Improving Mobility After Revascularization in Peripheral Artery Disease

NCT06686121 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: STU00222333
• Study Type: interventional
• Target: 386
• Locations: 1 country
• Sites: 7

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Six-Minute Walk Distance 6-month change

  Distance walked in six minutes

  Baseline to 6-month follow-up

Secondary Outcomes (6)

• Walking Impairment Questionnaire (WIQ) Distance Score 6-month change

  Baseline to 6-month follow-up.

• Walking Impairment Questionnaire (WIQ) Distance Score 12-month change

  Baseline to 12-month follow-up

• PROMIS Mobility Questionnaire Score 6-month change

  Baseline to 6-month follow-up

• PROMIS Mobility Questionnaire Score 12-month change

  Baseline to 12-month follow-up.

• Prevention of Hemodynamic Failure of The Revascularized Vessel

  Baseline to 12 month follow-up

Other Outcomes (4)

• Six-Minute Walk Distance

  Baseline to six-month follow-up at the time point that is twenty-four hours after the final study drink

• Plasma Nitrite Levels

  Baseline to 6-month follow-up

• BH4/BH2 6-month change

  Baseline to 6-month follow-up

Study Arms (4)

Home based exercise + nitrate rich beetroot juice

EXPERIMENTAL

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

Behavioral: Home Based Exercise; Drug: Nitrate Rich Beetroot Juice

Home-based exercise + placebo

PLACEBO COMPARATOR

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

Behavioral: Home Based Exercise; Drug: Placebo Beetroot Juice Without Nitrate

Attention control + nitrate-rich beetroot juice

EXPERIMENTAL

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

Drug: Nitrate Rich Beetroot Juice; Behavioral: Attention Control

Attention control + placebo

PLACEBO COMPARATOR

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

Behavioral: Attention Control; Drug: Placebo Beetroot Juice Without Nitrate

Interventions

Home Based Exercise BEHAVIORAL

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

Home based exercise + nitrate rich beetroot juice; Home-based exercise + placebo

Nitrate Rich Beetroot Juice DRUG

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

Attention control + nitrate-rich beetroot juice; Home based exercise + nitrate rich beetroot juice

Attention Control BEHAVIORAL

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.

Attention control + nitrate-rich beetroot juice; Attention control + placebo

Placebo Beetroot Juice Without Nitrate DRUG

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

Attention control + placebo; Home-based exercise + placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.
• Unstable angina
• Unwilling to drink study beverages
• Unwilling to adhere to the interventions and complete follow-up testing
• Currently taking sildenafil, tadalafil, or related drugs.
• Unwilling to accept randomization into either group (home-based exercise or attention control)
• 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.
• History of kidney stones that requires minimized intake of oxalate. Potential participants who need to minimize oxalate intake will be excluded from the trial.
• Baseline blood pressure \<100/45.
• Wheelchair confinement or requiring a walker to ambulate
• Walking is limited by a condition other than PAD
• Current foot ulcer

Sponsors & Collaborators

• Northwestern University: lead
• Rancho Research Institute: 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

Study Sites (7)

University of Arizona

Tucson, Arizona, 85724, United States

NOT YET RECRUITING

Rancho Research Institute

Downey, California, 90242, United States

RECRUITING

Emory University School of Medicine

Atlanta, Georgia, 30307, United States

NOT YET RECRUITING

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

RECRUITING

University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03766, United States

NOT YET RECRUITING

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Peripheral Arterial Disease; Intermittent Claudication; Peripheral Vascular Diseases; Mobility Limitation

Interventions

Nitrates

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Anions; Ions; Electrolytes; Inorganic Chemicals; Nitric Acid; Nitrogen Compounds; Organic Chemicals

Central Study Contacts

Mary M McDermott, MD

CONTACT

312-503-6438; mdm608@northwestern.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) For the beetroot juice vs. placebo comparison, this will be a double blinded study where both the participant and the people collecting data will be blinded. For the home-based exercise, the participant and investigator will not be blinded, but the outcomes assessor will be blinded.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Two x two factorial design

Study Record Dates

• First Submitted: November 8, 2024
• First Posted: November 13, 2024
• Study Start: August 4, 2025
• Primary Completion (Estimated): February 1, 2032
• Study Completion (Estimated): August 1, 2032
• Last Updated: August 26, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be available at the time the primary outcome manuscript is submitted for publication and will be available for up to 10 years.
• Access Criteria: Per BioLINCC

Locations

US (7)