Metabolomics-based Sleepiness Markers (ME-SMART)

Study of Identification of Metabolomics-based Sleepiness Markers for Risk Prevention and Traffic Safety

Estimating that people sleep on average up to two hours less over the last decades, sleepiness and fatigue need to be considered as significant societal problems of the modern world. Jurisdiction is precise on how to deal with overtired offenders since they were not allowed to use machines or vehicles in the first place, similar to drunk individuals or consumers of illicit drugs. In contrast to alcohol or illicit drug use, however, there are no quick roadside or workplace tests as objective (analytical) biomarkers for sleepiness.

Investigators hypothesize that increasing sleep drive or impaired wakefulness can be assessed by qualitative or quantitative fluctuations of certain metabolites in biological specimens, e.g., accumulation or decrease of endogenous substances related to sleep debt. Thus, this sleep study provides the necessary biological samples of either sleep-deprived, sleep-restricted, or control subjects, which are then analysed for appropriate metabolite biomarkers utilizing an untargeted metabolomics approach. In addition to established impairment tests, a state of the art driving simulator will be employed to objectively measure driving performance under all study conditions. Participants will also rate their subjective sleepiness using validated questionnaires.

Study Overview

• Status: Completed
• Conditions: Sleep Deprivation; Sleepiness; Insufficient Sleep Syndrome
• Intervention / Treatment: Behavioral: Sleep restriction; Behavioral: Sleep deprivation

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Zurich
    • Zürich, Zurich, Switzerland, 8057
      • Human Sleep Laboratory, University of Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• understanding and spoken command of German language
• good health condition
• Body Mass Index between 18.5-24.9 kg/m2
• habitual average sleep duration between 7-9 hours / night
• habitual consumption of 3 or fewer caffeinated beverages / day
• habitual consumption of 5 or fewer alcoholic beverages / week
• good sleep quality: Pittsburgh Sleep Quality Index score ≤ 5
• reasonable oral hygiene (≥1 tooth brushing / day)
• normal or corrected-to-normal vision
• car driving license holder since at least 2 years (obtained in a country with right hand traffic) and regular driver (≥ 1 per week)

Exclusion Criteria:

