rTMS: A Treatment to Restore Function After Severe TBI
试验速览
- 阶段
- 不适用
- 入组人数
- 58
- 试验地点
- 4
- 主要终点
- Disability Rating Scale
研究概览
简要总结
The purpose of this study is to address the need for targeted treatments that induce functional and structural changes in the brain, ultimately improving neurobehavioral functioning, the investigators propose examining the therapeutic effectiveness of repetitive Transcranial Magnetic Stimulation (rTMS). The objective is to improve functional recovery for persons remaining in vegetative (VS) and minimally conscious (MCS) states 3 to 24 months after severe TBI. The approach is to determine the neurobehavioral effect of rTMS, the relationship between neurobehavioral changes and net neural effects, and to identify and define the neural mechanisms related to neurobehavioral improvements by providing 30 active or placebo rTMS sessions.
详细描述
The specific aims (SA) of the CDMRP study are:
SA-1: To determine presence, direction and sustainability of rTMS induced neurobehavioral effects using the DRS (lower scores indicate more function).
SA-2: To determine presence, direction and sustainability of rTMS-induced changes in functional neural activation and whether these changes correlate with improving neurobehavioral function.
SA-3: To determine the rTMS effect on white fiber tracts and whether rTMS-related effects correlate with neurobehavioral gains. White fiber tracts will be examined according to changes in Fractional Anisotropy (FA), Mean Diffusivity (MD), Radial Diffusivity (RD), and Axial Diffusivity (AD).
SA-4: To confirm rTMS safety for severe TBI. The investigators hypothesize that there will be no difference between active and placebo groups according to average number of research related adverse events (AE) during treatment.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •At study screening, persons have remained in states of Seriously Impaired Consciousness (SIC) for at least 3 and up to 24 months after TBI
- •18 years of age or older
- •Traumatic Brain Injury etiology
- •Able to participate in all phases of study including follow-up re-admission
- •Able to identify legally authorized representative/surrogate who is able to read and understand informed consent document and provide written consent
排除标准
- •Primary injury is a non-traumatic brain injury (and is not secondary to TBI) (e.g., inflammatory, infectious, toxic and metabolic encephalopathies, anoxia, cancer, ischemic and hemorrhagic stroke)
- •History of TBI, psychiatric illness (DSM criteria) and or organic brain syndrome (e.g. Alzheimer's)
- •Left dorsal lateral pre-frontal cortex (DLPFC) is not accessible (e.g., left frontal lobectomy)
- •Incurred large cortically based ischemic infarction subsequent to TBI (size is determined collectively by neurosurgeon, neurologist, neuroradiologist and principal investigator)
- •At study screening, patient is receiving anti-epileptic medications to control active seizures
- •Have had a documented seizure within 3 months of study screening
- •Are ventilator dependent at time of study screening
- •Have recovered full consciousness at time of study screening as indicated by a Motor Function scale score of 6 and/or a Communication scale score of 2 on the CRS-R
- •Receiving central nervous system (CNS) stimulants that cannot be safely discontinued via titration
- •Patient did not speak English prior to injury (bedside testing is conducted in English)
- •Have implanted cardiac pacemaker or defibrillator, cochlear implant or nerve stimulator
- •Have MRI or TMS contraindications such as pre-injury claustrophobia, metal in eyes/face or brain
- •Other medical conditions, that in investigator's opinion, would preclude subject from completing study
研究组 & 干预措施
Active rTMS
The intervention consists of 30 active rTMS sessions. Each session is comprised of 300 trains of paired pulses with the following parameters: 100µs paired pulses separated by 100ms inter-pulse-intervals and a five second inter-train-interval. Pulse intensity will be set at 110% of each participant's motor threshold. Active rTMS sessions will be provided two times per day with a 70mm figure-of-eight coil over the left dorsolateral prefrontal cortex. Two Magstim-2002 units and a Bistim2 module will be used to administer active rTMS. Participants assigned to the active rTMS group will receive a total of 1.8 seconds of stimulation. Active rTMS will be administered 2 times daily with the following weekly schedule: 2 days of rTMS, 1 day of rest, 2 days of rTMS, 2 days of rest.
干预措施: rTMS (Device)
Placebo rTMS
The intervention consists of 30 placebo rTMS sessions. Each session is comprised of 300 paired-pulse trains with the following parameters: 100µs paired pulses separated by 100ms inter-pulse-intervals and a five second inter-train-interval. Placebo rTMS sessions will be provided two times per day with a 70mm figure-of-eight coil over the left DLPFC. Two Magstim-2002 units and a Bistim2 module will be used to administer placebo rTMS. The placebo coil simulates magnetic stimulation, but does not actually emit a pulse. Participants assigned to the placebo rTMS group will receive 0 seconds of stimulation. Placebo rTMS will be administered with the following weekly schedule: 2 days of rTMS, 1 day of rest, 2 days of rTMS, 2 days of rest.
干预措施: Placebo rTMS (Device)
结局指标
主要结局
Disability Rating Scale
时间窗: Change from Baseline in DRS total score at an average 22 days
The DRS consists of 8 items that address: arousability, awareness and responsivity; cognitive ability for self-care; dependence on others; and psychosocial adaptability. Scores on the DRS range from 0 to 29 with higher scores indicating greater levels of disability.
次要结局
- Modified Tardieu Scale(Change from Baseline in Modified Tardieu total score at an average 22 days)
- Disorders of Consciousness Scale-25(Change from Baseline in DOCS-25 score at 7 days, 14 days, 21 days, 28 days and 50 days)
- Coma Recovery Scale-Revised(Change from Baseline in CRS-R total score at an average 22 days)
- Coma Near Coma Scale(Change from Baseline in CNC total score at an average 22 days)
- Consciousness Screening Algorithm(Change from Baseline in consciousness level at 7 days, 14 days, 21 days, 28 days and 50 days)
- Functional Neuroimaging(Change from Baseline in amount of activation and connectivity at an average 22 days)
- Modified Ashworth Scale(Change from Baseline in Modified Ashworth total score at an average 22 days)
- Spaulding Limb Movement Protocol(Change from Baseline in Spaudling Limb Movement total score at an average 22 days)
- EEG Power Spectrum(Change Baseline in EEG frequency power at an average 22 days)
研究者
Theresa Pape
Research Health Scientist
Edward Hines Jr. VA Hospital