Pilot Study on the Correlation Between Accelerations Experienced

Official title

Pilot Study on the Correlation Between Accelerations Experienced During Matches by Professional Rugby Players and a Profile of Salivary Biomarkers Identified in the Literature as Related to Concussion.

Overview

Concussion, or mild traumatic brain injury, accounts for 85% of brain injuries and is common in both professional and amateur sports. It results from kinetic impacts causing a temporary disruption of brain function, often without visible abnormalities on imaging, making diagnosis difficult. The majority of concussions remain undetected, without specific management. To facilitate detection, the development of reliable salivary BMs is essential, as they offer a non-invasive, rapid, and simple method for early identification of biological changes related to concussions.

Detailed description

Concussion, or mild traumatic brain injury, accounts for 85% of brain injuries and is common in both professional and amateur sports. It results from kinetic impacts causing a temporary disruption of brain function, often without visible abnormalities on imaging, making diagnosis difficult.

The majority of concussions remain undetected, without specific management. Recently, several molecular biomarkers (BMs) of concussion in high-level athletes have been identified.

However, the physiological reference values of these BMs are not yet sufficiently established to allow optimal use of diagnostic tests for concussion. To facilitate detection, the development of reliable salivary BMs is essential, as they offer a non-invasive, rapid, and simple method for early identification of biological changes related to concussions.

It is also crucial to correlate these changes with the physical forces experienced by players during impacts. Indeed, the literature indicates that concussions can result from rapid head movements, often caused by violent linear and angular accelerations/decelerations, even if indirect.

Interventions

• Diagnostic test Analyze correlations between the measurements of the variations in biomarkers with those obtained by an instrumented mouthguard measuring accelerations.
  Nucleic acids will be extracted from the participants' saliva using a commercial extraction kit (Qiagen). The miRNAs will then be analyzed by RT-qPCR. The miRNAs will first undergo a reverse transcription step to generate complementary DNAs. Then, using specific primers, the complementary DNAs will be amplified and measured by quantitative PCR (qPCR). The levels of proteins of interest (NSE, UCHL1, and GFAP) will be measured in the participants' saliva using enzymatic assay methods or ELISA-typ

Primary outcome measures

• Assess the intensity and number of impacts [Time frame: 3 Years]

Secondary outcome measures (3)

• Measure the concentration of salivary BMs [Time frame: 3 Years]
• Measure the acceleration and deceleration forces [Time frame: 3 Years]
• Compare the profiles of BMs [Time frame: 3 Years]

Eligibility criteria

Inclusion criteria

• Male subject
• Subject aged between 19 and 20 years
• Subject willing to follow the study procedures
• Subject capable of understanding the purpose, nature, and methodology of the study
• Subject affiliated with a French social security scheme or a beneficiary of such a scheme
• Subject who has signed the non-opposition to participation in the research
• Subject who has signed the informed consent for salivary micro-RNA analysis
• Subject selected in the French under-20 rugby team (U20).

Exclusion criteria

• Subject not affiliated with a French Social Security scheme or not a beneficiary of such a scheme
• Subject deprived of liberty, protected adults, vulnerable persons, or minors
• Subject with proven or suspected chronic infectious disease that may pose a risk of contamination during sample handling (laboratories not equipped to handle this type of sample)
• Subject suffering from Gougerot-Sjögren syndrome (dry syndrome)
• Refusal to sign the non-opposition
• Refusal to sign the informed consent for salivary micro-RNA analysis.

Specific Non-Inclusion Criteria:

• Subject who has suffered a recent stroke or epileptic event (within the last 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

• Lefevre-Dognin C, Cogne M, Perdrieau V, Granger A, Heslot C, Azouvi P. Definition and epidemiology of mild traumatic brain injury. Neurochirurgie. 2021 May;67(3):218-221. doi: 10.1016/j.neuchi.2020.02.002. Epub 2020 May 6. PMID 32387427
• van Stegeren AH, Wolf OT, Kindt M. Salivary alpha amylase and cortisol responses to different stress tasks: impact of sex. Int J Psychophysiol. 2008 Jul;69(1):33-40. doi: 10.1016/j.ijpsycho.2008.02.008. Epub 2008 Mar 5. PMID 18417235
• Roe G, Sawczuk T, Owen C, Tooby J, Starling L, Gilthorpe MS, Falvey E, Hendricks S, Rasmussen K, Readhead C, Salmon D, Stokes K, Tucker R, Jones B. Head Acceleration Events During Tackle, Ball-Carry, and Ruck Events in Professional Southern Hemisphere Men's Rugby Union Matches: A Study Using Instrumented Mouthguards. Scand J Med Sci Sports. 2024 Jun;34(6):e14676. doi: 10.1111/sms.14676. PMID 38867444
• Tooby J, Till K, Gardner A, Stokes K, Tierney G, Weaving D, Rowson S, Ghajari M, Emery C, Bussey MD, Jones B. When to Pull the Trigger: Conceptual Considerations for Approximating Head Acceleration Events Using Instrumented Mouthguards. Sports Med. 2024 Jun;54(6):1361-1369. doi: 10.1007/s40279-024-02012-5. Epub 2024 Mar 9. PMID 38460080
• Hicks SD, Onks C, Kim RY, Zhen KJ, Loeffert J, Loeffert AC, Olympia RP, Fedorchak G, DeVita S, Rangnekar A, Leddy J, Haider MN, Gagnon Z, McLoughlin CD, Badia M, Randall J, Madeira M, Yengo-Kahn AM, Wenzel J, Heller M, Zwibel H, Roberts A, Johnson S, Monteith C, Dretsch MN, Campbell TR, Mannix R, Neville C, Middleton F. Diagnosing mild traumatic brain injury using saliva RNA compared to cognitive PMID 33135344
• Woodward J, Tooby J, Tucker R, Falvey EC, Salmon DM, Starling L, Tierney G. Instrumented mouthguards in elite-level men's and women's rugby union: characterising tackle-based head acceleration events. BMJ Open Sport Exerc Med. 2024 Aug 1;10(3):e002013. doi: 10.1136/bmjsem-2024-002013. eCollection 2024. PMID 39104376
• Tooby J, Woodward J, Tucker R, Jones B, Falvey E, Salmon D, Bussey MD, Starling L, Tierney G. Correction to: Instrumented Mouthguards in Elite-Level Men's and Women's Rugby Union: The Incidence and Propensity of Head Acceleration Events in Matches. Sports Med. 2024 May;54(5):1339-1341. doi: 10.1007/s40279-023-01968-0. No abstract available. PMID 37938534
• Daneshvar DH, Nair ES, Baucom ZH, Rasch A, Abdolmohammadi B, Uretsky M, Saltiel N, Shah A, Jarnagin J, Baugh CM, Martin BM, Palmisano JN, Cherry JD, Alvarez VE, Huber BR, Weuve J, Nowinski CJ, Cantu RC, Zafonte RD, Dwyer B, Crary JF, Goldstein LE, Kowall NW, Katz DI, Stern RA, Tripodis Y, Stein TD, McClean MD, Alosco ML, McKee AC, Mez J. Leveraging football accelerometer data to quantify associati PMID 37340004

Identifiers

NCT: NCT07507253 · 2024-A02331-46 · 24.05325.000379

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