Improving Exercise Rehabilitation Efficacy Outcomes Veterans Peripheral Artery Disease

NCT05648630 | Withdrawn

• 2 other identifiers: E3913-WRX003913
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

Physical activity is the most beneficial and cost-effective treatment for Veterans with PAD, however, issues with oxygen delivery and utilization dramatically impair exercise compliance. The cause of these oxygen delivery and utilization impairments is likely increased oxidative stress and inflammation. The proposed project will comprehensively examine the novel strategy of Nuclear Factor Erythroid-2-like 2 (Nrf2) activation using PB125, aimed at diminishing oxidative stress and inflammation, and thereby lessening the negative impacts of the disease. This therapeutic will be evaluated in isolation and in combination with exercise rehabilitation to determine if there is a complimentary benefit. The ultimate goal is to provide insight into a potential novel therapeutic treatment for this disease, therefore, improving exercise tolerance and quality of life in this growing population.

Conditions

Peripheral Artery Disease (D058729); Oxidative Stress (D018384); Inflammation (D007249)

Keywords

inflammation (D007249); Skeletal muscle (D018482); Antioxidants (D000975)

Outcome Measures

Primary Outcomes (3)

• Six-minute Walk Test (6MWT) Change

  6MWT will be quantified with total distance, last minute speed, and claudication onset time. Greater distance and higher speed indicates better functional capacity and greater change over time suggests improvement.

  Baseline, month 1, month 2, month 3, month 4

• Exercise pressor response (EPR) Change

  EPR will be quantified with the change in mean arterial blood pressure from rest to exercise. A greater EPR indicates elevated cardiovascular risk and a reduction in the EPR over time suggests improvement.

  Baseline, month 1, month 2, month 3, month 4

• Intramuscular maximal bioenergetics (Vmax) Change

  Vmax will be quantified as the rate of intramuscular phosphocreatine replenishment following exercise. A greater Vmax indicates better mitochondrial and hemodynamic function and greater change over time suggests improvement.

  Baseline, month 1, month 4

Study Arms (2)

Exercise Rehabilitation+PB125

EXPERIMENTAL

Participants will be assigned to the Exercise+Placebo or Exercise+PB125 rehabilitation interventions using block randomization.

Dietary Supplement: PB125; Behavioral: Exercise Rehabilitation

Exercise Rehabilitation with Placebo

PLACEBO COMPARATOR

Participants will be assigned to the Exercise+Placebo rehabilitation interventions using block randomization.

Dietary Supplement: Placebo; Behavioral: Exercise Rehabilitation

Interventions

PB125 DIETARY_SUPPLEMENT

PB125 is a naturally-derived plant-based supplement that activates the Nuclear Factor Erythroid-2-like 2 (Nrf2) system to stimulate induction of endogenous antioxidants and anti-inflammatory pathways.

Exercise Rehabilitation+PB125

Placebo DIETARY_SUPPLEMENT

A placebo will be used in combination with exercise rehabilitation allowing for a double blinded placebo controlled design.

Exercise Rehabilitation with Placebo

Exercise Rehabilitation BEHAVIORAL

A 12-week treadmill based supervised rehabilitation

Exercise Rehabilitation with Placebo; Exercise Rehabilitation+PB125

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 40 and older with clinically diagnosed femoropopliteal PAD (ankle-brachial index \< 0.9)
• Must understand the study requirements and be willing and able to sign an informed consent document
• Patients with mild cognitive impairment (i.e., montreal cognitive assessment (MOCA) \<26) will be included but must have a responsible caregiver or spouse present during the informed consent
• Women that are not pregnant, breastfeeding, or likely to become pregnant within the next 6 months

You may not qualify if:

• Patients with a bleeding disorder that would contraindicate the performance of a muscle biopsy, such as a history of clinically significant bleeding diathesis (i.e., Hemophilia A or B, Von Willebrand's Disease, or congenital Factor VII deficiency)
• Patients with a complex atherosclerotic lesion such that withholding medication creates disproportionate risk
• Women currently taking hormone replacement therapy

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (2)

University of Utah Dept of Vascular Surgery

Salt Lake City, Utah, 84132, United States

Location

VA Salt Lake City Health Care System, Salt Lake City, UT

Salt Lake City, Utah, 84148-0001, United States

Location

MeSH Terms

Conditions

Peripheral Arterial Disease; Inflammation

Interventions

Exercise Therapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Physical Therapy Modalities

Study Officials

• David W. Wray, PhD

  VA Salt Lake City Health Care System, Salt Lake City, UT

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Two separate groups of subjects (patients with PAD) receiving PB125 or Placebo
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Two separate groups of subjects (patients with PAD) receiving PB125 or Placebo

Study Record Dates

• First Submitted: November 4, 2022
• First Posted: December 13, 2022
• Study Start: July 3, 2023
• Primary Completion: October 1, 2025
• Study Completion: October 1, 2025
• Last Updated: November 10, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)