Transcranial Temporal Interference Stimulation (tTIS) for Chronic Insomnia

August 4, 2026 updated by: Ruijin Hospital

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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)
Device: Active Transcranial Temporal Interference Stimulation (tTIS)-Experimental
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.
Sham Comparator: 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).
Device: Sham Transcranial Temporal Interference Stimulation (tTIS)-Sham Comparator
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in Insomnia Severity Index (ISI) Score
Time Frame: 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.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Insomnia Severity Index (ISI) Response Rate
Time Frame: 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, %).
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
Time Frame: 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.
Change from baseline in Pittsburgh Sleep Quality Index (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.
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
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.
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
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.
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
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.
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
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.
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)
Time Frame: 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.
Overnight on Day 1 and overnight on Day 13.
Sleep onset latency (SOL) by polysomnography (PSG)
Time Frame: 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)
Time Frame: Overnight on Day 1 and overnight on Day 13.
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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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.

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Wearable-estimated light sleep proportion (HUAWEI Band 10)
Time Frame: 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.
Wearable-estimated deep sleep proportion (HUAWEI Band 10)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ruijin Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 30, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 30, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 30, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 26, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 4, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 10, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 10, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 4, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • (2026)Lin Lun Shen No.(466)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Sharing Time Frame

Data will be available immediately following the publication of the main study results, with no specified end date.

IPD Sharing Access Criteria

Data will be shared with researchers who provide a scientifically sound proposal. To gain access, data requestors must contact the Principal Investigator (PI) and sign a formal data use agreement. The shared data is intended exclusively to promote further scientific communication and evidence-based research regarding physical neuromodulation in the field of sleep medicine.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings