Identification of Predictive Neuroinflammatory Biomarkers of Neuro-radiological Evolution in Severe Traumatic Brain Injury (ICON-TBI)

Tertiary lesions responsible of the neurological decline after severe traumatic brain injury (TBI) are partially due to a persistent neuro-inflammation directly modulated by inflammatory mediators during the acute phase and detectable by using both multimodal MRI imaging and biological biomarkers during the acute phase after traumatic brain injury.

The main objective is to identify if the level of IL-1beta in cerebrospinal fluid predict in a reliable and reproducible way, the neuro-radiological evolution evaluated by the comparison of a quantitative MRI performed in post-resuscitation and at one year (quantitative ΔIRM) in traumatic brain injuried patients.

The secondary objectives are:

• To understand the links between the acute and chronic neuro-inflammatory phase in a population of TBI,
• To explore the contribution of the adaptive immune response in the persistent activation of the immune response,
• To Examine the links between persistent neuroinflammation, clinical deterioration and neuroimaging,
• To establish a correlation between the pathology and the physio-pathology of TBI.

Study Overview

• Status: Unknown
• Conditions: Severe Traumatic Brain Injury
• Intervention / Treatment: Biological: Biological Collection

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Paris, France, 75013
    • Recruiting
    • Anesthesy department - Hôpital Pitié Salpêtrière
    • Contact: DEGOS Vincent, MD; Phone Number: 0142163761; Email: vincent.degos@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. patient ≥ 18 years old at the time of inclusion
2. Written and informed consent obtained from the family / proxy
3. Patient hospitalized in neuro-ICU following severe TBI with GCS ≤ 8 at admission
4. Intubated / ventilated patient scheduled for external ventricular bypass within 24 hours of hospitalization
5. Absence of contraindications to perform an MRI
6. Patient affiliated to a social security scheme (free State medical aid excluded)

Exclusion Criteria:

1. Patient under protection of the law (guardianship or tutorship)
2. TBI of ballistic origin
3. Pregnant woman
4. Pre-existing cerebral disease that can bias the MRI scan evaluation
5. Contraindications to the MRI (pace maker, medical device incompatible with MRI, metal plates, ...)
6. Patient with severe impairment of vital and / or life-threatening function with disability prior TBI
7. Neurological antecedent susceptible to interfere with clinical evolution at one year
8. Severe cardiogenic shock
9. Severe respiratory impairment
10. Extra-brain injuries involving immediate life-threatening
11. Hemoglobin level below 9g / dL

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Biological Collection; Blood sampling on catheter and CSF sampling from VDE, multimodal MRI at D42 and D365, Neurological and neuropsychological evaluation at one year	Biological: Biological Collection; Blood sampling on catheter and CSF sampling from VDE, multimodal MRI at D42 and D365, Neurological and neuropsychological evaluation at one year

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Interleukin-1 level in blood predict changes in brain volume assessed by quantitative MRI.	Brain volume evolution assessed by quantitative MRI between Day 42 and Day 365	Day 42 and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentrations of biomarkers such as Tau protein and beta-amyloid plaques in serum and cerebrospinal fluid (Aβ1-42, T-tau, and P-tau181P and Interleukin 1)	Plasma and Serum biological collection, multimodal MRI database, clinical database	Blood and CSF samples collected at Day1, Day2, Day3, Day5 and Day7

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Hopital Universitaire Robert-Debre; University of Cambridge; Mario Negri Institute for Pharmacological Research
• Investigators: Principal Investigator: Vincent Degos, PU-PH, Assistance Publique - Hopitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2018
• Primary Completion (Anticipated): July 30, 2020
• Study Completion (Anticipated): July 30, 2020

Study Registration Dates

• First Submitted: July 9, 2018
• First Submitted That Met QC Criteria: September 3, 2018
• First Posted (Actual): September 6, 2018

Study Record Updates

• Last Update Posted (Actual): October 23, 2018
• Last Update Submitted That Met QC Criteria: October 22, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: inflammatory Biomarkers, Traumatic brain injury, multimodal MRI, tertiary lesion
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Wounds and Injuries; Brain Injuries, Traumatic
• Other Study ID Numbers: K171201J

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