Effect of epidural spinal cord stimulation combined with personalized neurorehabilitation in chronic motor-complete spinal cord injury: study protocol for the phase II single-arm feasibility RESTORES (RESToration Of Rehabilitative function with Epidural spinal Stimulation) trial

Abstract

Chronic motor-complete spinal cord injury (SCI) results in profound neurological disability with minimal prospects for functional recovery using conventional rehabilitation strategies. Emerging evidence suggests that epidural spinal cord stimulation (eSCS) can activate dormant spinal locomotor networks and restore volitional and autonomic functions when combined with intensive activity-based training. However, systematic evaluation of multimodal neuromodulation approaches integrating advanced rehabilitation and computational neurophysiology remains limited. The RESTORES trial (RESToration Of Rehabilitative function with Epidural spinal Stimulation) is a prospective, single-arm Phase II feasibility study enrolling 15 adults with chronic (≥1 year) motor-complete SCI (American Spinal Injury Association Impairment scale (AIS) A or B) between C5 and T12. Participants will undergo implantation of an epidural spinal cord stimulator followed by a 24-week program of structured stimulation-coupled personalised neurorehabilitation (five sessions per week). Clinical outcomes will be evaluated using standardized neurological and functional measures including the AIS motor score, Spinal Cord Independence Measure version III (SCIM-III), Walking Index for Spinal Cord Injury II (WISCI-II), and Trunk Assessment Scale (TASS). Autonomic function and quality of life will also be assessed. Multimodal neurophysiological measurements—including surface electromyography (sEMG), electroencephalography (EEG), resting-state functional magnetic resonance imaging (rs-fMRI), and computer-vision-based movement analysis—will be performed to investigate neural recovery mechanisms and inform the development of adaptive neuromodulation systems. The primary outcome is the safety of epidural spinal cord stimulation implantation, defined as the absence of device explantation for safety-related reasons within 6 months following implantation. Secondary outcomes include changes in AIS motor score, functional outcomes (SCIM, WISCI-II, TASS), autonomic function, quality of life, and neurophysiological biomarkers. This study integrates neuromodulation, advanced rehabilitation technologies, and multimodal computational neurophysiology to evaluate both clinical efficacy and neural mechanisms of recovery following chronic SCI. Findings from the RESTORES trial will provide critical safety and feasibility data to inform future multicenter trials and the development of closed-loop spinal cord stimulation systems. ClinicalTrials.gov , Identifier NCT05644171.