Exercise and Weight Loss for Obese PAD Patients

(PROVE Trial)

Recruiting at 4 trial locations

Overseen By Mary McDermott, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Northwestern University

Must not be taking: Weight loss medications

Disqualifiers: Amputation, Major surgery, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

Duration: 12 months

212 Participants Needed

Trial Summary

What is the purpose of this trial?

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\>25 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 \> 25 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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Exercise, Physical Activity, Workout, Fitness Training, Weight loss, Behavioral Weight Loss Program, Weight Management Program, Lifestyle Intervention for obese PAD patients?

Research shows that physical activity and exercise can help with weight loss and improve cardiovascular health, even if the weight loss is modest. Exercise also helps maintain weight loss and improve fitness, which can reduce health risks in obese individuals. ^{1 2 3 4 5}

Is exercise and weight loss safe for obese patients?

Exercise and weight loss programs, including those with behavioral strategies, are generally safe for obese patients and can lead to improvements in health indicators like blood pressure, cholesterol, and insulin sensitivity. ^{6 7 8 9 10}

How does the treatment of exercise and weight loss for obese PAD patients differ from other treatments?

This treatment is unique because it combines exercise and weight loss strategies to improve cardiovascular health and manage obesity, which can be more effective than exercise alone. It also emphasizes lifestyle changes and personalized support, such as personal trainers and financial incentives, to enhance adherence and long-term success. ^{5 11 12 13 14}

Research Team

Mary McDermott, MD

Principal Investigator

Northwestern University

Walter Ambrosius, PhD

Principal Investigator

Wake Forest University

Eligibility Criteria

This trial is for adults over 18 with Peripheral Artery Disease (PAD) and a Body Mass Index (BMI) of more than 25 kg/m2. They should have leg symptoms from PAD that improve with rest, and an ankle brachial index (ABI) below 0.90 or other diagnostic criteria for PAD. People can't join if they've had recent major surgery, are unable to use a smartphone, drink excessively, have certain medical conditions like severe lung disease or cancer under treatment, or if their walking is limited by something other than PAD.

Inclusion Criteria

Your body mass index (BMI) is higher than 25.

I have PAD, confirmed by specific leg blood flow tests showing changes after exercise.

I had surgery to improve blood flow in my legs due to PAD symptoms.

Exclusion Criteria

Unwilling/unable to use a smart phone and unwilling to attend weekly study sessions

Investigator discretion

You drink too much alcohol.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to either weight loss + exercise or exercise alone, with interventions including a Group Mediated Cognitive Behavioral framework, connective mobile technology, remote monitoring by a coach, and a calorie-restricted DASH-derived diet

12 months

Regular remote monitoring and periodic in-person assessments

Follow-up

Participants are monitored for changes in six-minute walk distance, exercise adherence, physical activity, and other health metrics

12 months

Follow-up assessments at 6 and 12 months

Exploratory Assessments

In a subset of participants, additional assessments such as calf muscle biopsies are conducted to measure mitochondrial biogenesis, capillary density, and inflammation

12 months

Treatment Details

Interventions

• Exercise
• Weight loss

Trial Overview The PROVE Trial tests whether combining weight loss strategies with walking exercises helps people with obesity and PAD walk better after one year compared to just exercise alone. The weight loss program includes group support, mobile tech monitoring by a coach, and a special low-calorie diet called the OMNIHeart diet.

Participant Groups

Group I: Weight loss + exercise (WL+EX) Experimental Treatment 2 Interventions

Weight loss + home based walking exercise (WL+EX)

Group II: Exercise alone (EX) Active Control 1 Intervention

Home based walking exercise (EX)

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Wake Forest University

Collaborator

Trials

193

Recruited

151,000+

Findings from Research

Physical activity plays a crucial role in weight loss and maintenance, showing a dose-response relationship where increased activity correlates with greater weight loss benefits.

Engaging in physical activity not only aids in weight management for individuals with severe obesity or those who have had bariatric surgery, but it also enhances cardiorespiratory fitness, reducing health risks associated with being overweight or obese.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity and physical activity. Jakicic, JM., Davis, KK.[2011]

The PREVAIL-P study will investigate how different amounts of aerobic exercise affect weight maintenance in overweight and obese adults after significant weight loss, involving 39 participants over a total of 28 weeks.

