Low-Frequency rTMS for In-Hospital Sleep Disturbance After Lung Transplantation (TMS-SLEEP-LTx)
Low-Frequency Repetitive Transcranial Magnetic Stimulation Combined With 64-Channel Electroencephalography for In-Hospital Sleep Disturbance in Lung Transplant Recipients: 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 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.
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 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.
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 18-70 years and able to provide independent written informed consent. First single- or double-lung transplantation. Postoperative day 7-21 at randomization; extubated for at least 48 hours, off ECMO, and off vasoactive medications for at least 24 hours.
Resting SpO2 ≥92% with stable oxygen requirements and able to complete study procedures in a seated or semi-recumbent position.
Negative CAM/CAM-ICU assessment during the preceding 24 hours, with clear consciousness and ability to complete sleep and cognitive assessments.
Stable trends in blood pressure, blood glucose, serum sodium, serum magnesium, and renal function; immunosuppressant concentrations considered acceptable by the transplant team.
Mean RCSQ score <70 across two consecutive valid inpatient nights and baseline ISI score ≥8.
Able to complete RCSQ, sleep diary, Lifesense HR6 monitoring, and 64-channel EEG assessments.
Expected to remain hospitalized for at least 10 days and able to complete 10 stimulation sessions and the primary outcome assessment within 14 days.
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.
Repeat lung transplantation, multiorgan transplantation, or current requirement for ECMO, mechanical ventilation, or vasoactive support.
Active delirium, encephalopathy, posterior reversible encephalopathy syndrome (PRES), central nervous system infection, new focal neurological deficit, or seizure within the previous 30 days.
Suspected calcineurin-inhibitor neurotoxicity, uncontrolled hypertension, clinically significant hypomagnesemia, hyponatremia, hypoglycemia, or other metabolic abnormality that may lower the seizure threshold.
Uncontrolled sepsis, active rejection requiring urgent intensified treatment, or rapidly deteriorating clinical status.
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 |
|---|---|
|
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 standard post-transplant 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 during the same hospitalization.
No more than one study stimulation session will be administered on the same calendar day.
|
|
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 standard post-transplant care and 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 locked study device.
The 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 within 10-14 days.
|
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
|
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.
|
Nights following stimulation sessions 8, 9, and 10, within the 10-14-day treatment period
|
|
Proportion of Participants Completing at Least 8 of 10 Stimulation Sessions
時間枠：During the 10-14-day treatment period
|
Treatment-course completion will be defined as completion of at least 8 of the 10 planned active or sham stimulation sessions.
|
During the 10-14-day treatment period
|
|
Generalized Anxiety Disorder-7 Score
時間枠：Baseline; 24-72 hours after the final stimulation session
|
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.
|
Baseline; 24-72 hours after the final stimulation session
|
|
Patient Health Questionnaire-9 Score
時間枠：Baseline; 24-72 hours after the final stimulation session
|
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.
|
Baseline; 24-72 hours after the final stimulation session
|
|
EQ-5D-5L Health-Related Quality of Life
時間枠：Baseline; 24-72 hours after the final stimulation session
|
Health-related quality of life will be assessed using the Simplified Chinese version of the EQ-5D-5L.
The China value-set utility index and EQ visual analog scale will be reported.
|
Baseline; 24-72 hours after the final stimulation session
|
|
Incidence of Adverse Events and Serious Adverse Events
時間枠：From the first study-specific procedure through the final safety follow-up at postoperative Month 6
|
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.
|
From the first study-specific procedure through the final safety follow-up at postoperative Month 6
|
その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Change in Prespecified EEG Frequency-Band Power
時間枠：Baseline and 2-24 hours after stimulation session 10.
|
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.
|
Baseline and 2-24 hours after stimulation session 10.
|
|
Change in Prespecified EEG Functional Connectivity
時間枠：Baseline and 2-24 hours after stimulation session 10.
|
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.
|
Baseline and 2-24 hours after stimulation session 10.
|
|
Change in TMS-Evoked Cortical Response
時間枠：Baseline and 2-24 hours after stimulation session 10.
|
Change in the prespecified TMS-evoked cortical response measured by TMS-EEG from baseline to the post-treatment assessment will be evaluated.
|
Baseline and 2-24 hours after stimulation session 10.
|
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
その他の研究ID番号
- TMS-SLEEP-LTx-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
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。