Salivary Biomarkers for Concussion

Official title

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

Overview

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.

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.

Interventions

• 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.

Primary outcome measures

• Evaluate the baseline level of salivary molecular biomarkers [Time frame: 3 years]
• Evaluate the baseline level of salivary molecular biomarkers [Time frame: 3 years]

Secondary outcome measures (6)

• Differential analysis of expression signatures of salivary sncRNAs of the three groups [Time frame: 3 years]
• Differential analysis of expression level of salivary UCH-L1, GFAP, NSE proteins of the three groups [Time frame: 3 years]
• Differential analysis of expression signatures of salivary sncRNAs of the three groups throughout different sport situations [Time frame: 3 years]
• Differential analysis of expression level of salivary UCH-L1, GFAP, NSE proteins of the three groups throughout different sport situations [Time frame: 3 years]
• Differential analysis of expression signatures of salivary sncRNAs of the three groups throughout the sports season [Time frame: 3 years]
• Differential analysis of expression level of salivary UCH-L1, GFAP, NSE proteins of the three groups throughout the sports season [Time frame: 3 years]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Cohort

Study locations

France · 1 center

• Sys2Diag - Umr9005 Cnrs/Alcen — Montpellier

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. PMID 28279125
• 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 2 PMID 33757972

Identifiers

NCT: NCT06149351 · 2023-A00188-37 · 2023-A00188-37

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