Efficacy of BodyMirror Clinical MS Multimodal Game-Based Digital Therapeutic for Remote Monitoring and Neurorehabilitation in Multiple Sclerosis: Protocol for a Multisite Randomised Controlled Trial

BackgroundMultiple sclerosis (MS) is a chronic neurodegenerative disease charac-terised by progressive neurological disability and heterogeneous symptom trajectories. Cur-rent clinical monitoring methods, including magnetic resonance imaging (MRI) and episodic neurological assessments, provide limited insight into subtle disease progression and real-world functional changes. Digital health technologies integrating multimodal biosignals and behavioural assessments may enable continuous monitoring and personalised rehabilitation for patients with MS. ObjectiveThis study aims to evaluate the clinical utility of the BodyMirror Clinical MS platform, a multimodal software-as-a-medical-device (SaMD) that combines wearable biosensors, neuroscience-based games, and machine learning algorithms to remotely monitor disease progression and deliver personalised neurorehabilitation for individuals with multiple sclerosis. MethodsThis study is a prospective, randomised, double-blind, controlled, multisite clinical trial enrolling 400 participants, including 300 individuals with multiple sclerosis and 100 healthy controls. MS participants will be randomly assigned (1:1) to either an adaptive neurorehabilitation intervention group or a control group receiving non-therapeutic digital activities matched for engagement and exposure. Participants will perform three 30-minute sessions per week over a 24-month period using the BodyMirror platform. The system integrates multiple biosignals, including electroencephalography (EEG), electromyography (EMG), inertial measurement unit (IMU) motion data, speech analysis, and behavioural performance metrics, to generate digital biomarkers of neurological function. The primary endpoint is change in Expanded Disability Status Scale (EDSS) score from baseline to 24 months. Secondary outcomes include changes in Multiple Sclerosis Functional Composite (MSFC), MRI brain volume, cognitive performance, patient-reported outcomes, adherence to digital rehabilitation, and health-economic outcomes. ConclusionsThis trial will provide the first large-scale clinical evaluation of a mul-timodal digital neurotechnology platform combining wearable biosensors and game-based neurorehabilitation for remote management of multiple sclerosis. If successful, BodyMirror Clinical MS may enable scalable remote monitoring, earlier detection of disease progres-sion, and personalised digital rehabilitation for individuals living with MS.