Transcranial Temporal Interference Stimulation (tTIS) for Chronic Insomnia
An Exploratory Randomized Controlled Clinical Trial of Transcranial Temporal Interference Stimulation (tTIS) for the Treatment of Chronic Insomnia
The purpose of this exploratory randomized controlled clinical trial is to evaluate the efficacy and safety of transcranial temporal interference stimulation (tTIS) in the treatment of chronic insomnia. The study aims to investigate whether non-invasive tTIS intervention can effectively modulate specific neural activities to improve sleep quality and alleviate related clinical symptoms in patients suffering from chronic insomnia.
Participants enrolled in this study will be randomly assigned to receive either active tTIS treatment or sham stimulation. Researchers will collect clinical assessments and sleep monitoring data before, during, and after the intervention to compare the outcomes between the different groups and determine the therapeutic potential of tTIS for insomnia management.
研究概览
地位
条件
详细说明
Background and Rationale:
Chronic insomnia involves not only difficulty initiating sleep but also continuous central hyperarousal, severely impairing daytime function and quality of life. Current sedative-hypnotic drugs typically provide only nighttime suppression of the central nervous system, which can lead to tolerance and next-day residual effects, and they fail to fundamentally restore normal brain network states. There is a clinical need for non-invasive neuromodulation targeting abnormal brain networks. The left dorsolateral prefrontal cortex (DLPFC) is implicated in regulating emotion and suppressing central hyperarousal. Transcranial temporal interference stimulation (tTIS) is a novel non-invasive technique that uses two high-frequency carriers to create a modulated envelope (e.g., 10Hz) at a specific cortical target. The 10Hz modulation is hypothesized to modulate alpha activity, potentially reducing cortical hyperarousal. This study will evaluate the clinical safety and preliminary efficacy of tTIS targeting the left DLPFC, and will test whether it is associated with network-level changes in insomnia patients.
Study Objective:
The primary objective is to evaluate the preliminary clinical efficacy of tTIS targeting the left DLPFC in treating chronic insomnia, utilizing the reduction rate of the Insomnia Severity Index (ISI) score as the primary endpoint. Secondary objectives include evaluating the clinical response rate and objective sleep structural changes via polysomnography (PSG) and sleep bands. The study will also explore the neurophysiological mechanisms by analyzing electroencephalogram (EEG) Alpha band power. Additionally, it will assess improvements in subjective arousal (PSAS) and emotional states (STAI-S, PHQ-9, GAD-7).
Study Design and Methodology:
This is a prospective, single-center, randomized, double-blind (participant and evaluator), sham-controlled exploratory clinical trial. Thirty eligible patients with primary or mild emotionally accompanied chronic insomnia will be enrolled and randomly assigned to either the experimental group (10Hz difference frequency tTIS) or the control group (0Hz difference frequency tTIS) in a 1:1 ratio. The study location is Ruijin Hospital, Shanghai Jiao Tong University School of Medicine.
Intervention Details:
Both groups will receive stimulation targeting the left DLPFC. The experimental group will receive 10Hz difference frequency tTIS (carrier frequencies of 2000Hz and 2010Hz), which creates an amplitude-modulated envelope. The control group will receive 0Hz difference frequency stimulation (identical carrier frequencies), which does not create a therapeutic modulated envelope. The intervention will be administered daily for 30 minutes per session, 5 times a week, over a continuous 2-week period (10 sessions in total). Follow-up assessments will cover the baseline, the end of the intervention, and one month post-intervention.
研究类型
注册 (估计的)
阶段
- 不适用
联系人和位置
学习联系方式
- 姓名：Yan Luo, MD, PhD
- 电话号码：666225 0086-021-64370045
- 邮箱：zhy12015@rjh.com.cn
参与标准
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
描述
Inclusion Criteria:
- Aged 18 to 65 years old, male or female.
- Eligibility required an ICD-11 diagnosis of chronic insomnia disorder, determined by investigator-administered clinical interviews (≥3 nights/week for ≥3 months, despite adequate opportunity/conditions for sleep, with daytime distress or functional impairment).
- Insomnia Severity Index (ISI) total score ≥ 15 at screening or baseline assessment.
- Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) total scores both ≤ 9 at screening assessment.
- Has full civil capacity, is able to proficiently operate a smartphone and wearable sleep band, and can understand and cooperate with clinical scale assessments and neurophysiological examinations.
- Voluntarily participates, can ensure on-time hospital visits for 10 transcranial temporal interference stimulation (tTIS) sessions over 2 consecutive weeks, and can cooperate with the 1-month longitudinal follow-up.
- Fully understands the study purpose, intervention procedures, and potential risks, and voluntarily signs the written informed consent form.
Exclusion Criteria:
- Psychiatric conditions: (1) schizophrenia spectrum disorder or bipolar disorder, determined based on participant self-report of prior clinician diagnosis and treatment history and, when feasible, review of available medical records; (2) moderate-to-severe depressive or anxiety symptoms (PHQ-9 ≥ 10 or GAD-7 ≥ 10; either threshold met); (3) current suicidal ideation/behavior or elevated suicide risk as assessed by the investigator.
- Secondary sleep disorders: Severe obstructive sleep apnea (OSA; AHI ≥ 30), restless legs syndrome (RLS), narcolepsy, or severe circadian rhythm disorders.
- Epilepsy risk: History of seizures/convulsions or a clear family history of epilepsy.
- Intracranial metal and implanted electronic devices: Intracranial metal implants (e.g., aneurysm clips, metal stents, repair patches; fixed dental fillings excluded) or implanted electronic devices (e.g., cardiac pacemakers, deep brain stimulators [DBS], vagus nerve stimulators [VNS]).
- Medical history (neurologic): Recent craniotomy, severe traumatic brain injury, or organic brain lesions (e.g., brain tumors).
- Special populations: Pregnant, lactating, or planning pregnancy during the study period.
- Skin and physical restrictions: Skin damage, infection, or severe rash at the scalp stimulation site (especially over the left DLPFC and the return electrode site), or severe allergy to conductive gel/electrodes.
- Somatic comorbidities/substance use: Severe cardiac, pulmonary, hepatic, or renal dysfunction, or other conditions deemed by the investigator to potentially affect participant safety or study assessments (e.g., severe alcohol or drug abuse).
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：三倍
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的：Experimental Group: 10Hz tTIS
Participants in this group will receive active 10Hz difference frequency tTIS targeting the left dorsolateral prefrontal cortex (DLPFC).
The intervention will be administered for 30 minutes per session, 5 times a week, over a continuous 2-week period (10 sessions in total)
|
Utilizing the NeuroDome TES NEURO-800 device to deliver active tTIS targeting the left dorsolateral prefrontal cortex (DLPFC).
The stimulation uses carrier frequencies of 2000Hz and 2010Hz to generate a 10Hz amplitude-modulated envelope at the target region.
Each session lasts for 30 minutes.
|
|
假比较器：Sham Comparator: 0Hz tTIS
Participants in this group will receive 0Hz difference frequency tTIS (sham stimulation) targeting the left DLPFC.
The intervention frequency and duration are identical to the experimental group: 30 minutes per session, 5 times a week, for 2 weeks (10 sessions in total).
|
Utilizing the NeuroDome TES NEURO-800 device to deliver sham tTIS targeting the left dorsolateral prefrontal cortex (DLPFC).
The stimulation uses carrier frequencies of 2000Hz and 2000Hz to generate a 0Hz amplitude-modulated envelope at the target region.
Each session lasts for 30 minutes.
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Change in Insomnia Severity Index (ISI) Score
大体时间：Baseline (Day 1) and within 24 hours (0-24 h) after completion of the final treatment session on Day 13.
|
The Insomnia Severity Index (ISI) is a validated 7-item self-report questionnaire used to assess the nature, severity, and impact of insomnia.
The total score ranges from 0 to 28, with higher scores indicating more severe insomnia symptoms.
The primary endpoint is the change from baseline in ISI total score at End of Intervention, calculated as ISI (Baseline) minus ISI (End of Intervention).
Positive values indicate improvement.
|
Baseline (Day 1) and within 24 hours (0-24 h) after completion of the final treatment session on Day 13.
