Low-Frequency Repetitive Transcranial Magnetic Stimulation Combined With 64-Channel Electroencephalography for Postoperative Inpatient Sleep Disturbance in Patients Undergoing Thoracoscopic Lung Resection: A Randomized, Double-Blind, Sham-Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 220
- 主要终点
- Mean Richards-Campbell Sleep Questionnaire Total Score Across Postoperative Inpatient Nights 1-3
研究概览
简要总结
This single-center randomized, double-blind, sham-controlled trial will evaluate whether low-frequency repetitive transcranial magnetic stimulation (rTMS) improves postoperative inpatient sleep in adults undergoing elective thoracoscopic lung resection for primary lung cancer. A total of 220 participants will be assigned 1:1 to active or matched sham stimulation. Five sessions will be delivered during seven perioperative calendar days, with no more than one session per day. The primary outcome is each participant's mean Richards-Campbell Sleep Questionnaire (RCSQ) total score across postoperative inpatient nights 1-3, calculated from at least two eligible nights. Secondary outcomes include length of postoperative hospitalization, pain, quality of life, actigraphy-derived sleep, anxiety, depression, electroencephalographic measures, and safety.
详细描述
Participants will be randomized in a 1:1 ratio to active low-frequency rTMS or matched sham stimulation using variable block sizes of 4 and 6. Randomization will be stratified by planned resection extent (wedge or segmental resection versus lobectomy or greater resection) and baseline Insomnia Severity Index (ISI) category (<15 versus ≥15). Allocation will be concealed with sequentially numbered, opaque, sealed envelopes or an equivalent controlled allocation system.
Active treatment will target the left dorsolateral prefrontal cortex at F3 using a figure-of-eight coil, 1 Hz stimulation, 100% of resting motor threshold, and 1,800 pulses over approximately 30 minutes per session. The five planned sessions are preoperative day -2, preoperative day -1, 2-6 hours after awake extubation when clinically stable, postoperative day 1, and postoperative day 2. No more than one session may be performed on any calendar day. The sham arm will use a dedicated compatible sham coil or coded active/sham module with matched procedures and no intended cortical stimulation.
The primary analysis will compare the participant-level mean RCSQ total score across postoperative inpatient nights 1-3. A nightly score is eligible when at least 4 of 5 RCSQ visual-analogue items are completed. The participant-level value will be the arithmetic mean of at least two eligible nightly scores; thus, it may be based on two or three nights. The model will adjust for the most recent evaluable pre-randomization inpatient RCSQ score, randomization strata, and regular hypnotic use.
The planned enrollment is 220 participants (110 per group). The protocol assumes a between-group RCSQ difference of 10 points, a common standard deviation of 20 points, a two-sided alpha of 0.05, and 90% power, requiring 86 evaluable participants per group before a 20% allowance for non-evaluable primary outcomes.
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
- Double (Participant, Outcomes Assessor)
盲法说明
Participants and outcome assessors will remain blinded to treatment assignment. Follow-up staff and statisticians will also be blinded whenever feasible. The rTMS operator cannot be blinded because the operator must deliver the assigned device program; the operator will not participate in recruitment, outcome assessment, database cleaning, or statistical analysis. Active and sham sessions will use matched procedures, positioning, sound, duration, and staff interaction. Emergency unblinding will occur only when knowledge of assignment is necessary for participant safety and will be documented.
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
- •Age 18-80 years and able to provide written informed consent.
- •Primary lung cancer confirmed by pathology or multidisciplinary evaluation and scheduled for elective thoracoscopic lung resection, including wedge resection, segmentectomy, lobectomy, bilobectomy, or pneumonectomy.
- •American Society of Anesthesiologists physical status I-III, with awake extubation and reliable self-report expected after surgery.
