Physical Activity Together for People With Multiple Sclerosis and Their Care Partners: Protocol for a Feasibility Randomized Controlled Trial of a Dyadic Intervention

Background Physical activity (PA) is beneficial for all people; however, people affected by multiple sclerosis (MS) find regular PA challenging. These people may include individuals with advanced disabilities and their care partners. Objective The objective of this study is to determine the feasibility of a dyadic PA intervention for people with advanced MS and their care partners. Methods This study is a randomized controlled feasibility trial of a 12-week intervention, with 1:1 allocation into an immediate intervention condition or delayed control condition. A target of 20 people with MS–care partner dyads will be included. The outcomes will be indicators of process, resources, management, and scientific feasibility. Participant satisfaction with the intervention components will be evaluated using a satisfaction survey. The subjective experience of participation in the study will be explored using semistructured interviews. Results The project is funded by the Consortium of Multiple Sclerosis Centers. This protocol was approved by the Ottawa Hospital Research Ethics Board (20190329-01H) and the University of Ottawa Research Ethics Board (H-09-19-4886). The study protocol was registered with ClinicalTrials.gov in February 2020. The findings of this feasibility trial will be disseminated through presentations at community events to engage the MS population in the interpretation of our results and in the next steps. The results will also be published in peer-reviewed journals and presented to the scientific community at national and international MS conferences. Conclusions The data collected from this feasibility trial will be used to refine the intervention and materials in preparation for a pilot randomized controlled trial. Trial Registration ClinicalTrials.gov NCT04267185; https://clinicaltrials.gov/ct2/show/NCT04267185. International Registered Report Identifier (IRRID) PRR1-10.2196/18410


Background
Multiple sclerosis (MS) is a neurodegenerative disease characterized by a variable course and largely unpredictable exacerbations leading to progressive disability [1]. Within 15-20 years of disease onset, it is estimated that approximately 50% of people with MS will require a walking aid (eg, cane) to walk about 100 m with or without rest (ie, Expanded Disability Status Scale [2] score≥6) [3]. Approximately 40%-80% of people with MS with walking impairment report a need for support from informal care partners to engage in everyday activities and to participate in aspects of daily life that are important and meaningful to them [4][5][6]. Care partners are relatives, family members, or friends who provide a broad spectrum of assistance, ranging from help in activities of daily living to emotional support for people with MS [7]. Although there are positive aspects of MS caregiving [8], the negative effect on care partners' own well-being is often great. MS care partners report poorer quality of life than the general population [9]. These MS care partners also experience a higher level of activity limitations, more emergency department visits, and hospitalizations than care partners of people with other chronic diseases [10]. Together, this evidence suggests that MS has life-altering consequences for people with MS and their care partners and points to an opportunity to identify strategies to improve the health of both partners to the benefit of each individual and the dyad (ie, partnership).
Physical activity (PA) is a health-promoting behavior in the general population and an emerging strategy for managing MS [11]. Researchers have reported that PA interventions that incorporate behavioral strategies (eg, goal setting) can increase PA levels and improve symptomatic and participatory outcomes among people with mild-to-moderate MS [12,13]. Emerging evidence from other chronic disease contexts (eg, dementia) suggests that dyadic behavioral PA interventions (ie, targeting both care recipients and care partners) can increase PA levels, improve physical and psychological health, and improve exercise adherence for both individuals [14,15]. Other researchers have reported a reduction in stress and improvement in coping skills among care partners of people with dementia after dyadic PA interventions [16,17]. Despite the promise of dyadic PA interventions, no studies to date have capitalized on the potential benefits of including both people with advanced MS and their care partners together as active participants in a dyadic behavioral PA intervention. We contend that a dyadic behavioral PA intervention could improve the well-being of people with MS and could help care partners maintain their roles for longer periods with lower health risks.
Within the literature specific to people with MS, there is limited research on behavioral PA interventions that can be widely disseminated for people with advanced MS who experience mobility and transportation limitations [18] and require high levels of caregiving support [19]. Dyadic health researchers have also been challenged to integrate telerehabilitation into intervention design to provide more sustainable and widely disseminated behavioral interventions for dyads with chronic health conditions [20]. Telephone delivery is one of the most widely available telerehabilitation modalities and holds distinct promise for its potential for adoption by public health systems and organizations (eg, MS Societies) that routinely provide telephone support for people with chronic health conditions [21,22]. In particular, group-based teleconferencing offers the added benefit of social modeling, social support, and opportunities for vicarious learning experiences [23,24]. Collectively, existing evidence suggests that telephone-based PA interventions have the potential to increase PA and improve the health of people with MS and their care partners.