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Insomnia Severity Index (ISI) Response Rate
大体时间：Baseline (Day 1) and within 24 hours (0-24 h) after completion of the final treatment session on Day 13.
|
ISI response is defined as a decrease of ≥6 points in the ISI total score from baseline to post-treatment.
Participants will be classified as responders if their ISI total score decreases by ≥6 points from baseline (Day 1) to the post-treatment assessment completed within 24 hours (0-24 h) after completion of the final treatment session (Day 13).
The response rate will be calculated as the proportion of responders in each group (n/N, %).
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Baseline (Day 1) and within 24 hours (0-24 h) after completion of the final treatment session on Day 13.
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Insomnia Severity Index (ISI) Remission Rate
大体时间：Baseline (Day 1) and within 24 hours (0-24 h) after completion of the final treatment session on Day 13.
|
ISI remission is defined as a post-treatment ISI total score <8 points.
Participants will be classified as in remission if their ISI total score is <8 points at the post-treatment assessment completed within 24 hours (0-24 h) after completion of the final treatment session (Day 13).
The remission rate will be calculated as the proportion of participants meeting this criterion in each group (n/N, %).
|
Baseline (Day 1) and within 24 hours (0-24 h) after completion of the final treatment session on Day 13.
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|
Change from baseline in Pittsburgh Sleep Quality Index (PSQI) total score
大体时间：Baseline (Day 1); within 24 hours (0-24 h) after completion of the final treatment session on Day 13; and end of follow-up on Day 44.
|
Pittsburgh Sleep Quality Index (PSQI) total score (range 0-21; higher scores indicate worse sleep quality).
Change from baseline will be calculated as baseline minus post-treatment and baseline minus end-of-follow-up; positive values indicate improvement (i.e., a reduction in PSQI total score).
|
Baseline (Day 1); within 24 hours (0-24 h) after completion of the final treatment session on Day 13; and end of follow-up on Day 44.
|
|
Pre-Sleep Arousal Scale (PSAS) score
大体时间：Baseline (Day 1); within 24 hours (0-24 h) after completion of the final treatment session on Day 13; and end of follow-up on Day 44.
|
PSAS score (range: 18-80; higher scores indicate greater pre-sleep arousal).
Change from baseline will be calculated as baseline minus post-treatment and baseline minus end-of-follow-up; positive values indicate improvement (i.e., a reduction in PSAS score).
|
Baseline (Day 1); within 24 hours (0-24 h) after completion of the final treatment session on Day 13; and end of follow-up on Day 44.
|
|
State-Trait Anxiety Inventory-State (STAI-S) total score
大体时间：Baseline (Day 1); within 24 hours (0-24 h) after completion of the final treatment session on Day 13 and end of follow-up on Day 44.
|
STAI-S total score (range: 20 to 80; higher scores indicate greater state anxiety).
Change from baseline will be calculated as baseline minus post-treatment; positive values indicate improvement (i.e., a reduction in STAI-S total score).
|
Baseline (Day 1); within 24 hours (0-24 h) after completion of the final treatment session on Day 13 and end of follow-up on Day 44.
|
|
Patient Health Questionnaire-9 (PHQ-9) total score
大体时间：Baseline (Day 1); within 24 hours (0-24 h) after completion of the final treatment session on Day 13; and end of follow-up on Day 44.
|
PHQ-9 total score (range: 0 to 27; higher scores indicate worse depressive symptoms).
Change from baseline will be calculated as baseline minus post-treatment and baseline minus end-of-follow-up; positive values indicate improvement (i.e., a reduction in PHQ-9 total score).
|
Baseline (Day 1); within 24 hours (0-24 h) after completion of the final treatment session on Day 13; and end of follow-up on Day 44.
|
|
Generalized Anxiety Disorder-7 (GAD-7) total score
大体时间：Baseline (Day 1); within 24 hours (0-24 h) after completion of the final treatment session on Day 13; and end of follow-up on Day 44.
|
GAD-7 total score (range: 0 to 21; higher scores indicate worse anxiety symptoms).
