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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Spinal Cord Injuries (SCI)
• Intervention / Treatment: Device: Transcranial Magnetic Stimulation; Device: Transcutaneous Spinal Cord Stimulation

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.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Gobinathan Chandran, MBBS; Phone Number: +65 94575924; Email: gobinathan_chandran@nuhs.edu.sg
• Study Contact Backup: Name: Tang Ning, PhD; Email: ning_tang@nuhs.edu.sg

Study Locations

• Singapore
  • Singapore, Singapore
    • Alexandra Hospital/ National University Hospital, Singapore
    • Contact: Gobinathan Chandran, MBBS; Phone Number: +65 94575924; Email: gobinathan_chandran@nuhs.edu.sg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: iTBS combined with tSCS plus standardized lower limb rehabilitation; 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; 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 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.
Active Comparator: tSCS plus standardized lower limb rehabilitation only; 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
10-Meter Walk Test (10MWT)	Assess walking speed over a 10-meter distance at both comfortable and maximum speeds, with excellent reliability (ICC > 0.95) established for SCI populations.	Week 0
10-Meter Walk Test (10MWT)	Assess walking speed over a 10-meter distance at both comfortable and maximum speeds, with excellent reliability (ICC > 0.95) established for SCI populations.	Week 8
10-Meter Walk Test (10MWT)	Assess walking speed over a 10-meter distance at both comfortable and maximum speeds, with excellent reliability (ICC > 0.95) established for SCI populations.	Week 16
6-Minute Walk Test (6MWT)	6-Minute Walk Test (6MWT) will measure walking endurance as the total distance walked in 6 minutes on a standardized course.	Week 0
6-Minute Walk Test (6MWT)	6-Minute Walk Test (6MWT) will measure walking endurance as the total distance walked in 6 minutes on a standardized course.	Week 8
6-Minute Walk Test (6MWT)	6-Minute Walk Test (6MWT) will measure walking endurance as the total distance walked in 6 minutes on a standardized course.	Week 16
6-Minute Walk Test (6MWT)	6-Minute Walk Test (6MWT) will measure walking endurance as the total distance walked in 6 minutes on a standardized course.	Week 20
Spinal Cord Independence Measure-III (SCIM-III)	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	Week 0
Spinal Cord Independence Measure-III (SCIM-III)	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	Week 8
Spinal Cord Independence Measure-III (SCIM-III)	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	Week 16
Spinal Cord Independence Measure-III (SCIM-III)	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	Week 20
Modified Ashworth Scale (MAS)	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).	Week 0
Modified Ashworth Scale (MAS)	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).	Week 8
Modified Ashworth Scale (MAS)	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).	Week 16
Modified Ashworth Scale (MAS)	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).	Week 20
10-Meter Walk Test (10MWT)	Assess walking speed over a 10-meter distance at both comfortable and maximum speeds, with excellent reliability (ICC > 0.95) established for SCI populations.	Week 20
Peak-to-peak amplitude of motor evoked potential (MEP)	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	Week 0
Peak-to-peak amplitude of motor evoked potential (MEP)	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	Week 8
Peak-to-peak amplitude of motor evoked potential (MEP)	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	Week 16
Peak-to-peak amplitude of motor evoked potential (MEP)	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	Week 20
Root-Mean-Square (RMS) of Electromyography (EMG)	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.	Week 0
Root-Mean-Square (RMS) of Electromyography (EMG)	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.	Week 8
Root-Mean-Square (RMS) of Electromyography (EMG)	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.	Week 16
Root-Mean-Square (RMS) of Electromyography (EMG)	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.	Week 20

Collaborators and Investigators

• Sponsor: National University Hospital, Singapore
• Investigators: Principal Investigator: Gobinathan Chandran, MBBS, NUH

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: May 12, 2026
• First Submitted That Met QC Criteria: May 12, 2026
• First Posted (Actual): May 19, 2026

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Neuromodulation; Transcranial Magnetic Stimulation; spinal cord injury; transcutaneous spinal cord stimulation; motor rehabilitation; lower extremity motor score
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Trauma, Nervous System; Spinal Cord Diseases; Spinal Cord Injuries; Therapeutics; Magnetic Field Therapy; Transcranial Magnetic Stimulation
• Other Study ID Numbers: 1773917

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: According to institution research polices, research agreement needs to be signed before sharing individual data with external parties.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes