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Clinical Trials/NCT06245434
NCT06245434
Recruiting
Not Applicable

Circadian Rhythmicity During Coma Awakening

Hospices Civils de Lyon1 site in 1 country90 target enrollmentDecember 2, 2024

Overview

Phase
Not Applicable
Intervention
Repeated behavioural assessment
Conditions
Acute Brain Injury Coma
Sponsor
Hospices Civils de Lyon
Enrollment
90
Locations
1
Primary Endpoint
Consciousness outcome
Status
Recruiting
Last Updated
2 months ago

Overview

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.

Registry
clinicaltrials.gov
Start Date
December 2, 2024
End Date
December 2, 2028
Last Updated
2 months ago
Study Type
Interventional
Study Design
Parallel
Sex
All

Investigators

Responsible Party
Sponsor

Eligibility Criteria

Inclusion Criteria

  • 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
  • Weaning from sedation : acquired / possible within 7 days of inclusion in the absence of new complications
  • 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
  • Urinary catheter in place at the time of inclusion and to remain in place until Visit N°1
  • Presence of relatives able to sign consent or of the minor's legal representative

Exclusion Criteria

  • 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
  • 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

Arms & Interventions

Main group with acute brain injury and initial Disorders of consciousness

50 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

Intervention: Repeated behavioural assessment

Main group with acute brain injury and initial Disorders of consciousness

50 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

Intervention: Act-Pass paradigm

Main group with acute brain injury and initial Disorders of consciousness

50 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

Intervention: Biological measures of circadian and monoamines biomarkers

Main group with acute brain injury and initial Disorders of consciousness

50 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

Intervention: Transcriptomic and genomic analysis

Main group with acute brain injury and initial Disorders of consciousness

50 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

Intervention: Polysomnography with concomitant environment recording

Main group with acute brain injury and initial Disorders of consciousness

50 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

Intervention: Actimetry

Main group with acute brain injury and initial Disorders of consciousness

50 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

Intervention: Morphological MRI

Main group with acute brain injury and initial Disorders of consciousness

50 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

Intervention: Assessment of correlation between patients' behaviour and neurophysiological markers of consciousness.

Comparative group with acute brain injury without Disorders of consciousness

20 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.

Intervention: Repeated behavioural assessment

Comparative group with acute brain injury without Disorders of consciousness

20 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.

Intervention: Act-Pass paradigm

Comparative group with acute brain injury without Disorders of consciousness

20 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.

Intervention: Biological measures of circadian and monoamines biomarkers

Comparative group with acute brain injury without Disorders of consciousness

20 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.

Intervention: Transcriptomic and genomic analysis

Comparative group with acute brain injury without Disorders of consciousness

20 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.

Intervention: Polysomnography with concomitant environment recording

Comparative group with acute brain injury without Disorders of consciousness

20 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.

Intervention: Actimetry

Comparative group with acute brain injury without Disorders of consciousness

20 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.

Intervention: Morphological MRI

Comparative group with acute brain injury without Disorders of consciousness

20 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.

Intervention: Assessment of correlation between patients' behaviour and neurophysiological markers of consciousness.

Comparative group with post-acute Disorders of consciousness

20 patients in the sub-acute or chronic phase of a consciousness disorder and admitted to the Post-Resuscitation Rehabilitation Service.

Intervention: Repeated behavioural assessment

Comparative group with post-acute Disorders of consciousness

20 patients in the sub-acute or chronic phase of a consciousness disorder and admitted to the Post-Resuscitation Rehabilitation Service.

Intervention: Act-Pass paradigm

Comparative group with post-acute Disorders of consciousness

20 patients in the sub-acute or chronic phase of a consciousness disorder and admitted to the Post-Resuscitation Rehabilitation Service.

Intervention: Biological measures of circadian and monoamines biomarkers

Comparative group with post-acute Disorders of consciousness

20 patients in the sub-acute or chronic phase of a consciousness disorder and admitted to the Post-Resuscitation Rehabilitation Service.

Intervention: Transcriptomic and genomic analysis

Comparative group with post-acute Disorders of consciousness

20 patients in the sub-acute or chronic phase of a consciousness disorder and admitted to the Post-Resuscitation Rehabilitation Service.

Intervention: Polysomnography with concomitant environment recording

Comparative group with post-acute Disorders of consciousness

20 patients in the sub-acute or chronic phase of a consciousness disorder and admitted to the Post-Resuscitation Rehabilitation Service.

Intervention: Actimetry

Comparative group with post-acute Disorders of consciousness

20 patients in the sub-acute or chronic phase of a consciousness disorder and admitted to the Post-Resuscitation Rehabilitation Service.

Intervention: Morphological MRI

Comparative group with post-acute Disorders of consciousness

20 patients in the sub-acute or chronic phase of a consciousness disorder and admitted to the Post-Resuscitation Rehabilitation Service.

Intervention: Assessment of correlation between patients' behaviour and neurophysiological markers of consciousness.

Outcomes

Primary Outcomes

Consciousness outcome

Time Frame: 2, 3, 4,6 months post injury

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)

Secondary Outcomes

  • Quality of life outcome SF-36 scale(6 months post injury)
  • Functional outcome(GOS: 2, 3, 4,6 months post injury GOSE: 6 months post injury)
  • Cognitive outcome(6 months post injury)

Study Sites (1)

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