BRAINI-2 Elderly Mild TBI European Study (BRAINI2ELDER)

Blood Biomarkers to Improve Management of Mild Traumatic BRAIN Injury in the Elderly

Mild traumatic brain injury (mTBI) is one of the most frequent emergencies in the elderly population. Despite most mTBI are managed with cranial computed tomography (CT), only 10% of CTs show lesions, determining CT overuse. The use of serum glial fibrillary acidic protein (GFAP) and Ubiquitin C-terminal Hydrolase-L1 (UCH-L1) have shown potential for ruling out the need for cranial CT. However evidence on biomarker use in mild TBI were not based on studies that included aged participants and patients with comorbidities for which biomarker levels could vary. This is why there is a need for a prospective study that assesses the predictive performance of these two biomarkers in the elderly population, both in elderly patients suffering mild TBI and in a reference population, including patients and participants with and without comorbidities.

Study Overview

• Status: Completed
• Conditions: Mild Traumatic Brain Injury
• Intervention / Treatment: Diagnostic test: GFAP and UCH-L1

• Study Type: Observational
• Enrollment (Actual): 2297

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France
    • CHU Clermont-Ferrand
  • Grenoble, France
    • CHU Grenoble-Alpes
  • Lyon, France
    • Hôpital Edouard Herriot
  • Lyon, France
    • Hôpital Lyon Sud HCL
• Germany
  • Munich, Germany
    • Klinikum rechts der Isar
• Spain
  • Barcelona, Spain
    • Hospital Universitari Vall d'Hebron
  • Madrid
    • Madrid, Madrid, Spain, 28041
      • Hospital Universitario 12 de Octubre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

2370 participants suffering mild TBI; 480 non TBI participants.

Description

Inclusion Criteria:

• BRAINI2-ELDERLY DIAGNOSTIC & PROGNOSTIC:

  • Patients ≥65 years of age
  • Mild TBI (GCS 13-15 on admission) with indication of brain CT scan in the 12 hours after injury ;
  • Blood sample obtained ≤12 h after injury and CT scan preferably ≤6h from blood sample.

• BRAINI2-ELDERLY REFERENCE:

  • Non TBI patients ≥65 years of age

Exclusion Criteria:

• BRAINI2-ELDERLY DIAGNOSTIC & PROGNOSTIC:

  • Age below 65 years.
  • GCS 3-12 on admission
  • Time of injury unknown
  • Time to injury exceeding 12 hours
  • Primary admission for non-traumatic neurological disorder (e.g., stroke, spontaneous, intracranial hematoma)
  • Penetrating head trauma
  • Patient with mechanical ventilation from the trauma scene or prehospital management.
  • Venipuncture not feasible
  • No realization of brain CT-scan
  • Subject under judiciary control
  • Subject in inclusion period of a drug interventional study

• BRAINI2-ELDERLY REFERENCE:

  • Subject in inclusion period of another drug interventional study
  • Patients harboring a brain tumor
  • Patients that have had a stroke or neurosurgical operation 1 month prior to the inclusion in the study.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
BRAINI2-ELDERLY DIAGNOSTIC & PROGNOSTIC; 2370 patients suffering mild Traumatic brain injury	Diagnostic test: GFAP and UCH-L1; 2x5mL blood samples will be used to determine the performance of the automated VIDAS TBI platform in assessing serum concentrations of GFAP and UCH-L1 to rule out the need for a CT-scan after mTBI.
BRAINI2-ELDERLY REFERENCE; 480 non-tbi elderly reference patients	Diagnostic test: GFAP and UCH-L1; 2x5mL blood samples will be used to determine the performance of the automated VIDAS TBI platform in assessing serum concentrations of GFAP and UCH-L1 to rule out the need for a CT-scan after mTBI.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers diagnostic performance	Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of GFAP and UCHL-1 used separately and in combination to detect the presence or absence of intracranial lesions on CT scan	12 hours after mild TBI

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determination of the potential of the two biomarkers in predicting neurological symptoms after TBI	Early and midterm biomarker predictive performance in terms of predicting neurological outcome. Neurological status at 1 week and 3 months after TBI and Rivermead post concussion questionnaire.	1 week and 3 months
GFAP reference values	GFAP serum level distribution in the non-TBI reference population, considering age and comorbidities.	1 Day, day of extraction of the sample
UCHL-1 reference values	UCHL-1 serum level distribution in the non-TBI reference population, considering age and comorbidities.	1 Day, day of extraction of the sample
Determination of the potential of the two biomarkers in predicting neurological outcome assessed by the Extended Glasgow Outcome Score (GOSE) after TBI	Early and midterm biomarker predictive performance in terms of predicting neurological outcome. Extended Glasgow Outcome Score (GOSE)	1 week and 3 months
Determination of the potential of the two biomarkers in predicting quality of life assessed by Qolibri-OS after TBI	Early and midterm biomarker predictive performance in terms of predicting quality of life after mild TBI assessed by Qolibri-OS	1 week and 3 months
Determination of the potential of the two biomarkers in predicting quality of life assessed by EQ-5D-5L after TBI	Midterm biomarker predictive performance in terms of predicting quality of life after mild TBI assessed by EQ-5D-5L	3 months
Determination of the potential of the two biomarkers in depression symptoms assessed by PHQ-9 after TBI	Midterm biomarker predictive performance in terms of predicting depression symptoms after mild TBI assessed by PHQ-9	3 months

Collaborators and Investigators

• Sponsor: Hospital Universitario 12 de Octubre
• Collaborators: University Hospital, Clermont-Ferrand; University Hospital, Grenoble; Technical University of Munich; Hospital Vall d'Hebron; BioMérieux; EIT Health
• Investigators: Principal Investigator: Alfonso Lagares Gómez-Abascal, MD, PhD, Hospital Universitario 12 de Octubre

Publications and helpful links

General Publications

• Lagares A, Payen JF, Biberthaler P, Poca MA, Mejan O, Pavlov V, Viglino D, Sapin V, Lassaletta A, de la Cruz J; Braini2_elderly_investigators Collaborative group. Study protocol for investigating the clinical performance of an automated blood test for glial fibrillary acidic protein and ubiquitin carboxy-terminal hydrolase L1 blood concentrations in elderly patients with mild traumatic BRAIN Injury and reference values (BRAINI-2 Elderly European study): a prospective multicentre observational study. BMJ Open. 2023 Jul 17;13(7):e071467. doi: 10.1136/bmjopen-2022-071467.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2022
• Primary Completion (Actual): December 31, 2024
• Study Completion (Actual): March 30, 2025

Study Registration Dates

• First Submitted: March 11, 2022
• First Submitted That Met QC Criteria: June 15, 2022
• First Posted (Actual): June 21, 2022

Study Record Updates

• Last Update Posted (Actual): December 29, 2025
• Last Update Submitted That Met QC Criteria: December 21, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Injuries, Traumatic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds, Nonpenetrating; Brain Injuries; Brain Concussion
• Other Study ID Numbers: HU 12Octubre; EIT-HEALTH 220325 (Other Grant/Funding Number: European Institute of Innovation and Technology - EU co-fund)

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
• product manufactured in and exported from the U.S.: No