Pilot Study to Evaluate the Safety and Tolerability of Spinal Cord Stimulation (SCS) and Paired Spine And Brain Stimulation For Movement Recovery After Spinal Cord Injury (SCI)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 4
- 主要终点
- Serious adverse events related to the study device
研究概览
简要总结
Stimulation of the spinal cord and brain represents a new experimental therapy that may have potential to restore movement after spinal cord injury. While some scientists have begun to study the effect of electrical stimulation on patient's ability to walk and move their legs after lower spinal cord injury, the use of stimulation of the upper (cervical) spine to restore arm and hand function after cervical spinal cord injury remains less well explored. The investigators are doing this research study to improve understanding of whether cervical spinal cord stimulation and brain stimulation can be used to improve arm and hand function. To do this, the investigators will combine spine stimulation (in the form of electrical stimulation from electrical stimulation wires temporarily implanted next to the cervical spinal cord) and brain stimulation (in the form of transcranial magnetic stimulation). The investigators will perform a series of experiments over 29 days to study whether these forms of stimulation can be applied and combined to provide improvement in arm and hand function.
详细描述
Loss of movement following spinal cord injury (SCI) often results from incomplete disruption of structures within the spinal cord, leaving some residual pathways of communication intact. Epidural spinal cord stimulation (SCS) has been used to recruit these residual communication pathways' spared circuits and restore walking in patients with leg paralysis. But SCS to improve arm and hand function remains largely unexplored, even though this is the commonest type of SCI and restoration of upper limb function is of highest priority to patients. The goal of this study is to understand the interactions between SCS and residual neural communication pathways in the brain and spine that control arm and hand function in order to restore movement after cervical SCI.
This is a pilot study in which patients with traumatic spinal cord injury will undergo temporary placement of small electronic stimulation wires near the cervical spinal cord followed by a series of experiments over 29 days focused on three main aims. In Aim 1 (mapping responses to SCS), the investigators will map patient's motor responses to SCS to identify how motor responses are affected by areas of spinal cord injury. In Aim 2 (pairing SCS with attempted motor activation and brain stimulation), the investigators will combine SCS with patient attempts to move in order to study how SCS interacts with conscious motor control and also pair SCS with brain stimulation using transcranial magnetic stimulation. Finally, in Aim 3 (therapeutic effects), the investigators seek to use SCS to change the natural electrical circuits in the spinal cord and observe changes in motor function in both the short- and long-term.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Given that this is a single-arm, open label study, complete masking is not possible. However, to the greatest extent possible, subjects will be blinded to the stimulation-on versus stimulation-off conditions during assessments. In support of the blind, the stimulation condition will be determined by randomization, and both the subjects and the assessors will be blinded to the assignment of the stimulation condition. The stimulation-on condition will begin with a gradual ramp up of stimulation over the course of a minute as subjects are known to acclimate to the presence of stimulation relatively quickly; likewise, the stimulation-off condition will begin with the same one-minute ramp up of stimulation followed by a ramp down of stimulation to off over one minute.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged ≥18 years with incomplete traumatic SCI (American Spinal Injury Association (ASIA) B-D, levels between C4 to T1) incurred > 1 year before the start of the study
- •At least 2/5 motor power in at least one upper extremity muscle group
- •International Standards for Neurological Classification of Spinal Cord Injury Upper Extremity Motor Score (ISNCSCI-UEMS) ≤ 40/50
- •Able to follow multistep commands
- •Ability and willingness to provide informed consent
- •English speaking
排除标准
- •Cervical or thoracic stenosis that would preclude safe lead placement
- •Any ongoing ventilator use (continuous or intermittent)
- •Urinary tract infection or pneumonia requiring treatment (within past 3 months)
- •Skin ulcers or other lesions
- •History of posterior cervical fusion
- •Autonomic dysreflexia requiring treatment (within past 3 months)
- •Implanted brain stimulators
- •Intracranial aneurysm clips
- •Ferromagnetic metallic implants in the head (except for within mouth)
- •Any active implanted device including intrathecal medication pumps or existing spinal cord stimulators (does not include non-active spinal instrumentation such as rods, screws, or interbody devices)
- •Cochlear implants
- •Cardiac pacemaker/defibrillator
- •Any history of seizures
- •Family history of idiopathic epilepsy in a first degree relative
- •Bipolar disorder
- •Any history of suicide attempt
- •Active psychosis
- •Intracranial lesion or increased intracranial pressure
- •History of stroke or intracranial neurologic conditions with structural damage
- •Medications that lower seizure threshold
- •Substance use that lowers seizure threshold (heavy alcohol use)
- •Moderate to severe heart disease
- •Pregnancy or plans to become pregnant within the study period
- •Any other medical or psychological condition that precludes involvement in the study as determined by a study physician
结局指标
主要结局
Serious adverse events related to the study device
时间窗: From enrollment to the end of follow up at 30 weeks
To assess safety of spinal cord stimulation and paired spine and brain stimulation for movement recovery after spinal cord injury, the investigators will record the number of serious adverse events related to the study device.
