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
11 affiliations
- 1Department of Neurosurgery, National Neuroscience Institute, Tan Tock Seng Hospital, Singapore, Singapore.
- 2Department of Neurosurgery, National Neuroscience Institute, Singapore General Hospital, Singapore, Singapore.
- 3Department of Rehabilitation Medicine, Tan Tock Seng Hospital, Singapore, Singapore.
- 4Singapore Institute of Technology, Singapore, Singapore.
- 5College of Computing and Data Science, Nanyang Technological University, Singapore, Singapore.
- 6Rehabilitation Research Institute of Singapore, Nanyang Technological University, Singapore, Singapore.
- 7Institute of Advanced Intelligence and Computing (IAIC), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
- 8Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore.
- 9Brain and Mental Health Program, QIMR Berghofer, Brisbane, QLD, Australia.
- 10School of Biomedical Sciences, University of Queensland, Brisbane, QLD, Australia.
- 11Department of Neurology, National Neuroscience Institute, Tan Tock Seng Hospital, Singapore, Singapore.
Abstract
Background: 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.
Methods: 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.
Study outcomes: 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.
Discussion: 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.
Clinical trial registration: ClinicalTrials.gov , Identifier NCT05644171.
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BibTeX
@article{wan2026effect,
title = {{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}},
author = {Kai Rui Wan and Zhi Yan Valerie Ng and Seng Kwee Wee and Fatimah Misbaah and Wen Li Lui and Min Wee Phua and Tegan Plunkett and Neethu Robinson and Aung Aung Phyo Wai and Cuntai Guan and Ananda Sidarta and Rosa Qi Yue So and Brian Premchand and Kezia Susanto and Luca Cocchi and Seyed Ehsan Saffari and Rui Xin Justin Ker and Wai Hoe Ng},
journal = {Frontiers in Neurology},
year = {2026},
month = oct,
doi = {10.3389/fneur.2026.1967078},
url = {https://www.frontiersin.org/articles/10.3389/fneur.2026.1967078/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - 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
AU - Kai Rui Wan
AU - Zhi Yan Valerie Ng
AU - Seng Kwee Wee
AU - Fatimah Misbaah
AU - Wen Li Lui
AU - Min Wee Phua
AU - Tegan Plunkett
AU - Neethu Robinson
AU - Aung Aung Phyo Wai
AU - Cuntai Guan
AU - Ananda Sidarta
AU - Rosa Qi Yue So
AU - Brian Premchand
AU - Kezia Susanto
AU - Luca Cocchi
AU - Seyed Ehsan Saffari
AU - Rui Xin Justin Ker
AU - Wai Hoe Ng
PY - 2026
DA - 2026/10/09
JO - Frontiers in Neurology
DO - 10.3389/fneur.2026.1967078
UR - https://www.frontiersin.org/articles/10.3389/fneur.2026.1967078/full
AB - Background: 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. Methods: 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. Study outcomes: 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. Discussion: 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. Clinical trial registration: ClinicalTrials.gov , Identifier NCT05644171.
SN - 1664-2295
ER -