Blood-based Biomarkers for the Prognosis of Sports Related Concussion

May 30, 2023 updated by: University of Limerick

A Blood Biomarker Study With Clinical Correlation for the Diagnosis and Prognosis of Sports Related Concussion in Elite Rugby

The diagnosis of sports related concussion still relies heavily on a subjective assessment. In this study the investigators want to assess the prognostic value of blood-based biomarkers with recovery from concussive episodes over specific time points post-injury. Our research aims to (1) assess that the World Rugby's head injury assessment (HIA) can identify that a concussion has taken place by measuring specific biomarkers in the blood and (2) to track these biomarkers over time post-injury as a means to assess player health.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The diagnosis and prognosis of sports related concussion (SRC) still rely on a subjective assessment based on the SCAT5 procedure. Our knowledge of how sports related concussion effects an athlete over time is limited as all patients may have different recovery times from concussion. Our research aims to quantitatively confirm that the head injury assessment has predicted a concussion against clinical assessment (SCAT5) and that a return to play protocol allows sufficient recovery time for an athlete.

Numerous novel areas of diagnosis are currently under investigation including protein-based biomarkers. In the context of SRC, these protein biomarkers typically consist of neurological proteins normally confined to the central nervous system or associated with neurological cell damage. Recent studies have compared biomarker levels at different time points post-diagnosis or investigated the relationship between early biomarker levels and return to play (RTP) times. However, the use of these biomarkers for actively evaluating player recovery following SRC has yet to be fully investigated. In this study, the investigators will measure biomarkers levels across multiple time points post-SRC to assess the value of these biomarkers to monitor player recovery. This is of significant for minimising premature RTP and, ultimately, aiming to reduce the chronic long-term effects associated with SRC.

To truly identify a biomarker specific to concussion this study will need to, first, analyse the bloods of concussion patients and compare to the clinical assessment of the head injury assessment (HIA), and, second, measure their levels over time to indicate recovery that may aid in a safe return to play.

Briefly, blood samples are taken from consented participants at the start of pre-season to act as a baseline. Once one of these participants enters the HIA process their bloods are taken post-injury, 6 days after injury and 13 days after injury. Next, the biomarkers are measured in the blood samples at each time point to examine if there is any increase/decrease in their levels.

Study Design:

A prospective cohort study with an uninjured and exercise free control groups.

Population:

All participants are professional rugby players from one professional rugby club were initially invited to participate. Initial contact was made to the Irish Rugby Football Union (IRFU) chief medical officer for permission to run the study over a three-year period. Next permission to run this cohort study was sought from the head coach and medical staff of the professional rugby team.

Baseline Questionnaire:

Participants will complete a baseline questionnaire that includes questions regarding their concussion history including symptoms associated with, length of, and outcome of previous injuries. The questionnaire was developed in line with previous sports-based concussion studies used for ice hockey and Australian football

Timeframes

As part of this study, any participant that enters the standard HIA process will undergo a HIA, a neuropsychometric assessment, and blood sampling at the following time points:

  1. Within 72 hours of injury,
  2. 6 days post-injury (± 1 day); this aligns with the minimum graduated return to play (GRTP) protocol for a professional rugby player, no player will return to play before 6 days,
  3. 13 days post-injury (± 1 day) to examine if biomarkers are still present despite the results the HIA and the neuropsychometric assessment.

Serial HIA Participants that suffer a suspected SRC will complete the HIA protocol at the time points outlined above. This is a form of the SCAT5 which has been modified for professional rugby and GRTP. This assessment will be carried out by the medical officer of the professional rugby club.

Neuropsychometric Assessment During preseason players complete a baseline computed based neuropsychometric assessment - ImPACT. This assessment measures different cognitive domains including visual memory, visual processing speed, reaction times and working memory as well as attention. Post injury players are re-assessed once symptom free to determine recovery fo these domains and to assess for any persistent patterns of deficit. This assessment forms a part of the overall concussion assessment and management plan.

Blood Draw:

The medical officer and/or clinical nurse will take the samples of blood at the timepoints outlined above. The medical officer or nurse usually takes the blood sample from the antecubital vein in the arm.

