Feasibility of a Home Exercise Program to Manage Post-transplant Metabolic Syndrome

Study Overview
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Brief Summary
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Post-transplant metabolic syndrome (PTMS) affects about 50% liver transplant (OLT) and 25% lung transplant (LTx) recipients at 12-18 months post-transplant. PTMS (comprised of glucose intolerance, obesity, hypercholesterolemia and hypertension) has been associated with increased risk for cardiovascular morbidity and long-term survival. Exercise studies in the early post-transplant period have shown some benefits on PTMS risk factors with facility-based training, but it remains unclear if exercise can be sustained in the home environment with sufficient adherence or training intensity to impact PTMS beyond the early post-transplant period. Objectives: 1) To evaluate the feasibility of a three-month individualized, virtual home-based exercise training program in OLT and LTx recipients starting at 1 year post-transplant. 2) To assess estimates of intervention efficacy on elements of PTMS, insulin resistance, exercise self-efficacy, and health related quality of life (HRQL). Methods: 20 OLT and 20 LTx recipients with 2 or more PTMS risk factors at 12-18 months post-transplant will be randomized to a home-based exercise program versus usual care. The exercise group will undergo aerobic training 3 to 5 times per week with resistance training at least twice weekly over a 12-week period. Exercises will be demonstrated by a qualified exercise professional during the first visit with weekly phone and video calls to guide exercise progression, ease communication and promote exercise self-efficacy and adherence based on guiding behavioral principles. As secondary measures, PTMS, insulin resistance, body composition (optional), HRQL, and assessment of self-efficacy will be assessed at baseline and 12-weeks.

Detailed Description
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Both LTx and OLT recipients have several common risk factors for PTMS including significant weight gain, immunosuppression, and physical inactivity. These risk factors have been shown to be partly reversible with an active lifestyle. A home-based exercise program may prove to be an effective post-transplant intervention for improving the metabolic profile of transplant recipients. Primary objective: To evaluate the feasibility (recruitment rate, program adherence, attrition, safety, and participant satisfaction) of a 12 week individualized, virtual home-based aerobic and resistance training program in OLT and LTx recipients that are 12-18 months post-transplant. Secondary objective: To assess estimates of intervention efficacy on elements of PTMS, insulin resistance, exercise self-efficacy, and HRQL. Hypotheses: We hypothesize that it will be feasible to recruit both OLT and LTx recipients into a home-based exercise program with ≥ 70% adherence to the prescribed exercise dose. Secondary Objective: PTMS risk factors, self-efficacy and HRQL will be improved with a home-based exercise program. The home-based exercise group will be asked to exercise 3 to 5 times per week (≥ 150 minutes of aerobic exercises at moderate intensity) and to also complete resistance training (resistance bands or free weights) over a 12-week period with the guidance of a qualified exercise professional. The control group will be counselled by a qualified exercise professional on the importance of accumulating at least 150 minutes of moderate physical activity during the first assessment at the beginning of the study. Both groups will also receive physical activity trackers (Fitbit), exercise training or physical activity logs, and a counselling session by the dietitian at the start of the study. A home-based exercise program may prove to be an effective post-transplant intervention for improving the metabolic profile of transplant recipients. Characterizing the feasibility, adherence, and effect estimates of home-based exercise training constitutes the first key step in promoting a healthy lifestyle in transplant recipients, and supporting the development of future trials aimed at reducing the morbidity associated with PTMS.

Official Title
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Feasibility of a Home-Based Exercise Program in Lung and Liver Transplant Recipients for Management of Post-Transplant Metabolic Syndrome: A Pilot Randomized Controlled Trial

Conditions
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Metabolic Syndrome

Intervention / Treatment
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* Behavioral: Exercise Training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult lung and liver transplant recipients 12 to 18 months post-transplant Presence of 2 or more metabolic risk factors (hypertension, hyperlipidemia, diabetes, obesity) Exclusion Criteria: Active cardiovascular disease (recent heart attack, significant coronary artery disease on cardiac catheterization, heart failure, uncontrolled arrhythmias, chest pain, dizziness, or fainting in the last 3 months) Neuro-muscular disease or orthopedic limitations Physically active with ≥ 150 minutes/week of moderate-intensity aerobic physical activity Residing outside the province of Ontario

