Metabolomics-based Sleepiness Markers

Sleep Deprivation Clinical Trial

— ME-SMART  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05585515
• Other study ID #: 2022-01273
• Secondary ID: SNCTP000005089
• Status: Completed
• Phase: N/A
• Start date: November 1, 2022
• Est. completion date: May 18, 2023

Study information

• Verified date: May 2023
• Source: University of Zurich
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: May 18, 2023
• Est. primary completion date: May 18, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 35 Years

Eligibility

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

Related Conditions & MeSH terms

• Insufficient Sleep Syndrome
• Sleep Deprivation
• Sleepiness

Intervention

Behavioral:
• Sleep deprivation
Total sleep deficit of consecutive 8 hours
• Sleep restriction
Total sleep deficit of cumulative 8 hours

Locations

Country	Name	City	State
Switzerland	Human Sleep Laboratory, University of Zurich	Zürich	Zurich

Sponsors (2)

Lead Sponsor	Collaborator
University of Zurich	Fonds für Verkehrssicherheit FVS

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)