Salivary Biomarkers for Concussion (SportCo)

Determination of the Physiological Profile and Evaluation of the Effect of Intense Physical Exertion Among Professional Athletes

Concussion (CC) (also called mild head trauma), which accounts for 85% of all head injuries, is very common in professional and amateur athletes. CC is an injury to the brain resulting from the direct or indirect impact of external mechanical forces, momentarily disrupting its function on a cellular level. Unlike more serious head injury (moderate and severe), which can be diagnosed using neuroimaging techniques (CT, MRI, etc.), patients suffering from CC do not necessarily show visible signs of structural abnormalities. As a result, diagnosis of CC is offen difficult.

Recently, several salivary biomarkers (proteins and nucleic acids) of sport related concussion have been identified in professional athletes. However, their reference values have not been determined with sufficient robustness to enable their employment in concussion diagnostic tests.

Study Overview

• Status: Recruiting
• Conditions: Sport Related Concussion
• Intervention / Treatment: Diagnostic test: Bio-fluid analysis for the implementation of a diagnostic test for sport related concussion

Detailed Description

Concussion (CC) (also called mild head trauma), which accounts for 85% of all head injuries, is very common in professional and amateur athletes. CC is an injury to the brain resulting from the direct or indirect impact of external mechanical forces, momentarily disrupting its function on a cellular level. Unlike more serious head injury (moderate and severe), which can be diagnosed using neuroimaging techniques (CT, MRI, etc.), patients suffering from CC do not necessarily show visible signs of structural abnormalities. As a result, diagnosis of CC is offen difficult. It is essentially based on subjective observational criteria and on the determination of the Glasgow Coma Scale (GCS) score, a score of 13 to 15 indicating potential CC. In approximately 15% of cases, symptoms such as momentary loss of consciousness (less than 30 minutes), amnesia lasting less than 24 hours, neurological deficit, or convulsions can be used to make a diagnosis. In the majority of cases, concussion goes undetected and no specific treatment or rehabilitation is put in place.

Recently, certain molecular biomarkers (BMs) of CC in elite athletes have been identified (Di Pietro et al. 2021; McCrea et al. 2020). However, the reference values of these BMs are not determined with sufficient robustness to enable the best use for concussion diagnostic tests.

To detect these biomarkers, it is first necessary to determine their physiological profiles as well as the changes in intensity associated with intense physical efforts during training session and/or matches.

• Study Type: Observational
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Wendpouiré A OUEDRAOGO, Msc; Phone Number: +33 (0) 467 047 481; Email: alimata.ouedraogo@sys2diag.cnrs.fr

Study Locations

• France
  • Montpellier, France, 34184
    • Recruiting
    • Sys2Diag - Umr9005 Cnrs/Alcen
    • Contact: Franck MOLINA, Phd; Phone Number: +33 (0) 467 047 460; Email: s2d.cpp@sys2diag.cnrs.fr
    • Contact: Wendpouiré A OUEDRAOGO, Msc; Phone Number: +33 (0) 467 047 481; Email: s2d.cpp@sys2diag.cnrs.fr
    • Principal Investigator: Thi Nhu Ngoc VAN, Phd
    • Sub-Investigator: Malik KAHLI, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

A total of 80 subjects will be recruited:

• 30 professional sport subject, playing in the professional team of the Montpellier HandBall club (MHB) or the Montpellier Hérault Rugby (MHR) - BRAS S-P.
• 30 leisure sport subjects with moderate physical activity playing in the leisure team of clubs associated with the Montpellier Handball (MHB) or the Rugby Club Méditerranée (RCM) or even to the clubs associated with the Montpellier Handball (MHB) or the Rugby Club Méditerranée (RCM) - BRAS S-L.
• 20 occasional sport subjects with low intensity physical activity and whose weekly sports practice is less than 4 hours, excluding contact sports, recruited at Sys2diag, delegation 13 of CNRS or in sports clubs linked to the study - BRAS S-O.

Description

Inclusion Criteria:

• Male participants aged between 18 and 50 years old.
• Participants willing to comply with the study procedures.
• Participants capable of understanding the purpose, nature, and methodology of the study.
• Participants affiliated to a French social security system or beneficiaries of such a system.
• Participants who have signed the non-opposition form to participate in the research.

Non-inclusion Criteria:

• Participant not affiliated to a French social security system or not a beneficiary of such a system.
• Participants deprived of liberty, protected adults, vulnerable individuals, or minors.
• Participants with a proven or suspected chronic infectious disease that may introduce a risk of contamination during sample handling (laboratories not equipped to handle this type of sample).
• Refusal to sign the non-opposition form to participate in the research.

