University of Pittsburgh Medical Center

  collaborator OTHER

• Emory University

  collaborator OTHER

• University of Arizona

  collaborator OTHER

• Dartmouth-Hitchcock Medical Center

  collaborator OTHER

• Northwestern University

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

FACTORIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-08-04

Primary Completion

2032-02-01

Completion

2032-08-01

FDA Drug

Yes

Countries

• United States

Study Locations