An Exploratory Randomized Controlled Clinical Trial of Transcranial Temporal Interference Stimulation (tTIS) for the Treatment of Chronic Insomnia
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 30
- 主要终点
- Change in Insomnia Severity Index (ISI) Score
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Participants, clinical investigators, and outcome assessors (including data statisticians) are strictly blinded to the group allocation. The device operators who set the tTIS stimulation parameters are unblinded, but they are strictly prohibited from participating in any clinical scale follow-up, PSG collection, or clinical outcome evaluation to prevent bias transmission.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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).
结局指标
主要结局
Change in Insomnia Severity Index (ISI) Score
时间窗: 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.
次要结局
- Insomnia Severity Index (ISI) Response Rate(Baseline (Day 1) and within 24 hours (0-24 h) after completion of the final treatment session on Day 13.)
- Insomnia Severity Index (ISI) Remission Rate(Baseline (Day 1) and within 24 hours (0-24 h) after completion of the final treatment session on Day 13.)
- Change from baseline in Pittsburgh Sleep Quality Index (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(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(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(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(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)(Overnight on Day 1 and overnight on Day 13.)
- Sleep onset latency (SOL) by polysomnography (PSG)(Overnight on Day 1 and overnight on Day 13.)
- N1 sleep percentage (N1%) by polysomnography (PSG)(Overnight on Day 1 and overnight on Day 13.)
- N2 sleep percentage (N2%) by polysomnography (PSG)(Overnight on Day 1 and overnight on Day 13.)
- N3 sleep percentage (N3%) by polysomnography (PSG)(Overnight on Day 1 and overnight on Day 13.)
- REM sleep percentage (REM%) by polysomnography (PSG)(Overnight on Day 1 and overnight on Day 13.)