In addition to weight changes, the study will also assess important health factors like blood lipids and glucose tolerance, which are crucial for understanding the overall health benefits of exercise beyond just weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prescribed exercise to Reduce Recidivism After Weight Loss-Pilot (PREVAIL-P): Design, methods and rationale. Swift, DL., McGee, JE., Huff, AC., et al.[2023]

A lifestyle-modification program that includes increased physical activity and a balanced diet can significantly reduce obesity-related health risks, even if there is minimal or no weight loss.

Such lifestyle changes can lead to improvements in abdominal obesity, visceral fat, and cardiometabolic risk factors, as well as increases in muscle mass and cardiorespiratory fitness, highlighting the importance of focusing on health improvements rather than just weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The future of obesity reduction: beyond weight loss. Ross, R., Bradshaw, AJ.[2021]

A network meta-analysis of 45 randomized controlled trials involving 3566 participants found that while any exercise is better than no exercise for people with obesity, the weight loss achieved is generally modest.

Combining high-intensity aerobic exercise with high-load resistance training was shown to be the most effective approach for reducing abdominal fat, improving lean body mass, and enhancing cardiorespiratory fitness, suggesting this combination should be prioritized in exercise prescriptions for adults with obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What exercise prescription is optimal to improve body composition and cardiorespiratory fitness in adults living with obesity? A network meta-analysis. O'Donoghue, G., Blake, C., Cunningham, C., et al.[2021]

Exercise has numerous benefits for individuals with obesity, including aiding in weight loss and improving cardiovascular health, but the direct impact on weight loss from exercise alone is modest, typically resulting in only a few kilograms of weight loss.

Physical activity is crucial for managing type 2 diabetes and preventing its complications, and a structured approach like the 5 A's strategy can help healthcare professionals effectively support patients in overcoming barriers to increasing their physical activity levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physical activity in management of persons with obesity. Oppert, JM., Bellicha, A., Ciangura, C.[2021]

Combining physical exercise with energy restriction diets leads to greater weight loss than exercise alone, making it the most effective strategy for significant weight loss.

Engaging in at least 150 minutes of moderate-intensity or 75 minutes of vigorous-intensity aerobic exercise weekly, along with resistance training, is recommended for weight loss and maintenance, which also helps improve obesity-related health issues like diabetes and cardiovascular disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity and physical exercise. Celik, O., Yildiz, BO.[2021]

In a pilot study of 77 overweight and obese adults, those who participated in a 3-month supervised exercise program showed significant improvements in fitness indicators, with 69% attending the gym at least 8 times per month.

However, adherence dropped significantly during the 9-month unsupervised phase, with only 8 out of 24 participants completing it, suggesting that ongoing supervision may be crucial for maintaining exercise habits, especially for individuals with joint symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of an exercise program on adherence and fitness indicators. Carpenter, R., Gilleland, D.[2017]

Obesity significantly increases the risk of coronary heart disease (CHD), with over 80% of CHD patients being overweight or obese, highlighting the need for effective weight loss interventions in cardiac rehabilitation (CR) programs.

Behavioral weight loss (BWL) interventions in CR settings lead to significantly greater weight loss compared to standard programs, resulting in improved insulin sensitivity and reductions in hypertension and lipid abnormalities, making BWL a crucial component for managing CHD risk factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity in coronary heart disease: An unaddressed behavioral risk factor. Ades, PA., Savage, PD.[2018]

Obesity significantly increases the risk of coronary heart disease (CHD), yet most cardiac rehabilitation programs do not effectively address weight loss, leading to poor outcomes in this area.

A new weight reduction strategy combining behavioral counseling and increased exercise, particularly walking, shows promise in improving various health markers in overweight CHD patients, highlighting the need for tailored obesity management in rehabilitation programs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The treatment of obesity in cardiac rehabilitation. Ades, PA., Savage, PD., Harvey-Berino, J.[2021]

In a study of 120 patients with stable coronary artery disease, those who were obese showed greater reductions in body mass index (BMI), blood pressure, and LDL cholesterol levels after a 12-week cardiac rehabilitation program compared to non-obese patients.

