Home-based Exercise Therapy for Patients With PAD

Study Overview
=================
Brief Summary
-----------------
Cardiovascular disease represents a considerable economic burden to society and effective preventive measures are necessary. Patients with peripheral arterial disease (PAD) have a severe impairment of functional ability, namely in walking distance due to muscle ischemia defined as intermittent claudication (IC). The discomfort related to IC contributes to a sedentary lifestyle, decreasing physical fitness level, aggravating cardiovascular risk factors leading to disease deterioration. Exercise programs are an effective, low-cost, low-risk option compared with more invasive therapies for IC. Home-based exercise therapy (HBET) is structured, unsupervised, self-directed programs that take place in the personal setting of the patient rather than in a clinical setting. HBET program implementation is feasible and eliminates barriers such as transportation issues, proximity to clinics, and conflicts with occupational responsibilities. Even though these programs have shown to be effective at improving walking performance and distance, their results fall below those seen in Supervised Exercise Therapy (SET) programs. Thus, innovative home-based walking programs need to be developed in order to improve results and make exercise therapy available to a larger percentage of the population. The use of Information and communication technology (ICT) tools for self-monitoring is considered key to change long-term behavior. The WalkingPAD project aims to develop health technology assessment methods and evaluate personal health intervention strategies. Investigators intend to demonstrate the technical feasibility and economic viability of a personalized medicine application in real-life healthcare settings. This project intends to find evidence for three major questions: Does an M-health monitored home-based exercise program supported by a virtual assistant empowers commitment to exercise plan and allows remote control of plan accomplishment? Is it superior to an M-health monitored home-based exercise program supported by a behavioral motivational intervention, in increasing maximum walking distance? Is it superior to a self-monitoring exercise, with a specific self-designed walking plan in the residence area, in increasing maximum walking distance?

Detailed Description
-----------------
Exercise training has been incorporated into current guidelines for the management of PAD. Multiple societal guidelines, including the American Heart Association Task Force on Clinical Practice Guidelines, Intersociety Consensus for the Management of PAD (TASC II), recommend supervised exercise therapy (SET) in the treatment of claudication symptoms in PAD. Consequently, the European Society of Cardiology proposes walking training as first-step therapy for claudicant patients before percutaneous or surgical options. Therefore, SET is the gold-standard for walking therapy in PAD patients. Although SET programs have proved to be more effective in increasing Maximum Walking Distance (MWD) and Pain-free Walking Distance (PFWD) compared with non-supervised exercise programs, they remain an underutilized tool and widespread implementation of SET is restricted by lack of facilities and funding. Home-based Exercise Therapy (HBET) has the advantage of providing a larger capacity of care, and in most cases, being feasibly close to the patients' home environment with reduced transport costs. Programs are self-directed with the guidance of healthcare providers that prescribe an exercise regimen similar to a supervised program. Thus, the primary goal of this study is to evaluate the effectiveness of an HBET program in increasing MWD, PFWD, and Functional Walking Distance (FWD). The study's primary outcomes will be MWD, PFWD, and FWD; secondary outcomes will be general and PAD-specific health-related quality of life (HRQoL) measures. A web platform and a mobile app will be created - WalkingPAD platform and app- allowing collaboration between several players, enhancing patient's compliance and accountability in their treatment strategy. Thus, an HBET will be prescribed to all the patients included in the study. The exercise prescription consists of: walking as the form of exercise, with a duration greater than 30 min per session, frequency of at least three sessions per week, using a near-maximal pain during training as claudication pain endpoint, and with a 6-month of duration. Participants will be randomized by three conditions - Active Control Group (ACG), an Experimental Group 1 (EG1), and an Experimental Group 2 (EG2) - stratified by age and MWD at baseline, and assessed at Time 1 (T1: before intervention), three months later (T2), and six months later (T3; follow-up). With WalkingPAD, investigators intend to demonstrate the technical feasibility and economic viability of a personalized medicine application in real-life healthcare settings and aspire to ensure coordination with national, regional, or local health authorities for dissemination and implementation of a new patient-centered, effective and low-cost therapeutic strategy. Sample size calculation: A total of 200 PAD patients with IC are expected to be recruited from the outpatient clinic of the Angiology & Vascular Surgery Department in CHUP-HSA in an attempt to account for the dropout rate and still achieve a large enough sample to obtain a 95% confidence interval. The minimum sample size of the total computerized sample for the 2 repeated measures (baseline and 3 months; and baseline and 6 months) was 54 participants, i.e. a minimum of 27 participants in each group (interventions groups and control group). The sample size was calculated for an effect size of 0.25, alfa of 0.05 and a power of 0,95 (1-beta) by the G*Power software. Data Analysis: Analyses of primary and secondary outcomes and process variables will be conducted on an intention-to-treat basis and all included participants will be analyzed as randomized. Procedure: Patients with PAD and IC, evaluated in the outpatient clinic of the Angiology & Vascular Surgery Department of CHUP-HSA between January and December of 2020 will be contacted by phone and invited to participate in the study. After obtaining oral consent by phone, a clinical, physical, hemodynamic and psychological evaluation will be scheduled at the hospital - Time 0 (T0 before assignment). In this assessment (T0), participants will sign a written consent and will be screened (1 hour +/-) to ascertain particular and specific exclusion and inclusion criteria. Then, block randomization with four stratum will be performed. Stratum will be defined by age and mean walking distance at baseline. All patients will be informed of the goals, experimental procedures, risks, and benefits of the study. Signed informed consent from all patients will be obtained confirming adequate understanding of all information, voluntary decision and free from undue influence such as manipulation or coercion. The right of the recruited participants to change their minds and to abandon the investigation without penalty and with no obligation to justify shall be respected. All participants will have access to information about the new knowledge generated by the research to which they contributed. The privacy and confidentiality of patients' clinical data and respect for autonomy will be guaranteed. At Time 1 (T1), patients who meet the inclusion criteria (at T0) and accept to collaborate in this study will be (blind) allocated to one of the study's arms - ACG, EG1, or EG2, and evaluated with psychological and physical measures. Patients will be assessed after 3 months (T2) and six months (T3).

