mTBI-Predict is a longitudinal prospective cohort study with nested variability and case-control studies in military and civilian populations, including sport.

1. Main study: Longitudinal prospective cohort study: 610 participants with mTBI will undergo assessments of candidate biomarkers at 0-24 hours, 21 days, and 3 months post-injury according to participant availability. Prognostic outcome assessments will follow at 6, 12, and 24 months with long term digital follow-up.
2. Nested study 1: Biological Variability Study: clinical biomarkers will be repeated over 12 days and imaging biomarkers over 19 days in 40 patients with mTBI and 40 healthy control participants.
3. Nested study 2: Observational case-control prospective study: 100 cases of mTBI will be compared to 100 healthy control participants to identify novel biomarkers.

• Evaluate the accuracy and precision of candidate biomarkers (imaging, cerebral, biofluid) in predicting prognosis of mTBI due to impact, blast, and sport concussion.
• Identify biomarkers at the time of injury that enable a rapid decision to return to play, work, or duty.
• Develop a multifaceted biomarker algorithm to predict prognosis in mTBI.
• Assess the variability of candidate biomarkers.
• Identify novel biomarkers in patients with mTBI

• Multi-centre recruitment and clinical assessment through the UK mTBI research network (including Defence Medical Rehabilitation Centre Stanford Hall, University Hospitals Birmingham NHS Foundation Trust, and further centres to be confirmed).
• Imaging at Centre for Human Brain Health, University of Birmingham; Sir Peter Mansfield Imaging Centre, University of Nottingham; Aston Institute for Health and Neurodevelopment, Aston University; and Defence Medical Rehabilitation Centre, Stanford Hall.

• Main study: Patients aged 18-60 with confirmed mTBI within the last 3 months.
• Healthy control: Participants aged 18-60 without confirmed mTBI within the last 3 months.

mTBI-Predict is an observational study and as such does not include any intervention. Patient treatment will be NHS standard care alongside study involvement.

Main study

• To evaluate the accuracy and precision of candidate biomarkers (imaging, clinical, biofluid) in predicting prognosis in mTBI.
• To identify biomarkers at the tme of injury to enable a rapid decision to return to play, work, or duty.
• To develop a multifaceted biomarker algorithm to predict prognosis in mTBI.

Biological Variability Study (nested study 1)

• To assess the variability of candidate biomarkers in healthy controls and mTBI patients to understand if biomarkers are reliable and that any change in a biomarker indicated change of random fluctuation.

Case-control study (nested study 2)

• To identify novel biomarkers in patients with mTBI compared to healthy controls.
• Exploratory studies will enable mechanistic insights to be gained.

Funding

mTBI-Predict is jointly-funded by the UK Ministry of Defence and US Department of Defense.

Ethics

mTBI-Predict has received favourable ethical opinion from the Ministry of Defence Research Ethics Service (ref: 2214MODREC23), and NHS Health Research Authority (ref: 319062).