Lesional ComaIMAGINANCT04575454
Imaging of the Neural Correlates of Arousal and Awareness
A study testing Multimodal evaluation of brain function : PET-MRI, electrophysiology, eye-tracking in people with Lesional Coma, run by Hospices Civils de Lyon at 1 site in France.
Trial summary
In last decades, several advances in the neuro-intensive management have lead to decrease mortality in Intensive Care Units. A significant morbidity remains as patients survive after a traumatic coma with uncertain quality of awakening and a high risk of functional disability. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Lesional Coma
- What is being tested?
- Multimodal evaluation of brain function : PET-MRI, electrophysiology, eye-tracking
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 85 participants
- Where
- 1 siteFrance
- Study dates
- 15 Nov 2020to 15 Nov 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Patients 1 Patients presenting either vascular or traumatic lesions or anoxic coma 2. For acute patients: Patients with no response to simple command 48h after sedation's cessation (coma, early vegetative state or MCS "minus") ; for chronic patients : patients without functional communication (including MCS "plus").
- 3. For acute patients: inclusion between 7 days (to reduce the effect of early oedema) and 30 days after the coma (to control the homogeneity of our cohort); for chronic patients: more than 3 months after anoxic coma or more than one year after 4. Patients included between 18 and 75 years old, to limit the risk of care withdrawal for poor previous medical condition 5. Patients evaluated by a global electrophysiological assessment at beside in ICU in a short delay before or after PET-MRI
- Volunteers Healthy subjects:
- Lack of neurological and / or psychiatric history, in particular without a history of head trauma with loss of consciousness lasting more than 30 min;
- Participant between 18 and 75 years old matched in age and sex a posteriori with the patients
- Subjects affiliated (or beneficiaries) to a social security scheme
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- Not subject to a legal protection measure;
- Having given their free and informed consent to participate in the study in writing.
- Subject having agreed to be registered in the national file of people who lend themselves to biomedical research
Who cannot join
- Patients
- Patient with an associated anoxic encephalopathy if the N20 response of SEP are not bilaterally abolished
- Patients with contra-indication to MRI
- Patients with hypersensibility to the active molecules (FDG) or to one of this excipient
- Pregnant women
- Minor patients
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- Patients under legal protection
- Patients not affiliated to French health care system
- Patients in poor medical condition (hemodynamic, respiratory instability)
- Patients moribund or with previous decision of care withdrawal
- Absence of relatives to give written consent
- Volunteers Healthy subjects:
- 1. Subjects benefiting (or having benefited in the last month) from a medicinal treatment for somatic purposes having a cerebral or psychic impact (e.g. antihistamine); 2. Subjects with present or past dependence on alcohol or any other addictive substance according to DSM-IV-TR criteria, with the exception of nicotine and caffeine; 3.Subjects already participating in another biomedical research project or having participated for less than a year in a study using ionizing radiation; 4;Subjects with an inability to understand or carry out the study (language barrier, obvious lack of motivation, etc.) judged by the investigator 5.Minor patient; Patient under guardianship or curatorship; Patient not affiliated with French social security.
- 6.Pregnant woman or woman of childbearing age without proof of the absence of a current pregnancy
Trial locations and contacts
1 site in 1 country.
