NCT06245434

Circadian Rhythmicity During Coma Awakening

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 90 (estimated)
• Sponsor: Hospices Civils de Lyon · Academic / Other
• Sex: All
• Age: 17 Years
• Healthy volunteers: Not accepted

Summary

Acute brain injury is a major cause of admission to intensive care units, as well as of mortality and morbidity, worldwide and for all age groups. With most patients surviving these injuries thanks to recent medical advances, society is facing not only the growing burden of disability, but above all the ethical issues involved in withdrawal of life-sustaining therapies (WSLT). To resolve this dilemma, effective treatment would be necessary, but this is hampered by our limited knowledge of the pathophysiological mechanisms of the natural history of coma, from onset to recovery. A more systematic description of coma awakening using a multimodal battery in intensive care unit patients would enable us to refine the awakening and re-emergence of consciousness and define appropriate biomarkers for selecting candidates in interventional studies. The investigators hypothesize that the current postulate of successive stages (i.e. from one clinical class to the next) of coma recovery is incomplete, as it does not take into account the rhythmic nature of wakefulness. The investigators propose that the best correlate of the natural history of coma recovery is a gradual shift from the loss of physiological cycles to a circadian rhythmicity of arousal indices (behavioural and neurophysiological) and a wide amplitude of metric fluctuations in assessing content richness.

Conditions

• Acute Brain Injury Coma

Interventions

Type	Name	Description
BEHAVIORAL	Repeated behavioural assessment	One CRS-R per visit * 4 SECONDs * Eye tracking during every clinical assessment * Recording every 2-4h of the Glasgow Coma Score * Recording every 2h of the temperature and pupillometer reactivity to light
BEHAVIORAL	Act-Pass paradigm	Before and after sedation withdrawal Assessment of infra-clinical response to an active paradigm (attention focalisation or diversion).
BEHAVIORAL	Biological measures of circadian and monoamines biomarkers	Systematic urinary sampling every 2 hours for melatonin, cortisol and monoamines metabolites
BEHAVIORAL	Transcriptomic and genomic analysis	Definition of the peripheral cellular clock by 2 transcriptomic measures Constitution of a genomic biobank to analyse the cofounding factors for circadian disruption and differential clinical recovery
BEHAVIORAL	Polysomnography with concomitant environment recording	One 48h polysomnography for the first visit \+ 3\* 24h polysomnography for each visit Synchronised recordings of light, sound, activity in patients' rooms
BEHAVIORAL	Actimetry	Continuous recording of movements at the wrist during 7 days after sedation withdrawal
BEHAVIORAL	Morphological MRI	Precise description of brain lesion by a 3T MRI within the 1st week after sedation withdrawal
BEHAVIORAL	Assessment of correlation between patients' behaviour and neurophysiological markers of consciousness.	Video recording of spontaneous patients' movements in the bed and synchronized during 2h with high-density EEG.

Timeline

• Start date: 2024-12-02
• Primary completion: 2028-12-02
• Completion: 2028-12-02
• First posted: 2024-02-07
• Last updated: 2026-02-06

Locations

1 site across 1 country: France