Cessation of spinal cord stimulation or brain stimulation due to participant request
时间窗: From enrollment to the end of follow up at 30 weeks
To assess tolerability of spinal cord and brain stimulation for movement recovery after spinal cord injury, the investigators will record the number of instances a participant requests permanent cessation of stimulation.
次要结局
- Efficacy derived from spine-only and brain-only recruitment curves(Compared at visit 7/8 to visit 24/25 (~end of week 2 and end of week 5))
- Selectivity derived from spine-only and brain-only recruitment curves(Compared at visit 7/8 to visit 24/25 (~end of week 2 and end of week 5))
- Immediate effect of volitional motor activation combined with spinal stimulation(Compared at visit 7/8 to visit 24/25 (~end of week 2 and end of week 5))
- Immediate pairing effect of spine and brain stimulation(Compared at visit 7/8 to visit 24/25 (~end of week 2 and end of week 5))
- Lasting effects of sustained spine and brain pairing(Compared at visit 7/8 to visit 24/25 (~end of week 2 and end of week 5))
- Magnitude of motor evoked potentials in TMS maps(Compared at visit 7/8 to visit 24/25 (~end of week 2 and end of week 5))
- Size of responsive cortex in TMS maps(Compared at visit 7/8 to visit 24/25 (~end of week 2 and end of week 5))
- Power of cortical field potentials from EEG(Compared with and without stimulation at visit 7/8 to visit 24/25 (~end of week 2 and end of week 5))
- Clinician Global Impression of Change(Study visit 25 (~end of week 5))
- Off Target Effects Questionnaire(Study visit 25 (~end of week 5))
- Canadian Occupational Performance Measure (COPM)- Task Importance(Compared with and without stimulation at visits 7/8, 16, and 24/25 (~end of week 2, beginning of week 4, and end of week 5))
- Canadian Occupational Performance Measure (COPM)- Self-perception of performance(Compared with and without stimulation at visits 7/8, 16, and 24/25 (~end of week 2, beginning of week 4, and end of week 5))
- Canadian Occupational Performance Measure (COPM)- Self-perception of satisfaction(Compared with and without stimulation at visits 7/8, 16, and 24/25 (~end of week 2, beginning of week 4, and end of week 5))
- Patient Global Impression of Change(Study visit 25 (~end of week 5))
- Patient-specific Daily Activity Assessment(Compared with and without stimulation at visits 7/8, 16, and 24/25 (~end of week 2, beginning of week 4, and end of week 5))
- Grasp force(Compared with and without stimulation at visits 7/8, 16, and 24/25 (~end of week 2, beginning of week 4, and end of week 5))
- Pinch force(Compared with and without stimulation at visits 7/8, 16, and 24/25 (~end of week 2, beginning of week 4, and end of week 5))
- Box and block test score(Compared with and without stimulation at visits 7/8, 16, and 24/25 (~end of week 2, beginning of week 4, and end of week 5))
- International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) score- Motor(Compared with and without stimulation at visits 7/8 and 24/25 (~end of week 2 and end of week 5))
- International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) score- Sensory(Compared with and without stimulation at visits 7/8 and 24/25 (~end of week 2 and end of week 5))
- International Standards for Neurological Classification of Spinal Cord Injury-Upper Extremity Measurement Scale (ISNCSCI-UEMS)(Compared with and without stimulation at visits 7/8, 16, and 24/25 (~end of week 2, beginning of week 4, and end of week 5))
- Threshold to detect passive motion (TTDPM)(Compared with and without stimulation at visit 6 (~end of week 2))
- Graded Redefined Assessment of Strength, Sensation and Prehension (GRASSP)- Strength(Compared with and without stimulation at visits 7/8 and 24/25 (~end of week 2 and end of week 5))
- Graded Redefined Assessment of Strength, Sensation and Prehension (GRASSP)- Sensation(Compared with and without stimulation at visits 7/8 and 24/25 (~end of week 2 and end of week 5))
- Graded Redefined Assessment of Strength, Sensation and Prehension (GRASSP)- Prehension Ability(Compared with and without stimulation at visits 7/8 and 24/25 (~end of week 2 and end of week 5))
- Graded Redefined Assessment of Strength, Sensation and Prehension (GRASSP)- Prehension Performance(Compared with and without stimulation at visits 7/8 and 24/25 (~end of week 2 and end of week 5))
- Capabilities of Upper Extremity Test (CUE-T)(Compared with and without stimulation at visits 7/8 and 24/25 (~end of week 2 and end of week 5))
- Portion of study visits completed(From enrollment to the end of follow up at 30 weeks)
研究者
Jason Carmel
Associate Professor of Neurology
Columbia University