A Randomized Controlled Trial Comparing Combined TMS-tSCS Neuromodulation Versus tSCS Alone Lower Limb Rehabilitation in Chronic Incomplete SCI
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Lower Extremity Motor Score (LEMS)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Transcranial Magnetic Stimulation (Device)
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.
干预措施: Transcutaneous Spinal Cord Stimulation (Device)
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.
干预措施: Transcutaneous Spinal Cord Stimulation (Device)
结局指标
主要结局
Lower Extremity Motor Score (LEMS)
时间窗: 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
Lower Extremity Motor Score (LEMS)
时间窗: Week 8
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
Lower Extremity Motor Score (LEMS)
时间窗: Week 16
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
Lower Extremity Motor Score (LEMS)
时间窗: Week 20
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
次要结局
- 6-Minute Walk Test (6MWT)(Week 8)
- 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 16)
- 6-Minute Walk Test (6MWT)(Week 20)
- Spinal Cord Independence Measure-III (SCIM-III)(Week 0)
- Spinal Cord Independence Measure-III (SCIM-III)(Week 8)
- Spinal Cord Independence Measure-III (SCIM-III)(Week 16)
- Spinal Cord Independence Measure-III (SCIM-III)(Week 20)
- Modified Ashworth Scale (MAS)(Week 0)
- Modified Ashworth Scale (MAS)(Week 8)
- Modified Ashworth Scale (MAS)(Week 16)
- Modified Ashworth Scale (MAS)(Week 20)
- 10-Meter Walk Test (10MWT)(Week 20)
- Peak-to-peak amplitude of motor evoked potential (MEP)(Week 0)
- Peak-to-peak amplitude of motor evoked potential (MEP)(Week 8)
- Peak-to-peak amplitude of motor evoked potential (MEP)(Week 16)
- Peak-to-peak amplitude of motor evoked potential (MEP)(Week 20)
- Root-Mean-Square (RMS) of Electromyography (EMG)(Week 0)
- Root-Mean-Square (RMS) of Electromyography (EMG)(Week 8)
- Root-Mean-Square (RMS) of Electromyography (EMG)(Week 16)
- Root-Mean-Square (RMS) of Electromyography (EMG)(Week 20)