Objectives
The objective of this study is to conduct the first randomized controlled trial (RCT) to determine the feasibility of a dyadic behavioral PA intervention-Physical Activity Together for People With Multiple Sclerosis (PAT-MS) and their care partners. Specifically, we will explore the 4 primary areas of focus of feasibility studies (ie, process, resources, management, and scientific feasibility) [25,26] recommended for PA studies involving people with MS [27].

Study Design
This protocol has been written following both the Standard Protocol Items: Recommendations for Interventional Trials and Consolidated Standards of Reporting Trials guidelines [28,29] (Multimedia Appendix 1). We will conduct a single site, assessor-blinded, parallel group, randomized controlled feasibility trial using a 1:1 allocation into an immediate intervention condition or a delayed intervention condition. A delayed intervention condition was deemed appropriate for PAT-MS based on the decision framework for appropriate control conditions for behavioral intervention trials [30,31].

Sample Size
As a feasibility trial, this study will provide robust estimates of the likely rates of recruitment and retention as well as estimates of the variability of the proposed scientific outcomes to inform a well-designed pilot RCT. With these considerations in mind, our goal is to recruit 10 people with MS-care partner dyads per condition within a 6-month recruitment window, consistent with sample size guidelines for feasibility trials [32] and previously published exercise trials for people with advanced MS [33]. Enrolling 10 dyads per condition will account for approximately 15% attrition rate, as recommended for feasibility trials [34].

Recruitment and Enrolment
Potential participants will be provided with a study information sheet at the local MS clinic and asked for consent to be contacted by the research team. A research coordinator will then contact interested participants by phone to discuss the study and conduct eligibility screening.
The inclusion criteria for people with MS are as follows: (1) a neurologist-confirmed MS diagnosis and stable course of disease-modifying therapies over the past 6 months, (2) an Expanded Disability Status Scale score between 6.0 and 6.5 based on a neurostatus-certified assessor examination, (3) relapse free in the past 30 days, and (4) having a care partner (ie, relative or close friend) who provides ≥1 hour per day of unpaid assistance or help. Additional inclusion criteria for both people with MS and care partners are as follows: (1) ≥18 years of age, (2) currently inactive (ie, purposeful exercise ≤2 days per week for 30 min), and (3) asymptomatic (ie, no major signs or symptoms of acute or uncontrolled cardiovascular, metabolic, or renal disease) based on the Get Active Questionnaire. The exclusion criteria for both people with MS and care partners are (1) presence of other neurological conditions and (2) inability to communicate in English. Figure 1 presents the flow of participants throughout the study. All eligible participants will be scheduled for a baseline assessment (T1) for the provision of informed consent and collection of baseline data (scientific feasibility outcomes) at a university research laboratory. People with MS and their care partners will complete the measures in separate rooms to ensure privacy and confidentiality during the data collection process. Outcome measures will be collected by treatment-blinded assessors who are experienced with the administration of the proposed measures. In the 7 days following the baseline assessment, both people with MS and their care partners will be asked to wear an accelerometer during all waking hours. The accelerometer will be placed in a pouch on an elastic belt worn around the waist, with the device placed on the nondominant hip. Prestamped, preaddressed envelopes will be provided for the return of the accelerometer. Randomization will occur after baseline data collection.

Study Procedures
The randomization sequence will be generated by an independent biostatistician using 1:1 permutated block randomization. Variable-sized blocks will be used to ensure approximately equal numbers in the 2 trial conditions. Participants will then complete the immediate intervention condition or the delayed intervention condition (ie, maintenance of usual activities) for 12 weeks. The same scientific feasibility outcomes as the baseline will be repeated immediately after the intervention (T2). We anticipate that each assessment session will last for approximately 2 hours. At the completion of the intervention, participants will also be asked to complete a satisfaction survey and an individual exit interview to assess their satisfaction with specific intervention components (ie, intervention content, interventionist, and delivery method) and their subjective experiences of participation in all aspects of PAT-MS, respectively. People with MS and their care partners will complete the same surveys. We anticipate that the survey will take approximately 15 minutes to complete. Individual exit interviews will be conducted over the phone by a member of the research team and will last for approximately 30 minutes. The same interview guide will be used for people with MS and their care partners. Participants in the delayed intervention condition will receive the intervention after the postintervention assessment (T2). We will follow the same intervention delivery procedures for the delayed condition as for the immediate intervention condition.

