Combined rTMS and tSCS for Upper Limb Recovery in Cervical SCI

NCT07586644 · tracked via the Priya Life Science Singapore tracker

Sponsor

National University Hospital, Singapore

Phase

Not applicable

Started

2027-03-30

Last updated

2026-05-14

Condition(s) studied

Spinal Cord Injuries (SCI)

Investigational drug(s) / intervention(s)

Transcranial Magnetic StimulationTranscutaneous Spinal Cord Stimulation

Transcranial Magnetic Stimulation: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that enhances cortical excitability and corticospinal drive. Intermittent theta burst stimulation (iTBS), a brief patterned form of rTMS, produces lasting facilitatory effects and is more time-efficient. Evidence indicates rTMS improves motor function, reduces spasticity, and enhances neuroplasticity in SCI.

Transcutaneous Spinal Cord Stimulation: Transcutaneous spinal cord stimulation (tSCS) is a non-invasive neuromodulation technique that delivers electrical stimulation over the spine to activate sensory afferents and enhance spinal motor circuit excitability. Early studies showed it can enable voluntary movement even in motor-complete spinal cord injury (SCI), with subsequent research demonstrating improvements in motor function, standing, and walking in incomplete SCI. Evidence suggests tSCS modulates both spinal and corticospinal pathways, supporting neuroplasticity. The Up-LIFT trial (2024) provided strong clinical evidence, showing that tSCS combined with rehabilitation significantly improved upper limb strength and function in chronic cervical SCI, with 72% of participants meeting effectiveness endpoints and no serious adverse events. Later studies confirmed its safety in home and community settings, though standardization and larger trials remain needed.

Study summary

This clinical trial investigates whether combining cortical and spinal neuromodulation can improve upper limb motor recovery in adults with chronic incomplete cervical spinal cord injury (SCI). Restoring upper limb function is the top rehabilitation priority for individuals with tetraplegia, yet effective interventions remain limited.

The study combines transcutaneous spinal cord stimulation (tSCS), which enhances spinal circuit excitability, with intermittent theta burst stimulation (iTBS), a form of repetitive transcranial magnetic stimulation that increases cortical excitability and strengthens descending motor pathways. While each approach has shown independent promise, their combined use has not been evaluated in a controlled trial.

Eligible participants are adults aged 21-65 with chronic (\>12 months post-injury) incomplete cervical SCI (ASIA Impairment Scale grade C or D, levels C2-C8). A total of 24 participants will be randomised 1:1 to either combined iTBS and tSCS plus standardised upper limb rehabilitation, or tSCS plus rehabilitation alone, across 24 sessions over 12 weeks.

The primary outcome is change in Upper Extremity Motor Score from baseline to week 12. Secondary outcomes cover functional performance, independence, spasticity, corticospinal excitability, quality of life, and goal attainment. Assessments occur at baseline, post-intervention, and at 4- and 12-week follow-up.

As a pilot randomised controlled trial, this study will generate the first controlled evidence on adjunctive cortical neuromodulation alongside tSCS-based rehabilitation, while also producing feasibility data to inform the design of a future definitive multicentre trial.