While obese patients had more significant improvements in certain cardiovascular risk factors, non-obese patients experienced a greater increase in left ventricular ejection fraction (LVEF), indicating different responses to rehabilitation based on obesity status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of a phase 2 cardiac rehabilitation program on obese and non-obese patients with stable coronary artery disease. El Missiri, A., Abdel Halim, WA., Almaweri, AS., et al.[2021]

In a study of 193 obese participants over 18 months, various strategies to enhance exercise adherence were tested, with personal trainers and monetary incentives showing the best results for attendance at supervised walks.

Despite improved attendance with these strategies, they did not lead to higher overall energy expenditure or better long-term weight loss, suggesting that the recommended levels of exercise for effective weight loss may need to be significantly increased.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of personal trainers and financial incentives to increase exercise in a behavioral weight-loss program. Jeffery, RW., Wing, RR., Thorson, C., et al.[2022]

A 6-month physical exercise program significantly improved weight, body mass index (BMI), waist circumference, and cardiovascular health in morbidly obese patients, particularly in those who adhered to the program (≥ 80% attendance).

The adherent group also showed notable improvements in cardiorespiratory fitness and reductions in diastolic blood pressure, basal glycemia, and triglycerides, while the non-adherent group did not experience significant changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptaciones al ejercicio físico en el perfil lipídico y la salud cardiovascular de obesos mórbidos. Delgado-Floody, P., Caamaño-Navarrete, F., Jerez-Mayorga, D., et al.[2022]

The TelePreSET program, which involved 12 weeks of in-home exercise training via telehealth, was highly attended (96%) and well-received by participants, indicating its feasibility for individuals awaiting bariatric surgery.

Participants in the TelePreSET group showed significant improvements in physical fitness compared to those receiving usual care, suggesting that this telehealth approach can effectively enhance fitness levels in women with severe obesity before surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and effect of in-home physical exercise training delivered via telehealth before bariatric surgery. Baillot, A., Boissy, P., Tousignant, M., et al.[2018]

Bariatric surgery can lead to weight loss and diabetes remission, but some patients experience weight regain and diabetes relapse over time, indicating that surgery alone may not be sufficient for long-term success.

Incorporating exercise as an adjunct therapy for bariatric surgery patients is suggested to be both feasible and effective, potentially playing a crucial role in maintaining weight loss and sustaining remission of type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise and Bariatric Surgery: An Effective Therapeutic Strategy. Coen, PM., Carnero, EA., Goodpaster, BH.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Obesity and physical activity. [2011]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Prescribed exercise to Reduce Recidivism After Weight Loss-Pilot (PREVAIL-P): Design, methods and rationale. [2023]

3. England pubmed.ncbi.nlm.nih.gov

The future of obesity reduction: beyond weight loss. [2021]

4. England pubmed.ncbi.nlm.nih.gov

What exercise prescription is optimal to improve body composition and cardiorespiratory fitness in adults living with obesity? A network meta-analysis. [2021]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Physical activity in management of persons with obesity. [2021]

6. Italy pubmed.ncbi.nlm.nih.gov

Obesity and physical exercise. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Impact of an exercise program on adherence and fitness indicators. [2017]

8. United States pubmed.ncbi.nlm.nih.gov

Obesity in coronary heart disease: An unaddressed behavioral risk factor. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

The treatment of obesity in cardiac rehabilitation. [2021]

10. Germany pubmed.ncbi.nlm.nih.gov

Effect of a phase 2 cardiac rehabilitation program on obese and non-obese patients with stable coronary artery disease. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Use of personal trainers and financial incentives to increase exercise in a behavioral weight-loss program. [2022]

12. Mexico pubmed.ncbi.nlm.nih.gov

Adaptaciones al ejercicio físico en el perfil lipídico y la salud cardiovascular de obesos mórbidos. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Feasibility and effect of in-home physical exercise training delivered via telehealth before bariatric surgery. [2018]

14. United States pubmed.ncbi.nlm.nih.gov

Exercise and Bariatric Surgery: An Effective Therapeutic Strategy. [2018]