REFRESH protocol: a non-inferiority randomised clinical trial comparing internet and teleconference to in-person 'Managing Fatigue' interventions on the impact of fatigue among persons with multiple sclerosis.

Introduction: Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system. It is considered a major cause of non-traumatic disability in young adults. One of the most common and disabling symptoms of MS is fatigue. MS fatigue can impact all aspects of quality of life, including physical, mental and social function. Fortunately, fatigue self-management interventions, such as ', can decrease the impact of fatigue and improve health-related quality of life. The purpose of this study is to compare three modes of delivering the intervention-two remote delivery formats (teleconference and internet) and one in-person format-on perceptions of fatigue and its impact on physical, mental and social function.

Methods And Analysis: A non-inferiority randomised clinical trial is being conducted to compare the three delivery formats (1:1:1 allocation ratio) among 582 participants with MS living in the Midwestern and Northeastern United States. The hypothesis is that teleconference and internet versions of the intervention are non-inferior to the traditional mode of clinical service delivery (ie, one to one, in person) in terms of the primary outcome of self-reported fatigue impact (ie, Fatigue Impact Scale) and the secondary outcome of health-related quality of life (ie, Multiple Sclerosis Impact Scale). Outcomes are being measured at baseline, 2 months, 3 months and 6 months. The primary analysis tool will be linear mixed effects model. The prespecified inferiority margin for the primary outcome is 10 points. We will also examine whether baseline characteristics (eg, sociodemographic) moderate outcomes of the intervention and whether changes in self-efficacy and fatigue self-management behaviours mediate changes in outcomes.

Ethics And Dissemination: The protocol is approved centrally by the institutional review board at Case Western Reserve University. Eligible participants give consent before being enrolled and randomised into the study. The study results will be disseminated through relevant advocacy organisations, newsletters to participants, publication in peer-reviewed journals and presentations at scientific conferences.

Trial Registration Number: NCT03550170; Pre-results.