Spinal Cord Injuries (SCI)
Conditions
Keywords
lower extremity motor score, motor rehabilitation, Neuromodulation, spinal cord injury, Transcranial Magnetic Stimulation, transcutaneous spinal cord stimulation
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.
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
DEVICETranscranial 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.
DEVICETranscutaneous 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.
Sponsors
National University Hospital, Singapore
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Intervention model description
Single-center, two-arm, assessor-blinded, pilot randomized controlled trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Lower Extremity Motor Score (LEMS) | Week 0 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 10-Meter Walk Test (10MWT) | Week 0 | Assess walking speed over a 10-meter distance at both comfortable and maximum speeds, with excellent reliability (ICC \> 0.95) established for SCI populations. |
| 6-Minute Walk Test (6MWT) | Week 0 | 6-Minute Walk Test (6MWT) will measure walking endurance as the total distance walked in 6 minutes on a standardized course. |
| Spinal Cord Independence Measure-III (SCIM-III) | Week 0 | Spinal Cord Independence Measure-III (SCIM-III) is a disability scale specifically developed for persons with SCI, assessing self-care (0- 20 points), respiration and sphincter management (0-40 points), and mobility (0-40 points). The total score ranges from 0-100, with higher scores indicating greater independence |
| Modified Ashworth Scale (MAS) | Week 0 | Modified Ashworth Scale (MAS) will be used to assess spasticity in bilateral hip flexors, knee extensors, and ankle plantarflexors, graded from 0 (no increase in tone) to 4 (limb rigid in flexion or extension). |
| Peak-to-peak amplitude of motor evoked potential (MEP) | Week 0 | Measured by transcranial magnetic stimulation (TMS). Amplitude, latency, resting and active motor thresholds from FDI and APB will be recorded. The bigger value of peak-to peak amplitude of MEP indicates better outcome |
| Root-Mean-Square (RMS) of Electromyography (EMG) | Week 0 | Surface electromyography (EMG) will be recorded bilaterally from the tibialis anterior, medial gastrocnemius, rectus femoris, and biceps femoris muscles. EMG signals will be recorded during resting state for 10s and isometric muscle contraction for 5s. Normalized EMG RMS will be calculated accordingly. Higher normalized EMG RMS during isometric muscle contraction indicates more muscle engagement. |
Countries
Singapore
Contacts
CONTACTGobinathan Chandran, MBBS
CONTACTTang Ning, PhD
PRINCIPAL_INVESTIGATORGobinathan Chandran, MBBS
NUH
Outcome results
None listed