Non-inclusion specific criteria

• Subject who has had a recent stroke or epilepsy event (within the past two months).
• Subject suffering from neurological diseases.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Sub-group S-P; 30 professional athletes whose weekly sport practice is more than 8 hours of contact sport.	Diagnostic test: Bio-fluid analysis for the implementation of a diagnostic test for sport related concussion; Saliva of participants will be sampled for analysis of biomarkers of interest (nucleic acids and proteins). The nucleic acids biomarkers will be quantified by reverse transcription followed by amplification (RT-PCR) and Next Generation Sequencing (NGS) techniques while enzymatic assay methods (ELISA) methods will be used to quantify protein biomarkers.
Sub-group S-L; 30 amateur athletes, having moderate physical activity whose weekly sport practice is between 4 and 8 hours of contact sport.	Diagnostic test: Bio-fluid analysis for the implementation of a diagnostic test for sport related concussion; Saliva of participants will be sampled for analysis of biomarkers of interest (nucleic acids and proteins). The nucleic acids biomarkers will be quantified by reverse transcription followed by amplification (RT-PCR) and Next Generation Sequencing (NGS) techniques while enzymatic assay methods (ELISA) methods will be used to quantify protein biomarkers.
Sub-group S-O; 20 control subjects who are occasional sport practitioners, having a low intensity physical activity with weekly practicing time is below 4h, excluding contacted sports.	Diagnostic test: Bio-fluid analysis for the implementation of a diagnostic test for sport related concussion; Saliva of participants will be sampled for analysis of biomarkers of interest (nucleic acids and proteins). The nucleic acids biomarkers will be quantified by reverse transcription followed by amplification (RT-PCR) and Next Generation Sequencing (NGS) techniques while enzymatic assay methods (ELISA) methods will be used to quantify protein biomarkers.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the baseline level of salivary molecular biomarkers	Quantification of salivary small non coding RNA (sncRNA) biomarkers of all study subjects: before, during and after intense or moderate sports practice (training and/or matches). Expression level of acid nucleic biomarkers are measured in copies/µL, number of read and fold change.	3 years
Evaluate the baseline level of salivary molecular biomarkers	Quantification of salivary biomarkers including ubiquitin c-terminal hydrolase L1 (UCH-L1), glial fibrillary acidic protein (GFAP) and neuron-specific enolase (NSE) proteins of all study subjects: before, during and after intense or moderate sports practice (training and/or matches). Expression level of protein biomarkers including UCL-L1, GFAP, NSE are measured in pg/mL.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differential analysis of expression signatures of salivary sncRNAs of the three groups	Comparison of expression signatures of salivary sncRNAs among the professional athletes, amateur athletes, and occasional sport practitioners. Expression level of acid nucleic biomarkers are measured in copies/µL and fold change.	3 years
Differential analysis of expression level of salivary UCH-L1, GFAP, NSE proteins of the three groups	Comparison of expression signatures of salivary UCH-L1, GFAP, NSE proteins among the professional athletes, amateur athletes, and occasional sport practitioners. Expression level of protein biomarkers including UCL-L1, GFAP, NSE are measured in pg/mL.	3 years
Differential analysis of expression signatures of salivary sncRNAs of the three groups throughout different sport situations	Comparison of expression signatures of salivary sncRNAs before, during and after different training sessions (bodybuilding, contact, etc) and matches. Expression level of acid nucleic biomarkers are measured in copies/µL, number of read and fold change.	3 years
Differential analysis of expression level of salivary UCH-L1, GFAP, NSE proteins of the three groups throughout different sport situations	Comparison of expression level of salivary UCH-L1, GFAP, NSE proteins before, during and after different training sessions (bodybuilding, contact, etc) and matches.	3 years
Differential analysis of expression signatures of salivary sncRNAs of the three groups throughout the sports season	Comparison of expression signatures of salivary sncRNAs at the beginning, in the middle and by the end of the sports season. Expression level of acid nucleic biomarkers are measured in copies/µL, number of read and fold change.	3 years
Differential analysis of expression level of salivary UCH-L1, GFAP, NSE proteins of the three groups throughout the sports season	Comparison of expression level of salivary UCH-L1, GFAP, NSE proteins at the beginning, in the middle and by the end of the sports season. Expression level of protein biomarkers including UCL-L1, GFAP, NSE are measured in pg/mL.	3 years

Collaborators and Investigators

• Sponsor: Sys2Diag
• Collaborators: Centre National de la Recherche Scientifique, France
• Investigators: Principal Investigator: Thi Nhu Ngoc VAN, Phd, Sys2Diag

Publications and helpful links

General Publications

• Di Pietro V, Ragusa M, Davies D, Su Z, Hazeldine J, Lazzarino G, Hill LJ, Crombie N, Foster M, Purrello M, Logan A, Belli A. MicroRNAs as Novel Biomarkers for the Diagnosis and Prognosis of Mild and Severe Traumatic Brain Injury. J Neurotrauma. 2017 Jun 1;34(11):1948-1956. doi: 10.1089/neu.2016.4857. Epub 2017 Apr 10.
• Di Pietro V, O'Halloran P, Watson CN, Begum G, Acharjee A, Yakoub KM, Bentley C, Davies DJ, Iliceto P, Candilera G, Menon DK, Cross MJ, Stokes KA, Kemp SP, Belli A. Unique diagnostic signatures of concussion in the saliva of male athletes: the Study of Concussion in Rugby Union through MicroRNAs (SCRUM). Br J Sports Med. 2021 Dec;55(24):1395-1404. doi: 10.1136/bjsports-2020-103274. Epub 2021 Mar 23.

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2023
• Primary Completion (Estimated): June 12, 2026
• Study Completion (Estimated): December 12, 2027

Study Registration Dates

• First Submitted: November 16, 2023
• First Submitted That Met QC Criteria: November 22, 2023
• First Posted (Actual): November 29, 2023

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: March 12, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Concussion, Biomarkers, Sport
• 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: 2023-A00188-37 (Other Identifier: Comité de protection des personnes (French Ethics committee))

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