Change from baseline will be calculated as baseline minus post-treatment and baseline minus end-of-follow-up; positive values indicate improvement (i.e., a reduction in GAD-7 total score).
|
Baseline (Day 1); within 24 hours (0-24 h) after completion of the final treatment session on Day 13; and end of follow-up on Day 44.
|
|
Total sleep time (TST) by polysomnography (PSG)
大体时间：Overnight on Day 1 and overnight on Day 13.
|
Total sleep time (TST) measured by overnight polysomnography (PSG), in minutes.
TST is defined as the total time scored as sleep during the PSG recording.
Change from baseline will be calculated as post-treatment minus baseline.
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Overnight on Day 1 and overnight on Day 13.
|
|
Sleep onset latency (SOL) by polysomnography (PSG)
大体时间：Overnight on Day 1 and overnight on Day 13.
|
Sleep onset latency (SOL) measured by overnight PSG, in minutes.
SOL is defined as the time from lights out to sleep onset per standard PSG scoring.
Change from baseline will be calculated as baseline minus post-treatment (positive values indicate shorter SOL).
|
Overnight on Day 1 and overnight on Day 13.
|
|
N1 sleep percentage (N1%) by polysomnography (PSG)
大体时间：Overnight on Day 1 and overnight on Day 13.
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Percentage of total sleep time spent in stage N1 sleep (N1%), measured by overnight PSG (0-100%).
Change from baseline will be calculated as post-treatment minus baseline (percentage points).
|
Overnight on Day 1 and overnight on Day 13.
|
|
N2 sleep percentage (N2%) by polysomnography (PSG)
大体时间：Overnight on Day 1 and overnight on Day 13.
|
Percentage of total sleep time spent in stage N2 sleep (N2%), measured by overnight PSG (0-100%).
Change from baseline will be calculated as post-treatment minus baseline (percentage points).
|
Overnight on Day 1 and overnight on Day 13.
|
|
N3 sleep percentage (N3%) by polysomnography (PSG)
大体时间：Overnight on Day 1 and overnight on Day 13.
|
Percentage of total sleep time spent in stage N3 sleep (N3%), measured by overnight PSG (0-100%).
Change from baseline will be calculated as post-treatment minus baseline (percentage points).
|
Overnight on Day 1 and overnight on Day 13.
|
|
REM sleep percentage (REM%) by polysomnography (PSG)
大体时间：Overnight on Day 1 and overnight on Day 13.
|
Percentage of total sleep time spent in REM sleep (REM%), measured by overnight PSG (0-100%).
Change from baseline will be calculated as post-treatment minus baseline (percentage points).
|
Overnight on Day 1 and overnight on Day 13.
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其他结果措施
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Wearable-estimated light sleep proportion (HUAWEI Band 10)
大体时间：Day 1 through Day 44.
|
Proportion of sleep time classified as "light sleep" by the HUAWEI Band 10 using the manufacturer's proprietary algorithm.
Values will be derived from wearable device records during the monitoring period.
|
Day 1 through Day 44.
|
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Wearable-estimated deep sleep proportion (HUAWEI Band 10)
大体时间：Day 1 through Day 44.
|
Proportion of sleep time classified as "deep sleep" by the HUAWEI Band 10 using the manufacturer's proprietary algorithm.
Values will be derived from wearable device records during the monitoring period.
|
Day 1 through Day 44.
|
|
Wearable-estimated REM sleep proportion (HUAWEI Band 10)
大体时间：Day 1 through Day 44.
|
Proportion of sleep time classified as "REM sleep" by the HUAWEI Band 10 using the manufacturer's proprietary algorithm.
Values will be derived from wearable device records during the monitoring period.
|
Day 1 through Day 44.
|
|
Heart rate variability (HRV) from wearable device (HUAWEI Band 10)
大体时间：Day 1 through Day 44.
|
Heart rate variability (HRV) measured by the HUAWEI Band 10 and calculated using the manufacturer's proprietary algorithm.
HRV metrics will be derived from wearable device records during the monitoring period.
|
Day 1 through Day 44.
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合作者和调查者
研究记录日期
研究主要日期
学习开始 (估计的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他研究编号
- (2026)Lin Lun Shen No.(466)
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IPD 共享访问标准
IPD 共享支持信息类型
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