Combined TMS-tSCS for Lower Limb Rehabilitation in Chronic Incomplete SCI

NCT07595497 | Not Yet Recruiting DMC FDA Device

• 1 other identifier: 1773917
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

he goal of this clinical trial is to learn if combined brain and spinal cord stimulation using TMS-tSCS can improve leg strength and walking recovery in adults with chronic incomplete spinal cord injury. The main questions it aims to answer are: Does combined TMS-tSCS improve lower limb motor function more than tSCS alone? Is combined TMS-tSCS safe and does it improve walking speed, independence, muscle activity, spasticity, and nerve pathway function? Researchers will compare combined TMS-tSCS with tSCS alone with sham TMS to see if adding brain stimulation leads to better recovery than spinal stimulation alone. Participants will: Attend 32 treatment sessions over 16 weeks. Receive either combined TMS-tSCS or tSCS with sham TMS. Undergo assessments of leg strength, walking speed, daily function, muscle stiffness, muscle activity, and nerve pathway function before and after treatment.

Conditions

Spinal Cord Injuries (SCI)

Keywords

lower extremity motor score; motor rehabilitation; Neuromodulation; spinal cord injury; Transcranial Magnetic Stimulation; transcutaneous spinal cord stimulation

Outcome Measures

Primary Outcomes (4)

• Lower Extremity Motor Score (LEMS)

  Description: The LEMS is a component of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), representing the summed strength of five key muscle groups in each lower extremity (hip flexors, knee extensors, ankle dorsiflexors, great toe extensors, and ankle plantarflexors), graded on a 0-5 scale for each muscle group. The total LEMS ranges from 0 to 50 points, with higher scores indicating greater motor strength

  Week 0

• Lower Extremity Motor Score (LEMS)

  The LEMS is a component of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), representing the summed strength of five key muscle groups in each lower extremity (hip flexors, knee extensors, ankle dorsiflexors, great toe extensors, and ankle plantarflexors), graded on a 0-5 scale for each muscle group. The total LEMS ranges from 0 to 50 points, with higher scores indicating greater motor strength

  Week 8

• Lower Extremity Motor Score (LEMS)

  Description: The LEMS is a component of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), representing the summed strength of five key muscle groups in each lower extremity (hip flexors, knee extensors, ankle dorsiflexors, great toe extensors, and ankle plantarflexors), graded on a 0-5 scale for each muscle group. The total LEMS ranges from 0 to 50 points, with higher scores indicating greater motor strength

  Week 16

• Lower Extremity Motor Score (LEMS)

  Description: The LEMS is a component of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), representing the summed strength of five key muscle groups in each lower extremity (hip flexors, knee extensors, ankle dorsiflexors, great toe extensors, and ankle plantarflexors), graded on a 0-5 scale for each muscle group. The total LEMS ranges from 0 to 50 points, with higher scores indicating greater motor strength

  Week 20

Secondary Outcomes (24)

• 10-Meter Walk Test (10MWT)

  Week 0

• 10-Meter Walk Test (10MWT)

  Week 8

• 10-Meter Walk Test (10MWT)

  Week 16

• 6-Minute Walk Test (6MWT)

  Week 0

• 6-Minute Walk Test (6MWT)

  Week 8

Study Arms (2)

iTBS combined with tSCS plus standardized lower limb rehabilitation

EXPERIMENTAL

Interventions are delivered twice weekly for 16 weeks (32 sessions): iTBS over M1 followed by combined tSCS plus lower limb rehabilitation (45-60 min). tSCS uses a constant-current stimulator with 5×10 cm electrodes at placed at one level above and below the site of the spinal cord injury, 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 iTBS protocol consists of bursts of 3 pulses at 50 Hz, repeated at 5 Hz (200 ms between bursts), delivered in 2-second trains with 8-second inter-train intervals. Each session will deliver 600 pulses total. The stimulation target will be the leg motor area of the primary motor cortex, identified using established anatomical landmarks and confirmed by eliciting motor evoked potentials (MEPs) in lower extremity muscles. Lower limb rehabilitation follows immediately, supervised by a physiotherapist.

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

tSCS plus standardized lower limb rehabilitation only

ACTIVE COMPARATOR

tSCS uses a constant-current stimulator with 5×10 cm electrodes at placed at one level above and below the site of the spinal cord injury, 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. Lower limb rehabilitation follows immediately, supervised by a physiotherapist.

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 lower 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 lower limb rehabilitation; tSCS plus standardized lower limb rehabilitation only

Eligibility Criteria

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

You may qualify if:

• Age 18-65 years at enrolment
• Chronic traumatic spinal cord injury, defined as ≥12 months post-injury
• Incomplete spinal cord injury, AIS grade C or D
• Neurological level of injury from C2 to L1
• Baseline Lower Extremity Motor Score (LEMS) \>10 points
• Medically stable
• Able to provide informed consent
• Able to commit to the full study duration
• Able to attempt the 10-Meter Walk Test and 6-Minute Walk Test, with or - without assistive devices and standby assistance

You may not qualify if:

• History of seizures or epilepsy
• Implanted electronic devices, such as: Pacemaker, Cochlear implant, Deep brain stimulator, Spinal cord stimulator, Metallic implants in the head or spine
• Pregnancy or planned pregnancy
• Active psychiatric disorder or cognitive impairment
• Concomitant neurological conditions, such as: Stroke, Traumatic brain injury and Neuropathy
• Skin breakdown at electrode sites
• Current participation in another clinical trial
• History of skull surgery or craniotomy
• Use of medications that alter cortical excitability within the past 2 weeks

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (1)

Alexandra Hospital/ National University Hospital, Singapore

Singapore, Singapore

Location

MeSH Terms

Conditions

Spinal Cord Injuries

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries

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 12, 2026
• First Posted: May 19, 2026
• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): March 1, 2028
• Last Updated: May 19, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)