Brain Network Disruptions Related to Traumatic Coma (Coma3D)

August 22, 2023 updated by: University Hospital, Toulouse

Whole Brain Connectivity Changes Induced by Traumatic Coma: Combined Structural, Functional and Neuroinflammatory Approaches

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

59

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Toulouse, France, 31059
        • CHU Purpan - Réanimation URM

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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
Other: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
First Visit, within three days after day 0

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Inclusion
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 months +/- 3 days after the primary brain insult
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
3 months +/- 3 days after the primary brain insult
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
First Visit, within three days after day 0

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Toulouse

Investigators

  • Principal Investigator: Stein SILVA, MD, PhD, University Hospital, Toulouse

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 7, 2018

Primary Completion (Actual)

November 7, 2021

Study Completion (Actual)

February 7, 2022

Study Registration Dates

First Submitted

February 8, 2018

First Submitted That Met QC Criteria

March 27, 2018

First Posted (Actual)

March 29, 2018

Study Record Updates

Last Update Posted (Actual)

August 23, 2023

Last Update Submitted That Met QC Criteria

August 22, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RC31/16/8257
  • 2017-001986-26 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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