Perioperative Low-Frequency rTMS for Sleep After Thoracoscopic Lung Resection (TMS-SLEEP-VATS)
Low-Frequency Repetitive Transcranial Magnetic Stimulation Combined With 64-Channel Electroencephalography for Postoperative In-Hospital Sleep Disturbance in Patients Undergoing Thoracoscopic Lung Resection: A Randomized, Double-Blind, Sham-Controlled Trial
This randomized, double-blind, sham-controlled trial will evaluate whether perioperative low-frequency repetitive transcranial magnetic stimulation (rTMS) can improve early postoperative in-hospital sleep quality in adults undergoing elective thoracoscopic lung resection for primary lung cancer.
A total of 220 participants with preoperative sleep impairment 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. Five stimulation sessions will be delivered within a 7-day perioperative window: two sessions before surgery, one session after extubation when the participant is clinically stable, and one session on each of postoperative days 1 and 2.
The primary outcome is sleep quality measured using the Richards-Campbell Sleep Questionnaire during the first three postoperative inpatient nights. The study will also evaluate wearable-device sleep measures, postoperative pain and analgesic use, recovery, safety, feasibility, and changes in brain activity measured by 64-channel electroencephalography.
Panoramica dello studio
Stato
Descrizione dettagliata
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.
Tipo di studio
Iscrizione (Stimato)
Fase
- Fase 2
Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
- Adulto
- Adulto più anziano
Accetta volontari sani
Descrizione
Inclusion Criteria:
Age 18-80 years and able to understand the study and provide written informed consent.
Primary lung cancer diagnosed or suspected based on pathology and/or thoracic surgical multidisciplinary assessment, with planned elective thoracoscopic lung resection.
ASA physical status I-III, with expected awake extubation after surgery and ability to complete postoperative sleep and pain assessments.
Preoperative sleep impairment, defined as an Insomnia Severity Index (ISI) score ≥8 or a Richards-Campbell Sleep Questionnaire (RCSQ) score <70 on the most recent evaluable preoperative inpatient night.
Able to complete TMS safety screening, resting motor threshold assessment, RCSQ/ISI assessments, at least one baseline night of Lifesense HR6 monitoring, and 64-channel EEG.
The preoperative hospitalization schedule permits completion of two preoperative stimulation sessions, and postoperative hospitalization is expected to last at least three nights, allowing completion of the remaining three stimulation sessions without delaying surgery, necessary clinical care, or discharge.
Exclusion Criteria:
Unable to provide valid informed consent, unwilling to participate, or unable to reliably complete the primary RCSQ assessment.
History of epilepsy or unexplained seizures, active intracranial hemorrhage, significant cerebral edema, elevated intracranial pressure, recent stroke, or severe traumatic brain injury.
Intracranial ferromagnetic metal, cochlear implant, deep brain stimulator, cardiac pacemaker/implantable cardioverter-defibrillator, or other TMS-incompatible implant.
Severe scalp infection, open wound, or inability to safely position the TMS coil or EEG cap.
Pregnancy or any condition considered by the investigator to pose unacceptable risk.
Emergency surgery, planned open thoracotomy, or planned prolonged postoperative mechanical ventilation or deep sedation.
Chronic pain requiring regular preoperative opioid treatment, or pre-existing pain with an NRS score ≥3 in the target thoracic region.
Persistent delirium, respiratory distress, hemodynamic instability, active bleeding, or need for urgent reoperation after extubation.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Doppio
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
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Sperimentale: Active Perioperative Low-Frequency rTMS
Participants assigned to this arm will receive active low-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex at the F3 position.
Stimulation will be delivered at 1 Hz and 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. Participants will continue to receive standard perioperative care and standardized inpatient sleep-support measures.
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Active rTMS will be delivered over the left dorsolateral prefrontal cortex at the F3 position using a figure-of-eight coil.
Stimulation parameters are 1 Hz, 100% of the resting motor threshold, and 1,800 pulses per session over approximately 30 minutes.
Five sessions will be delivered within a 7-day perioperative window: 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 administered on the same calendar day.
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Comparatore fittizio: Sham Perioperative rTMS
Participants assigned to this arm will receive matched sham rTMS using a dedicated sham coil or validated active/sham masking module.
The sham procedure will match active treatment in target location, participant positioning, stimulation rhythm, sound, session duration, and study interaction procedures, but will not produce the intended therapeutic cortical stimulation.
Five sham sessions will be delivered according to the same perioperative schedule as the active group.
Participants will receive the same standard perioperative care and inpatient sleep-support measures.
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Sham stimulation will be administered using a dedicated sham coil or validated active/sham masking module compatible with the study device.
Target location, participant positioning, stimulation rhythm, sound, session duration, and interaction procedures will match active rTMS, but the sham procedure will not produce the intended therapeutic cortical stimulation.
Five sham sessions will be delivered according to the same perioperative schedule as the active treatment.
