Combined repetitive transcranial magnetic stimulation and transcutaneous spinal cord stimulation for upper limb recovery in chronic incomplete cervical spinal cord injury: protocol for a pilot randomized controlled trial.

BACKGROUND: Cervical spinal cord injury (SCI) results in severe upper limb impairment, with restoration of hand and arm function ranked as the highest rehabilitation priority by individuals with tetraplegia. Transcutaneous spinal cord stimulation (tSCS) has emerged as a promising approach for enhancing upper limb recovery. Intermittent theta burst stimulation (iTBS), an efficient form of repetitive transcranial magnetic stimulation, can enhance cortical excitability and descending motor drive. However, the benefit of combining these complementary neuromodulation modalities to simultaneously target supraspinal and spinal circuits has not been evaluated in a controlled trial.

OBJECTIVE: This study aims to evaluate the feasibility, safety, and preliminary efficacy of combined cortical neuromodulation (iTBS) and spinal neuromodulation (tSCS) versus tSCS alone, each paired with standardized upper limb rehabilitation, for improving upper limb motor function in chronic incomplete cervical SCI.

METHODS: This single-center, two-arm, assessor-blinded, pilot randomized controlled trial will enroll 24 adults aged 21-65 years with chronic (more than 12 months post-injury) incomplete cervical SCI (American Spinal Injury Association Impairment Scale grade C or D, neurological level C2 to C8) at Alexandra Hospital, Singapore. Participants will be randomized 1:1 to receive either iTBS combined with tSCS plus standardized upper limb rehabilitation or tSCS plus upper limb rehabilitation alone. Interventions will be delivered twice weekly for 12 weeks (24 sessions). The primary outcome is the change in Upper Extremity Motor Score from baseline to 12 weeks. Secondary outcomes include measures of upper limb function, independence, spasticity, corticospinal excitability, quality of life, and goal attainment. Assessments will be conducted at baseline, post-intervention, and at 4- and 12-week follow-up.

RESULTS: This protocol was approved by the National Healthcare Group Domain Specific Review Board. Recruitment is expected to begin in the third quarter of 2026, with data collection anticipated to be completed by the fourth quarter of 2027.

CONCLUSION: This pilot trial will provide the first controlled evidence on whether adjunctive cortical neuromodulation via iTBS produces additional upper limb motor recovery beyond tSCS-based rehabilitation in chronic incomplete cervical SCI. Feasibility data and effect size estimates will inform the design of a subsequent multicenter confirmatory trial.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT07586644.