Combined TMS-tSCS for Lower Limb Rehabilitation in Chronic Incomplete SCI
12 de mayo de 2026 actualizado por: National University Hospital, Singapore
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.
Descripción general del estudio
Estado
Aún no reclutando
Condiciones
Intervención / Tratamiento
Descripción detallada
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.
Tipo de estudio
Intervencionista
Inscripción (Estimado)
24
Fase
- No aplica
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Estudio Contacto
- Nombre: Gobinathan Chandran, MBBS
- Número de teléfono: +65 94575924
- Correo electrónico: Gobinathan_CHANDRAN@nuhs.edu.sg
Copia de seguridad de contactos de estudio
- Nombre: Tang Ning, PhD
- Correo electrónico: ning_tang@nuhs.edu.sg
Ubicaciones de estudio
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-
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Singapore, Singapur
- Alexandra Hospital/ National University Hospital, Singapore
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Contacto:
- Gobinathan Chandran, MBBS
- Número de teléfono: +65 94575924
- Correo electrónico: Gobinathan_CHANDRAN@nuhs.edu.sg
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
No
Descripción
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
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Único
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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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.
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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.
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.
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Comparador activo: 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.
|
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.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Lower Extremity Motor Score (LEMS)
Periodo de tiempo: Week 0
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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
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Week 0
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Lower Extremity Motor Score (LEMS)
Periodo de tiempo: Week 8
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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
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Week 8
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Lower Extremity Motor Score (LEMS)
Periodo de tiempo: Week 16
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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
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Week 16
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Lower Extremity Motor Score (LEMS)
Periodo de tiempo: Week 20
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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
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Week 20
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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10-Meter Walk Test (10MWT)
Periodo de tiempo: Week 0
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Assess walking speed over a 10-meter distance at both comfortable and maximum speeds, with excellent reliability (ICC > 0.95) established for SCI populations.
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Week 0
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10-Meter Walk Test (10MWT)
Periodo de tiempo: Week 8
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Assess walking speed over a 10-meter distance at both comfortable and maximum speeds, with excellent reliability (ICC > 0.95) established for SCI populations.
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Week 8
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10-Meter Walk Test (10MWT)
Periodo de tiempo: Week 16
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Assess walking speed over a 10-meter distance at both comfortable and maximum speeds, with excellent reliability (ICC > 0.95) established for SCI populations.
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Week 16
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6-Minute Walk Test (6MWT)
Periodo de tiempo: Week 0
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6-Minute Walk Test (6MWT) will measure walking endurance as the total distance walked in 6 minutes on a standardized course.
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Week 0
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6-Minute Walk Test (6MWT)
Periodo de tiempo: Week 8
|
6-Minute Walk Test (6MWT) will measure walking endurance as the total distance walked in 6 minutes on a standardized course.
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Week 8
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6-Minute Walk Test (6MWT)
Periodo de tiempo: Week 16
|
6-Minute Walk Test (6MWT) will measure walking endurance as the total distance walked in 6 minutes on a standardized course.
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Week 16
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6-Minute Walk Test (6MWT)
Periodo de tiempo: Week 20
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6-Minute Walk Test (6MWT) will measure walking endurance as the total distance walked in 6 minutes on a standardized course.
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Week 20
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Spinal Cord Independence Measure-III (SCIM-III)
Periodo de tiempo: Week 0
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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
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Week 0
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Spinal Cord Independence Measure-III (SCIM-III)
Periodo de tiempo: Week 8
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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
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Week 8
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Spinal Cord Independence Measure-III (SCIM-III)
Periodo de tiempo: Week 16
|
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
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Week 16
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Spinal Cord Independence Measure-III (SCIM-III)
Periodo de tiempo: Week 20
|
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
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Week 20
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Modified Ashworth Scale (MAS)
Periodo de tiempo: Week 0
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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).
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Week 0
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Modified Ashworth Scale (MAS)
Periodo de tiempo: Week 8
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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).
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Week 8
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Modified Ashworth Scale (MAS)
Periodo de tiempo: Week 16
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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
|
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Modified Ashworth Scale (MAS)
Periodo de tiempo: Week 20
|
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
|
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10-Meter Walk Test (10MWT)
Periodo de tiempo: Week 20
|
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
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Peak-to-peak amplitude of motor evoked potential (MEP)
Periodo de tiempo: Week 0
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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
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Week 0
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Peak-to-peak amplitude of motor evoked potential (MEP)
Periodo de tiempo: Week 8
|
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
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Week 8
|
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Peak-to-peak amplitude of motor evoked potential (MEP)
Periodo de tiempo: Week 16
|
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
|
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Peak-to-peak amplitude of motor evoked potential (MEP)
Periodo de tiempo: Week 20
|
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
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Root-Mean-Square (RMS) of Electromyography (EMG)
Periodo de tiempo: Week 0
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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.
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Week 0
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Root-Mean-Square (RMS) of Electromyography (EMG)
Periodo de tiempo: Week 8
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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.
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Week 8
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Root-Mean-Square (RMS) of Electromyography (EMG)
Periodo de tiempo: Week 16
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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.
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Week 16
|
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Root-Mean-Square (RMS) of Electromyography (EMG)
Periodo de tiempo: Week 20
|
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.
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Week 20
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Investigadores
- Investigador principal: Gobinathan Chandran, MBBS, NUH
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Estimado)
1 de enero de 2027
Finalización primaria (Estimado)
30 de diciembre de 2027
Finalización del estudio (Estimado)
1 de marzo de 2028
Fechas de registro del estudio
Enviado por primera vez
12 de mayo de 2026
Primero enviado que cumplió con los criterios de control de calidad
12 de mayo de 2026
Publicado por primera vez (Actual)
19 de mayo de 2026
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
19 de mayo de 2026
Última actualización enviada que cumplió con los criterios de control de calidad
12 de mayo de 2026
Última verificación
1 de mayo de 2026
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 1773917
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
NO
Descripción del plan IPD
According to institution research polices, research agreement needs to be signed before sharing individual data with external parties.
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
No
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
Sí
producto fabricado y exportado desde los EE. UU.
Sí
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .