EEG Analysis for the Objective Assessment of Drowsiness (MEEGASAFE)

• ClinicalTrials.gov Identifier: NCT05453643
• Recruitment Status: Not yet recruiting
• First Posted: July 12, 2022
• Last Update Posted: October 6, 2022
• Sponsor: Physip S.A
• Collaborators: University of Bordeaux; National Research Agency, France
• Information provided by (Responsible Party): Physip S.A

Study Description

Brief Summary:

The objective of this clinical study is to develop solutions for the evaluation and management of drowsiness, based on 2 EEG sensors only, aiming at reducing the risk of accidents related to secondary hypersomnolence (sleepiness induced by sleep restriction or abnormal sleep/wake cycle). This project will allow a better understanding of the determinants of drowsiness and its impact on cognitive performance and the development of methods and models for the evaluation and prediction of cognitive performance deficit related to sleepiness. The secondary hypersomnolence will be objectified by continuous EEG recording and analysed by visual reading according to Objective Sleepiness Scale (OSS) criteria and automatically analyzed using the MEEGAWAKE algorithm (developed by PHYSIP). The level of secondary hypersomnolence will be modified by varying the duration and maintening of prior sleep or the sleep timing. The ability to stay awake will be measured by the maintenance of wakefulness test (MWT). Subjective sleepiness and mind wandering will be measured before and/or after all measurements. Simulated driving task, maintenance of wakefulness tests and several cognitive tasks to measure sustained attention, alertness, selective attention will be performed every 4 hours.

Condition or disease	Intervention/treatment	Phase
Sleep Deprivation	Behavioral: sleep deprivation patterns	Not Applicable

Detailed Description:

Chronotype and general tendency to daydream in daily life will be evaluated at the inclusion visit. Healthy volunteers will be placed in sleep deprivation patterns that will modify the level of secondary hypersomnolence. These patterns correspond to sleep deprivation caused by work schedules usually observed: shift work (SDP1) or night on-call (SDP2). shift work will be simulated by total sleep deprivation for 24 hours (comparable to the first day of a night worker) followed by early morning sleep, and an extended 17 hours wakefulness (comparable to second day of night shift). Secondary hypersomnolence will be assessed throughout prolonged awakenings (24 hours + 17 hours). The night on-call will be simulated by two half-hour awakenings during the nocturnal sleep. Hypersomnolence will be measured within 17 hours of wakefulness following this sleep fragmentation. The sleep history (quantity and quality of sleep) will be evaluated by actigraphy + ambulatory polysomnography (1 day before the experiment) and 2 polysomnographies in the laboratory during the experiment. Polysomnography recordings will be visually and automatically analyzed by the ASEEGA algorithm. Ambulatory recordings are automatically analyzed by ASEEGA. Throughout these sleep deprivation patterns, electrophysiological variables (EEG, EOG and EMG) will be continuously recorded in order to identify objective drowsiness states determined visually using the OSS or automatically by the MEEGAWAKE algorithm. Subjective sleepiness scale, Mind wandering scale, maintenance of wakefulness tests (MWT, electrophysiological test) and cognitive tests will be repeated, every 4hr, throughout the sleep deprivation patterns in order to determine abilities to stay awake, driving performance, sustained and selective attention, vigilance.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: EEG Analysis for the Objective Assessment of Secondary Hypersomnolence in Order to Limit the Accidental Risk
• Estimated Study Start Date: November 2022
• Estimated Primary Completion Date: September 2024
• Estimated Study Completion Date: March 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Sleep deprivation; healthy volunteers	Behavioral: sleep deprivation patterns; Sleep deprivation patterns 1 (SDP1) ; total sleep deprivation for 24 hours followed by early morning sleep and an extended 17 hours wakefulness. Sleep deprivation patterns 2 (SDP2) : Sleep interrupted by two half-hour awakenings

Outcome Measures

Primary Outcome Measures :

1. Change in Objective Sleepiness Scale (OSS) during extended wakefulness [ Time Frame: Once every 4 hours during SDP1 and SDP2 wakefulness ]

   OSS is based on the visual analysis of electrophysiological variables (EEG (C4, O2, C3, P3), 1 vertical EOG and 1 horizontal EOG).

