Clinical trial NCT02538900: Low InTensity Exercise Intervention in PAD
Official title: Low InTensity Exercise Intervention in PAD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Peripheral Artery Disease
Keywords: peripheral arterial disease, peripheral artery disease, PAD, exercise
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2015-09-02
Enrollment: 305
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This proposed study will determine whether a home-based exercise intervention that avoids continuous supervision and exercise-related ischemic pain improves walking performance at 52-week follow-up in people with PAD, compared to an attention control group and compared to a high intensity exercise intervention. In our secondary aims, we will determine whether high intensity exercise improves six-minute walk distance as compared to the attention control group. In secondary aims, we will also determine whether low intensity exercise and high intensity home-based exercise, respectively, improve patient reported outcomes, physical activity, and treadmill walking performance compared to attention control. Our intervention directly addresses two aspects of current practice guidelines that are major barriers to exercise for patients with PAD: 1) the recommendation for supervised exercise and 2) the recommendation for high intensity ischemic-pain inducing walking exercise.

Detailed description: We will randomize 305 PAD participants to one of three parallel arms: Group 1: Low-intensity, self-paced walking exercise; Group 2: Standard high intensity, ischemic pain-inducing walking exercise; Group 3: Non-exercising attention control group. The low and high intensity exercise groups will attend center-based exercise sessions once per week for four weeks followed by transition to an entirely home-based exercise program for an additional 48 weeks (52 weeks total). Coaches will contact participants weekly by telephone after the first four weeks of the intervention. The low and high intensity exercise interventions will use identical self-regulatory and support strategies. However, the low intensity exercise group will be instructed to exercise with minimal to no ischemic leg discomfort and the high intensity group will be instructed to exercise to maximal ischemic leg pain. These two distinct exercise prescriptions will be reinforced during 48 weeks of home-based exercise, using a well-validated behavioral coaching model that can be delivered by telephone once weekly. Our primary outcome is change in six-minute walk distance at 52-week follow-up. If our hypotheses are correct, millions of people with PAD will benefit from this alternative exercise regimen which will be accessible to most of the 8 million people in the U.S. who suffer from PAD.

Eligibility criteria: Inclusion Criteria:

All participants will have PAD. PAD will be defined as follows. First, an ABI \< or = 0.90 at the baseline study visit is a well-accepted standard for the diagnosis of PAD and will be an inclusion criterion. Second, people with an ABI of \>0.90 and \< or = 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 have vascular lab evidence of PAD or angiographic evidence of PAD who have ischemic symptoms during the six-minute walk and/or treadmill exercise stress test will be eligible. In addition to meeting a criterion for PAD, all participants must be symptomatic, defined by one of the following criteria:; a) ischemic leg symptoms (primarily assessed with the San Diego Claudication Questionnaire); b) report ischemic leg symptoms at the end of the six-minute walk; c) report ischemic leg symptoms at the end of the baseline treadmill stress test; d) walking impairment questionnaire results, e) interview with the potential participant about the presence and nature of leg symptoms during walking activity.

Exclusion Criteria:

1. Above or below knee amputation, critical limb ischemia, wheelchair confinement, or foot ulcer.
2. Individuals whose walking is limited by a condition other than PAD.
3. \> Class II NYHA heart failure or angina. Increase in angina, angina at rest, or abnormal baseline treadmill stress test.
4. Major surgery including lower extremity revascularization or orthopedic surgery during the prior three months or anticipated in the next twelve months.
5. Major medical illness including renal disease requiring dialysis, lung disease requiring oxygen other than at night, or cancer (other than non-melanoma skin cancer) requiring treatment in the prior three years. Potential participants may still qualify if they have had treatment for early stage cancer in the previous three years and the prognosis is excellent.
6. Mini-mental status examination score \<23, dementia, or psychiatric illness including severe depression or anxiety. Investigator discretion may be used to allow some people with an MMSE below 23 to participate if the investigator determines there is another reason for their lower score, including lack of sufficient familiarity with the English language or lack of sufficient education to achieve a score of 23 or higher.
7. Currently walking regularly for exercise at a level comparable to the amount of exercise prescribed in the intervention.
8. Current or recent (within 3 months) participation in another clinical trial or cardiac rehabilitation. For a clinical trial of a stem cell or gene therapy intervention, potential participants will be potentially eligible immediately after the final study visit for the clinical trial, so long as long as at least six months has passed since the participant received their final treatment in the stem cell or gene therapy intervention. For a clinical trial involving open-label therapy in which the treatment is not related to functional performance and will not change during the LITE Trial, participants may still qualify for the LITE Trial based on investigator discretion.
9. Individuals with PAD who have a history of lower extremity revascularization and have a normal ABI.
10. Individuals who are not able to walk for exercise at a sufficiently slow pace to avoid ischemic leg symptoms.

