Promote Weight Loss in Obese Peripheral Artery Disease (PAD) Patients to Prevent Mobility Loss

Overview

The PROVE Trial is a randomized clinical trial that will determine whether a weight loss intervention combined with walking exercise achieves greater improvement or less decline in six-minute walk distance at 12 month follow-up than walking exercise alone in people with PAD and BMI>28 kg/m2. The intervention uses a Group Mediated Cognitive Behavioral framework, connective mobile technology, remote monitoring by a coach, and a calorie restricted Dietary Approaches to Stop Hypertension (DASH)-derived Optimal Macronutrient Intake Trial for Heart Health (OMNIHeart) diet.

212 participants with PAD and BMI > 28 kg/m2 will be randomized to one of two groups: weight loss + exercise (WL+EX) vs. exercise alone (EX). Participants will be randomized at Northwestern, Tulane University, and University of Minnesota. Our primary outcome is change in six-minute walk distance at 12-month follow-up. Secondary outcomes are change in 6-minute walk distance at 6-month follow-up and change in exercise adherence, physical activity, patient-reported walking ability (measured by the Walking Impairment Questionnaire (WIQ) distance score), and mobility (measured by the Patient-Reported Outcomes Measurement Information System [PROMIS] mobility questionnaire) at 12-month follow-up. Tertiary outcomes are perceived exertional effort (measured by the Borg scale at the end of the 6-minute walk at 12-month follow-up), and diet quality. Exploratory outcomes consist of change in the short physical performance battery (SPPB), the WIQ stair climbing and walking speed scores, and calf muscle biopsy measures at 12-month follow-up. Study investigators will perform calf muscle biopsies in 50 participants to compare changes in mitochondrial biogenesis and activity, capillary density, and inflammation between WL+EX vs. EX.

Full Title of Study: “PROmote Weight Loss in Obese Peripheral Artery Disease (PAD) Patients to preVEnt Mobility Loss: The PROVE Trial”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Single (Outcomes Assessor)
  • Study Primary Completion Date: May 31, 2026

Interventions

  • Behavioral: Weight loss
    • Walking exercise combined with weight loss
  • Behavioral: Exercise
    • Walking exercise

Arms, Groups and Cohorts

  • Experimental: Weight loss + exercise (WL+EX)
    • Weight loss + home based walking exercise (WL+EX)
  • Active Comparator: Exercise alone (EX)
    • Home based walking exercise (EX)

Clinical Trial Outcome Measures

Primary Measures

  • 12-month change in six-minute walk distance
    • Time Frame: Baseline to 12 months
    • Change in six-minute walk distance at 12-month follow-up will be compared between individuals randomized to weight loss + exercise vs. those randomized to exercise alone.

Secondary Measures

  • 12-month change in minutes of walking exercise/week
    • Time Frame: Baseline to 12 months
    • Change in minutes walked for exercise in a week will be compared between individuals randomized to the weight loss + exercise vs. those randomized to exercise alone
  • 12-month change in physical activity measured by accelerometer data
    • Time Frame: Baseline to 12 months
    • Change in physical activity at 12-month follow-up will be compared between individuals randomized to the weight loss + exercise vs. those randomized to exercise alone. Change in physical activity will be compared using accelerometer data.
  • 12-month change in Walking Impairment Questionnaire (WIQ) distance score
    • Time Frame: Baseline to 12 months
    • Change in Walking Impairment Questionnaire (WIQ) distance score at 12-month follow-up will be compared between individuals randomized to the weight loss + exercise vs. those randomized to exercise alone. The WIQ distance score ranges from 0-100 with a higher score is better.
  • 12-month change in Patient-Reported Outcomes Measurement Information System (PROMIS) mobility questionnaire
    • Time Frame: Baseline to 12 months
    • Change in Patient-Reported Outcomes Measurement Information System (PROMIS) mobility questionnaire score at 12-month follow-up will be compared between individuals randomized to the weight loss + exercise vs. those randomized to exercise alone. A higher score is better. There is no set minimum and maximum values for the PROMIS questionnaire. However, a higher PROMIS score indicates a better outcome.
  • 6-month change in 6-minute walk distance
    • Time Frame: Baseline to 6 months
    • Change in six-minute walk distance at 6-month follow-up will be compared between individuals randomized to weight loss + exercise vs. those randomized to exercise alone.

