Back to resultsMetabolomics-based Sleepiness Markers (ME-SMART)
Primary Purpose
Sleep Deprivation, Sleepiness, Insufficient Sleep Syndrome
Status
Completed
Phase
Not Applicable
Locations
Switzerland
Study Type
Interventional
Intervention
Sleep deprivation
Sleep restriction
Sponsored by
About this trial
This is an interventional basic science trial for Sleep Deprivation focused on measuring metabolomics, sleep, biomarker, impairment
Eligibility Criteria
Inclusion Criteria:
- understanding and spoken command of German language
- good health condition
- Body Mass Index between 18.5-24.9 kg/m2
- right-handedness (required for standardized performance tests)
- 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
Sites / Locations
- Human Sleep Laboratory, University of Zurich
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
No Intervention
Experimental
Experimental
Arm Label
Control
Sleep restriction
Sleep deprivation
Arm Description
16/8 hours wake/sleep regime for 3 consecutive days at home and for consecutive 2 days in sleep laboratory
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
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
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Psychomotor Vigilance Test
The Psychomotor Vigilance Test is a gold standard reaction time test to assess vigilance and sustained attention.
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.
Visual attention test
The visual attention test is a virtual reality glasses test to assess visual skills in a complex visual environment.
Subjective situational sleepiness
Participants will complete the Karolinska Sleepiness Scale questionnaire.
Subjective sleepiness
Participants will complete the Stanford Sleepiness Scale questionnaire.
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.
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.
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.
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.
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.
Full Information
NCT ID
NCT05585515
First Posted
October 5, 2022
Last Updated
June 1, 2023
Sponsor
University of Zurich
Collaborators
Fonds für Verkehrssicherheit FVS
1. Study Identification
Unique Protocol Identification Number
NCT05585515
Brief Title
Metabolomics-based Sleepiness Markers
Acronym
ME-SMART
Official Title
Study of Identification of Metabolomics-based Sleepiness Markers for Risk Prevention and Traffic Safety
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
November 1, 2022 (Actual)
Primary Completion Date
May 18, 2023 (Actual)
Study Completion Date
May 18, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Zurich
Collaborators
Fonds für Verkehrssicherheit FVS
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sleep Deprivation, Sleepiness, Insufficient Sleep Syndrome
Keywords
metabolomics, sleep, biomarker, impairment
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
29 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Control
Arm Type
No Intervention
Arm Description
16/8 hours wake/sleep regime for 3 consecutive days at home and for consecutive 2 days in sleep laboratory
Arm Title
Sleep restriction
Arm Type
Experimental
Arm Description
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
Arm Title
Sleep deprivation
Arm Type
Experimental
Arm Description
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
Intervention Type
Behavioral
Intervention Name(s)
Sleep deprivation
Intervention Description
Total sleep deficit of consecutive 8 hours
Intervention Type
Behavioral
Intervention Name(s)
Sleep restriction
Intervention Description
Total sleep deficit of cumulative 8 hours
Primary Outcome Measure Information:
Title
Changes in metabolite concentrations in oral fluid quantified by liquid chromatography with mass spectrometry
Description
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.
Time Frame
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 Measure Information:
Title
Driving performance
Description
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.
Time Frame
morning after experimental night (10am)
Title
Psychomotor Vigilance Test
Description
The Psychomotor Vigilance Test is a gold standard reaction time test to assess vigilance and sustained attention.
Time Frame
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)
Title
d2 Test of Attention
Description
The d2 Test of Attention is a paper and pencil test to assess selective and sustained attention and visual scanning speed.
Time Frame
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)
Title
Visual attention test
Description
The visual attention test is a virtual reality glasses test to assess visual skills in a complex visual environment.
Time Frame
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)
Title
Subjective situational sleepiness
Description
Participants will complete the Karolinska Sleepiness Scale questionnaire.
Time Frame
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)
Title
Subjective sleepiness
Description
Participants will complete the Stanford Sleepiness Scale questionnaire.
Time Frame
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)
Title
Electroencephalographic changes
Description
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.
Time Frame
During scheduled sleep, driving simulation test (10am), and at two time points during scheduled wakefulness (12pm, 7pm)
Title
Behavioral markers of drowsy driving
Description
Investigators will examine participants after driving simulation test for behavioral abnormalities concerning orientation, coordination, speech, mood, appearance, reaction, and pupillary light reflex.
Time Frame
Once per study arm after driving simulation test (11am)
Title
Changes in metabolite concentrations in exhaled breath quantified by liquid chromatography with mass spectrometry
Description
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.
Time Frame
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)
Title
Changes in metabolite concentrations in finger sweat quantified by liquid chromatography with mass spectrometry
Description
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.
Time Frame
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)
Title
Correlation of metabolic changes between blood and non-invasive specimens
Description
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.
Time Frame
immediately after driving simulation test (11am)
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kristina Keller, Dr
Organizational Affiliation
University of Zurich, Zurich
Official's Role
Principal Investigator
Facility Information:
Facility Name
Human Sleep Laboratory, University of Zurich
City
Zürich
State/Province
Zurich
ZIP/Postal Code
8057
Country
Switzerland
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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
Learn more about this trial
Metabolomics-based Sleepiness Markers
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