AzTrials
AzTrials

Acute Brain Injury ComaCOMARHYTHMNCT06245434

Circadian Rhythmicity During Coma Awakening

A study testing Repeated behavioural assessment, Act-Pass paradigm and Biological measures of circadian and monoamines biomarkers in people with Acute Brain Injury Coma, run by Hospices Civils de Lyon at 1 site in France.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 17 years and older
Conditions the study is for
Acute Brain Injury Coma
What is being tested?
Repeated behavioural assessment, Act-Pass paradigm and Biological measures of circadian and monoamines biomarkers
Could I receive a placebo?
No, everyone receives an active treatment
How many people
90 participants
Where
1 siteFrance
Study dates
2 Dec 2024to 2 Jun 2029
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 17 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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 with 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
Show all 34Show fewer
  • 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
  • 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, in the Neurological Multidisciplinary Intensive Care Unit
  • 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

Who cannot join

  • Group 1
  • 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)
Show all 37Show fewer
  • 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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

GOBERT FLORENT, M.D. Ph.D. contact

0472681296 ext. +33

florent.gobert01@chu-lyon.fr

France1 site, 1 recruiting

  • Service de Réanimation Polyvalente Neurologique Hôpital Neurologique Pierre Wertheimer

    Bron, Lyon, 69500

    FLORENT, GOBERT, M.D. Ph.D., 0472681296 ext. +33, florent.gobert01@chu-lyon.fr

    Recruiting

Other trials in France

About this study

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.

Being tested
Repeated behavioural assessment, Act-Pass paradigm, Biological measures of circadian and monoamines biomarkers, Transcriptomic and genomic analysis, Polysomnography with concomitant environment recording
Keywords
Circadian rhythms, Consciousness, Wakefulness, Biomarkers, Monoamines

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Repeated behavioural assessmentBehavioural

    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 paradigmBehavioural

    Before and after sedation withdrawal Assessment of infra-clinical response to an active paradigm (attention focalisation or diversion).

  • Biological measures of circadian and monoamines biomarkersBehavioural

    Systematic urinary sampling every 2 hours for melatonin, cortisol and monoamines metabolites

  • Transcriptomic and genomic analysisBehavioural

    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 recordingBehavioural

    One 48h polysomnography for the first visit

    + 3* 24h polysomnography for each visit Synchronised recordings of light, sound, activity in patients' rooms

  • ActimetryBehavioural

    Continuous recording of movements at the wrist during 7 days after sedation withdrawal

  • Morphological MRIBehavioural

    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.Behavioural

    Video recording of spontaneous patients' movements in the bed and synchronized during 2h with high-density EEG.

Study groups in NCT06245434
Study groupRoleWhat they receive
Main group with acute brain injury and initial Disorders of consciousnessExperimental50 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
Receives: Behavioral: Repeated behavioural assessment; Behavioral: Act-Pass paradigm; Behavioral: Biological measures of circadian and monoamines biomarkers; Behavioral: Transcriptomic and genomic analysis; Behavioral: Polysomnography with concomitant environment recording; Behavioral: Actimetry; Behavioral: Morphological MRI; Behavioral: Assessment of correlation between patients' behaviour and neurophysiological markers of consciousness.
Comparative group with acute brain injury without Disorders of consciousnessActive 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.
Receives: Behavioral: Repeated behavioural assessment; Behavioral: Act-Pass paradigm; Behavioral: Biological measures of circadian and monoamines biomarkers; Behavioral: Transcriptomic and genomic analysis; Behavioral: Polysomnography with concomitant environment recording; Behavioral: Actimetry; Behavioral: Morphological MRI; Behavioral: Assessment of correlation between patients' behaviour and neurophysiological markers of consciousness.
Comparative group with post-acute Disorders of consciousnessActive comparator20 patients in the sub-acute or chronic phase of a consciousness disorder and admitted to the Post-Resuscitation Rehabilitation Service.
Receives: Behavioral: Repeated behavioural assessment; Behavioral: Act-Pass paradigm; Behavioral: Biological measures of circadian and monoamines biomarkers; Behavioral: Transcriptomic and genomic analysis; Behavioral: Polysomnography with concomitant environment recording; Behavioral: Actimetry; Behavioral: Morphological MRI; Behavioral: Assessment of correlation between patients' behaviour and neurophysiological markers of consciousness.

What is being measured

The primary outcome is the main question the study is designed to answer.

  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)

    Measured: 2, 3, 4,6 months post injury

Secondary outcomes (3)

  1. Functional outcome

    Glasgow Outcome Scale (GOS) Glasgow Outcome Scale Extended (GOSE)

    Minimum score 1 and maximum score 5. The lowest score is 5.

    Measured: GOS: 2, 3, 4,6 months post injury GOSE: 6 months post injury

  2. 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.

    Measured: 6 months post injury

  3. 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)

    Measured: 6 months post injury

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Feb 2024
  2. Study start2 Dec 2024
  3. Primary completion2 Jun 2029 (estimated)
  4. Study completion2 Jun 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Basic science
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
90 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06245434
Sponsor's protocol ID
69HCL23_0053
Acronym
COMARHYTHM
Status last verified
Jul 2026
First submitted
30 Jan 2024
Last updated
30 Jul 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A study testing Repeated behavioural assessment, Act-Pass paradigm and Biological measures of circadian and monoamines biomarkers in people with Acute Brain Injury Coma, run by Hospices Civils de Lyon at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 34 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 30 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact GOBERT FLORENT, M.D. Ph.D. (0472681296 ext. +33, florent.gobert01@chu-lyon.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Consciousness outcome (time frame: 2, 3, 4,6 months post injury). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06245434.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in