Efficacy and safety of high-definition transcranial direct current stimulation combined with digital rehabilitation on upper limb function in stroke patients: study protocol for a randomized, double-blind, sham-controlled confirmatory trial.

BACKGROUND

Stroke remains a leading cause of long-term disability worldwide, with a significant proportion of survivors suffering from persistent upper limb impairments despite conventional rehabilitation. High-definition transcranial direct current stimulation (HD-tDCS) has emerged as a promising neuromodulation technique capable of precise cortical targeting, potentially enhancing motor recovery when combined with structured rehabilitation. This study aims to confirm the efficacy and safety of HD-tDCS combined with digital upper limb rehabilitation in improving upper limb motor function among stroke survivors.

METHODS

This multicenter, randomized, parallel-group, double-blind, sham-controlled superiority trial will enroll 64 participants with chronic unilateral stroke who will be randomized to receive either active HD-tDCS or sham stimulation, both combined with standardized digital upper limb rehabilitation. The intervention will consist of 10 sessions over 4 weeks (40 min per session). Each session will include 10 min of HD-tDCS at rest targeting the ipsilesional primary motor cortex and anterior intraparietal sulcus, followed by 20 min of task-based digital rehabilitation with concurrent HD-tDCS, and a final 10 min of digital rehabilitation alone. The primary outcome will be the postintervention change in the Fugl-Meyer Assessment of Upper Extremity score from baseline. Secondary outcomes will include grip and pinch strength, 9-Hole Pegboard Test, Box and Block Test, finger-tapping performance, Short Form-36, and cortical activation measured via integrated functional near-infrared spectroscopy (fNIRS). fNIRS will help characterize task-related cortical hemodynamic responses in the stimulated area, which are associated with motor recovery.

DISCUSSION: This trial provides promising exploratory findings and is designed to rigorously assess both behavioral and hemodynamic brain responses. By integrating real-time brain monitoring, this study seeks to contribute to existing evidence on the mechanisms underlying HD-tDCS-enhanced neuroplasticity and inform the development of future precision neurorehabilitation strategies.

TRIAL REGISTRATION: This trial has been registered at the Clinical Research Information Service (Registration number: KCT0010556). Registration date: May 28, 2025.