Brain Network Disruptions Related to Traumatic Coma

NCT03482115 | Completed

• 2 other identifiers: RC31/16/82572017-001986-26
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

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).

Conditions

Traumatic Coma

Keywords

coma; traumatic brain injury; anoxic encephalopathy; brain connectome; neuroinflammation; prognosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Glasgow Coma Scale (GCS)

  Inclusion

• Coma Recovery Scale Revised (CRS-R)

  3 months +/- 3 days after the primary brain insult

• FOUR score

  3 months +/- 3 days after the primary brain insult

• analysis of imaging parameters obtained in MRI

  First Visit, within three days after day 0

Study Arms (2)

Comatose patient

EXPERIMENTAL

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; Diagnostic Test: MRI examination; Biological: Blood samples

control volunteers

OTHER

subject control : PET examination with radiopharmaceutical drug \[18F\] DPA-714, MRI examination and Blood samples.

Radiation: PET examination with radiopharmaceutical drug [18F] DPA-714; Diagnostic Test: MRI examination; Biological: Blood samples

Interventions

PET examination with radiopharmaceutical drug [18F] DPA-714 RADIATION

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

Comatose patient; control volunteers

MRI examination DIAGNOSTIC_TEST

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).

Comatose patient; control volunteers

Blood samples BIOLOGICAL

Characterization of the TSPO phenotype (mitochondrial translocase) for tracer affinity

Comatose patient; control volunteers

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Patients without public insurance regime.
• Pregnancy.
• Specific contraindication to the use of MRI (metallic material) or PET (specific allergy related to the ligand).
• \- pharmacological treatments which could interfere with consciousness (left to the judgement of the investigator)

Sponsors & Collaborators

• University Hospital, Toulouse: lead

Study Sites (1)

Hospital

Toulouse, 31059, France

Location

Related Publications (7)

• 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.

  PMID: 15324722 BACKGROUND

• 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.

  PMID: 19954851 BACKGROUND

• 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.

  PMID: 26561296 BACKGROUND

• 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.

  PMID: 19223401 BACKGROUND

• 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.

  PMID: 22172392 BACKGROUND

• 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 neurological outcome in anoxic and traumatic coma. Brain. 2024 Apr 4;147(4):1321-1330. doi: 10.1093/brain/awae045.

  PMID: 38412555 RESULT

• Mattia GM, Sarton B, Villain E, Vinour H, Ferre F, Buffieres W, Le Lann MV, Franceries X, Peran P, Silva S. Multimodal MRI-Based Whole-Brain Assessment in Patients In Anoxoischemic Coma by Using 3D Convolutional Neural Networks. Neurocrit Care. 2022 Aug;37(Suppl 2):303-312. doi: 10.1007/s12028-022-01525-z. Epub 2022 Jul 25.

  PMID: 35876960 DERIVED

MeSH Terms

Conditions

Coma, Post-Head Injury; Coma; Brain Injuries, Traumatic; Hypoxia, Brain; Neuroinflammatory Diseases

Interventions

N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Unconsciousness; Consciousness Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Brain Injuries; Brain Diseases; Central Nervous System Diseases; Hypoxia; Signs and Symptoms, Respiratory; Inflammation; Pathologic Processes

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Stein SILVA, MD, PhD

  University Hospital, Toulouse

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2018
• First Posted: March 29, 2018
• Study Start: March 7, 2018
• Primary Completion: November 7, 2021
• Study Completion: February 7, 2022
• Last Updated: May 31, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)