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Mean Richards-Campbell Sleep Questionnaire Total Score Across Postoperative Inpatient Nights 1-3
Lasso di tempo: Mornings after postoperative inpatient nights 1, 2, and 3
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The Richards-Campbell Sleep Questionnaire (RCSQ) total score is calculated as the mean of five visual analog items and ranges from 0 to 100, with higher scores indicating better sleep.
The primary outcome is the participant-level mean RCSQ total score obtained on the mornings after postoperative inpatient nights 1, 2, and 3.
At least two valid RCSQ nights are required to calculate the mean.
The primary analysis will adjust for the preoperative baseline RCSQ score.
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Mornings after postoperative inpatient nights 1, 2, and 3
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Mean Total Sleep Time Measured by Lifesense HR6 Across Postoperative Inpatient Nights 1-3
Lasso di tempo: Postoperative inpatient nights 1, 2, and 3
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Total sleep time (TST), measured in minutes by the Lifesense HR6 wearable device, will be averaged across valid device nights corresponding to postoperative inpatient nights 1, 2, and 3.
At least two valid device nights are required to calculate the participant-level mean TST.
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Postoperative inpatient nights 1, 2, and 3
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Generalized Anxiety Disorder-7 Score
Lasso di tempo: Preoperative baseline; within 24-72 hours after the final stimulation session
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Anxiety symptoms will be assessed using the Generalized Anxiety Disorder-7 (GAD-7) scale, with total scores ranging from 0 to 21 and higher scores indicating greater symptom severity.
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Preoperative baseline; within 24-72 hours after the final stimulation session
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Patient Health Questionnaire-9 Score
Lasso di tempo: Preoperative baseline; within 24-72 hours after the final stimulation session;
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Depressive symptoms will be assessed using the Patient Health Questionnaire-9 (PHQ-9), with total scores ranging from 0 to 27 and higher scores indicating greater symptom severity.
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Preoperative baseline; within 24-72 hours after the final stimulation session;
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EORTC QLQ-C30 Global Health Status/Quality of Life Score
Lasso di tempo: Preoperative baseline; within 24-72 hours after the final stimulation session;
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Health-related quality of life will be assessed using the authorized Chinese Mandarin (China) version of the EORTC QLQ-C30.
The prespecified outcome is the Global Health Status/Quality of Life score, ranging from 0 to 100, with higher scores indicating better overall health-related quality of life.
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Preoperative baseline; within 24-72 hours after the final stimulation session;
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Proportion of Participants Completing at Least 4 of 5 Stimulation Sessions
Lasso di tempo: During the 7-day perioperative treatment window
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Treatment-course completion will be defined as completion of at least 4 of the 5 planned active or sham stimulation sessions.
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During the 7-day perioperative treatment window
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Incidence of Adverse Events and Serious Adverse Events
Lasso di tempo: From the first study-specific procedure through the final prespecified safety follow-up at postoperative Month 12
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Adverse events and serious adverse events will be recorded, including headache, scalp discomfort, dizziness, auditory discomfort, syncope, seizure, altered consciousness, new focal neurological deficits, vital-sign abnormalities, and interruptions related to study procedures.
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From the first study-specific procedure through the final prespecified safety follow-up at postoperative Month 12
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Altre misure di risultato
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Change in Prespecified EEG Frequency-Band Power
Lasso di tempo: Baseline and 2-24 hours after stimulation session 10.
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Change in prespecified 64-channel EEG frequency-band power from baseline to the post-treatment assessment will be evaluated using the predefined EEG analysis pipeline.
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Baseline and 2-24 hours after stimulation session 10.
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Change in Prespecified EEG Functional Connectivity
Lasso di tempo: Baseline and 2-24 hours after stimulation session 10.
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Change in prespecified functional connectivity derived from 64-channel EEG recordings from baseline to the post-treatment assessment will be evaluated using the predefined connectivity analysis pipeline.
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Baseline and 2-24 hours after stimulation session 10.
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Change in TMS-Evoked Cortical Response
Lasso di tempo: Baseline and 2-24 hours after stimulation session 10.
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Change in the prespecified TMS-evoked cortical response measured by TMS-EEG from baseline to the post-treatment assessment will be evaluated.
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Baseline and 2-24 hours after stimulation session 10.
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Collaboratori e investigatori
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Studia le date principali
Inizio studio (Stimato)
Completamento primario (Stimato)
Completamento dello studio (Stimato)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Manifestazioni neurologiche
- Malattie del sistema nervoso
- Disordini mentali
- Neoplasie per sede
- Neoplasie
- Malattie delle vie respiratorie
- Malattie polmonari
- Neoplasie delle vie respiratorie
- Neoplasie toraciche
- Condizioni patologiche, segni e sintomi
- Segni e sintomi
- Neoplasie polmonari
- Disturbi del sonno e della veglia
Altri numeri di identificazione dello studio
- TMS-SLEEP-VATS-01
Informazioni su farmaci e dispositivi, documenti di studio
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