Individualized Temporally Interfering Electrical Stimulation in Major Depressive Disorder

November 6, 2026 updated by: Xianyun Kang, Tianjin Medical University General Hospital

Closed-Loop Bio-Machine Interaction System and Applications in Psychiatric Diagnosis and Treatment

Temporally interfering (TI) electrical stimulation is a novel noninvasive neuromodulation technique with high spatial resolution. Although its effects on human brain function and behavior have been increasingly investigated, its clinical utility in major depressive disorder (MDD) has not been established. This trial aims to evaluate the efficacy and safety of TI electrical stimulation in MDD patients.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
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

This is a multicenter, double-blind, randomized, sham-controlled trial including three parallel arms: (1)single-target active stimulation targeting the right primary auditory cortex (A1); (2) dual-target active stimulation targeting the right A1 and the right dorsolateral prefrontal cortex (DLPFC); (3)sham stimulation. All interventions will be delivered over two consecutive weeks, comprising ten treatment visits, with 20 minutes of stimulation applied to each target.

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.
75

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.

Study Locations

  • China
    • Fujian
      • Fuzhou, Fujian, China, 350007
        • Recruiting
        • Fuzhou Neuropsychiatric Hospital Affiliated to Fujian Medical University
        • Contact:
    • Tianjin Municipality
      • Tianjin, Tianjin Municipality, China, 300222
        • Recruiting
        • Tianjin Anding Hospital
        • Contact:

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

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Meets Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria for MDD, confirmed independently by two psychiatrists;
  2. Currently experiencing a depressive episode;
  3. Hamilton Depression Rating Scale 17-item (HAMD-17) score ≥ 17;
  4. Aged between 18-65 years;
  5. No restrictions on sex or gender;
  6. Attained at least junior high school education; lower education permitted if cognitive capacity is confirmed by a physician;
  7. Normal or corrected-to-normal vision and normal hearing;
  8. No use of antidepressant within two weeks prior to enrollment, or ongoing antidepressant treatment judged by a psychiatrist to be in a stable treatment phase;
  9. Ability to read and understand informed consent and self-report assessment scales;
  10. Willingness to participate in the study, with written informed consent provided by the participant or a legal guardian.

Exclusion Criteria:

  1. History of any psychiatric disorder other than MDD;
  2. History of traumatic brain injury or coma;
  3. History of organic brain disease or severe systemic medical illness;
  4. History of cochlear implants, pacemakers, or other implanted brain devices;
  5. History of epileptic seizures or family history of epilepsy;
  6. Obvious suicidal or impulsive violent behavior;
  7. Receipt of electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), or other neuromodulation therapies within the past six months;
  8. History of alcohol use disorder or use of other psychoactive substances;
  9. Participation in other interventional clinical trials;
  10. Any condition precluding informed consent or compliance with study procedures.

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: Double

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: single-target active TI electrical stimulation group
Device: Single-target active temporally interfering electrical stimulation

Single-target active stimulation targeting the right primary auditory cortex (A1), each target stimulation phase will last 20 minutes, including a 30-second ramp-up at onset and a 30-second ramp-down at termination. Alternating currents with frequencies of f1 = 2000 Hz and f2 = 2040 Hz will be delivered through the two electrode pairs, and the total current intensity across the two electrode pairs will be fixed at 4 mA (AC, peak-to-base). The intervention will be administered over two consecutive weeks, with participants receiving stimulation on five days per week.
Experimental: dual-target active TI electrical stimulation group
Device: Dual-target active temporally interfering electrical stimulation

Dual-target active stimulation targeting the right A1 and the right dorsolateral prefrontal cortex (DLPFC), each target stimulation phase will last 20 minutes, including a 30-second ramp-up at onset and a 30-second ramp-down at termination. For each target, two pairs of electrodes will be used; the alternating current frequency and total stimulation intensity will be the same as those in the single-target active TI electrical stimulation group.The intervention will be administered over two consecutive weeks, with participants receiving stimulation on five days per week.
Sham Comparator: sham TI electrical stimulation group
Device: Sham temporally interfering electrical stimulation

Sham TI electrical stimulation group will follow the same session duration, treatment frequency, and procedural setup as the active stimulation groups. However, electrical stimulation will be limited to an initial 30-second ramp-up followed immediately by a 30-second ramp-down, after which no current will be delivered for the remainder of the session.

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
Hamilton Depression Rating Scale 17-item (HAMD-17)
Time Frame: Baseline, Week 1, Week 2, Week 4.

Total scores range from 0 to 52, with higher scores indicating greater depressive symptom severity (worse outcomes).
Baseline, Week 1, Week 2, Week 4.

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
Patient Health Questionnaire-9 (PHQ-9)
Time Frame: Baseline, Week 1, Week 2, Week 4.

