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Brain Network Disruptions Related to Traumatic Coma (Coma3D)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03482115
Recruitment Status : Unknown
Verified March 2018 by University Hospital, Toulouse.
Recruitment status was:  Recruiting
First Posted : March 29, 2018
Last Update Posted : March 29, 2018
Sponsor:
Information provided by (Responsible Party):
University Hospital, Toulouse

Brief Summary:
To provide a fine-grained description of the brain network dysfunctions induced by severe traumatic brain injury (TBI) or anoxic encephalopathy, that are responsible for the acute state of unarousable unawareness, named coma, this trial wants to explore the usefulness in this setting of a combined neuroimaging approaches encompassing several up-to-date techniques as structural MRI, fMRI and positron emission tomography (PET) scan (neuroinflammation ligands).

Condition or disease Intervention/treatment Phase
Traumatic Coma Radiation: PET examination with radiopharmaceutical drug [18F] DPA-714 Diagnostic Test: MRI examination Biological: Blood samples Not Applicable

Detailed Description:
So far, the gold standard for neuroprognostication of severe traumatic brain injury (TBI) or anoxic encephalopathy is the bedside behavioural evaluation. Nevertheless, the predictive value of such an exclusive clinical approach has been consistently reported as limited and insufficient in this challenging clinical setting. Recent theoretical and experimental data converge towards the idea of the critical implication of long-range brain connection in consciousness access and maintain. Nevertheless, previous studies have focused on the specific analysis of some targeted connections (regions of interest), and have used exclusively a single approach in neuroimaging (structural or functional imaging), with no interest in the neuro-inflammatory and neurodegenerative mechanisms likely associated with these disconnection phenomena. So, cerebral disconnection characterization at the level of the whole brain, at different stages of pathological abolition of consciousness must be made, on an anatomical, functional and metabolic scale. This descriptive study represents a first step in the identification of relevant multimodal imaging biomarkers. This will then lead to a larger study to identify the prognostic impact of these different biomarkers obtained in the acute phase of patient management.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Whole Brain Connectivity Changes Induced by Traumatic Coma: Combined Structural, Functional and Neuroinflammatory Approaches
Actual Study Start Date : March 7, 2018
Estimated Primary Completion Date : November 7, 2019
Estimated Study Completion Date : February 7, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Coma

Arm Intervention/treatment
Experimental: Comatose patient
Subject with coma of traumatic or anoxic aetiology : PET examination with radiopharmaceutical drug [18F] DPA-714, MRI examination and Blood samples.
Radiation: PET examination with radiopharmaceutical drug [18F] DPA-714
Using a Biograph 6 Truepoint device. Establishment of a venous route. It will be injected 4 MBq / kg of 18F-DPA714 by the venous route with a maximum dose of 280 MBq. The patient will be placed along the orbito-meatal line. Brain acquisition will begin 60 minutes post-injection

Diagnostic Test: MRI examination
MRI device Philips Achieva - 3Tesla. The acquisition of the data will include different sequences (anatomical MRI, diffusion MRI, resting fMRI) and will last a total of one hour (installation and removal of the patient in the machine included).anatomical MRI associated with FLAIR (Fluid Attenuation Inversion Recovery) and diffusion tensor (tractography).

Biological: Blood samples
Characterization of the TSPO phenotype (mitochondrial translocase) for tracer affinity

control volunteers
subject control : PET examination with radiopharmaceutical drug [18F] DPA-714, MRI examination and Blood samples.
Radiation: PET examination with radiopharmaceutical drug [18F] DPA-714
Using a Biograph 6 Truepoint device. Establishment of a venous route. It will be injected 4 MBq / kg of 18F-DPA714 by the venous route with a maximum dose of 280 MBq. The patient will be placed along the orbito-meatal line. Brain acquisition will begin 60 minutes post-injection

Diagnostic Test: MRI examination
MRI device Philips Achieva - 3Tesla. The acquisition of the data will include different sequences (anatomical MRI, diffusion MRI, resting fMRI) and will last a total of one hour (installation and removal of the patient in the machine included).anatomical MRI associated with FLAIR (Fluid Attenuation Inversion Recovery) and diffusion tensor (tractography).

