Rehabilitation Involving Tailored Subsymptomatic Aerobic Exercise in Adult Patients With Persistent Postconcussion Symptoms (REPCon Project): Protocol for an Assessor-Blinded, Parallel-Group, Randomized Controlled Trial.

Background: Persistent postconcussion symptoms (PPCSs) represent a complex phenomenon following mild traumatic brain injury (mTBI), and this phenomenon is characterized by a diverse range of symptoms that greatly impact daily functioning, including the ability to engage in physical, cognitive, and social activities. Effective rehabilitation strategies and a nuanced understanding of brain function and patient perception remain insufficiently explored in adults with PPCSs. Objective: This study aims to assess the physiological and neurofunctional effects of targeted physical exercise carried out as a graded subsymptomatic aerobic exercise program. Furthermore, the project seeks to alleviate the complex symptomatology and perception of PPCSs through the planned intervention. In addition, the study aims to obtain feedback from patients and researchers involved in this interprofessional project and to conduct a comprehensive 360-degree evaluation combining subjective and objective data in order to obtain novel insights into the symptom complexity of PPCSs, ultimately paving the way for future strategic initiatives in mTBI treatment. Methods: This randomized controlled trial enrolled 70 patients with PPCSs. The patients were randomized in a 1:1 ratio to either a control group or a training group. Patients in the control group maintained their usual activities and care. Patients in the training group underwent a 12-week tailored aerobic exercise program designed to stay below symptom-provocation thresholds, using the Buffalo Concussion Bike Test (BCBT) as the assessment instrument. The study consisted of qualitative patient interviews, physical tests, exercise evaluations, neurofunctional and structural magnetic resonance imaging (MRI) scans, and process evaluations. MRI assessed neurophysiological changes, including blood-brain barrier integrity and cerebral metabolism. The primary outcome is improvement in physical performance on the BCBT. The secondary outcomes are symptom severity, neurophysiological function, and quality of life. The study will incorporate 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 PPCSs. Results: Study funding was awarded in December 2022. Enrollment and randomization of 70 patients were completed in March 2025. The 12-week postintervention assessments concluded in August 2025. Data analysis is ongoing and expected to conclude in 2026. The results will be published in separate manuscripts in 2027. Conclusions: This study is innovative in its approach to patients with PPCSs, focusing on the effect of an individualized exercise regimen and exploring the neurofunctional underpinnings of symptom improvements as well as the patient perceptions of dealing with PPCSs. The findings are anticipated to contribute greatly to the field of PPCS management, potentially transforming current rehabilitation practices.