Low-Frequency rTMS for In-Hospital Sleep Disturbance in Advanced NSCLC
Low-Frequency Repetitive Transcranial Magnetic Stimulation Combined With 64-Channel Electroencephalography for In-Hospital Sleep Disturbance in Patients With Advanced Non-Small Cell Lung Cancer: A Randomized, Double-Blind, Sham-Controlled Trial
This randomized, double-blind, sham-controlled trial will evaluate whether low-frequency repetitive transcranial magnetic stimulation (rTMS) can improve in-hospital sleep quality in adults with advanced non-small cell lung cancer (NSCLC) and clinically significant in-hospital sleep disturbance.
A total of 160 participants with unresectable stage IIIB-IIIC or stage IV NSCLC, or recurrent NSCLC not suitable for curative local treatment, 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 completed 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 and symptom burden, psychological symptoms, quality of life, safety, feasibility, and changes in brain activity measured by 64-channel electroencephalography.
調査の概要
状態
詳細な説明
This is an investigator-initiated, single-center, prospective, randomized, double-blind, parallel-group, sham-controlled trial in adults with advanced non-small cell lung cancer (NSCLC) and in-hospital sleep disturbance. Eligible participants will have pathologically or cytologically confirmed unresectable stage IIIB-IIIC or stage IVA-IVB NSCLC, or recurrent disease after curative-intent treatment that is considered unsuitable for further curative local therapy. In-hospital sleep disturbance is defined as a mean Richards-Campbell Sleep Questionnaire (RCSQ) score below 70 across two consecutive valid inpatient nights together with a baseline Insomnia Severity Index (ISI) score of at least 8.
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. One session will be administered daily for a total of 10 sessions completed within 10-14 days. Participants will continue to receive their clinically indicated anticancer treatment and supportive care, and study procedures will not delay or interfere with necessary clinical treatment.
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. The stimulation operator cannot be blinded because of device-operation requirements but will not participate in participant recruitment, primary 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. RCSQ scores range from 0 to 100, with higher scores indicating better sleep. The primary analysis will compare the active and sham groups using ANCOVA/linear regression adjusted for the mean RCSQ score from two consecutive valid baseline inpatient nights and prespecified randomization stratification factors.
Secondary and exploratory outcomes include total sleep time measured using the Lifesense HR6 wearable device, other device-derived sleep measures when reliably available, ISI, pain and opioid exposure, lung cancer-related symptom burden, fatigue, anxiety, depressive symptoms, health-related quality of life, functional status, length of hospital stay, anticancer-treatment interruption, treatment feasibility, and adverse events. Resting-state 64-channel EEG and a prespecified TMS-EEG mechanistic substudy will explore changes in frequency-band power, alpha peak frequency, functional connectivity, network topology, and TMS-evoked cortical responses.
研究の種類
入学 (推定)
段階
- フェーズ2
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria:
Age 18-80 years and able to understand the study and provide written informed consent.
Pathologically or cytologically confirmed non-small cell lung cancer (NSCLC), classified according to the IASLC 9th edition TNM system as unresectable stage IIIB-IIIC, stage IVA-IVB, or recurrent disease after curative-intent treatment and considered by a multidisciplinary team to be unsuitable for further curative local therapy.
Receiving a stable first-line or later-line systemic anticancer treatment regimen, or receiving inpatient symptom/supportive care after anticancer treatment; the treatment plan must be established before randomization, with no planned initiation of new radiotherapy or change in systemic anticancer therapy before assessment of the primary outcome.
Mean Richards-Campbell Sleep Questionnaire (RCSQ) score <70 across two consecutive valid inpatient nights and baseline Insomnia Severity Index (ISI) score ≥8.
Eastern Cooperative Oncology Group (ECOG) performance status 0-2 and estimated life expectancy ≥3 months.
Hospitalized for anticancer treatment-related observation, symptom control, or supportive care, with an expected remaining hospital stay of at least 10 days from randomization and ability to complete 10 stimulation sessions and the primary outcome assessment within 14 days.
