Circadian Rhythmicity During Coma Awakening
ConditionAcute Brain Injury Coma
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age17+
SponsorHospices Civils de Lyon
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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 with no response to simple commands
Weaning from sedation : acquired / possible within 7 days of inclusion in the absence of new complications
Disqualifiers
Subjects with a contraindication to MRI scans
Admission for status epilepticus
Existence of status epilepticus during the stay and persisting for > 24h or presenting an electrical remission for less than 48h prior to inclusion
Post-anoxic coma with bilateral abolition of N20 PES cortical responses
Trial design
Design model
Parallel
Treatments tested in this trial
Repeated behavioural assessment
BehavioralOne 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
Act-Pass paradigm
BehavioralBefore and after sedation withdrawal Assessment of infra-clinical response to an active paradigm (attention focalisation or diversion).
Biological measures of circadian and monoamines biomarkers
BehavioralSystematic urinary sampling every 2 hours for melatonin, cortisol and monoamines metabolites
Transcriptomic and genomic analysis
BehavioralDefinition 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
Polysomnography with concomitant environment recording
BehavioralOne 48h polysomnography for the first visit \+ 3\* 24h polysomnography for each visit Synchronised recordings of light, sound, activity in patients' rooms
Actimetry
BehavioralContinuous recording of movements at the wrist during 7 days after sedation withdrawal
Morphological MRI
BehavioralPrecise description of brain lesion by a 3T MRI within the 1st week after sedation withdrawal
Assessment of correlation between patients' behaviour and neurophysiological markers of consciousness.
BehavioralVideo recording of spontaneous patients' movements in the bed and synchronized during 2h with high-density EEG.
Treatment groups
90 Participants
are divided into 3 treatment groupsGroup A: Main group with acute brain injury and initial Disorders of consciousnessExperimental treatment 8 interventions
Group B: Comparative group with acute brain injury without Disorders of consciousnessActive comparator 8 interventions
Group C: Comparative group with post-acute Disorders of consciousnessActive comparator 8 interventions
Trial outcomes
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)
Time frame
2, 3, 4,6 months post injurySecondary outcomes
1
Functional outcome
Glasgow Outcome Scale (GOS) Glasgow Outcome Scale Extended (GOSE) Minimum score 1 and maximum score 5. The lowest score is 5.
Time frame
GOS: 2, 3, 4,6 months post injury GOSE: 6 months post injury2
Cognitive outcome
MOCA scale The MOCA is a short 30-question test that assesses several cognitive domains and allows for early detection of cognitive disorders. The MOCA test takes about 10-15 minutes to administer and consists of several sections, the first of which is an assessment of orientation in time and space. Then there are tasks that assess memory, concentration and reasoning ability, as well as language and visuospatial ability tasks. The MOCA score can range from 0 to 30 points, with a score of 26 points or more considered normal.
Time frame
6 months post injury3
Quality of life outcome SF-36 scale
At the end, a score for each dimension of the SF-36 was calculated, ranging from 0 to 100. A low score reflects a perception of poor health, loss of function, presence of pain. A high score reflects a perception of good health, absence of functional deficit, and pain (3,6,7)
Time frame
6 months post injurySponsors and contacts
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Source ClinicalTrials.gov