Primary outcomes:
measure: Six-minute Walk Distance
timeFrame: change from baseline to week 52
Secondary outcomes:
measure: Six-minute Walk Distance
timeFrame: change from baseline to week 26
measure: Maximal Treadmill Walking Time
timeFrame: change from baseline to week 52
measure: Physical Activity Levels
timeFrame: Change from baseline to week 52
measure: Walking Impairment Questionnaire (WIQ) Distance and Speed Score.
timeFrame: change from baseline to week 52
measure: Health-related Quality of Life Measure
timeFrame: change from baseline to week 52
measure: Adherence to Intervention
timeFrame: from baseline to week 52
measure: Change in Muscle Biopsy Measures of Mitochondrial Oxidative Metabolism and Oxidative Stress.
timeFrame: change from baseline to week 52
Other outcomes:
measure: Qualitative Assessment
timeFrame: At 52 week follow up
measure: Physical Activity Levels Over Seven Days
timeFrame: 26 week follow-up.
measure: WIQ Distance and Speed Score
timeFrame: 26 week follow-up
measure: Health Related Quality of Life
timeFrame: 26 weeks
measure: Adherence to Assigned Intervention
timeFrame: 26 weeks.
Locations:
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: New Orleans
country: United States
facility: Ochsner Baptist, Tulane University
state: Louisiana
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
Study officials:
affiliation: Northwestern University
name: Mary McDermott, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hammond MM, Spring B, Rejeski WJ, Sufit R, Criqui MH, Tian L, Zhao L, Xu S, Kibbe MR, Leeuwenburgh C, Manini T, Forman DE, Treat-Jacobson D, Polonsky TS, Bazzano L, Ferrucci L, Guralnik J, Lloyd-Jones DM, McDermott MM. Effects of Walking Exercise at a Pace With Versus Without Ischemic Leg Symptoms on Functional Performance Measures in People With Lower Extremity Peripheral Artery Disease: The LITE Randomized Clinical Trial. J Am Heart Assoc. 2022 Aug 2;11(15):e025063. doi: 10.1161/JAHA.121.025063. Epub 2022 Jul 27.
citation: Slysz JT, Rejeski WJ, Treat-Jacobson D, Bazzano LA, Forman DE, Manini TM, Criqui MH, Tian L, Zhao L, Zhang D, Guralnik JM, Ferrucci L, Kibbe MR, Polonsky TS, Spring B, Sufit R, Leeuwenburgh C, McDermott MM. Sustained physical activity in peripheral artery disease: Associations with disease severity, functional performance, health-related quality of life, and subsequent serious adverse events in the LITE randomized clinical trial. Vasc Med. 2021 Oct;26(5):497-506. doi: 10.1177/1358863X21989430. Epub 2021 Apr 8.
citation: McDermott MM, Spring B, Tian L, Treat-Jacobson D, Ferrucci L, Lloyd-Jones D, Zhao L, Polonsky T, Kibbe MR, Bazzano L, Guralnik JM, Forman DE, Rego A, Zhang D, Domanchuk K, Leeuwenburgh C, Sufit R, Smith B, Manini T, Criqui MH, Rejeski WJ. Effect of Low-Intensity vs High-Intensity Home-Based Walking Exercise on Walk Distance in Patients With Peripheral Artery Disease: The LITE Randomized Clinical Trial. JAMA. 2021 Apr 6;325(13):1266-1276. doi: 10.1001/jama.2021.2536.