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

Official title

A Randomized Controlled Trial Comparing Combined TMS-tSCS Neuromodulation Versus tSCS Alone Lower Limb Rehabilitation in Chronic Incomplete SCI

Overview

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.

Detailed description

Background: Spinal cord injury (SCI) affects 15.4 million people worldwide, with 30-40% of incomplete SCI patients remaining nonambulatory, highlighting the importance of gait recovery in rehabilitation. While transcutaneous spinal cord stimulation (tSCS) has emerged as a promising non-invasive neuromodulation technique for enhancing motor recovery, the therapeutic potential of combining tSCS with transcranial magnetic stimulation (TMS) remains largely unexplored. This combination may leverage the complementary mechanisms of supraspinal and spinal neuromodulation to enhance corticospinal tract plasticity and functional motor outcomes. Objective: To evaluate the efficacy and safety of combined TMS-tSCS intervention compared to tSCS alone for improving lower extremity motor function in individuals with chronic incomplete spinal cord injury. Methods: This prospective, randomized, controlled, assessor-blinded clinical trial will enroll 60 participants with chronic (\>12 months post-injury) incomplete spinal cord injury (AIS C or D) aged 18-65 years from Alexandra Hospital, Singapore. Participants will be randomized 1:1 to receive either combined TMS-tSCS (intervention group) or tSCS with sham TMS (control group) for 16 weeks (32 sessions). The primary outcome is change in Lower Extremity Motor Score (LEMS) from baseline to 16 weeks. Secondary outcomes include walking speed (10-Meter Walk Test), functional independence (Spinal Cord Independence Measure-III), spasticity (Modified Ashworth Scale), electromyography of the lower limb muscles and neurophysiological measures of corticospinal excitability. Expected Outcomes: We hypothesize that combined TMS-tSCS will yield superior improvements in LEMS (≥2 points greater improvement) compared to tSCS alone, with enhanced corticospinal tract plasticity as evidenced by neurophysiological measures.

Interventions

• Device 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.
• Device 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 pat

Primary outcome measures

• Lower Extremity Motor Score (LEMS) [Time frame: Week 0]
• Lower Extremity Motor Score (LEMS) [Time frame: Week 8]
• Lower Extremity Motor Score (LEMS) [Time frame: Week 16]
• Lower Extremity Motor Score (LEMS) [Time frame: Week 20]

Secondary outcome measures (12)

• 10-Meter Walk Test (10MWT) [Time frame: Week 0]
• 10-Meter Walk Test (10MWT) [Time frame: Week 8]
• 10-Meter Walk Test (10MWT) [Time frame: Week 16]
• 6-Minute Walk Test (6MWT) [Time frame: Week 0]
• 6-Minute Walk Test (6MWT) [Time frame: Week 8]
• 6-Minute Walk Test (6MWT) [Time frame: Week 16]
• 6-Minute Walk Test (6MWT) [Time frame: Week 20]
• Spinal Cord Independence Measure-III (SCIM-III) [Time frame: Week 0]
• Spinal Cord Independence Measure-III (SCIM-III) [Time frame: Week 8]
• Spinal Cord Independence Measure-III (SCIM-III) [Time frame: Week 16]
• Spinal Cord Independence Measure-III (SCIM-III) [Time frame: Week 20]
• Modified Ashworth Scale (MAS) [Time frame: Week 0]

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Singapore · 1 center

• Alexandra Hospital/ National University Hospital, Singapore — Singapore

Publications

• Shankar R, Chandran G. Lower limb rehabilitation in chronic incomplete SCI: a randomized controlled trial protocol comparing combined TMS-tSCS neuromodulation vs. tSCS alone. Front Neurosci. 2026 Jul 7;20:1773917. doi: 10.3389/fnins.2026.1773917. eCollection 2026. PMID 42483221

Identifiers

NCT: NCT07595497 · 1773917

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