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

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ClinicalTrials.gov Identifier: NCT04228978
Recruitment Status : Recruiting
First Posted : January 14, 2020
Last Update Posted : May 5, 2021
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
Wake Forest University
Information provided by (Responsible Party):
Mary McDermott, Northwestern University

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Peripheral Artery Disease Overweight or Obesity Behavioral: Weight loss Behavioral: Exercise Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 212 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Masking Description: Assessors performing outcome measures will be unaware of participants' group assignment.
Primary Purpose: Treatment
Official Title: PROmote Weight Loss in Obese Peripheral Artery Disease (PAD) Patients to preVEnt Mobility Loss: The PROVE Trial
Actual Study Start Date : March 1, 2020
Estimated Primary Completion Date : May 31, 2026
Estimated Study Completion Date : May 31, 2027

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Weight loss + exercise (WL+EX)
Weight loss + home based walking exercise (WL+EX)
Behavioral: Weight loss
Walking exercise combined with weight loss

Behavioral: Exercise
Walking exercise

Active Comparator: Exercise alone (EX)
Home based walking exercise (EX)
Behavioral: Exercise
Walking exercise




Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. 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 at 12-month follow-up.

  2. 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.

  3. 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 indicating a better outcome.

  4. 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.

  5. 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.


Other Outcome Measures:
  1. 12-month change in perceived exertional effort at the end of the six-minute walk test [ Time Frame: Baseline to 12 months ]
    Change in perceived exertional effort at the end of the six-minute walk test at 12-month follow-up will be compared between individuals randomized to the weight loss + exercise vs. those randomized to exercise alone. Perceived exertional effort will be measured using the Borg scale. The Borg scale is a 15-point scale ranging from six to 20. A higher score indicates greater perceived exertion.

  2. 12-month change in diet quality measured by change in Healthy Eating Index [ Time Frame: Baseline to 12 months ]
    Change in diet quality measured by change in Healthy Eating Index (HEI) will be compared between individuals randomized to weight loss + exercise vs. those randomized to exercise alone. Change in diet quality will be measured at 12-month follow-up. The maximum HEI score is 100 points. A higher total HEI score indicates a diet that aligns better with dietary recommendations.

  3. Change in the short physical performance (SPPB) battery questionnaire at 12-month follow-up [ Time Frame: Baseline to 12 months ]
    Change in the short physical performance (SPPB) battery questionnaire will be compared between individuals randomized to weight loss + exercise vs. those randomized to exercise alone. The SPPB questionnaire ranges from 0 to 12 (12 = best).

  4. Change in the WIQ walking speed score at 12-month follow-up [ Time Frame: Baseline to 12 months ]
    Change in the WIQ walking speed score at 12-month follow-up will be compared between individuals randomized to weight loss + exercise vs. those randomized to exercise alone. The WIQ walking speed score ranges from 0-100. A higher score is better.

  5. 12-month change in calf muscle biopsy measured COX enzyme activity [ Time Frame: Baseline to 12 months ]
    In a subset of 50 participants, study investigators will compare improvement in calf muscle biopsy measures of mitochondrial activity (COX enzyme activity) between individuals randomized to weight loss + exercise vs. those randomized to exercise alone.

  6. 12-month change in the calf muscle biopsy measure mitochondrial biogenesis (PGC-1α) [ Time Frame: Baseline to 12 months ]
    In a subset of 50 participants, study investigators will compare the calf muscle biopsy measures of mitochondrial biogenesis (PGC-1α) between individuals randomized to weight loss + exercise vs. those randomized to exercise alone.

  7. Change in the WIQ stair climbing questionnaire score at 12-month follow-up [ Time Frame: Baseline to 12 months ]
    Change in the WIQ stair climbing questionnaire score at 12-month follow-up will be compared between individuals randomized to weight loss + exercise vs. those randomized to exercise alone. The WIQ stair climbing score ranges from 0-100. A higher score is better.

  8. 12-month change in capillary density (capillaries per muscle fiber) [ Time Frame: Baseline to 12 months ]
    In a subset of 50 participants, study investigators will compare calf muscle biopsy measures of capillary density (capillaries per muscle fiber) between individuals randomized to weight loss + exercise vs. those randomized to exercise alone. Change in capillary density will be measured at 12-month follow-up.

