Low-Frequency rTMS for In-Hospital Sleep Disturbance After Lung Transplantation

Overview

This randomized, double-blind, sham-controlled trial will evaluate whether low-frequency repetitive transcranial magnetic stimulation (rTMS) can improve in-hospital sleep quality in adult lung transplant recipients during early postoperative recovery. A total of 152 participants with in-hospital sleep disturbance after first single- or double-lung transplantation will be randomly assigned in a 1:1 ratio to active rTMS or matched sham stimulation. Active rTMS will target the left dorsolateral prefrontal cortex and will be delivered once daily for 10 sessions within 10-14 days. The primary outcome is sleep quality measured using the Richards-Campbell Sleep Questionnaire during the nights following stimulation sessions 8, 9, and 10. The study will also evaluate wearable-device sleep measures, insomnia symptoms, pain, mood, cognitive and functional outcomes, safety, feasibility, and changes in brain activity measured by 64-channel electroencephalography.

This is an investigator-initiated, single-center, prospective, randomized, double-blind, parallel-group, sham-controlled trial conducted in adult recipients of a first single- or double-lung transplantation. Eligible participants will be enrolled during postoperative days 7-21 after clinical stabilization and must have evidence of in-hospital sleep disturbance, defined by a mean Richards-Campbell Sleep Questionnaire (RCSQ) score below 70 across two consecutive valid inpatient nights together with an Insomnia Severity Index (ISI) score of at least 8. Participants will be randomized 1:1 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. One session will be administered daily for a total of 10 sessions completed within 10-14 days. The sham group will undergo matched procedures using a dedicated sham coil or validated active/sham masking module with the same target, positioning, rhythm, sound, duration, and interaction procedures but without intended therapeutic cortical stimulation. Participants and outcome assessors will remain blinded to treatment allocation. Clinical study personnel and statistical personnel will also remain blinded as specified in the protocol; stimulation operators cannot be blinded because of device-operation requirements but will not participate in recruitment, outcome assessment, data entry, or statistical analysis. The primary outcome is the participant-level mean RCSQ total score obtained on the mornings after the nights following stimulation sessions 8, 9, and 10. The RCSQ ranges from 0 to 100, with higher scores indicating better sleep. The primary analysis will compare active and sham groups using an ANCOVA/linear-regression model adjusted for baseline RCSQ and prespecified randomization stratification factors. Secondary and exploratory outcomes include total sleep time measured using the Lifesense HR6 wearable device, ISI and other sleep measures, pain and opioid exposure, delirium, cognitive function, anxiety, depressive symptoms, fatigue, health-related quality of life, hospital and transplant-related outcomes, treatment feasibility, and adverse events. 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. All participants will continue to receive standard post-transplant clinical care and standardized inpatient sleep-support measures. Necessary clinical treatment will take priority over study procedures, and the study intervention will not be used to delay treatment, rehabilitation, transfer, or discharge.