Salivary Biomarkers for Concussion

Study Overview
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Brief Summary
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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. Toward a proper interpretation of the signal for a reliable diagnostic test, we aim to evaluate the physiological variations as well as the effect of different intensive trainings on the profile of these salivary biomarkers in professional athletes. Data generated form such analysis will help establish a baseline profile for these biomarkers whose change in intensity associated with concussion could be diagnosed in the future.

Official Title
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Salivary Biomarkers for Concussion : Determination of the Physiological Profile and Evaluation of the Effect of Intense Physical Exertion Among Professional Athletes

Conditions
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Sport Related Concussion

Intervention / Treatment
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* Diagnostic Test: Bio-fluid analysis for the implementation of a diagnostic test for sport related concussion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male participants aged between 18 and 40 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Sub-group S-P<br>20 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<br>* 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.<br>|
| Other: Sub-group S-L<br>20 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<br>* 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.<br>|
| Other: Sub-group S-O<br>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<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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; short nucleic acids or small non coding RNA (sncRNA) of all study subjects: before, during and after intense or moderate sports practice (training and/or matches). | 2 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. | 2 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. | 2 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. | 2 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. | 2 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. | 2 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. | 2 years |