Circadian Rhythmicity During Coma Awakening
COMARHYTHM
1 other identifier
interventional
90
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for not_applicable
Started Dec 2024
Longer than P75 for not_applicable
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 30, 2024
CompletedFirst Posted
Study publicly available on registry
February 7, 2024
CompletedStudy Start
First participant enrolled
December 2, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 2, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 2, 2028
February 6, 2026
February 1, 2026
4 years
January 30, 2024
February 4, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Consciousness outcome
Coma Recovery Scale - revised used to define 4 possible consciousness outcomes (the best observed before death if the patient died at the date of assessment): * Coma * Unresponsive Wakefulness Syndrome * Minimally Conscious State * Exit-Minimally Conscious State (conscious patient)
2, 3, 4,6 months post injury
Secondary Outcomes (3)
Functional outcome
GOS: 2, 3, 4,6 months post injury GOSE: 6 months post injury
Cognitive outcome
6 months post injury
Quality of life outcome SF-36 scale
6 months post injury
Study Arms (3)
Main group with acute brain injury and initial Disorders of consciousness
EXPERIMENTAL50 patients in the initial phase of acute brain injury with disturbed consciousness, hospitalized in the Neurological Intensive Care Unit and at risk of delayed awakening
Comparative group with acute brain injury without Disorders of consciousness
ACTIVE COMPARATOR20 patients in the initial phase of brain damage WITHOUT disturbance of consciousness, hospitalized in the Neurological Intensive Care Unit and presenting similar causes of brain damage.
Comparative group with post-acute Disorders of consciousness
ACTIVE COMPARATOR20 patients in the sub-acute or chronic phase of a consciousness disorder and admitted to the Post-Resuscitation Rehabilitation Service.
Interventions
Video recording of spontaneous patients' movements in the bed and synchronized during 2h with high-density EEG.
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
Before and after sedation withdrawal Assessment of infra-clinical response to an active paradigm (attention focalisation or diversion).
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
One 48h polysomnography for the first visit \+ 3\* 24h polysomnography for each visit Synchronised recordings of light, sound, activity in patients' rooms
Continuous recording of movements at the wrist during 7 days after sedation withdrawal
Precise description of brain lesion by a 3T MRI within the 1st week after sedation withdrawal
Systematic urinary sampling every 2 hours for melatonin, cortisol and monoamines metabolites
Eligibility Criteria
You may qualify if:
- Group 1
- Admission to the Neurological Intensive Care Unit
- Initial disorder of consciousness (GCS \< 8) or initial brain lesion (on CT or MRI) requiring intubation and sedation during management (for upper airway protection or due to coma)
- Intubated patient under mechanical ventilation wwith no response to simple commands
- Severity of clinical or morphological impairment leading to risk of persistent disturbance of consciousness
- Sedation discontinued or able to be discontinued within 3 month of initial management of the disorder of consciousness or brain injury
- Effective treatment of the cause of admission without risk of short-term recurrence
- Patient aged 17 or over
- Presence of relatives able to sign consent or of the minor's legal representative
- Group 2
- Admission to the Neurological Intensive Care Unit or the Neurological Continuing Care Unit
- Absence of severe disorder of consciousness but possibility of minimal alteration of the initial Glasgow score (GCS between 9 and 15) with no time limit, with a stratification of three consecutive patient populations distinguished by the initial neurological alteration:
- GCS = 15
- GCS \< 15 by predominance of an initial defect in responses to simple or complex commands obtained by motor or verbal means, without abnormality of arousal (E score = 4 but M score \< 6 and/or V score \< 5)
- GCS \< 15 with predominant initial somnolence, with or without abnormal motor or verbal responses to simple or complex commands (E score = 2 or 3 but M score = 6 and/or V score = 5).
- +15 more criteria
You may not qualify if:
- Group 1
- Subjects with a contraindication to MRI scans
- Admission for status epilepticus
- Post-anoxic coma with bilateral abolition of N20 PES cortical responses
- Coma related to a potentially recurrent cause of coma (tumours, infectious diseases with risk of relapse and inflammatory diseases)
- Moribund patient (life expectancy \< 24h) or in WLST (no assessment possible of the dynamics of ongoing awakening)
- Haemodynamic or respiratory instability incompatible with a prolonged attempt to stop sedation (except in the case of scheduled surgery outside the visit dates)
- Patients under guardianship, curatorship or safeguard of justice
- Patients not affiliated to the French health insurance system
- Pregnant women or women of childbearing age without proof of the absence of a current pregnancy
- Group 2
- Subjects with a contraindication to MRI scans
- Epileptic seizures on admission or during the stay
- Single seizure: if no rapid return to consciousness (GCS \< 8 for \> 12 hours)
- \> 2 distinct epileptic seizures regardless of the duration of loss of consciousness
- +18 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Service de Réanimation Polyvalente Neurologique Hôpital Neurologique Pierre Wertheimer
Bron, Lyon, 69500, France
Study Officials
- PRINCIPAL INVESTIGATOR
GOBERT FLORENT, M.D. Ph.D.
Hospices Civils de Lyon
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- BASIC SCIENCE
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 30, 2024
First Posted
February 7, 2024
Study Start
December 2, 2024
Primary Completion (Estimated)
December 2, 2028
Study Completion (Estimated)
December 2, 2028
Last Updated
February 6, 2026
Record last verified: 2026-02