Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
NA
90 participants
INTERVENTIONAL
2024-12-02
2028-02-15
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
PARALLEL
BASIC_SCIENCE
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
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
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
Act-Pass paradigm
Before and after sedation withdrawal Assessment of infra-clinical response to an active paradigm (attention focalisation or diversion).
Biological measures of circadian and monoamines biomarkers
Systematic urinary sampling every 2 hours for melatonin, cortisol and monoamines metabolites
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
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
Actimetry
Continuous recording of movements at the wrist during 7 days after sedation withdrawal
Morphological MRI
Precise 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.
Video recording of spontaneous patients' movements in the bed and synchronized during 2h with high-density EEG.
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.
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
Act-Pass paradigm
Before and after sedation withdrawal Assessment of infra-clinical response to an active paradigm (attention focalisation or diversion).
Biological measures of circadian and monoamines biomarkers
Systematic urinary sampling every 2 hours for melatonin, cortisol and monoamines metabolites
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
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
Actimetry
Continuous recording of movements at the wrist during 7 days after sedation withdrawal
Morphological MRI
Precise 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.
Video recording of spontaneous patients' movements in the bed and synchronized during 2h with high-density EEG.
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.
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
Act-Pass paradigm
Before and after sedation withdrawal Assessment of infra-clinical response to an active paradigm (attention focalisation or diversion).
Biological measures of circadian and monoamines biomarkers
Systematic urinary sampling every 2 hours for melatonin, cortisol and monoamines metabolites
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
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
Actimetry
Continuous recording of movements at the wrist during 7 days after sedation withdrawal
Morphological MRI
Precise 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.
Video recording of spontaneous patients' movements in the bed and synchronized during 2h with high-density EEG.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
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
Act-Pass paradigm
Before and after sedation withdrawal Assessment of infra-clinical response to an active paradigm (attention focalisation or diversion).
Biological measures of circadian and monoamines biomarkers
Systematic urinary sampling every 2 hours for melatonin, cortisol and monoamines metabolites
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
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
Actimetry
Continuous recording of movements at the wrist during 7 days after sedation withdrawal
Morphological MRI
Precise 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.
Video recording of spontaneous patients' movements in the bed and synchronized during 2h with high-density EEG.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
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)
* Duration of sedation by general anesthesia (Propofol, Midazolam) \> 24 h or any use of barbiturate coma or surgery to treat intracranial hypertension
* Intubated patient under mechanical ventilation with ongoing sedation in sufficient dose (Propofol \> 1 mg/Kg/h and/or Midazolam \< 0.05 mg/Kg/h and/or any dose of Nesdonal)
* Weaning from sedation 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 on discontinuation of sedations
* Sedation discontinuation can be scheduled within 1 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
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).
* Existence of functional communication or functional use of objects at inclusion
* Mechanism of injury for which the aetiology is no longer active or at risk of recurrence
* Patient aged 17 or over
* Urinary catheter in place at the time of inclusion and to remain in place until Visit N°1
* In the case of impaired judgement despite functional communication or in the case of aphasia with functional use of objects: presence of relatives able to sign consent or of the legal representative of the minor or of the legal representative of the protected adult.
Group 3
* Admission to the Adult Post-Resuscitation Rehabilitation Department
* Disturbance of consciousness defined by an absence of communication or an absence of functional use of objects (for patients with aphasia), i.e. the two signs that could indicate emergence from the pauci-relational state, which includes patients presenting :
* persistent coma
* a vegetative state (or unresponsive wakefulness syndrome)
* a pauci-relational state (MCS- or MCS+ if responding to simple commands).
* Persistent within the following timeframe
* More than 3 months after the initial management of the disorder of consciousness or brain injury
* More than 1 month after a post-anoxic coma.
* Mechanism of injury for which the aetiology is no longer active or at risk of recurrence
* Patient aged 17 or over
* Presence of relatives likely to sign the consent or of the legal representative of a minor or of the legal representative of a protected adult
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
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
* Status epilepticus
* Post-anoxic coma with bilateral abolition of N20 cortical PES responses.
* Coma linked to a potentially recurrent cause of coma (tumour, infection with risk of relapse and inflammation).
* A moribund patient (life expectancy \< 24 hours) or a patient undergoing WLST with a high risk of death before the end of the study (inclusion possible if no therapeutic escalation is decided in a stabilised patient).
* Haemodynamic or respiratory instability incompatible with prolonged evaluation of the absence of sedation (risk of general anaesthesia for further failure, 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 3
* Subjects with a contraindication to MRI scans
* Epileptic seizures during the week preceding inclusion:
* Single seizure: if no rapid return to usual state of consciousness for \> 12 hours
* \> 2 separate comitial seizures regardless of duration of loss of consciousness
* Epileptic malaise
* Post-anoxic coma with bilateral abolition of N20 cortical responses to SEP
* Coma related to a potentially recurrent cause of coma (tumour, infection with risk of relapse and inflammation)
* Moribund patients (life expectancy \< 24 hours) or patients undergoing WSLT with a high risk of death before the end of the study (inclusion possible if no therapeutic escalation is decided in a stabilised patient).
* Haemodynamic or respiratory instability incompatible with prolonged evaluation of the absence of sedation (risk of general anaesthesia for further failure, except in the case of scheduled surgery outside the visit dates).
* Patients under guardianship, curatorship or safeguard of justice prior to the event that provoked their state of chronic disturbance of consciousness. Patients under guardianship because of their chronic disorder of consciousness are eligible for the study.
* 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
17 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Hospices Civils de Lyon
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
GOBERT FLORENT, M.D. Ph.D.
Role: PRINCIPAL_INVESTIGATOR
Hospices Civils de Lyon
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Service de Réanimation Polyvalente Neurologique Hôpital Neurologique Pierre Wertheimer
Bron, Lyon, France
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
FLORENT, GOBERT, M.D. Ph.D.
Role: primary
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
69HCL23_0053
Identifier Type: -
Identifier Source: org_study_id