   Each state of drowsiness (score) corresponds to a specific EEG activity accompanied by well-differentiated blinking and eye movements

Secondary Outcome Measures :

1. Change in Karolinska sleepiness scale (KSS) during extended wakefulness [ Time Frame: 12 assessments every 4 hours during SDP1 and SDP2 wakefulness ]
   The KSS is a self-administered questionnaire that measures, on a 10 point Likert scale ranging from=1 to "fully awake" to 10 ="extremely drowsy". This measure has very good external validity on EEG synchronization measures and on the cognitive and behavioral performance of subject in relation to his or her ability to maintain wakefulness.
2. Change in sleep onset mesured by Maintenance of Wakefulness Test (MWT) during extended wakefulness [ Time Frame: Once every 4 hours during SDP1 and SDP2 wakefulness ]
   This is test ability to stay awake in laboratory conditions conductive to falling asleep. The sleep onset latency is obtained during an electrophysiological test (EEG, EMG and EOG).
3. Change in number of inappropriate line crossings (driving performance) during extended wakefulness [ Time Frame: Once every 4 hours during SDP1 and SDP2 wakefulness ]

   On the driving simulator the subjects will drive on a highway scenario representing a reconstruction of the real highway. Number of inappropriate line crossings (ILC) will mesured.

   An ILC was recorded when the car crossed a right or left lateral lane marker, whatever the duration and the amplitude of the crossing. Exceptions were overtaking manoeuvres or some other necessary driving action.

4. Change in Standard deviation of the lateral position of the car (driving performance) during extended wakefulness [ Time Frame: Once every 4 hours during SDP1 and SDP2 wakefulness ]

   On the driving simulator the subjects will drive on a highway scenario representing a reconstruction of the real highway. Standard deviation of the lateral position of the car (SDLP in cm) will mesured.

   Lateral Position was defined as being 0 when the car was in the center of the lane, with positive value to the right and negative values to the left.

5. Change Sustained and selective attention during extended wakefulness [ Time Frame: Once every 4 hours during SDP1 and SDP2 wakefulness ]
   The reaction time of subject to the presentation of a "target" stimulus (Continuous Performance Test, CPT)
6. Change in Vigilance during extended wakefulness [ Time Frame: Once every 4 hours during SDP1 and SDP2 wakefulness ]
   The test examines the ability to concentrate and maintain attention over a long period (30mn) (TAP vigilance test)
7. Change in Simple reaction time test (PVT) during extended wakefulness [ Time Frame: 1 time every 4 hours during SDP1 and SDP2 wakefulness ]
   Reaction-timed task that measures the consistency with which subjects respond to a visual stimulus.
8. Change in conscious experience during extended wakefulness [ Time Frame: 5 assessments every 4 hours during SDP1 and SDP2 wakefulness ]
   Questionnaire suggests participant's attention and thoughts were entirely focused on task-related stimuli
9. Munich Chorotype Questionnaire [ Time Frame: Once time during inclusion. Visit V0 ]
   The Munich Chorotype Questionnaire (MCTQ) quantifies the chronotype according to the phase of entrainment based on the reported the mid-time of sleep; The MCTQ parameters are mid-sleep on weekdays (MSW in hr), mid-sleep on free days (MSF in hr) and mid-sleep on free days corrected for sleep debt on weekdays (MSFsc in hr). The MSFsc score (used as a chronotype indicator) represents a continuum of circadian preference, with an increasing tendency toward the evening type. MCTQ parameters are represented by hours, ranging from 0 hour (extreme morningness) to 12 hours (extreme eveningness).
10. Horne and Ostberg morning/evening questionnaire (MEQ) [ Time Frame: Once time during inclusion. Visit V0 ]

    The Horne and Ostberg morning/evening questionnaire (MEQ) quantifies the chronotype.

    The MEQ contains19 questions on life preferences (activity, sleep-wake cycle, meals) and the state of fatigue and drowsiness at certain times of the day. The MEQ score ranges from 16-86, with evening type ranging from16-41, neither or intermediate type from 42-58, and morning type from 59-86.

