Metabolomics-based Sleepiness Markers for Risk Prevention and Traffic Safety (ME-SMART): a monocentric, controlled, randomized, crossover trial.

Background: Too little sleep and the consequences thereof are a heavy burden in modern societies. In contrast to alcohol or illicit drug use, there are no quick roadside or workplace tests for objective biomarkers for sleepiness. We hypothesize that changes in physiological functions (such as sleep-wake regulation) are reflected in changes of endogenous metabolism and should therefore be detectable as a change in metabolic profiles. This study will allow for creating a reliable and objective panel of candidate biomarkers being indicative for sleepiness and its behavioral outcomes.

Methods: This is a monocentric, controlled, randomized, crossover, clinical study to detect potential biomarkers. Each of the anticipated 24 participants will be allocated in randomized order to each of the three study arms (control, sleep restriction, and sleep deprivation). These only differ in the amount of hours slept per night. In the control condition, participants will adhere to a 16/8 h wake/sleep regime. In both sleep restriction and sleep deprivation conditions, participants will accumulate a total sleep deficit of 8 h, achieved by different wake/sleep regimes that simulate real-life scenarios. The primary outcome is changes in the metabolic profile (i.e., metabolome) in oral fluid. Secondary outcome measures will include driving performance, psychomotor vigilance test, d2 Test of Attention, visual attention test, subjective (situational) sleepiness, electroencephalographic changes, behavioral markers of sleepiness, changes in metabolite concentrations in exhaled breath and finger sweat, and correlation of metabolic changes among biological matrices.

Discussion: This is the first trial of its kind that investigates complete metabolic profiles combined with performance monitoring in humans over a multi-day period involving different sleep-wake schedules. Hereby, we aim to establish a candidate biomarker panel being indicative for sleepiness and its behavioral outcomes. To date, there are no robust and easily accessible biomarkers for the detection of sleepiness, even though the vast damage on society is well known. Thus, our findings will be of high value for many related disciplines.

Trial Registration: ClinicalTrials.gov Identifier NCT05585515, released on 18.10.2022; Swiss National Clinical Trial Portal SNCTP000005089, registered on 12 August 2022.