France1 site
Hôpital Neurologique Pierre Wertheimer
Bron, 69500
FLORENT GOBERT, MD, 0472681296, florent.gobert01@chu-lyon.fr
About this study
Official title: Translational and Multimodal Brain Imaging of the Neural Correlates of Arousal and Awareness During Coma and Post-coma
In last decades, several advances in the neuro-intensive management have lead to decrease mortality in Intensive Care Units. A significant morbidity remains as patients survive after a traumatic coma with uncertain quality of awakening and a high risk of functional disability. Predicting awareness recovery and functional disability of those who will awake constitutes a major challenge to inform patients' relatives, to give the best chances in terms of rehabilitation resources or to adapt intensive cares to a reasonable level. Tools currently available are not sufficient neither to predict bad awakening outcome nor to predict good functional outcome. In many countries, life's support cessation is a constant call for robust evaluation as soon as possible in ICU but it is mandatory to reach a positive predictive value of non-awaking close to 100%. Many clinical, electro-physiological, biological, radiological and functional parameters have been conducted with comatose patients assuming the purpose to predict outcome. Regarding unfavourable outcome, the gold standard is the abolition of the N20 component of somatosensory evoked potentials but the specificity is high enough only for patients with anoxic coma. Several neurophysiological markers such as MMN, P300 are correlated to a favourable outcome but the sensitivity and specificity remains low for patients who suffered a severe traumatic brain injury. New Diffusion Tensor imaging sequences provide complementary information to detect small structural lesions (diffuse axonal lesions). Recently, functional MRI analyzing Resting State has also been proposed as a prognostic marker during coma. PET using Fluoro-Desoxy-Glucose is able to assess the metabolism in key regions of the awakening network in either anaesthesia or sleep. Recent studies have reported interesting results at the chronic stage but to our knowledge, these tools have only been used to address pathophysiology's issues and never to improve coma prognosis at the initial stage. We hypothesize that the heterogeneity of the population requires a global and accurate assessment of the central nervous system, combining structural, metabolic and functional information in order to refine the prognosis.
Our protocol integrates in one-sequence most radiological markers of brain injury within a unique PET-MRI in Lyon. Our most relevant originality consists in confronting FDG-PET and MRI sequences to a large clinical, electrophysiological and biological battery. The added clinical value would be to question the synergistic effect of each parameter and to find out which ones are the most useful for awakening prediction, as they have not been compared in a multi-parametric database.
Read more
PET-MRI, as a new device combining physiological and prognostic questioning, allows us:
- to implement a more integrative physio-pathological analysis
- to avoid the cofounding effect of awareness' fluctuations in recording simultaneously multiple functional imaging techniques.
The RS will be analyzed at 2 epochs in order to assess the stability of brain connectivity, related to neuronal activity (glucose metabolism) and brain perfusion.
The interest of imaging result will be compared across morphological and functional sequences and in comparison, to classical marker (clinical, electrophysiological and behavioural) to build the most precise prognostic tool for acute comatose patients in ICU or diagnostic/prognostic tool for chronic patients in rehabilitation unit.
- Conditions
- Lesional Coma
- Being tested
- Multimodal evaluation of brain function : PET-MRI, electrophysiology, eye-tracking
- Keywords
- coma, prognosis, diagnosis, functional imaging, PET-MRI, electrophysiology, eye-tracking
- Medical subject headings
- Coma, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Multimodal evaluation of brain function : PET-MRI, electrophysiology, eye-trackingOther
After 2 days of sedation withdrawal, each data should be collected within 3 days for organisation purposes :
- After installation and movement management with standardized routine care protocol: 18Fluoro-Desoxy-Glucose's infusion for PET
- Starting PET continuous acquisition
- Morphological MRI sequences
- MRI in Resting state N°1
- MRI DTI acquisition
- IRM in 2D-Arterial Spin Labelling
- IRM in Resting state 2
- End of PET continuous acquisition The day before or the day after PET-MR: standard 20 min EEG, somaesthetic evoked potentials, auditory evoked potentials, mismatch negativity, P300 oddball paradigm, local-global paradigm, P300 after music stimulation, EEG resting state for 10 min, CRS-R repeated before each examination (and at least 5 times for chronic patients), eye-tracking study of the environmental exploration.
| Study group | Role | What they receive |
|---|---|---|
| Comatose or post-comatose patients | Other | Not described Receives: Other: Multimodal evaluation of brain function : PET-MRI, electrophysiology, eye-tracking |
What is being measured
The primary outcome is the main question the study is designed to answer.
Awakening outcome at one year of coma onset
Predictive value of PET-MR multimodal assessment of brain function during early post-comatose period : Building a prognostic tool including miscellaneous parameters (clinical, biological, electrophysiological, metabolic PET and multimodal MRI) for the prediction of an unfavourable outcome (death, vegetative state, minimally conscious state) at 1 year post-coma.