- •Protocol-defined sleep impairment: Insomnia Severity Index score ≥8 or the most recent evaluable preoperative inpatient RCSQ total score <
- •Baseline TMS safety screening, resting motor threshold, RCSQ, ISI, HR6 actigraphy, and 64-channel EEG can be completed before randomization and the first study stimulation.
- •The clinical schedule permits two preoperative and three postoperative sessions and at least three postoperative inpatient nights without delaying necessary clinical care or discharge.
排除标准
- •History of epilepsy or seizure; intracranial hemorrhage, cerebral edema, increased intracranial pressure, recent stroke, or recent traumatic brain injury judged to increase TMS risk.
- •Ferromagnetic or electronic implants incompatible with TMS, including incompatible intracranial metal, cochlear implant, deep-brain stimulator, or other implanted electronic device near the stimulation field.
- •Severe scalp infection, open wound, or other local condition preventing safe coil placement.
- •Pregnancy or another condition judged by the investigator to create unacceptable risk from study procedures.
- •Emergency surgery, planned open thoracotomy, planned prolonged postoperative mechanical ventilation or deep sedation, or another perioperative plan that makes the stimulation and assessment schedule infeasible.
- •Regular opioid treatment for chronic pain or baseline chest-wall pain numeric rating scale score ≥
- •Unstable consciousness, respiratory status, circulation, or another acute condition that prevents reliable self-report or safe study procedures.
研究组 & 干预措施
Active Low-Frequency rTMS
Participants will receive five active low-frequency rTMS sessions during seven perioperative calendar days in addition to standard perioperative care.
干预措施: Active Low-Frequency Repetitive Transcranial Magnetic Stimulation (Device)
Matched Sham rTMS
Participants will receive five matched sham sessions during the same perioperative schedule in addition to standard perioperative care.
干预措施: Matched Sham Repetitive Transcranial Magnetic Stimulation (Device)
结局指标
主要结局
Mean Richards-Campbell Sleep Questionnaire Total Score Across Postoperative Inpatient Nights 1-3
时间窗: Postoperative inpatient nights 1-3; each questionnaire is completed the following morning, preferably 07:00-10:00 and no later than 12:00 if delayed by clinical care.
The RCSQ contains five visual-analogue items scored from 0 to 100, with higher scores indicating better perceived sleep. A nightly total score is the mean of completed items and is eligible when at least 4 of 5 items are completed. For each participant, the outcome is the arithmetic mean of at least two eligible nightly total scores collected on postoperative inpatient nights 1-3; the mean may therefore use two or three nights. The primary model will adjust for the most recent evaluable pre-randomization inpatient RCSQ score, randomization strata, and regular hypnotic use.
次要结局
- Time From End of Surgery to Live Discharge From the Continuous Acute-Care Hospitalization(From end of surgery until live discharge, in-hospital death, or 90 days after surgery, whichever occurs first.)
- Mean Standardized Cough Pain Numeric Rating Scale Score Across the First 3 Postoperative Mornings(Postoperative mornings 1-3.)
- Change From Baseline in Quality of Life, Anxiety, and Depression at Postoperative Day 30(Baseline and postoperative day 30 ± 7 days.)
- Change From Baseline in EORTC QLQ-C30 Global Health Status/Quality of Life Score on Postoperative Day 3(Baseline before randomization and postoperative day 3, 12-24 hours after the fifth stimulation session.)
- Mean Actigraphy-Estimated Total Sleep Time Across Postoperative Inpatient Nights 1-3(Postoperative inpatient nights 1-3.)
- Change From Baseline in Generalized Anxiety Disorder-7 Score on Postoperative Day 3(Baseline before randomization and postoperative day 3, 12-24 hours after the fifth stimulation session.)
- Change From Baseline in Patient Health Questionnaire-9 Score on Postoperative Day 3(Baseline before randomization and postoperative day 3, 12-24 hours after the fifth stimulation session.)
研究者
Jianxing He
PhD
The First Affiliated Hospital of Guangzhou Medical University