Usefulness of Biomarkers in the Management of Mild Traumatic Brain Injury in Adults (Biotraumap) (Biotraumap)

Usefulness of Biomarkers in the Management of Mild Traumatic Brain Injury in Adults

The indication of cranial computed tomography (CCT) is difficult to define for patients with mild traumatic brain injury (mTBI). For mTBI patients with a medium risk of intracranial complications, CCT scans are indicated although 90% of them are normal.

The interest of the S100B protein has been widely demonstrated in the management of mTBI in adults. Its serum concentration (for blood sampling drawn less than 3 hours after trauma) can accurately predict a normal CCT scan for mTBI patients with a medium risk of intracranial complications. That's why, serum assay of the S100B protein is routinely used in the Emergency Department of Clermont-Ferrand University Hospital for the treatment of patients with mTBI.

The objective of the study is to optimize the management strategy for mTBI patients by blood testing of new brain biomarkers. These biomarkers are synthesized by brain cells and are released into the blood in case of intracranial lesions.

Study Overview

• Status: Unknown
• Conditions: Traumatic Brain Injury; Intracranial Injury

Detailed Description

Other biomarkers of brain damage, involved in the pathophysiology of head trauma, are also known. These are, for example, GFAP (Glial Fibrillary Acidic Protein), UCH-L1 (Ubiquitine Carboxy Terminal Hydrolase L1), NSE (Neurone Specific Enolase), Tau, SBDP (Spectrin Breakdown Products) or NFL (Neurofilament) protein. To date, the too limited number of studies doesn't enable the use of these biomarkers routinely. Therefore we will study the interest of these biomarkers in the management of adult patients' mTBI. We wish to set a collection of biological samples drawn from 1500 patients consulting for mTBI (with a medium risk of intracranial complications) at the Emergency Department of Clermont-Ferrand University Hospital, and requiring an assay of the S100B protein.

The study will take place over a period of 36 months at Clermont-Ferrand University Hospital. Patients cared for mTBI when they come to the Emergency Department will be recruited according to the inclusion criteria. In case of no opposition, when having their blood drawn, one more tube will be drawn per patient. Then, the obtained serum will be frozen at -80 ° C for the next assays of the cerebral biomarkers such as: GFAP, UCH-L1, NSE, Tau, SBDP, NFL, etc. A later 2-weeks' telephone call after the head trauma will be made by a member of the staff of the Department of Biochemistry and Molecular Genetics.

• Study Type: Observational
• Enrollment (Anticipated): 1500

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France, 63000
    • Recruiting
    • CHU Clermont-Ferrand
    • Contact: Damien Bouvier; Email: dbouvier@chu-clermontferrand.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

• Sampling Method: Non-Probability Sample

Study Population

Patients with mild Traumatic Brain Injury

Description

Inclusion Criteria:

• Male and female patient, major
• Patient admitted to the Emergency Department for mTBI, with a medium risk of intracranial lesions according to the SFMU (French Emergency Medicine Society) criteria, for which an S100B protein assay is indicated:
• GCS score of 15 with at least one associated risk factor: amnesia facts more than 30 minutes before the mTBI loss of consciousness, anti platelet aggregating agent
• Time between mTBI and blood draw (for the S100B protein assay) less than 3 hours.
• Patient covered by a Social Security scheme.

Exclusion Criteria:

• Patient classified in the high risk group of intracranial lesions according to SFMU criteria :
• GCS score less than 15, 2 hours after the trauma
• Focused neurological deficit
• Post-traumatic convulsion
• Suspicion of open fracture of the skull or embarrassment
• Any sign of fracture of the base of the skull (hemotympanum, bilateral periorbital bruise, otorrhea or rhinorrhea of cerebrospinal fluid)
• Treatment with anticoagulants
• More than one episode of vomiting.
• Patient classified in the group at low risk of intracranial lesions according to the SFMU criteria, presenting a GCS score of 15 without any criteria for moderate or high risk groups of intracranial lesions.
• Patient consulting for moderate or severe head trauma (GCS score less than 13).
• Refusal of the patient (signature of the opposition form).

