Low-Frequency rTMS for Sleep After Thoracoscopic Lung Resection

N/ANot Yet RecruitingNCT07796451

The First Affiliated Hospital of Guangzhou Medical University220 enrolled

Overview

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.

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.

Interventions

Active Low-Frequency Repetitive Transcranial Magnetic StimulationDEVICE

Stimulation will target the left dorsolateral prefrontal cortex at F3 with a figure-of-eight coil. Each session will use 1 Hz stimulation at 100% of resting motor threshold, 1,800 pulses, and a duration of approximately 30 minutes. Sessions are planned for preoperative day -2, preoperative day -1, 2-6 hours after awake extubation when clinically stable, postoperative day 1, and postoperative day 2. A maximum of one session is allowed per calendar day.

Matched Sham Repetitive Transcranial Magnetic StimulationDEVICE

A dedicated compatible sham coil or coded active/sham module will be used. Target, participant posture, coil placement procedure, acoustic cues, session duration, staff interaction, and visit schedule will match the active arm, but no intentional cortical stimulation will be delivered. The standard active coil rotated 90 degrees will not be used as the sham method. A maximum of one session is allowed per calendar day.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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 \<70. * 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. Exclusion Criteria: * 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 ≥3. * Unstable consciousness, respiratory status, circulation, or another acute condition that prevents reliable self-report or safe study procedures.

Outcomes

Primary Outcomes

Mean Richards-Campbell Sleep Questionnaire Total Score Across Postoperative Inpatient Nights 1-3

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.

Time frame: 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.

Secondary Outcomes

Time From End of Surgery to Live Discharge From the Continuous Acute-Care Hospitalization

Time in hours or days from the recorded end of surgery to live discharge from the same continuous acute-care hospitalization. Death before discharge will be handled as a competing event according to the statistical analysis plan.

Time frame: 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

Cough pain will be rated from 0 to 10, with higher scores indicating worse pain. The participant-level outcome will be the mean of at least two available standardized morning assessments during postoperative days 1-3.

Time frame: Postoperative mornings 1-3.

Change From Baseline in Quality of Life, Anxiety, and Depression at Postoperative Day 30

Supportive follow-up will assess EORTC QLQ-C30 Global Health Status/Quality of Life, GAD-7, and PHQ-9 scores. Each change is follow-up minus baseline, with direction interpreted according to the corresponding scale.

Time frame: 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

The EORTC QLQ-C30 Global Health Status/Quality of Life domain is transformed to a 0-100 score, with higher scores indicating better global health and quality of life. Change is calculated as postoperative day 3 minus baseline; positive values indicate improvement.

Time frame: 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

Total sleep time will be estimated by HR6 actigraphy. The participant-level outcome will be the mean of at least two valid nights. The analysis will adjust for the available pre-randomization actigraphy value according to the statistical analysis plan.

Time frame: Postoperative inpatient nights 1-3.

Change From Baseline in Generalized Anxiety Disorder-7 Score on Postoperative Day 3

The GAD-7 total score ranges from 0 to 21, with higher scores indicating more severe anxiety symptoms. Change is postoperative day 3 minus baseline; negative values indicate improvement.

Time frame: 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

The PHQ-9 total score ranges from 0 to 27, with higher scores indicating more severe depressive symptoms. Change is postoperative day 3 minus baseline; negative values indicate improvement. Responses to item 9 will trigger the protocol-defined safety assessment and referral pathway.

Time frame: Baseline before randomization and postoperative day 3, 12-24 hours after the fifth stimulation session.

Low-Frequency rTMS for Sleep After Thoracoscopic Lung Resection

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes