Combining Non-invasive Brain and Spinal Cord Stimulation for Improving Arm and Hand Function Following Spinal Cord Injury.
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
- Feasibility outcomes
研究概览
简要总结
Cervical spinal cord injury (SCI) disrupts communication between the brain and spinal circuits, affecting voluntary movement control and contributing to arm and hand impairments, the top recovery priority for people with tetraplegia. Although rehabilitation and emerging neuromodulation approaches can support meaningful gains, many individuals experience persistent limitations in reaching and grasping. Current noninvasive stimulation strategies typically target the brain OR the spinal cord alone, despite strong reciprocal interactions between these structures. Cervical transcutaneous spinal cord stimulation (tSCS) can enhance upper limb function. Cerebellar stimulation, given its key role in sensorimotor integration and modulation of corticospinal excitability, represents a promising but underexplored therapeutic target. Theta burst stimulation (TBS), a rapid form of repetitive transcranial magnetic stimulation (TMS), induces lasting changes in cortical excitability and may promote associative plasticity when paired with spinal cord stimulation. This double-blind, randomized, sham-controlled pilot trial (n=24) will evaluate the feasibility, preliminary efficacy, and mechanisms of combined cerebellar TBS + cervical tSCS in people with chronic cervical SCI (AIS B, C or D). Participants will either receive cerebellar TBS + cervical tSCS, tSCS only, or sham stimulation while engaging in functional task practice such as pinching and grasping 3x/week for 8 weeks. Feasibility outcomes include adherence, retention, and safety. Efficacy will be assessed using the GRASSP strength sub-score and KINARM-based measures of sensorimotor control. Mechanistic outcomes will assess changes in cortical and spinal cord functional connectivity using resting state fMRI, corticospinal excitability using motor evoked potentials, and spinal excitability using the H reflex. Findings will establish whether combined cerebellar TBS and cervical tSCS is feasible, safe, and capable of enhancing upper limb recovery.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 19 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •At least 19 years of age and no older than 75 years at the time of enrollment. Previous research has demonstrated the safety and efficacy of stimulation-based interventions in adults up to 75 years of age. The lower age limit reflects the legal age for independent informed consent in British Columbia.7,8
- •Non-progressive cervical SCI from C2-C8 inclusive
- •AIS classification B, C or D
- •Indicated for upper extremity training procedures by the participant's treating physician, occupational therapist, or physical therapist
- •GRASSP-Prehension score ≥10 or GRASSP-Strength score ≥30
- •Minimum 12 months after injury (i.e., chronic SCI)
- •If prescribed anti-spasticity or pain medications, must be at a stable dose for at least 4 weeks before commencing study procedures
- •Stable management of spinal cord related clinical issues (e.g., spasticity management, autonomic dysreflexia)
- •Capable of providing informed consent
排除标准
- •Has any unstable or significant medical condition that is likely to interfere with study procedures or likely to confound study endpoint evaluations, such as severe neuropathic pain, depression, mood disorders or other cognitive disorders
- •Has been diagnosed with autonomic dysreflexia that is severe, unstable and uncontrolled
- •History of additional neurologic disease, such as stroke, multiple sclerosis and traumatic brain injury
- •History of seizures (e.g. epilepsy).
- •Any implanted metal (other than dental implants) in the skull or presence of pacemakers, stimulators, or medication pumps in the trunk.
- •Participant has undergone electrode implantation surgery.
研究组 & 干预措施
Cerebellar TBS + Cervical tSCS
Participants will recieve 60 min of active cervical transcutaneous spinal cord stimulation with intermittent bouts of active Cerebellar theta burst stimulation 3x/week for 8 weeks, alongside functional task practice.
干预措施: Functional task practice (Behavioral)
Cervical tSCS only
Participant will recieve 60 min of active cervical transcutaneous spinal cord stimulation only 3x/week for 8 weeks, alongside functional task practice.
干预措施: Cervical transcutaneous spinal cord stimulation (Device)
Cervical tSCS only
Participant will recieve 60 min of active cervical transcutaneous spinal cord stimulation only 3x/week for 8 weeks, alongside functional task practice.
干预措施: Functional task practice (Behavioral)
Sham Cerebellar TBS + Sham Cervical tSCS
Participants will recieve 60 min of sham cervical transcutaneous spinal cord stimulation with intermittent bouts of sham Cerebellar theta burst stimulation 3x/week for 8 weeks, alongside functional task practice.
干预措施: Cerebellar theta burst stimulation (Device)
Sham Cerebellar TBS + Sham Cervical tSCS
Participants will recieve 60 min of sham cervical transcutaneous spinal cord stimulation with intermittent bouts of sham Cerebellar theta burst stimulation 3x/week for 8 weeks, alongside functional task practice.
干预措施: Cervical transcutaneous spinal cord stimulation (Device)
Sham Cerebellar TBS + Sham Cervical tSCS
Participants will recieve 60 min of sham cervical transcutaneous spinal cord stimulation with intermittent bouts of sham Cerebellar theta burst stimulation 3x/week for 8 weeks, alongside functional task practice.
干预措施: Functional task practice (Behavioral)
Cerebellar TBS + Cervical tSCS
Participants will recieve 60 min of active cervical transcutaneous spinal cord stimulation with intermittent bouts of active Cerebellar theta burst stimulation 3x/week for 8 weeks, alongside functional task practice.
干预措施: Cerebellar theta burst stimulation (Device)
Cerebellar TBS + Cervical tSCS
Participants will recieve 60 min of active cervical transcutaneous spinal cord stimulation with intermittent bouts of active Cerebellar theta burst stimulation 3x/week for 8 weeks, alongside functional task practice.
干预措施: Cervical transcutaneous spinal cord stimulation (Device)
结局指标
主要结局
Feasibility outcomes
时间窗: From enrollment to the end of stimulation at 8 weeks
Feasibility, which will be assessed through adherence, recruitment, retention, and adverse event rates across all groups. We will specifically document session numbers, dates and times, as well as the frequency and severity of skin irritations, abnormal blood pressure responses (e.g., autonomic dysreflexia), cardiac responses (e.g., tachycardia, bradycardia) and any symptoms. Participant safety will be monitored throughout the intervention via regular skin integrity checks and cardiovascular recordings (blood pressure and heart rate) throughout each session.
Upper limb strength
时间窗: Baseline and after 8 weeks of stimulation
Change in upper limb strength from pre- to post-intervention using the Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) strength sub-score. The GRASSP evaluates three domains: strength manual muscle testing of key upper limb muscles), sensibility (light touch and pinprick discrimination), and prehension, which includes both a qualitative analysis of grasp patterns and a performance-based component (GRASSP-Prehension Performance) that assesses functional use of the hand during object manipulation tasks. Strength will be the primary dependent measure from this measure.
Sensorimotor network connectivity
时间窗: Baseline and after 8 weeks of stimulation
Change in functional connectivity strength of the cortical sensorimotor network from pre- to post- intervention using resting-state functional MRI (fMRI). We will use a Philips Ingenia Elition 3.0T MRI scanner with a 32-channel sensitivity head coil to scan brain and a separate 20 channel dStream head/neck coil for cervical spinal cord. We will collect T1 and resting state functional MRI scans of both brain and cervical spinal cord at baseline and post-intervention. Resting state functional MRI will be acquired to characterize functional reorganization of the brain and/or spinal cord driven by cerebellar TBS + cervical tSCS (or tSCS alone) alongside functional task practice. Brain and spinal cord functional connectivity: We will characterize properties of the sensorimotor network, particularly global efficiency, which represents the overall capacity that the network has to transfer information (i.e., quantifies the extent to which nodes of the network are integrated).
次要结局
- Arm and hand sensorimotor control(Baseline and after 8 weeks of stimulation)
- Corticospinal excitability (Motor Evoked Potentials [MEPs]):(Baseline and after 8 weeks of stimulation)
- Cerebellar-brain inhibition (CBI)(Baseline and after 8 weeks of stimulation)
- Spinal reflex excitability (H-reflex):(Baseline and after 8 weeks of stimulation)
研究者
Lara Boyd
Professor
University of British Columbia