Biological: Blood samples
Characterization of the TSPO phenotype (mitochondrial translocase) for tracer affinity




Primary Outcome Measures :
  1. Matrix of the neuroimaging data in PET examination [ Time Frame: First Visit, within three days after day 0 ]
    neuroinflammation by [18F] DPA-714 during PET imaging


Secondary Outcome Measures :
  1. Glasgow Coma Scale (GCS) [ Time Frame: Inclusion ]

    The Glasgow Coma Scale is divided into three components : ocular response (assessment 1-4 points), motor response (assessment 1-6 points) verbal response (evaluation of 1-5 points).

    Scores for each component are added together to get the total that will range between a minimum of 3 points (which corresponds to a patient who does not open his eyes and no motor response to stimulation or verbal response) and a maximum value of 15 points (corresponding to a patient with open eyes, obeying orders and maintaining a consistent language).

    It has been considered that the GCS score between 15 and 13 points corresponds to a slight alteration of consciousness, a score of 12-9 points with moderate impairment and 8 points or less with a serious deterioration in level of consciousness.


  2. Coma Recovery Scale Revised (CRS-R) [ Time Frame: 3 months +/- 3 days after the primary brain insult ]

    The Coma Recovery Scale Revised is divided into three components : return to consciousness (RECUP), vegetative neurological state (ENV) or minimal state of consciousness (ECM).

    This scale has been validated in French, with a value of Cronbach's Alpha estimated at 0.8.

    It is a score whose values are between 100 (normal level of consciousness) and 10 (coma). ENV and ECM have intermediate values (approximately 30 and 60, respectively).


  3. FOUR score [ Time Frame: 3 months +/- 3 days after the primary brain insult ]
    The FOUR score is a scale of 4 items and 16 points concerning qualitative behavioural assessment

  4. analysis of imaging parameters obtained in MRI [ Time Frame: First Visit, within three days after day 0 ]
    assessing the strength of connectivity between different regions for the whole brain, measurement of anatomical connectivity, measurement of cortical thickness. All this measure use voxel/volume unit of the brain



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion criteria for patients:

  • Male or female / age between 18 to 75 years.
  • Coma of traumatic or anoxic aetiology (GCS < 10).
  • Early (< 1 month after TBI) and after the complete withdrawal of sedative agents.
  • Written agreement for participation (legal responsible).

Inclusion criteria for controls:

  • Male or female / age between 18 to 75 years, paired with patients (gender and age).
  • Written agreement for participation

Exclusion criteria:

  • Patients without public insurance regime.
  • Pregnancy.
  • Specific contraindication to the use of MRI (metallic material) or PET (specific allergy related to the ligand).

Exclusion criteria for controls:

- pharmacological treatments which could interfere with consciousness (left to the judgement of the investigator)


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03482115


Contacts
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Contact: Stein SILVA, MD, PhD 5 61 77 97 28 ext 33 silva.s@chu-toulouse.fr

Locations
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France
CHU Purpan - Réanimation URM Recruiting
Toulouse, France, 31059
Contact: Stein SILVA, MD, PhD         
Sponsors and Collaborators
University Hospital, Toulouse
Investigators
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Principal Investigator: Stein SILVA, MD, PhD University Hospital, Toulouse

Publications:
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Responsible Party: University Hospital, Toulouse
ClinicalTrials.gov Identifier: NCT03482115    
Other Study ID Numbers: RC31/16/8257
2017-001986-26 ( EudraCT Number )
First Posted: March 29, 2018    Key Record Dates
Last Update Posted: March 29, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Toulouse:
coma
traumatic brain injury
anoxic encephalopathy
brain connectome
neuroinflammation
prognosis
Additional relevant MeSH terms:
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Coma
Coma, Post-Head Injury
Unconsciousness
Consciousness Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
Radiopharmaceuticals
Molecular Mechanisms of Pharmacological Action