Accepted for/Published in: JMIR Research Protocols
Date Submitted: Feb 19, 2026
Date Accepted: May 8, 2026
The Rehabilitation in persistent Post-Concussion Symptoms trial (The REPCon-trial): Study protocol for an assessor blinded, parallel-group, randomized controlled trial of tailored sub-symptomatic aerobic exercise in adult patients with persistent post-concussion symptoms (PPCS)
ABSTRACT
Background:
Persistent post-concussion symptoms (PPCS) is a complex phenomenon following mild traumatic brain injury (mTBI), characterized by a diverse range of symptoms that significantly impact daily functioning including abilities to engage in physical, cognitive and social activities. Effective rehabilitation strategies as well as nuanced understandings of brain function and patient perception remain insufficiently explored in adults with PPCS
Objective:
This study aims to assess the physiological and neurofunctional effects of targeted physical exercise carried out as a graded sub-symptomatic aerobic exercise program. Furthermore, the project seeks to alleviate the complex symptomatology and perception of PPCS through the planned intervention. In addition, the aim is to obtain feedback from patients and researchers of this interprofessional project and to conduct a comprehensive 360-degree evaluation combining subjective and objective data to achieve novel explanations of the symptom complexity of PPCS, ultimately pave the way for future strategic initiatives within mTBI treatment
Methods:
This randomised controlled trial enrolled 70 PPCS patients, randomly allocated them into a training group, and a control group, which maintained their usual activities and care. The training group underwent a 12-week tailored aerobic exercise program designed to stay below symptom-provocation thresholds using Buffalo Concussion Bike Test (BCBT) as the instrument. The study consisted of qualitative patient interviews, physical test and exercise evaluations, neurofunctional and structural MRI, and a process evaluation. The primary outcome was improvement in physical performance on BCBT. Secondary outcomes were symptom severity, neurophysiological function, and quality of life. MRI assessed neurophysiological changes, including blood-brain barrier integrity and cerebral metabolism. The study incorporates a multimodal approach, combining subjective patient reports with objective clinical and neuroimaging data enabling the interdisciplinary research group to perform comprehensive evaluations of the complexity of PPCS
Results:
Study funding was awarded in December 2022. The ongoing enrolment phase and randomization of 70 participants was completed by March 2025. Data analysis is ongoing and expected to conclude in 2026, with results to be published in separate manuscripts
Conclusions:
This study is innovative in its approach to patients with PPCS, focusing on the effect of an individualised exercise regime and exploring the neurofunctional underpinnings of symptom improvements as well as the patient perceptions of dealing with PPCS. The findings are anticipated to contribute significantly to the field of PPCS management, potentially transforming current rehabilitation practices Clinical Trial: ClinicalTrials.gov NCT05785000; https://clinicaltrials.gov/study/NCT05785000
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