Validating a novel driving simulation-based MWT against the standard MWT in an OSA-cohort challenged by CPAP-withdrawal (DS-MWT2) - Protocol for a monocentric, controlled, randomized, crossover trial

BackgroundExcessive daytime sleepiness (EDS) is a major yet under-recognized contributor to road traffic accidents. Traditional diagnostic tools, such as the Maintenance of Wakefulness Test (MWT), assess wakefulness under passive conditions but may not accurately reflect real-world driving risks. To address this gap, we have piloted a Driving Simulation-based MWT (DS-MWT), designed to evaluate sleepiness in an ecologically valid driving scenario. The present study aims to validate the novel DS-MWT against the classical MWT in a functionally relevant cohort of patients with obstructive sleep apnoea (OSA). MethodsThe present monocentric, randomized, controlled, within-subject crossover trial will include 54 participants: 36 patients with OSA undergoing[≥] 7-day CPAP withdrawal (W) or continuation (C), and 18 healthy controls. The study employs a well-established CPAP-withdrawal model in patients with prior optimal treatment adherence to transiently induce EDS under controlled conditions. A healthy control group is included to enable between-group comparisons. The primary expected outcome is the difference in mean latencies between MWT and DS-MWT, determined during four standardized test sessions per condition. Secondary exploratory outcomes are defined as the presence, direction, and magnitude of differences or correlations between treatment status (CPAP withdrawal vs. continuation) and driving performance metrics (e.g., lateral position, speed, lane departures, etc.), EEG and eye-tracking features, subjective sleepiness scores, at-home polysomnography (PSG) parameters, and metabolomic biomarkers (saliva, exhaled breath and dried blood spots). Data will be analyzed using linear mixed models, repeated-measures ANOVA, and predictive modeling with cross-validation. DiscussionThis trial addresses a critical limitation in sleep and traffic medicine by introducing a realistic, supposedly more ecologically valid alternative to standard sleepiness assessment tools. The DS-MWT may enhance clinical decision-making regarding fitness to drive (FTD) and provide a framework for identifying physiological and behavioral markers of sleepiness in realistic conditions. Trial registrationClinicalTrials.gov Identifier: NCT06872593, released on 12.03.2025, https://clinicaltrials.gov/study/NCT06872593 Swiss National Clinical Trial Portal SNCTP000006301, released on 19.03.2025, https://www.humanforschung-schweiz.ch/en/trial-search/study-detail/66469