Repetitive Transcranial Magnetic Stimulation and Electroencephalography in Patients With Disorders of Consciousness
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 90
- 试验地点
- 4
- 主要终点
- Change from Baseline Coma Recovery Scale - Revised for Parallel Study 2
研究概览
简要总结
Background:
Severe brain injury could cause chronic disorders of consciousness (DOC). Treating DOC patients to improve recovery remains very challenging. A few randomized controlled studies have been published in the recent years, focusing on non-invasive brain stimulation (NIBS) treatments to improve patients' neurobehavioural functioning. Among NIBS, repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that can modulate cortical excitability, enhance neural plasticity, and induce strong neuromodulatory effects that outlast the period of stimulation. It is thought to modulate cortical activity and could therefore be effective for treating DOC patients. Currently, there is no unified protocol for rTMS in DOC patients and studies vary in many aspects.
In this study, the investigators aim to improve the functional recovery of DOC patients following severe brain injury using rTMS in two multi-center double-blind studies.
Methods/design:
The investigators will recruit 90 DOC patients. Patients will have three rTMS sessions that will be randomized within patients in a crossover design: (i) one real stimulation on the left dorsolateral prefrontal cortex (DLPFC); (ii) one real stimulation on the left angular cortex (AG) and (iii) one sham stimulation. Sessions will be separated by at least 5 days washout period. Each stimulation session will last 20 minutes with a frequency of 20Hz (train duration: 4s; inter-train interval: 26s; 3200 pulses at 80% of the resting motor threshold - RMT). The RMT, i.e., the minimum stimulus intensity that generated a motor evoked potential response of at least 50μV at rest for 5 out of 10 trials, will be calculated for the stimulation target using single-pulses on the right abductor pollicis brevis muscle.
After an interval of one week, a parallel design study will begin. Ninety patients will be randomly divided in two experimental groups and one sham group (30 patients per group). Stimulation will be performed for 20 working days once a day with the same stimulation parameters as in the crossover study.
Primary outcome will be determined as behavioral response to treatment as measured using the Coma Recovery Scale - Revised (CRS-R). Resting-state high-density EEG will be also recorded to investigate the neurophysiological correlates by rTMS.
Discussion:
This study will contribute to define the role of rTMS for the treatment of DOC patients and characterise the neural correlates of its action. In addition, the investigators will define the responders' profile based on patients' characteristics and functional impairments and develop biomarkers of responsiveness using machine learning to categorize EEG signals according to clinical responsiveness to the treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, 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
- •over 18 years old
- •> 28 days post-injury
- •patients with DOC due to acquired brain lesions classified according to international guidelines as UWS or MCS with repeated behavioural assessments with the CRS-R
- •stable vital parameters
- •no previous neurological deficits anterior to the brain lesions
- •no pregnancy
- •no contraindication for rTMS or EEG (e.g., uncontrolled epilepsy, that is, seizure within 4 weeks prior to enrollment, metallic implant in the skull, pacemaker, craniotomy under the stimulated site, implanted brain device, sensitive skin)
- •no sedative drugs and drugs thought to interfere with brain stimulation such as Na or Ca channel blockers (e.g., carbamazepine) or NMDA receptor antagonists (e.g., dextromethorphan)
- •no drugs or substances which have strong potential of seizure induction (imipramine, amitriptyline, doxepin, nortriptyline, maprotiline, chlorpromazine, clozapine, foscarnet, ganciclovir, ritonavir, amphetamines, cocaine, phencyclidine, ketamine, gamma-hydroxybutyrate, alcohol, and theophylline).
- •All etiologies (e.g., trauma, stroke, and anoxia)
排除标准
- 未提供
结局指标
主要结局
Change from Baseline Coma Recovery Scale - Revised for Parallel Study 2
时间窗: 1 week after the last rTMS session
The Coma Recovery Scale - Revised is a non-invasive behavioural examination. It contains 23 items hierarchically presented and divided in 6 sub-scales (auditory, visual, motor, oro-motor/verbal, communication and arousal). The score is based on presence or absence of behaviours in response to sensory stimulations. The quantitative score can be calculated by adding the best observed response in each sub-scale. The diagnosis is obtained from the quality of observed behaviours (e.g., the ability of visual tracking means that the patient is minimally conscious). The total score ranges between 0 and 23. Higher scores mean a better outcome.
Change from Baseline Coma Recovery Scale - Revised for Parallel Study 3
时间窗: 2 week after the last rTMS session
The Coma Recovery Scale - Revised is a non-invasive behavioural examination. It contains 23 items hierarchically presented and divided in 6 sub-scales (auditory, visual, motor, oro-motor/verbal, communication and arousal). The score is based on presence or absence of behaviours in response to sensory stimulations. The quantitative score can be calculated by adding the best observed response in each sub-scale. The diagnosis is obtained from the quality of observed behaviours (e.g., the ability of visual tracking means that the patient is minimally conscious). The total score ranges between 0 and 23. Higher scores mean a better outcome.
Change from Baseline Coma Recovery Scale - Revised for Crossover Study
时间窗: immediately after each rTMS session
The Coma Recovery Scale - Revised is a non-invasive behavioural examination. It contains 23 items hierarchically presented and divided in 6 sub-scales (auditory, visual, motor, oro-motor/verbal, communication and arousal). The score is based on presence or absence of behaviours in response to sensory stimulations. The quantitative score can be calculated by adding the best observed response in each sub-scale. The diagnosis is obtained from the quality of observed behaviours (e.g., the ability of visual tracking means that the patient is minimally conscious). The total score ranges between 0 and 23. Higher scores mean a better outcome.
Change from Baseline Coma Recovery Scale - Revised for Parallel Study 1
时间窗: immediately after the last rTMS session
The Coma Recovery Scale - Revised is a non-invasive behavioural examination. It contains 23 items hierarchically presented and divided in 6 sub-scales (auditory, visual, motor, oro-motor/verbal, communication and arousal). The score is based on presence or absence of behaviours in response to sensory stimulations. The quantitative score can be calculated by adding the best observed response in each sub-scale. The diagnosis is obtained from the quality of observed behaviours (e.g., the ability of visual tracking means that the patient is minimally conscious). The total score ranges between 0 and 23. Higher scores mean a better outcome.
次要结局
- Change from Baseline Resting-State EEG for Crossover Study 1(during each rTMS session)
- Change from Baseline Resting-State EEG for Crossover Study 2(immediately after each rTMS session)
- Change from Baseline Resting-State EEG for Parallel Study 1(immediately after the last rTMS session)
- Change from Baseline Resting-State EEG for Parallel Study 2(1 week after the last rTMS session)
- Change from Baseline Resting-State EEG for Parallel Study 3(2 week after the last rTMS session)
研究者
Olivia Gosseries
Principal Investigator
University of Liege