Intervention
PAT-MS is a dyadic behavioral PA intervention approach that incorporates a toolbox of evidence-based strategies adapted from previous trials on promoting PA in care partners of people with Alzheimer disease [35,36], a comprehensive program of research [20,[37][38][39], and input from people with MS and care partners. PAT-MS is grounded in the theory of dyadic illness management [40]. Behavior change techniques [41] that target key theoretical constructs from the social cognitive theory [42] and self-determination theory [43] are included to facilitate behavior change. The social cognitive theory and self-determination theory have proven effective for increasing PA in the general population [44] and among people with MS [45][46][47]. Table 1 provides a summary of the content and main behavior change techniques [41] that will be targeted across the six teleconference sessions. In brief, the intervention includes the following main components: • Education: Participants will be provided with a PAT-MS manual that includes information on PA and introduces the concepts of shared appraisal of disease impact and dyadic coping. The benefits of shared participation in PA as a coping strategy to optimize well-being at the individual and dyadic levels will be discussed.
• Guidance from a trained interventionist: Participants will be provided with specific verbal and written guidance to improve their confidence in engaging in PA behavior. Given that PA interventions are more effective when combined with behavior change techniques [48], PAT-MS will include techniques commonly used in dyadic health interventions for persons with chronic neurological conditions and their care partners [20]. These techniques include, but are not limited to, goal setting and review, problem solving and action planning, behavioral practice, and instruction from a credible source.
• Social support: Participants will be provided practical, emotional, and informational social support during the intervention (eg, links to community programs for continued PA participation and opportunities to engage with and learn from other group members).

Intervention Structure and Delivery
People with MS-care partner dyads will receive six group teleconferencing sessions (approximately 60 min each) every other week for a period of 12 weeks (Table 1). Each session is structured to include a review of material from the previous week, teaching content, group discussions, and explanation of practice activities to be completed before the next session. The group sessions will be interspersed with brief (approximately 15 min each) one-on-one support telephone calls in the weeks in which the group sessions do not occur. The intervention schedule will provide regular contact with the research team but will recognize the time commitment of the participants. We will seek to have 2-3 dyads on each teleconference call to manage the call more easily and to monitor the intervention process. The group-based teleconference format will provide opportunities for social modeling, social support, and vicarious learning experiences [23,24], which in turn will support behavior change, consistent with the theoretical foundations of PAT-MS [42,43]. Makeup sessions will be offered to those who miss teleconference sessions. The intervention will be delivered by a trained interventionist who will be provided with a structured manual for intervention delivery. Compliance to the protocol by the interventionist will be monitored using a checklist, weekly review meetings, and episodic monitoring of the teleconference sessions according to the guidelines of Bellg [49].

Outcomes
The outcomes will relate to process, resources, management, and scientific feasibility, as outlined below.

Process Outcomes
Process outcomes will include assessing recruitment rates (ie, response of participants to recruitment strategies, number of potential participants who remain interested in the study after information and screening, and reasons for refusal to participate).

Resource Outcomes
Resource outcomes will include assessing the rates of participant compliance (ie, number of practice activities, teleconference sessions, and one-on-one phone calls completed), attrition (ie, percentage of participants who drop out of the study and reasons for dropping out), suitability of eligibility criteria (ie, percentage of interested participants who meet the inclusion criteria and reasons for exclusion), and total cost of intervention delivery (ie, cost of equipment, personnel, and participant remuneration).

Management Outcomes
Management outcomes will include assessing staff time (ie, staff preparation and training time, call time, attempted call time, and report-taking time), use of technical support (ie, number of equipment-related data collection problems and number of technical support calls made by staff and/or participants), intervention fidelity (ie, interventionist's compliance to the protocol), and efficiency and accuracy of data collection and entry (ie, data completeness and time to collect, enter, and check data).

Scientific Outcomes
These will include assessing safety, treatment effect, participant satisfaction with intervention components (ie, intervention content, interventionist, and delivery method), and subjective experience of participating in the intervention.

Safety
Safety will involve reporting of adverse events (AEs). AEs are defined as any unfavorable change in health experienced by a participant during the trial period [50]. Each AE will be rated based on severity (grade 1 [mild] through 5 [death]), expectedness, and potential relation to study participation (ie, not related, possibly related, or definitely related) using the National Institutes of Health terminology and classification scheme [50]. AEs will be reported as the overall rate, severity, and characteristics of the AEs.

Treatment Effect
This will involve assessing changes in the following outcomes between T1 (baseline) and T2 (12 weeks): accelerometer-measured PA, self-reported PA, resilience, social support, dyadic relationship quality, quality of life, MS self-efficacy, experiential aspects of participation, and coping. Table 2 provides a summary of the treatment outcomes and psychometric properties of the outcome measures included in the study.

Satisfaction With Intervention Components-Content, Interventionist, and Delivery Method
This will be assessed in both people with MS and care partners using a satisfaction survey developed for this study. Items will be scored using a 5-point Likert-type scale, with higher scores reflecting greater satisfaction.