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Lung and liver transplant recipients will be randomized to home exercise group versus usual care group.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Home Exercise Group<br>The home-based exercise group will be asked to exercise 3 to 5 times per week (≥ 150 minutes of aerobic exercises (i.e. walking, cycling, or treadmill) of at least moderate intensity) and to also complete resistance training (resistance bands or free weights) at least twice weekly over a 12-week period supervised by an exercise professional. The resistance training will be personalized, aiming for 6 to 10 exercises targeting the major muscle groups, progressing to 3 sets of 8 to 12 repetitions. Exercise prescriptions will be developed and monitored by an exercise professional with weekly follow-up meetings and supported with a web application (Physiotec) that allows customizable exercise prescriptions, tracking of exercise completion, and video tutorials. Participants will receive one counselling session on healthy eating and physical activity at the start of the study along with an exercise manual. | Behavioral: Exercise Training<br>* The intervention group will be asked to complete aerobic exercises 3 to 5 times per week (≥ 150 minutes of at least moderate aerobic intensity) and resistance training at least twice a week over a 12-week period.<br>|
| No Intervention: Control Group<br>Participants will receive one counselling session on healthy eating and physical activity at the start of the study. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recruitment | We will measure recruitment-success percentage and will record reasons for non-participation. | When recruitment is complete (approximately 18 months after study initiation) | 
| Adherence to Exercise Training | Adherence to the home-based exercise program (aerobic and resistance) will be measured through an exercise diary completed by participants and reviewed through weekly communication. | Over a 12 week period | 
| Study Retention | Retention will be assessed by measuring attrition throughout the intervention period. | Over a 12 week period | 
| Adverse Events During Exercise Training (Safety and Tolerability) | Adverse events with exercise training will be assessed throughout the study period. | Over a 12 week period | 
| Participant Satisfaction with Exercise Training and Study Participation (Exercise Group) | Multiple choice and free form questionnaire assessing the participants' satisfaction with the home exercise program and study intervention. | Change over the study period assessed at weeks 2, 6, and 12 | 
| Participant Satisfaction with Study Participation (Control Group) | Multiple choice and free form questionnaire assessing participants' satisfaction with the study intervention. | 12 weeks from baseline assessment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Cholesterol | Participants will undergo fasting blood work to assess total cholesterol levels. | Change from baseline at 12 weeks | 
| Triglycerides | Participants will undergo fasting blood work to assess triglyceride levels. | Change from baseline at 12 weeks | 
| High Density Lipoprotein | Participants will undergo fasting blood work to assess high density lipoprotein. | Change from baseline at 12 weeks | 
| Low Density Lipoprotein | Participants will undergo fasting blood work to assess low density lipoprotein. | Change from baseline at 12 weeks | 
| Fasting Blood Glucose Levels | Fasting blood glucose levels will be ascertained from blood testing results. | Change from baseline at 12 weeks | 
| Hemoglobin A1C | Hemoglobin A1C results will be assessed from bloodwork, which allows assessment of the average level of blood sugar over the previous 3 months. | Change from baseline at 12 weeks | 
| Insulin Resistance | Insulin resistance will be captured using the Homeostatic Model Assessment of Insulin Resistance protocol (fasting insulin * fasting blood glucose). | Change from baseline at 12 weeks | 
| C-peptide Levels | C-peptide levels will be analyzed via blood testing in a subset of participants on exogenous insulin therapy. | Change from baseline at 12 weeks | 
| C-reactive Protein Levels | C-reactive protein levels will be ascertained from blood testing results. | Change from baseline at 12 weeks | 
| Health Related Quality of Life assessed with the Short-Form 36 Health Survey | The Short-Form 36 Health Survey (SF-36) will be used to assess general health-related quality of life. The SF-36 consists of eight scaled scores (total score ranging from 0 to 100), with lower scores representing lower health-related quality of life. | Change from baseline at 12 weeks | 
| Physical Function assessed with the Short-Physical Performance Battery | The Short-Physical Performance Battery will assess participants' balance, gait speed, and ability to rise from a chair 5 times. | Change from baseline at 12 weeks | 
| Physical Activity Questionnaire | The Physical Activity Scale for the Elderly (PASE) is a short survey created to assess physical activity levels in older adults. The PASE uses frequency, duration, and intensity level of physical activities over one week to assign a score (ranging from 0 to 793), with higher scores indicating greater levels of physical activity. | Change from baseline at 12 weeks | 
| Self-Efficacy with Exercise Training (Exercise Group) | The Exercise Self-Efficacy Scale (ESES) is a 4-point rating Likert scale in which participants rate their confidence with carrying out their regular physical activities and exercise. The ESES uses a 100-point percentage scale, ranging from 0% (not at all confident) to 100% (highly confident). Higher scores represent higher self-efficacy to exercise. | Change from baseline at 2, 6, and 12 weeks | 
| Self-Efficacy with Exercise Training (Control Group) | The Exercise Self-Efficacy Scale (ESES) is a 4-point rating Likert scale in which participants rate their confidence with carrying out their regular physical activities and exercise. The ESES uses a 100-point percentage scale, ranging from 0% (not at all confident) to 100% (highly confident). Higher scores represent higher self-efficacy to exercise. | Change from baseline at 12 weeks | 
| Nutritional Questionnaire | The Rapid Eating and Activity Assessment for Patients (REAP) survey assesses nutrient intake and helps with lifestyle counseling. The survey contains 27 questions with higher scores indicating higher diet quality (score range, 27 to 81). | Change from baseline at 12 weeks | 
| Lifestyle and Environmental Questionnaire | The Lifestyle and Environmental Questionnaire is a questionnaire developed by our research team to assess familiarity and comfort levels surrounding technology, barriers to exercise and assess previous experience with exercise. It is composed of 10 multiple-choice questions with each question assessed independently. | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung Transplant Recipients, Liver Transplant Recipients, Exercise Training