• two or more time zone crossings in the last 3 months
• habitual napper
• history or presence of neurological disorder, psychiatric disorder, cardiovascular disorder, dental disorder or any disorder that could pose a risk in participating or that could possibly influence study measurements
• history or presence of a sleep disorder (screening night)
• use of illicit drugs (urinary drug screening)
• use of current medication (urinary drug screening) known to influence study measurements
• extreme chronotype (reduced Morningness-Eveningness-Questionnaire score ≤7 or ≥22)
• current smoker
• habitual use of energy drinks (>1 / week)
• severe skin allergies or hypersensitivities
• food allergies
• hospital stay in past 6 months
• shift worker, night worker
• recent past (last 3 months) or present Covid-19 infection
• fainting at the sight of blood or needles
• participation in a clinical study less than 30 days ago or is currently participating in other clinical studies
• simulator sickness syndrome
• refusal to sign informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; 16/8 hours wake/sleep regime for 3 consecutive days at home and for consecutive 2 days in sleep laboratory
Experimental: Sleep restriction; 18/6 hours wake/sleep regime for 3 consecutive days at home and one day in sleep laboratory, followed by recovery night of 8 hours sleep	Behavioral: Sleep restriction; Total sleep deficit of cumulative 8 hours
Experimental: Sleep deprivation; 16/8 hours wake/sleep regime for 3 consecutive days at home, one night of sleep deprivation (24/0 hours) in sleep laboratory, followed by recovery night of 8 hours sleep	Behavioral: Sleep deprivation; Total sleep deficit of consecutive 8 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in metabolite concentrations in oral fluid quantified by liquid chromatography with mass spectrometry	Investigators will collect oral fluid samples from participants for quantification of all detectable metabolites. Investigators will analyze which metabolite concentration values undergo significant changes during sleep deficit conditions in comparison to control condition and also show effects of recovery sleep. These will serve as candidate biomarkers.	After arrival at study site (6pm, baseline), repeatedly during scheduled wakefulness (8am, 12pm, 4pm, 7pm, 11pm), and morning after recovery night of 8 hours of sleep (8am)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Driving performance	Investigators will gather driving simulation results via Standardized Application for Fitness to Drive Evaluations (S.A.F.E. scale), and analyze their changes after sleep deficit in comparison to control condition. This scale has a range from 0 (best) to 10 (worst) in full steps.	morning after experimental night (10am)
Psychomotor Vigilance Test	The Psychomotor Vigilance Test is a gold standard reaction time test to assess vigilance and sustained attention.	After arrival at study site (6pm, baseline), repeatedly during scheduled wakefulness (8am, 12pm, 4pm, 7pm, 11pm), and morning after recovery night of 8 hours of sleep (8am)
d2 Test of Attention	The d2 Test of Attention is a paper and pencil test to assess selective and sustained attention and visual scanning speed.	After arrival at study site (6pm, baseline), repeatedly during scheduled wakefulness (8am, 12pm, 4pm, 7pm, 11pm), and morning after recovery night of 8 hours of sleep (8am)
Visual attention test	The visual attention test is a virtual reality glasses test to assess visual skills in a complex visual environment.	After arrival at study site (8pm, baseline), repeatedly during scheduled wakefulness (10am, 2pm, 6pm, 8pm), and morning after recovery night of 8 hours of sleep (8am)
Subjective situational sleepiness	Participants will complete the Karolinska Sleepiness Scale questionnaire.	After arrival at study site (6pm, baseline), repeatedly during scheduled wakefulness (8am, 12pm, 4pm, 7pm, 11pm), and morning after recovery night of 8 hours of sleep (8am)
Subjective sleepiness	Participants will complete the Stanford Sleepiness Scale questionnaire.	After arrival at study site (6pm, baseline), repeatedly during scheduled wakefulness (8am, 12pm, 4pm, 7pm, 11pm), and morning after recovery night of 8 hours of sleep (8am)
Electroencephalographic changes	Investigators will analyze changes in sleep and wake electroencephalographic patterns of participants by calculating sleep scores according to American Academy of Sleep Medicine (AASM) scoring manual.	During scheduled sleep, driving simulation test (10am), and at two time points during scheduled wakefulness (12pm, 7pm)
Behavioral markers of drowsy driving	Investigators will examine participants after driving simulation test for behavioral abnormalities concerning orientation, coordination, speech, mood, appearance, reaction, and pupillary light reflex.	Once per study arm after driving simulation test (11am)
Changes in metabolite concentrations in exhaled breath quantified by liquid chromatography with mass spectrometry	Investigators will collect exhaled breath samples from participants for quantification of all detectable metabolites. Investigators will analyze which metabolite concentration values undergo significant changes during sleep deficit conditions in comparison to control condition and also show effects of recovery sleep. These will serve as secondary candidate biomarkers.	After arrival at study site (8pm, baseline), repeatedly during scheduled wakefulness (10am, 2pm, 6pm, 8pm, 11pm), and morning after recovery night of 8 hours of sleep (8am)
Changes in metabolite concentrations in finger sweat quantified by liquid chromatography with mass spectrometry	Investigators will collect finger sweat samples from participants for quantification of all detectable metabolites. Investigators will analyze which metabolite concentration values undergo significant changes during sleep deficit conditions in comparison to control condition and also show effects of recovery sleep. These will serve as secondary candidate biomarkers.	After arrival at study site (8pm, baseline), repeatedly during scheduled wakefulness (10am, 2pm, 6pm, 8pm, 11pm), and morning after recovery night of 8 hours of sleep (8am)
Correlation of metabolic changes between blood and non-invasive specimens	Investigators will compare metabolite concentrations in non-invasive matrices (oral fluid, finger sweat, exhaled breath, and dried blood spots) and compare those with blood sample.	immediately after driving simulation test (11am)

Collaborators and Investigators

• Sponsor: University of Zurich
• Collaborators: Fonds für Verkehrssicherheit FVS
• Investigators: Principal Investigator: Kristina Keller, Dr, University of Zurich, Zurich

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2022
• Primary Completion (Actual): May 18, 2023
• Study Completion (Actual): May 18, 2023

Study Registration Dates

• First Submitted: October 5, 2022
• First Submitted That Met QC Criteria: October 13, 2022
• First Posted (Actual): October 18, 2022

Study Record Updates

• Last Update Posted (Estimated): June 2, 2023
• Last Update Submitted That Met QC Criteria: June 1, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: sleep; biomarker; metabolomics; impairment
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Dyssomnias; Sleep Wake Disorders; Neurologic Manifestations; Sleep Deprivation; Sleepiness
• Other Study ID Numbers: 2022-01273; SNCTP000005089 (Registry Identifier: Swiss National Clinical Trials Portal)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Results will be published in peer-reviewed journals. Anonymized raw data will be made available upon request.
• IPD Sharing Time Frame: starting after publication
• IPD Sharing Access Criteria: upon request via e-mail
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No