Participating in This Clinical Trial

Inclusion Criteria

  • presence of PAD
  • BMI> 28 kg/m2
  • Age 18 to 85 The diagnosis of PAD will be based on the following. First, an ankle brachial index (ABI) value < 0.90, which is a well-accepted standard for diagnosing PAD. Second, people with an ABI of >0.90 and <1.00 who experience a 20% ankle systolic pressure drop after the heel-rise test will also be included. Third, potential participants with an ABI > 0.90 who provide angiographic evidence of PAD or proof of prior lower extremity revascularization will be included, only if they are symptomatic or have a positive heel rise test. A positive heel rise test is defined as a 20% ankle systolic pressure drop after the heel rise test. The heel rise test consists of 50 heel rises at a rate of one per second. Study investigators will use the BMI inclusion criterion of > 28 kg/m2 because overweight and obesity are defined as a BMI of 25 to 29 kg/m2 and > 30 kg/m2, respectively, and because in our PAD cohorts, those with BMI > 28 kg/m2 have significantly greater functional impairment and faster functional decline than those with BMI of 20-28 kg/m2.

Exclusion Criteria

1. Above or below knee amputation, critical limb ischemia, wheelchair confinement, or foot ulcer

2. Walking is limited by a condition other than PAD.

3. Failure to complete the 1-week run-in.

4. Major surgery, coronary or leg revascularization in the past 3 months or anticipated in the next year.

5. Major medical illness including lung disease requiring oxygen or life-threatening illness, Parkinson's disease, a life-threatening illness with life expectancy less than six months, or cancer requiring treatment in the previous two years. [Note: potential participants may still qualify if they have had treatment for an early stage cancer in the past two years and the prognosis is excellent.

6. Mini-Mental Status Examination score < 23, dementia, psychiatric illness, substance abuse.

7. BMI > 45 kg/m2

8. History of an eating disorder or any weight loss treatment in the past 6 months. Weight loss treatment includes weight watchers, any history of weight loss surgery, and using weight loss medications now or in the past six months.

9. Gained or lost more than 15 pounds in the past six months

10. Potential participants unwilling/unable to use a smart phone and unwilling to attend weekly study sessions.

11. Excessive alcohol use, defined as >14 drinks/week in men and > 10 alcoholic drinks/week in women.

12. Age > 85 years

13. Current ulcer on bottom of foot

14. Current participation in supervised treadmill exercise, participation in supervised treadmill exercise in the past six months, or planning to participate in supervised treadmill exercise in the next year

15. Increase in angina or angina at rest. Potential participants may become eligible following an abnormal baseline treadmill stress test if they have evidence of an absence of coronary ischemia based on testing with their own physician.

16. Non-English speaking

17. Visual impairment that limits walking ability

18. Currently walking regularly for exercise at a level comparable to the amount of exercise prescribed in the intervention

19. Participation in or completion of a clinical trial in the previous three months. [NOTE: after completing a stem cell or gene therapy intervention, participants will become eligible after the final study follow-up visit of the stem cell or gene therapy study so long as at least six months have passed since the final intervention administration. After completing a supplement or drug therapy (other than stem cell or gene therapy), participants will be eligible after the final study follow-up visit as long as at least three months have passed since the final intervention of the trial.]

20. 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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 85 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Northwestern University
  • Collaborator
    • National Heart, Lung, and Blood Institute (NHLBI)
  • Provider of Information About this Clinical Study
    • Principal Investigator: Mary McDermott, Jeremiah Stamler Professor – Northwestern University
  • Overall Official(s)
    • Mary McDermott, MD, Principal Investigator, Northwestern University
    • Walter Ambrosius, PhD, Principal Investigator, Wake Forest University
  • Overall Contact(s)
    • Mary McDermott, MD, 312-503-6419, mdm608@northwestern.edu

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