Perioperative Low-Frequency rTMS for Sleep After Thoracoscopic Lung Resection (TMS-SLEEP-VATS)

This is an investigator-initiated, single-center, prospective, randomized, double-blind, parallel-group, sham-controlled trial in adults undergoing elective thoracoscopic lung resection for primary lung cancer. Eligible participants will have evidence of preoperative sleep impairment, defined as an Insomnia Severity Index (ISI) score of at least 8 or a Richards-Campbell Sleep Questionnaire (RCSQ) score below 70 on the most recent evaluable preoperative inpatient night.

Participants will be randomized in a 1:1 ratio to active or sham stimulation. Active treatment will consist of 1-Hz repetitive transcranial magnetic stimulation over the left dorsolateral prefrontal cortex at the F3 position, delivered at 100% of the resting motor threshold with 1,800 pulses per session over approximately 30 minutes. Five sessions will be delivered within a 7-day perioperative window: on preoperative day 2, preoperative day 1, 2-6 hours after extubation when clinically stable, postoperative day 1, and postoperative day 2. No more than one study stimulation session will be delivered on the same calendar day, and study procedures will not delay surgery, necessary clinical care, or discharge.

The sham group will undergo matched stimulation using a dedicated sham coil or validated active/sham masking module. Target location, participant positioning, stimulation rhythm, sound, session duration, and study interaction procedures will be matched to active treatment, but the sham procedure will not provide the intended therapeutic cortical stimulation. Participants and outcome assessors will remain blinded to treatment allocation; stimulation operators cannot be blinded because of device-operation requirements but will not participate in recruitment, primary outcome assessment, data entry, or statistical analysis.

The primary outcome is the participant-level mean RCSQ total score across postoperative inpatient nights 1, 2, and 3. RCSQ scores range from 0 to 100, with higher scores indicating better sleep. The primary analysis will compare active and sham groups using ANCOVA/linear regression adjusted for the preoperative baseline RCSQ score and prespecified randomization stratification factors.

Secondary and exploratory outcomes include total sleep time measured using the Lifesense HR6 wearable device, sleep efficiency and other device-derived sleep measures when reliably available, postoperative pain, opioid consumption, rescue analgesia, quality of recovery, chest-tube duration, length of hospital stay, postoperative complications, longer-term sleep symptoms and chronic postsurgical pain, psychological symptoms, health-related quality of life, safety, and feasibility. Resting-state 64-channel EEG and a prespecified TMS-EEG mechanistic substudy will explore changes in spectral power, alpha peak frequency, functional connectivity, network topology, and TMS-evoked cortical responses.