Brain Network Disruptions Related to Traumatic Coma

Traumatic Coma Clinical Trial

— Coma3D  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03482115
• Other study ID #: RC31/16/8257
• Secondary ID: 2017-001986-26
• Status: Completed
• Phase: N/A
• Start date: March 7, 2018
• Est. completion date: February 7, 2022

Study information

• Verified date: May 2024
• Source: University Hospital, Toulouse
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: February 7, 2022
• Est. primary completion date: November 7, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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)

Related Conditions & MeSH terms

• Coma
• Traumatic Coma

Intervention

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

Locations

Country	Name	City	State
France	Hospital	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Toulouse

Country where clinical trial is conducted

France, 

References & Publications (6)

Arlicot N, Vercouillie J, Ribeiro MJ, Tauber C, Venel Y, Baulieu JL, Maia S, Corcia P, Stabin MG, Reynolds A, Kassiou M, Guilloteau D. Initial evaluation in healthy humans of [18F]DPA-714, a potential PET biomarker for neuroinflammation. Nucl Med Biol. 2012 May;39(4):570-8. doi: 10.1016/j.nucmedbio.2011.10.012. Epub 2011 Dec 14. — View Citation

Chauveau F, Van Camp N, Dolle F, Kuhnast B, Hinnen F, Damont A, Boutin H, James M, Kassiou M, Tavitian B. Comparative evaluation of the translocator protein radioligands 11C-DPA-713, 18F-DPA-714, and 11C-PK11195 in a rat model of acute neuroinflammation. J Nucl Med. 2009 Mar;50(3):468-76. doi: 10.2967/jnumed.108.058669. Epub 2009 Feb 17. — View Citation

Laureys S, Owen AM, Schiff ND. Brain function in coma, vegetative state, and related disorders. Lancet Neurol. 2004 Sep;3(9):537-46. doi: 10.1016/S1474-4422(04)00852-X. — View Citation

Sarton B, Tauber C, Fridman E, Peran P, Riu B, Vinour H, David A, Geeraerts T, Bounes F, Minville V, Delmas C, Salabert AS, Albucher JF, Bataille B, Olivot JM, Cariou A, Naccache L, Payoux P, Schiff N, Silva S. Neuroimmune activation is associated with ne — View Citation

Schiff ND. Recovery of consciousness after brain injury: a mesocircuit hypothesis. Trends Neurosci. 2010 Jan;33(1):1-9. doi: 10.1016/j.tins.2009.11.002. Epub 2009 Dec 1. — View Citation

Silva S, de Pasquale F, Vuillaume C, Riu B, Loubinoux I, Geeraerts T, Seguin T, Bounes V, Fourcade O, Demonet JF, Peran P. Disruption of posteromedial large-scale neural communication predicts recovery from coma. Neurology. 2015 Dec 8;85(23):2036-44. doi: 10.1212/WNL.0000000000002196. Epub 2015 Nov 11. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Matrix of the neuroimaging data in PET examination	neuroinflammation by [18F] DPA-714 during PET imaging	First Visit, within three days after day 0
Secondary	Glasgow Coma Scale (GCS)	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
Secondary	Coma Recovery Scale Revised (CRS-R)	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
Secondary	FOUR score	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
Secondary	analysis of imaging parameters obtained in MRI	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