Effectiveness of Theta-Burst Patterned Temporal Interference Stimulation for Improving Awareness in Patients With Disorders of Consciousness: A Multicenter Randomized Double-Blind Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 136
- 试验地点
- 1
- 主要终点
- Change in Coma Recovery Scale-Revised (CRS-R) Total Score
研究概览
简要总结
The goal of this clinical trial is to learn if a new type of brain stimulation called theta-burst patterned temporal interference stimulation (tTIs) works to improve awareness in people with disorders of consciousness (DoC). The main questions it aims to answer are:
- Does tTIs help people with disorders of consciousness show more signs of awareness?
- Does tTIs improve the brain's ability to process information and connect different brain areas? Is tTIs safe and easy for people with disorders of consciousness to tolerate? Researchers will compare a group receiving active tTIs to a group receiving a "sham" stimulation (a look-alike stimulation that delivers no real current) to see if the real stimulation works better.
Participants will:Receive either active tTIs or sham stimulation twice a day for 5 consecutive days (total of 10 sessions). Undergo brain activity tests (EEG) and physical exams to check their level of awareness before and after the 5 days of treatment. Have their progress followed by researchers through phone calls at 1, 3, and 6 months after the treatment ends.
详细描述
- Study Overview and Mechanism This study is a multicenter, randomized, double-blind, sham-controlled clinical trial designed to evaluate the efficacy of theta-burst patterned temporal interference stimulation (tTIs) in patients with disorders of consciousness (DoC). The intervention targets the centromedian-parafascicular nuclei complex (CM-pf) of the thalamus, a critical hub for maintaining and modulating consciousness. By utilizing high-frequency carrier waves (>1 kHz), tTIs creates a low-frequency interference field at the deep target without directly activating the superficial cortex, thereby improving spatial selectivity and patient comfort.
- Intervention Protocol (Revised 5-Day Course) Participants will be randomly assigned to either the tTIs-active group or the tTIs-control group (1:1 ratio).
(1) Active Group: Participants will receive tTIs with a 100 Hz pulse burst repeated at a 5 Hz (theta) rhythm. Stimulation will be administered for 30 minutes per session, twice daily, for 5 consecutive days (totaling 10 sessions). The current intensity is set at 2 mA per channel (total 4 mA).
(2) Control (Sham) Group: Participants will receive sham stimulation using the same device setup, but the current will be set to 0 mA after a brief initial ramp-up to simulate the sensation.
3. Assessment and Monitoring Individualized MRI-based navigation will be used for precise targeting of the CM-pf complex. Awareness levels will be assessed using the Coma Recovery Scale-Revised (CRS-R) at baseline and within 24 hours after the completion of the 5-day intervention. Neurophysiological changes will be monitored via high-density EEG (ABCD typing), TMS-EEG (Perturbational Complexity Index, PCI), and Event-Related Potentials (MMN and P3a).
4. Follow-up and Safety Safety and tolerability will be monitored throughout the treatment. Long-term behavioral changes will be followed via telephone at 1, 3, and 6 months post-intervention to record CRS-R score variations
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age: 18 to 70 years old.
- •Condition: Patients diagnosed with Disorders of Consciousness (DoC), including Vegetative State (VS)/Unresponsive Wakefulness Syndrome (UWS) or Minimally Conscious State (MCS) according to international guidelines.
- •Duration: Disease course ≤ 1 year.Medical History: No history of neuro-psychiatric disorders prior to the brain injury.
- •Handedness: Right-handed.Safety: No contraindications for tTIs, EEG, or MRI.
- •Medication: Not currently using sedative drugs or medications that interfere with brain stimulation, such as Na2+ or Ca2+ channel blockers, or NMDA receptor antagonists.
排除标准
- •Concurrent Trials: Participation in other non-invasive or invasive neuromodulation trials.
- •Epilepsy: Uncontrolled epilepsy, defined as a seizure within 4 weeks prior to enrollment.
- •Implants: Presence of metal implants in the skull, brain pacemakers, or implanted brain devices (e.g., spinal cord stimulator).
- •Structural Issues: Skull defects at the site of stimulation that prevent the implementation of tTIs.
- •Systemic Implants: Presence of systemic metal implants, such as cardiac pacemakers.
研究组 & 干预措施
tTIs-Active Group
Participants will receive active theta-burst patterned temporal interference stimulation (tTIs) targeting the centromedian-parafascicular nuclei complex (CM-pf). The stimulation consists of 3-pulse bursts at 100 Hz, repeated at a 5 Hz (theta) rhythm. Treatment will be administered for 30 minutes per session, twice daily, for 5 consecutive days (totaling 10 sessions). The current intensity is 2 mA per channel (total 4 mA).
干预措施: Theta-burst Patterned Temporal Interference Stimulation (tTIs) (Device)
tTIs-Control Group
Participants will receive sham stimulation using the same device and electrode placement as the active group. The device will deliver 0 mA current after a brief initial ramp-up period to mimic the skin sensation. The procedure lasts 30 minutes per session, twice daily, for 5 consecutive days (totaling 10 sessions).
干预措施: Sham Temporal Interference Stimulation (Device)
结局指标
主要结局
Change in Coma Recovery Scale-Revised (CRS-R) Total Score
时间窗: Baseline and within 24 hours after the completion of the 5-day intervention.
The Coma Recovery Scale-Revised(CRS-R), a total of 23 points, is widely used to define the level of consciousness and assess neurobehavioral recovery of patients with DOC. It is based on six subscales that assess auditory(4 points), visual(5 points), motor(6 points), motor/speech(3 points), communication(2 points), and arousal processes(3 points). Each item of CRS-R is in good agreement with the diagnostic and differential diagnostic criteria of VS/UWS, MCS and EMCS. The higher scores mean a better outcome.
次要结局
- Change from Baseline Resting-State EEG(Baseline and within 24 hours after the completion of the 5-day intervention.)
- Change from Baseline TMS-EEG(Baseline and within 24 hours after the completion of the 5-day intervention.)
- Change from Baseline in Mismatch Negativity (MMN) Amplitude(Baseline and within 24 hours after the completion of the 5-day intervention.)
- Change from Baseline in P3a Amplitude(Baseline and within 24 hours after the completion of the 5-day intervention.)
- Long-term Changes in Coma Recovery Scale-Revised (CRS-R) Total Score(Baseline, and at 1 month, 3 months, and 6 months after the completion of the 5-day intervention.)