Prepare the mind: can coaching in goal-directed behavior increase the success of cognitive rehabilitation in people with multiple sclerosis? - a study protocol of a multicenter randomized controlled trial

Up to 70% of people with multiple sclerosis (PwMS) experience cognitive impairment, particularly in information processing speed and memory. Although cognitive rehabilitation (CR) can improve cognitive function, treatment response varies substantially, limiting routine clinical implementation. Higher trait conscientiousness (i.e., the tendency to be diligent, organized, and goal-oriented) has been associated with better cognitive outcomes, slower disease progression, and reduced brain atrophy in PwMS. Conscientiousness coaching (C-Coach), a blended intervention combing tele-coaching and smartphone support, has been shown to enhance conscientiousness and goal-directed behavior. It may therefore optimize responsiveness to CR. To investigate whether PwMS receiving C-Coach prior to CR show greater improvement in processing speed and self-reported everyday cognitive functioning, compared with PwMS receiving a sham intervention before CR. In this international, multicenter, randomized double-blinded, parallel-group trial will include 126 PwMS (aged 18–65 years) allocated 1:1 to C-Coach or an active sham intervention for 12-weeks followed by 6-weeks of home-based digital CR (Brain HQ). C-Coach includes one initial coaching session and two booster sessions focused on identifying core values and associated goals, supported by weekly check-ins and the smartphone app. The sham intervention is an active control with the same coaching interactions but focused on reflecting on daily experiences. Participants will be recruited from the Netherlands, US, New Zealand, and Switzerland. Main outcomes at baseline, 12-weeks (post-C-Coach), and 18-weeks (post-BrainHQ) are processing speed measured (Symbol Digit Modalities Test) and self-reported cognition (Multiple Sclerosis Instrumental Activities of Daily Living Questionnaire), and secondary outcomes are psychological (meaning of life, fatigue, depression, anxiety, health-related quality of life), neurobiological (cognitive performance and functional brain networks), and social support. Dutch participants additionally undergo MRI scanning. We hypothesize that strengthening conscientiousness before CR will enhance treatment responsiveness, resulting in superior cognitive and psychosocial outcomes. By targeting behavioral readiness for rehabilitation, this study advances a scalable and theory-driven model for personalized neurorehabilitation in MS. Registered prospectively on ClinicalTrials.gov (NCT07225868) on 06 November 2025.