Able to complete the prespecified RCSQ assessments and brief sleep diary, continuous Lifesense HR6 monitoring, and 64-channel EEG assessment.
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.
Active or uncontrolled brain metastases, or brain metastases associated with cerebral edema, hemorrhage, focal neurological symptoms, or a need for escalating corticosteroid treatment.
Untreated or unstable obstructive sleep apnea, or another primary sleep disorder requiring priority specialist management.
Initiation, discontinuation, or ≥50% dose change of sedative-hypnotic medication within 48 hours before randomization, or a planned initiation/discontinuation of medication expected to substantially affect sleep before assessment of the primary outcome.
Planned initiation of new whole-brain or local radiotherapy, first use of high-dose corticosteroids, or switching of systemic anticancer therapy before assessment of the primary outcome.
ECOG performance status ≥3, uncontrolled respiratory failure, delirium, or inability to reliably complete the prespecified sleep assessments.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：ダブル
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：Active 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, once daily for a total of 10 sessions completed within 10-14 days.
Participants will continue to receive clinically indicated anticancer treatment, supportive care, and standardized inpatient sleep-support measures.
|
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.
Treatment will be administered once daily for a total of 10 sessions completed within 10-14 days.
No more than one study stimulation session will be administered on the same calendar day.
Study stimulation will not be performed during intravenous anticancer drug infusion, blood transfusion, sedated bronchoscopy, or clinically significant infusion reactions.
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偽コンパレータ：Sham 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 the 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.
Participants will receive the same clinically indicated anticancer treatment, supportive care, and standardized inpatient sleep-support measures as the active rTMS group.
|
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.
Sham stimulation will be administered once daily for a total of 10 sessions completed within 10-14 days.
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Mean Richards-Campbell Sleep Questionnaire Total Score Across the Nights Following Stimulation Sessions 8-10
時間枠：Mornings after the nights following stimulation sessions 8, 9, and 10, within the 10-14-day treatment period
|
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 the nights following stimulation sessions 8, 9, and 10.
At least two valid RCSQ nights are required to calculate the mean.
The primary analysis will adjust for the mean RCSQ score from two consecutive valid baseline inpatient nights.
|
Mornings after the nights following stimulation sessions 8, 9, and 10, within the 10-14-day treatment period
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Mean Total Sleep Time Measured by Lifesense HR6 Across the Nights Following Stimulation Sessions 8-10
時間枠：Nights following stimulation sessions 8, 9, and 10, within the 10-14-day treatment period
|
Total sleep time (TST), measured in minutes by the Lifesense HR6 wearable device, will be averaged across valid device nights corresponding to the nights following stimulation sessions 8, 9, and 10.
At least two valid device nights are required to calculate the participant-level mean TST.
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Nights following stimulation sessions 8, 9, and 10, within the 10-14-day treatment period
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Generalized Anxiety Disorder-7 Score
時間枠：Baseline and 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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Baseline and within 24-72 hours after the final stimulation session
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Patient Health Questionnaire-9 Score
時間枠：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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Baseline; within 24-72 hours after the final stimulation session
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EORTC QLQ-C30 Global Health Status/Quality of Life Score
時間枠：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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Baseline; within 24-72 hours after the final stimulation session;
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Proportion of Participants Completing at Least 8 of 10 Stimulation Sessions
時間枠：During the 10-14-day treatment period
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Treatment-course completion will be defined as completion of at least 8 of the 10 planned active or sham stimulation sessions.
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During the 10-14-day treatment period
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Incidence of Adverse Events and Serious Adverse Events
時間枠：From the first study-specific procedure through the final prespecified safety follow-up at 12 weeks after hospital discharge
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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 12 weeks after hospital discharge
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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Change in Prespecified EEG Frequency-Band Power
時間枠：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
時間枠：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
時間枠：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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協力者と研究者
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- TMS-SLEEP-NSCLC-01
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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