Describing the diagnostic utility of chronic disorder of consciousness classification and a late predictive value compared to the functional outcome at 1-year post-evaluation.
Measured: 12 months
Secondary outcomes (1)
Functional clinical evolution in presence of awareness (ordinal criteria within favorable outcome) defined by the Glasgow Outcome Scale - Extended (> 3, ranking from 4 - severe disability upper - to 8 - good recovery upper).
Building a prognostic tool including miscellaneous parameters (clinical, biological, electrophysiological, metabolic PET and multimodal MRI) for the prediction of cognitive and motor function when awakening appeared.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2020
- Study start15 Nov 2020 (estimated)
- Primary completion15 Nov 2020 (estimated)
- Study completion15 Nov 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lesional ComaStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 85 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- FLORENT GOBERT, MD, Study director, Hospices Civils de Lyon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04575454
- Sponsor's protocol ID
- 69HCL19_0672
- Other IDs
- 2020-A00375-34
- Acronym
- IMAGINA
- Status last verified
- Sep 2020
- First submitted
- 18 Sep 2020
- Last updated
- 3 Nov 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Translational and Multimodal Brain Imaging of the Neural Correlates of Arousal and Awareness During Coma and Post-coma
- ClinicalTrials.gov ID
- NCT04575454
- Acronym / sponsor ID
- IMAGINA / 69HCL19_0672
- Conditions
- Lesional Coma
- Keywords
- coma, prognosis, diagnosis, functional imaging, PET-MRI, electrophysiology, eye-tracking
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 85 participants (estimated)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 15 Nov 2020 (estimated)
- Primary completion
- 15 Nov 2020 (estimated)
- Study completion
- 15 Nov 2025 (estimated)
- First posted
- 5 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In last decades, several advances in the neuro-intensive management have lead to decrease mortality in Intensive Care Units. A significant morbidity remains as patients survive after a traumatic coma with uncertain quality of awakening and a high risk of functional disability. Predicting awareness recovery and functional disability of those who will awake constitutes a major challenge to inform patients' relatives, to give the best chances in terms of rehabilitation resources or to adapt intensive cares to a reasonable level. Tools currently available are not sufficient neither to predict bad awakening outcome nor to predict good functional outcome. In many countries, life's support cessation is a constant call for robust evaluation as soon as possible in ICU but it is mandatory to reach a positive predictive value of non-awaking close to 100%. Many clinical, electro-physiological, biological, radiological and functional parameters have been conducted with comatose patients assuming the purpose to predict outcome. Regarding unfavourable outcome, the gold standard is the abolition of the N20 component of somatosensory evoked potentials but the specificity is high enough only for patients with anoxic coma. Several neurophysiological markers such as MMN, P300 are correlated to a favourable outcome but the sensitivity and specificity remains low for patients who suffered a severe traumatic brain injury. New Diffusion Tensor imaging sequences provide complementary information to detect small structural lesions (diffuse axonal lesions). Recently, functional MRI analyzing Resting State has also been proposed as a prognostic marker during coma. PET using Fluoro-Desoxy-Glucose is able to assess the metabolism in key regions of the awakening network in either anaesthesia or sleep. Recent studies have reported interesting results at the chronic stage but to our knowledge, these tools have only been used to address pathophysiology's issues and never to improve coma prognosis at the initial stage. We hypothesize that the heterogeneity of the population requires a global and accurate assessment of the central nervous system, combining structural, metabolic and functional information in order to refine the prognosis.
Our protocol integrates in one-sequence most radiological markers of brain injury within a unique PET-MRI in Lyon. Our most relevant originality consists in confronting FDG-PET and MRI sequences to a large clinical, electrophysiological and biological battery. The added clinical value would be to question the synergistic effect of each parameter and to find out which ones are the most useful for awakening prediction, as they have not been compared in a multi-parametric database.
PET-MRI, as a new device combining physiological and prognostic questioning, allows us:
- to implement a more integrative physio-pathological analysis
- to avoid the cofounding effect of awareness' fluctuations in recording simultaneously multiple functional imaging techniques.
