Transcranial Temporal Interference Stimulation (tTIS) for Chronic Insomnia

N/ANot Yet RecruitingNCT07755852

Ruijin Hospital30 enrolled

Overview

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.

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Aged 18 to 65 years old, male or female. 2. 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). 3. Insomnia Severity Index (ISI) total score ≥ 15 at screening or baseline assessment. 4. Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) total scores both ≤ 9 at screening assessment. 5. 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. 6. 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. 7. Fully understands the study purpose, intervention procedures, and potential risks, and voluntarily signs the written informed consent form. Exclusion Criteria: 1. 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. 2. Secondary sleep disorders: Severe obstructive sleep apnea (OSA; AHI ≥ 30), restless legs syndrome (RLS), narcolepsy, or severe circadian rhythm disorders. 3. Epilepsy risk: History of seizures/convulsions or a clear family history of epilepsy. 4. 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 \[VNS\]). 5. Medical history (neurologic): Recent craniotomy, severe traumatic brain injury, or organic brain lesions (e.g., brain tumors). 6. Special populations: Pregnant, lactating, or planning pregnancy during the study period. 7. 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. 8. 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).

Outcomes

Primary Outcomes

Change in Insomnia Severity Index (ISI) Score

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.

Time frame: Baseline (Day 1) and within 24 hours (0-24 h) after completion of the final treatment session on Day 13.

Secondary Outcomes

Insomnia Severity Index (ISI) Response Rate

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, %).

Time frame: 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

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, %).

Time frame: 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

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).

Time frame: 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

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).

Time frame: 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

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).

Time frame: 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

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).

Time frame: 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

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).

Time frame: 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)

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.