11. Daydreaming frequency scale [ Time Frame: Once time during inclusion. Visit V0 ]
    To assess participants' general tendency to daydream in daily life
12. Total sleep time (PSG) [ Time Frame: 2 times before SDP1 and SDP2 ]
    Total sleep time, the number of minutes asleep in bed after "lights off", will be calculated using a polysomnographic recording (PSG). EEG, EOG and EMG will be recorded during sleep.
13. Sleep onset latency (PSG) [ Time Frame: 2 times before SDP1 and SDP2 ]
    Sleep onset latency, the minutes from lights off to sleep onset, will be calculated using a polysomnographic recording (PSG). EEG, EOG and EMG will be recorded during sleep.
14. Sleep efficiency (PSG) [ Time Frame: 2 times before SDP1 and SDP2 ]
    Sleep efficiency, the ratio of the total time spent asleep (total sleep time) in a night compared to the total amount of time spent in bed, will be calculated using a polysomnographic recording (PSG). EEG, EOG and EMG will be recorded during sleep.
15. Amount of sleep stages (PSG) [ Time Frame: 2 times before SDP1 and SDP2 ]
    Amount of N1,N2,N3 and R stage (expressed in p% of TST) will be calculated using a polysomnographic recording (PSG). EEG, EOG and EMG will be recorded during sleep.
16. Wake after sleep onset (PSG) [ Time Frame: 2 times before SDP1 and SDP2 ]
    Wake after sleep onset, number of minutes scored as wake from sleep onset to the last minute scored as sleep while in bed, will be calculated using a polysomnographic recording (PSG). EEG, EOG and EMG will be recorded during sleep.
17. Total sleep time (actigraphy) [ Time Frame: 2 times before SDP1 and SDP2 ]
    Total sleep time, the number of minutes asleep in bed after "lights off", will be calculated using an actigraph (wearable sleep test that tracks wrist movements)
18. Sleep onset latency (actigraphy) [ Time Frame: 2 times before SDP1 and SDP2 ]
    Sleep onset latency, the minutes from lights off to sleep onset, will be calculated using an actigraph (wearable sleep test that tracks wrist movements)
19. Sleep efficiency (actigraphy) [ Time Frame: 2 times before SDP1 and SDP2 ]
    Sleep efficiency, the ratio of the total time spent asleep (total sleep time) in a night compared to the total amount of time spent in bed will be calculated using an actigraph (wearable sleep test that tracks wrist movements)
20. Wake after sleep onset (actigraphy) [ Time Frame: 2 times before SDP1 and SDP2 ]
    Wake after sleep onset, number of minutes scored as wake from sleep onset to the last minute scored as sleep while in bed will be calculated using an actigraph (wearable sleep test that tracks wrist movements)

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• BMI between 18 and 27,
• With a score on the PHQ-4 scale less than or equal to 2 for scores A (Anxiety) and D (Depression),
• Subjects with no complaints of excessive daytime sleepiness (total ESS score <11),
• Non-professional drivers,
• Subjects who have held their driving license for at least one year,
• Subjects affiliated to a social security scheme,
• Subjects able to understand the study,
• Subjects available to come to the 3 visits required by the study,
• Free, informed and written consent signed

Exclusion Criteria:

• Pathologies that can induce excessive daytime sleepiness: untreated narcolepsy or idiopathic hypersomnia, untreated restless legs syndrome, untreated periodic leg movement syndrome,
• Chronic insomnia disorder,
• Excessive alcohol consumption (> 2 glasses per day) during the last 6 months,
• Excessive consumption of coffee, tea or cola-type caffeinated beverages (> 5 cups/day),
• Severe pathologies involving the vital prognosis in the short term,
• Uncontrolled endocrine pathologies (dysthyroidism, diabetes),
• All progressive cardiac pathologies, treated or untreated,
• All progressive neurological conditions treated or not (brain tumor, epilepsy, migraine, stroke, sclerosis, myoclonus, chorea, neuropathy, muscular dystrophies, myotonic dystrophy, etc.),
• Substance dependence,
• Shift workers or night workers who have performed on-call or on-call duty in the last 72 hours,
• Patients taking psychotropic drugs (antidepressants, antihistamines),
• Long-term treatment with benzodiazepines and z-drugs,
• Patients on cardiotropic,
• Deprived of liberty by a judicial or administrative decision,
• Pregnant or breastfeeding woman,
• Subject under legal protection (guardianship, wardship) or deprived from his rights following administrative or judicial decision

Contacts and Locations

Contacts

Contact: Jean-Arthur MICOULAUD-FRANCHI, MD/PhD; 05 57 82 01 73; jean-arthur.micoulaud-franchi@chu-bordeaux.fr

Contact: jacques Taillard, PhD; 05 57 82 01 73; jacques.taillard@u-bordeaux.fr

Locations

France

CHU bordeaux

Bordeaux, France, 33076

Contact: Jean-Arthur Micoulaud-Franchi, MD-Phd

Sponsors and Collaborators

Physip S.A

University of Bordeaux

National Research Agency, France

Investigators

• Principal Investigator: Jean-Arthur Micoulaud-Franchi, MD/PhD; CHU Bordeaux

More Information

• Responsible Party: Physip S.A
• ClinicalTrials.gov Identifier: NCT05453643
• Other Study ID Numbers: MGSF
• First Posted: July 12, 2022
• Last Update Posted: October 6, 2022
• Last Verified: July 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Physip S.A:

Sleep deprivation; Secondary hypersomnolence; Objective Sleepiness; Subjective Sleepiness; Cognitive performance; Driving

Additional relevant MeSH terms:

Sleep Deprivation; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Neurologic Manifestations; Mental Disorders