  9. 12-month change in calf muscle inflammation (IL-6, TNF-α, and IL1β) [ Time Frame: Baseline to 12 months ]
    In a subset of 50 participants, study investigators will compare calf muscle biopsy measures of calf muscle inflammation (IL-6, TNF-α, and IL1β) between individuals randomized to weight loss + exercise vs. those randomized to exercise alone. Change in calf muscle inflammation will be measured at 12-month follow-up.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 89 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion criteria are a) presence of PAD; b) BMI> 28 kg/m2; c) Age > 18 and < 90. 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 (98-103). People with a toe brachial index of <0.70, performed at the study visit, will be eligible. Second, people with an ABI of >0.90 and <1.00 who experience a 20% or greater drop in ABI after the heel-rise test will also be included. Third, potential participants with an ABI > 0.90 who provide vascular laboratory evidence or angiographic evidence of PAD will be included. Prior vascular laboratory evidence consists of objective evidence of PAD including toe brachial index (TBI) < 0.70, Duplex measure showing 70% stenosis or greater, a post heel-rise or post-exercise ABI drop of 20% or greater, or ABI values < 0.90. Angiographic evidence of PAD consists of a stenosis of 70% or greater in a lower extremity artery. Fourth, people with a history of lower extremity revascularization who do not meet the criterion above and have an ABI > 0.90 with a 20% or higher drop in ABI after the heel-rise test will be eligible if they have symptomatic PAD. Symptomatic PAD will be defined as leg symptoms associated with exertion that resolved within 10 minutes of rest. The presence of symptomatic PAD will be determined based on the claudication questionnaire, the six-minute walk, or principal investigator interview/discussion with the potential participant. A positive heel-rise test is defined as a 20% or greater drop in ABI after the heel-rise test. The heel-rise test consists of 50 heel rises at a rate of one per second. We 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, or wheelchair confinement.
  2. Walking is limited by a condition other than PAD.
  3. Failure to complete the study run-in, defined as not entering at least 800 Kcal of consumed calories per day for at least five days during the 14 day run-in*.
  4. Major surgery, coronary or leg revascularization in the past 3 months or anticipated in the next year.
  5. Experienced a heart attack or stroke in the past 3 months.
  6. 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.
  7. Mini-Mental Status Examination score < 23 (108), dementia and substance abuse.
  8. History of being treated for new onset or an acute episode of schizophrenia or psychosis in the past 6 months.
  9. Hospitalization for a psychiatric disorder in the past 6 months.
  10. BMI > 45 kg/m2
  11. 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.
  12. Weight gain or loss of more than 25 pounds in the past six months
  13. Potential participants unwilling/unable to use a smart phone and unwilling to attend weekly study sessions.
  14. Excessive alcohol use, defined as >14 drinks/week in men and > 10 alcoholic drinks/week in women.
  15. Age > 90 years
  16. Current ulcer on bottom of foot
  17. 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
  18. 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.
  19. Non-English speaking
  20. Visual impairment that limits walking ability
  21. Currently walking regularly for exercise at a level comparable to the amount of exercise prescribed in the intervention
  22. 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.]
  23. 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

    • The run-in will also be used to assist participants with learning the app. However, they must demonstrate ability to enter at least 800 Kcal per day for at least five days of the run-in.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04228978


Contacts
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Contact: Mary M McDermott, MD 312-503-6419 ext 6419 mdm608@northwestern.edu
Contact: Kathryn J Domanchuk, BS 312-503-6438 ext 6438 k-domanchuk@northwestern.edu

Locations
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United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Mary M McDermott, MD    312-503-6419 ext 6419    mdm608@northwestern.edu   
Contact: Kathryn E Domanchuk, BS    312-503-6438 ext 6438    k-domanchuk@northwestern.edu   
Sponsors and Collaborators
Northwestern University
National Heart, Lung, and Blood Institute (NHLBI)
Wake Forest University
Investigators
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Principal Investigator: Mary M McDermott, MD Northwestern University
Principal Investigator: Walter Ambrosius, PhD Wake Forest University
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Responsible Party: Mary McDermott, Jeremiah Stamler Professor, Northwestern University
ClinicalTrials.gov Identifier: NCT04228978    
Other Study ID Numbers: STU00209524
UG3HL141729-01A1 ( U.S. NIH Grant/Contract )
First Posted: January 14, 2020    Key Record Dates
Last Update Posted: May 5, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Peripheral Arterial Disease
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Peripheral Vascular Diseases
Overweight
Weight Loss
Body Weight
Body Weight Changes
Atherosclerosis
Arteriosclerosis