Noninvasive Brain Stimulation Therapy in Subacute Human Spinal Cord Injury: A Translational Study
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Eligibility - (Percentage candidates eligible of screened patients)
研究概览
简要总结
No accepted clinical therapies exist for repair of motor pathways following spinal cord injury (SCI) in humans, leaving permanent disability and devastating personal and socioeconomic cost. A robust neural repair strategy has been demonstrated in preclinical studies, that is ready for translation to recovery of hand and arm function in human SCI, comprising daily transcranial magnetic stimulation treatment at the inpatient rehabilitation facility. This study will establish clinical effect size of the intervention, as well as safety and feasibility necessary for a subsequent controlled efficacy trial and inform preclinical studies for dosing optimization.
详细描述
The objective of this proposal is to begin translating findings from pre-clinical studies to human motor deficits following cervical SCI (cervSCI). This HF-rTMS treatment protocol has not been previously assessed in human SCI and is qualitatively different from rTMS protocols reported to transiently modulate excitability of existing pathways, previously demonstrated in the literature. The protocol involves a daily stimulation of ~10 mins bilateral HF-rTMS for 2 weeks. SCI participants will be studied in a United States inpatient setting for this phase I study.
Given the findings in the pre-clinical model of robust axonal sprouting and functional synapse formation close to the damaged tissue using the above stimulation parameters, the transcranial magnetic stimulation treatment will target the hand-forearm region of the primary motor cortex, bilaterally. The aim is to include the cortical representation of affected muscles adjacent to the neurological level of injury. This zone often contains a mix of clinically and neurophysiologically intact, weakly innervated and denervated corticospinal pathways. Under standard sub-acute rehabilitation care, recovery of up to 1 neurological level of injury (NLI) is often the case, but improvement of 2 or more levels is far less common (<30% of patients). To examine the feasibility and safety of this novel intervention is the principal aim of the study. The associated potential clinical and neurophysiological changes will also be evaluated. These preliminary data will be used to power a subsequent efficacy trial to test the hypothesis that rTMS induced corticospinal augmentation will result in greater than typical extension of the NLI in human SCI, assessed up to the stable recovery phase at 6 months post-injury.
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, Care Provider, Outcomes Assessor)
盲法说明
Patients will be equally randomized to either the Active rTMS or Sham rTMS group following the Baseline Assessment. Device will be set up to active/sham mode prior to intervention using a unique patient and intervention code by an unblinded study team member. Subjects, outcome assessors and staff administering rTMS intervention (care provider) will be blinded to the device setting (Active/Sham).
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Post traumatic or non-traumatic cervical spinal cord injury (SCI) with residual upper-extremity paralysis
- •Time post-injury less than six weeks
- •Neurological Level of Injury (NLI) C4-C6
- •ASIA Impairment Scale (AIS) A-D
- •Sensory and motor zone of partial preservation (ZPP, clinically complete or incomplete)
- •Age 18 to 80 years old
排除标准
- •Ventilator dependence;
- •Concurrent neurological condition affecting sensory or motor pathways or otherwise limiting ability to participate in the study;
- •Evidence of trauma-related brain injury;
- •Contraindications for TMS or history of seizure or seizure risk;
- •Spinal instability;
- •Uncontrolled autonomic dysreflexia;
- •Severe muscular or skeletal or neuropathic pain;
- •Known or suspected pregnancy;
- •Medically unstable or any reason the physician may deem as inappropriate for the participant to enroll or continue in the study.
研究组 & 干预措施
Active rTMS
10 daily sessions of High-frequency Transcranial Magnetic Stimulation (HF-rTMS) applied bilaterally over the hand primary motor area informed by e-field modelling and targeting will be aided by neuronavigation system for precise targeting during each intervention session. Active group will receive HF-rTMS intensity calculated using electric field modelling to create electric field intensity of approximately motor threshold, using the cool-B65 A/P rTMS coil.
干预措施: Active rTMS (Device)
Sham rTMS
10 daily sessions of Sham High-frequency Transcranial Magnetic Stimulation (HF-rTMS) applied bilaterally over the hand primary motor area informed by e-field modelling and targeting will be aided by neuronavigational system for precise targeting during each intervention session Sham group receives no active magnetic stimulation. Cool-B65 A/P rTMS coil will be used to avoid unblinding of administrator and/or study participant.
干预措施: sham rTMS (Device)
结局指标
主要结局
Eligibility - (Percentage candidates eligible of screened patients)
时间窗: 21 months (Recruitment period)
The proportion of patients who can take part in the study, whether they later agree to or not.
Recruitment - (Percentage candidates enrolled of approached patients)
时间窗: 21 months (Recruitment period)
The proportion of eligible patients who agree to take part in the study.
Adherence to intervention - (Percentage candidates who dropout during the intervention period of enrolled candidates)
时间窗: 2 years (Duration of human subjects' involvement)
Proportion of intervention-related dropouts.
Adherence to outcome assessment - (Percentage candidates who do not complete outcome assessments of enrolled candidates)
时间窗: 2 years (Duration of human subjects' involvement)
Proportion of patients that complete the assessments at the start and the end of the intervention.
Adverse Events
时间窗: 2 years (Duration of human subjects' involvement)
Rate of adverse and serious adverse events
Retention - (Percentage candidates who do not complete 6-month follow up of enrolled candidates)
时间窗: 2 years (Duration of human subjects' involvement)
The number of patients who drop out or were 'lost' at the 6-month follow-up.
次要结局
- Incidence of reconnectivity (Proportion: MEP absent, covert to MEP present)(Baseline and 6 months after injury)
- Change in motor threshold between groups (Difference in %Maximum Stimulator Output to achieve motor threshold)(Baseline and 6 months after injury)
- Motor neurological level change (ISNCSCI assessment)(Baseline and 6 months after injury)
研究者
Dylan Edwards
Director, Jefferson Moss Rehabilitation Research Institute
Albert Einstein Healthcare Network