Official Title
-----------------
Patient Education on a Quantified Supervised Home-based Exercise Therapy to Improve Walking Ability in Patients With Peripheral Arterial Disease and Intermittent Claudication: WalkingPad Protocol

Conditions
-----------------
Peripheral Arterial Disease (PAD), Intermittent Claudication

Intervention / Treatment
-----------------
* Behavioral: WalkingPad plus Psychological Intervention - PsyWPad Group
* Behavioral: WalkingPad plus Virtual Assistant - CyberWPad Group
* Behavioral: WalkingPad group - Paper WPad Group


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: PAD with IC (Fontaine II ou Rutherford 1-3) due to atherosclerotic disease; ABI below 0.9 at rest or below 0.73 after exercise (20% decrease); Age range between 50 and 80; MWD in treadmill test between 50 and 500 meters; Exclusion Criteria: Asymptomatic PAD; Critical Ischemia (Fontaine III/IV or Rutherford 4-6); Previous lower extremity vascular surgery, angioplasty, or lumbar sympathectomy; Any condition other than PAD that limits walking; Miocardial Infarction or Unstable Angina in the last 6 months; Inability to obtain ABI measure because of non-compressible vessels; Use of cilostazol and pentoxifylline initiated within 3 months before the investigation; Active cancer, renal disease, or liver disease; Severe chronic obstructive pulmonary disease (GOLD stage III/IV); Severe congestive heart failure (NYHA class III/IV);

