Testing non-inferiority of blended versus face-to-face cognitive behavioural therapy for severe fatigue in patients with multiple sclerosis and the effectiveness of blended booster sessions aimed at improving long-term outcome following both therapies: study protocol for two observer-blinded randomized clinical trials

BACKGROUND: Cognitive behavioural therapy (CBT) has been found to be effective in reducing fatigue severity in MS patients directly following treatment. However, long-term effects are inconsistent leaving room for improvement. In addition, individual face-to-face CBT draws heavily on limited treatment capacity, and the travel distance to the treatment centre can be burdensome for patients. Therefore, we developed “MS Fit”, a blended CBT for MS-related fatigue, based on a face-to-face CBT protocol found effective in a previous study, and “MS Stay Fit”, internet-based booster sessions to improve long-term effectiveness of CBT for MS-related fatigue. This article presents the protocol of two randomised clinical trials (RCTs) conducted within one study investigating (1) the non-inferiority of MS Fit compared with evidence-based face-to-face CBT for MS-related fatigue and (2) the effectiveness of MS Stay Fit on the long-term outcome of fatigue compared with no booster sessions. METHODS/DESIGN: The first part of this study is an observer-blinded non-inferiority multicentre RCT, in which 166 severely fatigued MS patients will be randomly assigned (1:1 ratio, computer-generated sequence) to either face-to-face CBT or blended CBT (MS Fit) for fatigue. The primary endpoint is at 20 weeks after baseline. After this post-treatment assessment, patients will be randomly assigned again (1:1 ratio, computer generated sequence) to either MS Stay Fit consisting of two booster sessions at 2 and 4 months after end of treatment or no booster sessions. The primary endpoint of the second study is 52 weeks after baseline. Primary outcome measure in both studies is fatigue severity assessed with the fatigue severity subscale of the Checklist Individual Strength (CIS20r). Outcomes will be assessed at baseline (T0), at the end of treatment (T20), and after 39 and 52 weeks (T39 and T52). DISCUSSION: If MS Fit is found to be non-inferior to face-to-face CBT, it will improve the accessibility of this treatment. In addition, the study aims to test whether it is possible to improve long-term effectiveness of CBT for MS-related fatigue with MS Stay Fit. TRIAL REGISTRATION: Dutch Trial Register (NTR6966), registered 18 January 2018 https://www.trialregister.nl/trial/6782 WORLD HEALTH ORGANIZATION (WHO) TRIAL REGISTRATION DATA SET: All items from the WHO Trial Registration Data Set can be found within the protocol.