Eligibility

Sex

ALL

Min age

21 Years

Max age

65 Years

Healthy volunteers

Inclusion Criteria: * Chronicity: More than 12 months post-injury at enrollment * Injury type: Traumatic or non-traumatic incomplete cervical SCI, neurological level C2 to C8 * AIS classification: Grade C or D * UEMS: 10 to 20 out of 25 on the more impaired side; lower bound 10 ensures sufficient voluntary activation for task training and elicitable MEPs, upper bound avoids ceiling effects. * Grip strength: MMT grade 3 or higher in finger flexors (C8 myotome) on at least one side. * Hand function: Able to transfer at least 1 block across the partition within 60 seconds on the more impaired side. * Sitting tolerance: Able to tolerate upright seated posture in own wheelchair for at least 1 continuous hour without symptomatic orthostatic hypotension or pressure-related discomfort requiring position change. * Medical stability: No acute medical complications * Informed consent: Able to provide written informed consent and comply with the study schedule * Medications: Stable regimen for 4 weeks prior, AND participant plus clinician agreement that dosage (baclofen, tizanidine, botulinum toxin) remains unchanged throughout the 12-week intervention; any change logged as protocol deviation * Surgical clearance: Cleared by neurosurgeon or orthopedic surgeon for participation in tSCS-based rehabilitation Exclusion Criteria: * Seizure history: History of seizures or epilepsy * Implanted devices: Intracranial metallic implants, cochlear implants, cardiac pacemakers, or other implanted electronic devices. Cervical spinal instrumentation (e.g., posterior rods, plates, or screws at C2 to T1) is not an exclusion for tSCS provided overlying skin is intact; participants with hardware directly beneath planned electrode sites will undergo low-intensity test stimulation during screening, and electrode placement will be shifted by one interspace if current distortion, focal discomfort, or unexpected motor thresholds are observed. Intracranial hardware remains an absolute exclusion for iTBS. * Prior craniotomy: Prior neurosurgical procedure involving craniotomy * Pregnancy: Currently pregnant or intending to become pregnant during the study period * Psychiatric or cognitive: Active psychiatric illness (eg, untreated major depression, psychosis) or cognitive impairment precluding informed consent * Concurrent neurological disease: Progressive or degenerative neurological condition (eg, multiple sclerosis, motor neuron disease) * Concurrent trials: Participation in another interventional rehabilitation or neurostimulation trial * Skin integrity: Skin lesions or breakdown at electrode placement sites (scalp or posterior cervical spine) * Cortical excitability medications: Medications known to alter cortical excitability (eg, antiepileptic drugs, high-dose benzodiazepines) that cannot be stabilized for at least 2 weeks prior to enrollment * Severe spasticity: Modified Tardieu Scale muscle reaction grade 4 (unfatigable clonus \>10 s) at elbow or wrist flexors on the more impaired side, or spasticity judged by the treating physician as unresponsive to optimised pharmacological management.

Primary outcome measure(s)

Upper Extremity Motor Score (UEMS) — Week 0
The UEMS is a component of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) examination and assesses the strength of 10 key muscles of the upper extremities (5 per side) on a 0 to 5 scale, yielding a score of 0 to 25 per side or 0 to 50 bilaterally. The UEMS has well-established psychometric properties, is sensitive to change in SCI populations. Higher score indicates better outcomes.
Upper Extremity Motor Score (UEMS) — Week 12
The UEMS is a component of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) examination and assesses the strength of 10 key muscles of the upper extremities (5 per side) on a 0 to 5 scale, yielding a score of 0 to 25 per side or 0 to 50 bilaterally. The UEMS has well-established psychometric properties, is sensitive to change in SCI populations. Higher score indicates better outcomes.
Upper Extremity Motor Score (UEMS) — Week 16
The UEMS is a component of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) examination and assesses the strength of 10 key muscles of the upper extremities (5 per side) on a 0 to 5 scale, yielding a score of 0 to 25 per side or 0 to 50 bilaterally. The UEMS has well-established psychometric properties, is sensitive to change in SCI populations. Higher score indicates better outcomes.
Upper Extremity Motor Score (UEMS) — Week 24
The UEMS is a component of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) examination and assesses the strength of 10 key muscles of the upper extremities (5 per side) on a 0 to 5 scale, yielding a score of 0 to 25 per side or 0 to 50 bilaterally. The UEMS has well-established psychometric properties, is sensitive to change in SCI populations. Higher score indicates better outcomes.

Trial sites (1)

Facility	City	Region	Status
Alexandra Hospital/ National University Hospital	Singapore	Singapore

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Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT07586644 on ClinicalTrials.gov ↗ ← All trials in Singapore