Combined rTMS and tSCS for Upper Limb Recovery in Cervical SCI

NCT07586644 | Not Yet Recruiting DMC FDA Device

• 1 other identifier: 1833493
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Spinal Cord Injuries (SCI)

Keywords

transcutaneous spinal cord stimulation; intermittent theta burst stimulation; repetitive transcranial magnetic stimulation; cervical spinal cord injury; upper limb rehabilitation; neuromodulation; convergent neuromodulation; tetraplegia

Outcome Measures

Primary Outcomes (4)

• Upper Extremity Motor Score (UEMS)

  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.

  Week 0

• Upper Extremity Motor Score (UEMS)

  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.

  Week 12

• Upper Extremity Motor Score (UEMS)

  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.

  Week 16

• Upper Extremity Motor Score (UEMS)

  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.

  Week 24

Secondary Outcomes (44)

• Graded and Redefined Assessment of Strength, Sensibility, and Prehension Version 2 (GRASSP-2)

  Week 0

• Graded and Redefined Assessment of Strength, Sensibility, and Prehension Version 2 (GRASSP-2)

  Week 12

• Graded and Redefined Assessment of Strength, Sensibility, and Prehension Version 2 (GRASSP-2)

  Week 16

• Graded and Redefined Assessment of Strength, Sensibility, and Prehension Version 2 (GRASSP-2)

  Week 24

• Grip/Pinch Strength

  Week 0

Study Arms (2)

iTBS combined with tSCS plus standardized upper limb rehabilitation

EXPERIMENTAL

Interventions are delivered twice weekly for 12 weeks (24 sessions): iTBS over M1 followed by combined tSCS plus upper limb rehabilitation (45-60 min). tSCS uses a constant-current stimulator with 5×10 cm electrodes at C3-C4 and/or C6-C7, with reference electrodes over the ASIS or clavicles. Parameters: biphasic pulses at 30 Hz, 1 ms pulses with 10 kHz carrier frequency, intensity 40-120 mA, delivered continuously for \~45 minutes. iTBS is delivered over the M1 hand area contralateral to the more impaired limb. Protocol: 600 pulses (3-pulse bursts at 50 Hz, repeated at 5 Hz, 80% AMT over 3-4 minutes. Upper limb rehabilitation follows immediately, supervised by a physiotherapist and occupational therapist, based on the Up-LIFT trial protocol. Sessions include reaching, finger movements, pinch, grip, bimanual coordination, and individualised functional tasks, with difficulty progressed systematically.

Device: Transcranial Magnetic Stimulation; Device: Transcutaneous Spinal Cord Stimulation

tSCS plus standardized upper limb rehabilitation only

ACTIVE COMPARATOR

Interventions are delivered twice weekly for 12 weeks (24 sessions). tSCS uses a constant-current stimulator with 5×10 cm electrodes at C3-C4 and/or C6-C7, with reference electrodes over the ASIS or clavicles. Parameters: biphasic pulses at 30 Hz, 1 ms pulses with 10 kHz carrier frequency, intensity 40-120 mA, delivered continuously for \~45 minutes. The carrier frequency reduces skin discomfort and enables deeper dorsal root activation. Upper limb rehabilitation follows immediately, supervised by a physiotherapist and occupational therapist, based on the Up-LIFT trial protocol. Sessions include reaching, finger movements, pinch, grip, bimanual coordination, and individualised functional tasks, with difficulty progressed systematically.

Device: Transcutaneous Spinal Cord Stimulation

Interventions

Transcranial Magnetic Stimulation DEVICE

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.

iTBS combined with tSCS plus standardized upper limb rehabilitation

Transcutaneous Spinal Cord Stimulation DEVICE

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.

iTBS combined with tSCS plus standardized upper limb rehabilitation; tSCS plus standardized upper limb rehabilitation only

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Seizure history: History of seizures or epilepsy
• 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.

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (1)

Alexandra Hospital/ National University Hospital

Singapore, Singapore

Location

MeSH Terms

Conditions

Spinal Cord Injuries; Quadriplegia

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Paralysis; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Gobinathan Chandran, MBBS

  NUH

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gobinathan Chandran, MBBS

CONTACT

+65 94575924; gobinathan_chandran@nuhs.edu.sg

Tang Ning, PhD

CONTACT

ning_tang@nuhs.edu.sg

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single-center, two-arm, assessor-blinded, pilot randomized controlled trial

Study Record Dates

• First Submitted: May 8, 2026
• First Posted: May 14, 2026
• Study Start (Estimated): March 30, 2027
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 30, 2028
• Last Updated: May 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)