This randomized controlled trial protocol describes the REPCon project, which enrolled 70 adult patients with persistent postconcussion symptoms to assess the physiological, neurofunctional, and symptomatic effects of a 12-week tailored subsymptomatic aerobic exercise program compared to usual care.
Key Findings
Methods
The REPCon trial enrolled 70 patients with persistent postconcussion symptoms (PPCSs) following mild traumatic brain injury (mTBI) and randomized them 1:1 to either a training group or a control group.
Enrollment and randomization of 70 patients were completed in March 2025.
Patients were randomized in a 1:1 ratio to either a control group or a training group.
The control group maintained their usual activities and care.
The training group underwent a 12-week tailored aerobic exercise program.
Methods
The intervention consists of a 12-week graded subsymptomatic aerobic exercise program individualized to stay below symptom-provocation thresholds.
The Buffalo Concussion Bike Test (BCBT) was used as the assessment instrument to guide exercise intensity.
The program was designed to stay below symptom-provocation thresholds, i.e., subsymptomatic.
The exercise program is described as 'tailored' and 'graded,' suggesting individualization based on patient tolerance.
The 12-week postintervention assessments concluded in August 2025.
Methods
The primary outcome of the trial is improvement in physical performance as measured by the Buffalo Concussion Bike Test (BCBT).
The BCBT serves both as the assessment instrument guiding the intervention and as the primary outcome measure.
Secondary outcomes include symptom severity, neurophysiological function, and quality of life.
The study is assessor-blinded and parallel-group in design.
Methods
The study employs a multimodal assessment approach combining subjective and objective data, including neuroimaging, physical tests, qualitative interviews, and process evaluations.
MRI assessed neurophysiological changes including blood-brain barrier integrity and cerebral metabolism.
The study included qualitative patient interviews, physical tests, exercise evaluations, neurofunctional and structural MRI scans, and process evaluations.
The approach is described as a 'comprehensive 360-degree evaluation combining subjective and objective data.'
Both neurofunctional and structural MRI modalities were used.
An interprofessional research group conducted the evaluations.
Background
PPCSs are characterized as a complex phenomenon following mTBI that greatly impacts daily functioning, including physical, cognitive, and social activities.
The abstract notes that 'effective rehabilitation strategies and a nuanced understanding of brain function and patient perception remain insufficiently explored in adults with PPCSs.'
PPCSs involve 'a diverse range of symptoms' that affect multiple domains of daily life.
The study was designed in part to address gaps in understanding of both brain function and patient perception in this population.
Results
Study funding was awarded in December 2022, with data analysis ongoing and results expected to be published in separate manuscripts in 2026-2027.
Study funding was awarded in December 2022.
Enrollment and randomization were completed in March 2025.
The 12-week postintervention assessments concluded in August 2025.
Data analysis is ongoing and expected to conclude in 2026.
Results will be published in separate manuscripts in 2027.
What This Means
This paper describes the protocol (study plan) for a clinical trial called the REPCon project, which investigates whether a carefully designed exercise program can help adults who continue to experience symptoms after a concussion (mild traumatic brain injury). These persistent postconcussion symptoms — such as headaches, fatigue, and difficulty with physical, mental, and social activities — can last for months and significantly reduce quality of life. The researchers enrolled 70 patients and randomly assigned them either to continue their usual care or to participate in a 12-week exercise program that was individually tailored to keep them below the threshold at which exercise provokes their symptoms.
The study is notable for its comprehensive approach: in addition to measuring physical fitness using a standardized bike test, the researchers collected brain MRI scans to look at changes in brain structure and function (including the blood-brain barrier and brain metabolism), had patients complete symptom and quality-of-life questionnaires, and also conducted qualitative interviews to understand patients' personal experiences. This combination of objective and subjective data, alongside input from an interprofessional team, is intended to give a fuller picture of how and why the exercise program might — or might not — help.
This research suggests that individualized, symptom-guided aerobic exercise may be a promising rehabilitation approach for people with persistent postconcussion symptoms, and the neuroimaging component could reveal the biological mechanisms behind any improvements observed. The trial has completed enrollment and data collection as of mid-2025, with full results expected to be published in 2027. If the intervention proves effective, it could have meaningful implications for how clinicians manage and rehabilitate patients struggling with long-term effects of concussion.
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