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
patients with Mild Traumatic Brain Injury

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic value of cerebral biomarkers GFAP	Evaluate the diagnostic value of cerebral biomarkers GFAP (ng/L)	Day 0
Diagnostic value of cerebral biomarkers UCH-L1	Evaluate the diagnostic value of cerebral biomarkers UCH-L1 (ng/L)	Day 0
Diagnostic value of cerebral biomarkers NSE	Evaluate the diagnostic value of cerebral biomarkers NSE (µg/L)	Day 0
Diagnostic value of cerebral biomarkers Tau	Evaluate the diagnostic value of cerebral biomarkers TAU (ng/L)	Day 0
Diagnostic value of cerebral biomarkers SBDP	Evaluate the diagnostic value of cerebral biomarkers SBDP (µg/L)	Day 0
Diagnostic value of cerebral biomarkers NFL	Evaluate the diagnostic value of cerebral biomarkers NFL (ng/L)	Day 0

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Utility of serum biomarker measurement with respect to reduction of the cost of management	Calculate this cost reduction compared to the cost of a cerebral tomodensitometry	Day 0
Risk factors (antiplatelet agent) on biomarker results	Collect information from medical records and assess the impact on biomarker results from statistical tests	Day 0
risk factors (loss of consciousness) on biomarker results	Collect information from medical records and assess the impact on biomarker results from statistical tests	Day 0
risk factors (amnesia) on biomarker results	Collect information from medical records and assess the impact on biomarker results from statistical tests	Day 0

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand

Publications and helpful links

General Publications

• Allouchery G, Moustafa F, Roubin J, Pereira B, Schmidt J, Raconnat J, Pic D, Sapin V, Bouvier D. Clinical validation of S100B in the management of a mild traumatic brain injury: issues from an interventional cohort of 1449 adult patients. Clin Chem Lab Med. 2018 Oct 25;56(11):1897-1904. doi: 10.1515/cclm-2018-0471.
• Biberthaler P, Linsenmeier U, Pfeifer KJ, Kroetz M, Mussack T, Kanz KG, Hoecherl EF, Jonas F, Marzi I, Leucht P, Jochum M, Mutschler W. Serum S-100B concentration provides additional information fot the indication of computed tomography in patients after minor head injury: a prospective multicenter study. Shock. 2006 May;25(5):446-53. doi: 10.1097/01.shk.0000209534.61058.35.
• Bouvier D, Oddoze C, Ben Haim D, Moustafa F, Legrand A, Alazia M, Jehle E, Schmidt J, Sapin V. [Interest of S100B protein blood level determination for the management of patients with minor head trauma]. Ann Biol Clin (Paris). 2009 Jul-Aug;67(4):425-31. doi: 10.1684/abc.2009.0347. French.
• Calcagnile O, Unden L, Unden J. Clinical validation of S100B use in management of mild head injury. BMC Emerg Med. 2012 Oct 27;12:13. doi: 10.1186/1471-227X-12-13.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 2, 2019
• Primary Completion (ANTICIPATED): October 1, 2022
• Study Completion (ANTICIPATED): February 1, 2023

Study Registration Dates

• First Submitted: September 26, 2019
• First Submitted That Met QC Criteria: September 8, 2020
• First Posted (ACTUAL): September 10, 2020

Study Record Updates

• Last Update Posted (ACTUAL): September 10, 2020
• Last Update Submitted That Met QC Criteria: September 8, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Mild Traumatic Brain Injury; S100B; Brain biomarkers; Glasgow Coma Scale (GCS) score of 15; Cerebral biomarkers; Intracranial lesions
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds, Nonpenetrating; Brain Injuries; Wounds and Injuries; Brain Injuries, Traumatic; Brain Concussion
• Other Study ID Numbers: RNI 2019 BOUVIER (Biotraumap); 2019-A01228-49 (OTHER: ANSM)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No