Subjective Experience of Participation in All Aspects of PAT-MS
This will be explored in both people with MS and care partners using a semistructured exit interview. Suggestions for intervention improvement and participants' willingness and concerns regarding future participation in PA will also be explored.

Quantitative Data Analysis
Data management and analysis will be performed using IBM SPSS Statistics for Windows (IBM Corp). Descriptive statistics, including means and SDs (continuous variables) and frequencies and proportions (categorical variables), will be used to summarize all demographic and feasibility data. Within-subject changes and effect sizes for improvement in scientific outcomes from T1 to T2 will be calculated using Cohen d separately for people with MS and care partners and by condition (immediate vs delayed control).

Qualitative Data Analysis
All audiorecorded interviews will be transcribed and anonymized before the analysis. The qualitative analysis will be underpinned by a social constructivism paradigm [67], which will allow exploration of the meaning and understanding of the experiences of our participants relative to participation in PAT-MS. The systematic six-phase process of thematic analysis as described by Braun and Clark [68] will be undertaken. The rigor of the qualitative analysis will be maximized through a range of strategies recommended by Smith and McGannon [69].

Determining Progression to a Definitive Trial
Progression to a pilot RCT will be considered if minimum success criteria are achieved in key feasibility metrics or if we can identify strategies for overcoming any identified challenges in these areas [70]. These criteria were selected based on the guidelines for prospectively defining progression to future evaluative studies [71,72]. The criteria include the following:

Results
The project is funded by the Consortium of Multiple Sclerosis Centers. This protocol was approved by the Ottawa Hospital Research Ethics Board (20190329-01H) and the University of Ottawa Research Ethics Board (H-09-19-4886). The study protocol was registered with ClinicalTrials.gov (NCT04267185) in February 2020. The findings of this feasibility trial will be disseminated through presentations at community events to engage the MS population in the interpretation of our results and in the next steps. The results will also be published in peer-reviewed journals and presented to the scientific community at national and international MS conferences.

Principal Findings
Several direct outcomes are anticipated from this trial. First, the delivery of this trial will provide important insights for the research team on the practicality of running a future pilot trial, if the proposed intervention is feasible. Second, this trial will provide key information on the feasibility of PAT-MS, including estimates of recruitment, compliance, and attrition. It will also enable us to assess the acceptability of the intervention from the participants' perspective. Finally, conducting this work will lead to the development of a manualized research protocol for PAT-MS. This manual will include the recruitment and selection criteria, details about the intervention and training of intervention staff, recommendations for managing study logistics, and possible challenges and strategies for overcoming them. The development of this manual will facilitate the delivery of future efficacy and effectiveness trials, including those using a multicenter approach. In addition, it will ensure the fidelity of the intervention and its long-term delivery in community, health care, or other multiservice settings.

Strengths and Limitations
The PAT-MS intervention is unique in several ways. PAT-MS uses a novel approach that combines both people with MS and their care partners together as active and collaborative participants in the intervention. There are potential synergistic benefits of this intervention on the health of each partner individually and on the dyad (ie, partnership). In addition, the focus on people with advanced MS disability is novel, as few interventions target this segment of the MS population. This MS cohort requires accessible strategies for disease management and requires high levels of caregiving support. Finally, the use of a telerehabilitation offers a cost-effective strategy for widespread long-term dissemination and is one of the preferred delivery formats for PA interventions among people with MS [73].
When executing the proposed trial, foreseeable challenges are compliance and attrition, which may be related to disease symptoms, comorbidities, or changes in medications. Care partners who are often working outside of the home, in addition to their caregiving role, may perceive participating in the intervention as a dyad to be burdensome, rather than beneficial. We have incorporated various methods into the study design to maximize retention and compliance: (1) flexibility in assessment sessions and phone call times; (2) follow-up by telephone and makeup session options; (3) offsetting participation costs through remuneration, toll-free calling, and reserved parking for testing visits; (4) including intervention content on the potential benefits of regular PA participation and how participants can safely engage in PA; and (5) incorporating behavior change techniques and using group-based delivery to reinforce social support, social modeling, and vicarious learning. Another potential challenge is the fidelity of the intervention. To promote the standard application of the intervention, an interventionist manual will be provided and incorporated into the interventionist's training.

Conclusions
This is the first study to examine the feasibility of the PAT-MS intervention. PAT-MS offers people with MS who have advanced disability and their care partners an opportunity to achieve important health and well-being benefits associated with PA participation. The findings from this study will be relevant in informing future dyadic health promotion research in MS.