The RS will be analyzed at 2 epochs in order to assess the stability of brain connectivity, related to neuronal activity (glucose metabolism) and brain perfusion.
The interest of imaging result will be compared across morphological and functional sequences and in comparison, to classical marker (clinical, electrophysiological and behavioural) to build the most precise prognostic tool for acute comatose patients in ICU or diagnostic/prognostic tool for chronic patients in rehabilitation unit.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Comatose or post-comatose patients | Other | Other: Multimodal evaluation of brain function : PET-MRI, electrophysiology, eye-tracking |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients 1 Patients presenting either vascular or traumatic lesions or anoxic coma 2. For acute patients: Patients with no response to simple command 48h after sedation's cessation (coma, early vegetative state or MCS "minus") ; for chronic patients : patients without functional communication (including MCS "plus").
- 3. For acute patients: inclusion between 7 days (to reduce the effect of early oedema) and 30 days after the coma (to control the homogeneity of our cohort); for chronic patients: more than 3 months after anoxic coma or more than one year after 4. Patients included between 18 and 75 years old, to limit the risk of care withdrawal for poor previous medical condition 5. Patients evaluated by a global electrophysiological assessment at beside in ICU in a short delay before or after PET-MRI
- Lack of neurological and / or psychiatric history, in particular without a history of head trauma with loss of consciousness lasting more than 30 min;
- Participant between 18 and 75 years old matched in age and sex a posteriori with the patients
- Subjects affiliated (or beneficiaries) to a social security scheme
Key exclusion criteria (14 listed)
- Patients
- Patient with an associated anoxic encephalopathy if the N20 response of SEP are not bilaterally abolished
- Patients with contra-indication to MRI
- Patients with hypersensibility to the active molecules (FDG) or to one of this excipient
- Pregnant women
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Multimodal evaluation of brain function : PET-MRI, electrophysiology, eye-trackingAfter 2 days of sedation withdrawal, each data should be collected within 3 days for organisation purposes : 1. After installation and movement management with standardized routine care protocol: 18Fluoro-Desoxy-Glucose's infusion for PET 2. Starting PET continuous acquisition 3. Morphological MRI sequences 4. MRI in Resting state N°1 5. MRI DTI acquisition 6. IRM in 2D-Arterial Spin Labelling 7. IRM in Resting state 2 8. End of PET continuous acquisition The day before or the day after PET-MR: standard 20 min EEG, somaesthetic evoked potentials, auditory evoked potentials, mismatch negativity, P300 oddball paradigm, local-global paradigm, P300 after music stimulation, EEG resting state for 10 min, CRS-R repeated before each examination (and at least 5 times for chronic patients), eye-tracking study of the environmental exploration. | Other | Comatose or post-comatose patients |
Primary outcome
Awakening outcome at one year of coma onset
Time frame: 12 months
Predictive value of PET-MR multimodal assessment of brain function during early post-comatose period : Building a prognostic tool including miscellaneous parameters (clinical, biological, electrophysiological, metabolic PET and multimodal MRI) for the prediction of an unfavourable outcome (death, vegetative state, minimally conscious state) at 1 year post-coma. Describing the diagnostic utility of chronic disorder of consciousness classification and a late predictive value compared to the functional outcome at 1-year post-evaluation.
1 secondary outcome
Functional clinical evolution in presence of awareness (ordinal criteria within favorable outcome) defined by the Glasgow Outcome Scale - Extended (> 3, ranking from 4 - severe disability upper - to 8 - good recovery upper).
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2020.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
FLORENT GOBERT, MD study director
Hospices Civils de Lyon
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Multimodal evaluation of brain function : PET-MRI, electrophysiology, eye-tracking in people with Lesional 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 9 inclusion and 14 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: status not confirmed, as of the sponsor's last update on 3 Nov 2020. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact FLORENT GOBERT, MD (0472681296, 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?
Awakening outcome at one year of coma onset (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Nov 2020.