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a single-center three-arm parallel prospective, randomized controlled and superiority trial, with stratified random allocation, aiming to test the effectiveness of a Home-based Exercise Therapy (HbET) for claudicant patients to increase the Maximum Walking Distance (MWD), the Pain-free Walking Distance (PFWD) and the Functional Walking Distance (FWD). Patients will be assigned to one of three groups: an active control group (ACG); an experimental group 1 (GE1) and an experimental group 2 (EG2). All groups will have in common the prescription of a walking plan on a route defined by one of the team members through WalkingPAD web-platform and customized to the patient's home area. Participants from all three groups will undergo standard treatment for PAD and IC, according to the guidelines of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: WalkingPad plus Psychological Intervention - PsyWPad Group<br>The participants in Experimental Group 1 will receive a prescription of an HBET consisting of a walking plan with a duration greater than 30 min per session, frequency of at least three sessions per week, use of near-maximal pain during training as claudication pain endpoint, with the support of a behavioral motivational intervention delivered by a health psychologist. | Behavioral: WalkingPad plus Psychological Intervention - PsyWPad Group<br>* The 24-week walking program will be monitored by the WalkingPAD application that will accompany the patient on their walks and record their adherence to the previously defined individual program. Motivational support for a behavioral intervention will include two face-to-face sessions and the following contacts will be made over the phone. The behavioral motivational intervention will follow the principles of 1) motivational interview, will be based on 2) Theory of self-determination, taking into account 3) components of the Transtheoretical Model of Change and the Theory of Planned Behavior.<br>* Other names: Behavioral Change;|
| Experimental: WalkingPad plus Virtual Assistant - CyberWPad Group<br>The participants in Experimental Group 2 will receive a prescription of an HbET consisting of a walking plan with a duration greater than 30 min per session, frequency of at least three sessions per week, use of near-maximal pain during training as claudication pain endpoint, with the support of a virtual assistant that will give motivational support. | Behavioral: WalkingPad plus Virtual Assistant - CyberWPad Group<br>* The 24-week walking program will be monitored by the WalkingPAD application, which will accompany the patient on their walks and record their adherence to the previously defined individual program. Motivational support will be provided by a virtual assistant through daily and on-the-spot interactions and through support and motivational messages.<br>* Other names: Behavioral Change;|
| Active Comparator: Paper WalkingPad group - PaperWPad Group<br>The participants in the Active Control Group will receive a prescription of an HbET consisting of a walking plan with a duration greater than 30 min per session, frequency of at least three sessions per week, use of near-maximal pain during training as claudication pain endpoint, with the support of a behavioral motivational intervention delivered by a health psychologist. | Behavioral: WalkingPad group - Paper WPad Group<br>* The 24-week walking program will be supported by a printed prescription of an individualized HbET previously defined on the WalkingPAD platform. However, this group of patients will not have the support of an application to monitor and record adherence to the program. Motivational support for a behavioral intervention will include two face-to-face sessions and the following contacts will be made over the phone. The behavioral motivational intervention will follow the principles of 1) motivational interview, will be based on 2) Theory of self-determination, taking into account 3) components of the Trans-Theoretical Model of Change and the Theory of Planned Behavior.<br>* Other names: Behavioral Change;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Walking Distance (MWD) | Maximum Walking Distance will be measured through the Treadmill Test and the 6 Minute Walk Test (6 MWT), in meters. The 6 MWT is a performance-based measure that evaluates the functional capacity of the individual to walk over a total of 6 min on a 100ft (≈30m) hallway, providing information regarding all the systems during physical activity. | Changes from before-assignment (T0 - treadmill and T1 - 6min walk test) to T2 (3 months), and to T3 (six-months) | 
| Pain-free Walking Distance (PFWD) | Pain-free Walking Distance (PFWD) will be measured through the Treadmill Test and the 6 Minute Walk Test (6 MWT), in meters. The 6 MWT is a performance-based measure that evaluates the functional capacity of the individual to walk over a total of 6 min on a 100ft (≈30m) hallway, providing information regarding all the systems during physical activity. | Changes from before-assignment (T0 - treadmill and T1 - 6min walk test) to T2 (3 months), and to T3 (six-months) | 
| Functional Walking Distance (FWD) | Functional Walking Distance (FWD) will be measured through the Treadmill Test and the 6 Minute Walk Test (6 MWT), in meters. The 6 MWT is a performance-based measure that evaluates the functional capacity of the individual to walk over a total of 6 min on a 100ft (≈30m) hallway, providing information regarding all the systems during physical activity. | Changes from before-assignment (T0 - treadmill and T1 - 6min walk test) to T2 (3 months), and to T3 (six-months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical Quality of Life | Physical Quality of Life will be assessed through the Short-Form Health Survey (SF-36). Raw scores are transformed into a scale from 0 to 100. Higher results correspond to better physical quality of life. Higher results correspond to a better physical quality of life. | Changes from T0 (before-assignment) to T2 (3 months), and to T3 (six-months) | 
| Mental Quality of Life | Mental Quality of Life will be assessed through the Short-Form Health Survey (SF-36). Raw scores are transformed into a scale from 0 to 100. Higher results correspond to better mental quality of life. Higher results correspond to a better mental quality of life. | Changes from T0 (before-assignment) to T2 (3 months), and to T3 (six-months) | 
| Vascular Disease specific Quality of Life | Vascular disease-specific quality of Life will be assessed through the Vascular Disease-specific Quality of Life (VAsQoL-6). This is a specific measure for patients with PAD, assessing health-related quality of life in PAD. Scores range between 6 and 24, with higher results corresponding to a better quality of life associated with vascular disease. | Changes from T0 (before-assignment) to T2 (3 months), and to T3 (six-months) | 
| Walking Impairment | Walking impairment will be assessed through the Walking Impairment Questionnaire (WIQ) that assesses walking abilities in three domains: distance (distances that the individual can walk) with scores ranging between 0 and 28, with higher results corresponding to greater distance; speed (the speed that the individual can walk) with scores ranging between 0 and 16, with higher results corresponding to greater speed; stairs (number of stairs that the individual can climb) with scores ranging between 0 and 12, with higher results corresponding to greater ability to climb stairs; | Changes from T0 (before-assignment) to T2 (3 months), and to T3 (six-months) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Peripheral Arterial Disease, Arterial Occlusive Diseases, Vascular Diseases, Cardiovascular Diseases, Intermittent Claudication, Walking ability, Health-related Quality of Life, Home-based Exercise Therapy, Pervasive virtual assistant