Bloods are collected by a member of the study team from the medical officer or nurse after the participant has left to ensure confidentiality. Three types of sample vials are used to ensure different types of biochemical techniques can be used and certain markers can be examined; serum, plasma and whole blood. Whole blood samples are immediately aliquoted in 2 mL cryo-vials of 1- 1.5 mL each. For serum samples the blood is allowed to clot within the tube for up to 30 minutes. For both serum and plasma vials, they are centrifuged at 2,000 xg for 10 minutes at 4 °C. The serum and plasma are carefully pipetted and aliquoted into respective 2 mL cryo-vials with no less than 400 µL in each cryo-vial. All aliquoted cryo-vials are placed into storage boxes within a -80 °C freezer for long-term storage. Each aliquot can be removed to probe for different biomarkers without multiple freeze-thaw cycles on the core sample.

Blood Biomarkers The blood-based biomarkers that can be analysed using standard biochemical techniques for a targeted and hypothesis-based procedures using ELISA kits or Luminex multiplex assays. Serum and plasma samples allows for a multitude of targets to be analysed which may be found in either serum or plasma. For this type of analysis common targets can be used to compare across the timepoints. The biomarkers under investigation can be but not limited to s100β, ubiquitin carboxyl-terminal hydrolase isoenzyme L1, glial fibrillar acidic protein and total, Tau protein and Brain-derived neurotrophic factor.

Outcomes Each participant that is believed to have a SRC will enter the HIA process. These participants will have clinical assessments conducted at pre-defined time points, in line with the World Rugby guidelines. Blood samples will also be acquired at these time points to quantify the levels of blood-based biomarkers. Biomarker levels will be correlated to the results of the HIA and neuropsychometric assessments. This will facilitate preliminary investigation of the correlation between clinical assessments and biomarker levels to determine if the biomarkers can be used to objectively assess SRC recovery

Investigations:

A collaborative relationship exists between this research group and the University of Limericks (UL) Clinical Research Support Unit (CRSU). The CRSU provided advice and supported the delivery of this research project to the highest standard of research and clinical governance in accordance with the requirements of ICH Good Clinical Practice (ICH-GCP) Guidelines and all applicable regulatory requirements. The participant contact element of this study was conducted by adhering to the CRSU's Quality Management System (QMS).

Study Type

Observational

Enrollment (Actual)

45

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Ireland
    • Munster
      • Limerick, Munster, Ireland
        • Munster Rugby

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 40 years (Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

All participants are professional rugby players from a professional rugby club were have been invited to participate. Initial contact was made to the Irish Rugby Football Union (IRFU) chief medical officer for permission to run the study over a three-year period. Next permission to run this cohort study was sought from the head coach and medical staff of the professional rugby team.

Description

Inclusion Criteria:

Participants are eligible to participate if they

  1. are part of the professional rugby team's senior squad or the academy;
  2. aged over 18;
  3. consent to the study over the whole season.

Exclusion Criteria:

Participants are excluded if they

  1. are unable to attend the preseason baseline draw;
  2. unable to give informed consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Professional Rugby Athletes
These are the cohort of players that consent to the study and have a preseason baseline blood sample taken. If the participant from this cohort then receives a concussion they are assessed by the World Rugby's Head Injury Assessment (HIA) and then enter into the return to play (RTP) protocol which means they cannot play a competitive game for 6 days.
Diagnostic test: Biochemical Analysis of Blood Biomarkers
Using established biochemical techniques, the bloods will be probed for specific biomarkers s100B, UCH-L1, GFAP, and BDNF. The techniques include individual ELISA kits for each biomarker mentioned and Luminex multiplate assay which will probe for all biomarkers in one plate. Ultimately, these techniques will be able to measure the level of these biomarkers in the blood relative to the participants baseline reading.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Diagnosis
Time Frame: Bloods to be taken within 72 hours of injury
Measure the levels of blood biomarkers in rugby players that have experienced a concussion, confirmed via HIA and neuropsychometric assessment, to assess the utility of these biomarkers for concussion diagnosis
Bloods to be taken within 72 hours of injury
Clinical Recovery
Time Frame: Bloods to be taken within 6 and 13 days post-injury
Track the levels of the blood biomarkers over time, post-injury to determine if biomarker levels correlate with clinical recovery.
Bloods to be taken within 6 and 13 days post-injury

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Limerick

Investigators

  • Principal Investigator: Jamie Kearns, MD, Munster Rugby

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2018

Primary Completion (Actual)

May 1, 2023

Study Completion (Actual)

May 1, 2023

Study Registration Dates

First Submitted

July 21, 2020

First Submitted That Met QC Criteria

July 21, 2020

First Posted (Actual)

July 24, 2020

Study Record Updates

Last Update Posted (Actual)

June 2, 2023

Last Update Submitted That Met QC Criteria

May 30, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CRSU-016

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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