Feasibility, Safety, and Preliminary Efficacy of Median Nerve Stimulation for Cognitive Dysfunction in Patients With Acute Traumatic Brain Injury: Study Protocol for a Pilot Randomized Controlled Trial.

Background: Currently, the treatment of cognitive dysfunction after acute traumatic brain injury (TBI) remains a challenge, and novel therapeutic methods are urgently needed. Median nerve stimulation (MNS) is a noninvasive neuromodulation technique that has recently shown positive effects in promoting recovery from coma after acute brain injury. It has been shown to improve cognition in healthy volunteers, and may be a potential therapeutic approach for cognitive dysfunction in patients with acute TBI. Objective: The primary aim of this study is to evaluate the feasibility, safety, and preliminary efficacy of MNS for cognitive dysfunction in patients with acute TBI. Methods: This study is designed as a prospective, single-center, assessor-blinded, sham-controlled, randomized pilot study. Thirty adult patients with cognitive dysfunction after TBI will be enrolled and randomized to either the stimulation or sham group in a 1:1 allocation ratio. In the stimulation group, MNS is performed on the right wrist (40 Hz, pulse width 300 µs, 20 s on/40 s off, 8 hours per day). The sham group will receive stimulation using an identical device set to deliver 0 mA. Feasibility, safety, and preliminary efficacy will be evaluated at 1 and 3 months after the injury. Feasibility and acceptability will be assessed via recruitment, adherence, retention, and participant-reported acceptability using Likert scales. These measures will be summarized descriptively, and completion rates will be calculated and reported. Safety will be primarily assessed by ascertainment of adverse events from enrollment to 3 months. Further safety assessment will examine side effects using a Likert questionnaire and the impact on peripheral hemodynamic responses. Additionally, the potential efficacy of MNS on cognitive dysfunction will be assessed using multiple cognitive scales; neuroradiological tests, including magnetic resonance imaging and magnetoencephalography; and cognitive-related serum biomarkers. Results: Ethics approval was obtained in January 2025, and the trial was registered on ClinicalTrials.gov in February 2026. Participant recruitment is scheduled to begin in July 2026, with completion anticipated in June 2027. Data analysis will commence after completion of follow-up assessments, and study findings are expected to be published in late 2027. Conclusions: This pilot trial will provide preliminary evidence on the feasibility and safety of MNS as a novel intervention for cognitive dysfunction after acute TBI. The results will guide the development of larger-scale trials and optimization of study design.