Circadian Rhythmicity During Coma Awakening

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

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.

Sponsors & Collaborators

• Hospices Civils de Lyon

  lead OTHER

Principal Investigators

• GOBERT FLORENT, M.D. Ph.D. · Hospices Civils de Lyon

Study Design

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

17 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-12-02

Primary Completion

2028-12-02

Completion

2028-12-02

Countries

• France

Study Locations