Total scores range from 0 to 27, with higher scores indicating greater depressive symptom severity (worse outcomes).
Baseline, Week 1, Week 2, Week 4.
Hamilton Anxiety Rating Scale (HAMA)
Time Frame: Baseline, Week 1, Week 2, Week 4.

Total scores range from 0 to 56, with higher scores indicating greater anxiety symptom severity (worse outcomes).
Baseline, Week 1, Week 2, Week 4.
Generalized Anxiety Disorder 7-item (GAD-7)
Time Frame: Baseline, Week 1, Week 2, Week 4.

Total scores range from 0 to 21, with higher scores indicating greater anxiety symptom severity (worse outcomes).
Baseline, Week 1, Week 2, Week 4.
Young Mania Rating Scale (YMRS)
Time Frame: Baseline, Week 1, Week 2, Week 4.

Total scores range from 0 to 60, with higher scores indicating greater manic symptom severity (worse outcomes).
Baseline, Week 1, Week 2, Week 4.
Electroencephalographic (EEG) Power in the Gamma Frequency Band
Time Frame: Baseline, Week 1, Week 2, Week 4.

Gamma-band EEG power will be assessed using spectral analysis of EEG recordings.
Baseline, Week 1, Week 2, Week 4.
40-Hz Auditory Steady-State Response (ASSR) Event-Related Spectral Perturbation (ERSP)
Time Frame: Baseline, Week 1, Week 2, Week 4.

The 40-Hz ASSR will be assessed using electroencephalography (EEG). Event-related spectral perturbation (ERSP) quantifies stimulus-induced changes in oscillatory power relative to a prestimulus baseline. ERSP will be expressed in decibels (dB), with higher values indicating greater stimulus-related power enhancement.
Baseline, Week 1, Week 2, Week 4.
40-Hz Auditory Steady-State Response (ASSR) Inter-Trial Coherence (ITC)
Time Frame: Baseline, Week 1, Week 2, Week 4.

The 40-Hz ASSR will be assessed using electroencephalography (EEG). Inter-trial coherence (ITC) quantifies the consistency of oscillatory phase across repeated auditory stimulus presentations. ITC values range from 0 to 1, with higher values indicating greater phase consistency.
Baseline, Week 1, Week 2, Week 4.
Magnetic Resonance Imaging (MRI)
Time Frame: Baseline, Week 2.

Changes in brain structure and functional organization, assessed using MRI, will be included as secondary neuroimaging outcomes.
Baseline, Week 2.

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
Athens Insomnia Scale (AIS)
Time Frame: Baseline, Week 1, Week 2, Week 4.

Total scores range from 0 to 24, with higher scores indicating greater insomnia symptom severity (worse outcomes).
Baseline, Week 1, Week 2, Week 4.
Attention Control Scale (ACS)
Time Frame: Baseline, Week 1, Week 2, Week 4.

The ACS consists of 20 items assessing two dimensions of attentional control: Attentional Focusing and Attentional Shifting. Total scores range from 20 to 80, with higher scores indicating better overall attentional control abilities (better outcomes). Attentional Focusing reflects the ability to maintain attention and resist distractions, whereas Attentional Shifting reflects the ability to flexibly shift attention between tasks or stimuli.
Baseline, Week 1, Week 2, Week 4.
Chinese 10-item Rumination Response Scale (RRS-10)
Time Frame: Baseline, Week 1, Week 2, Week 4.

The RRS-10 consists of 10 items assessing two dimensions of rumination: Brooding and Reflection, each comprising five items. Total scores range from 10 to 40, with higher scores indicating greater overall rumination (generally worse outcomes). Brooding reflects maladaptive rumination, whereas Reflection reflects purposeful self-focused thinking and does not necessarily indicate worse outcomes.
Baseline, Week 1, Week 2, Week 4.
Emotion Regulation Questionnaire (ERQ) - Cognitive Reappraisal Subscale
Time Frame: Baseline, Week 1, Week 2, Week 4.

The Cognitive Reappraisal subscale of the ERQ consists of 6 items assessing the tendency to regulate emotions by reinterpreting emotional situations. Total scores range from 6 to 42, with higher scores indicating greater use of cognitive reappraisal, generally considered a more adaptive emotion regulation strategy (better outcomes).
Baseline, Week 1, Week 2, Week 4.
Emotion Regulation Questionnaire (ERQ) - Expressive Suppression Subscale
Time Frame: Baseline, Week 1, Week 2, Week 4.

The Expressive Suppression subscale of the ERQ consists of 4 items assessing the tendency to inhibit outward emotional expression. Total scores range from 4 to 28, with higher scores indicating greater use of expressive suppression, generally considered a less adaptive emotion regulation strategy (worse outcomes).
Baseline, Week 1, Week 2, Week 4.
Cognitive Flexibility Inventory (CFI)
Time Frame: Baseline, Week 1, Week 2, Week 4.

The CFI consists of 20 items assessing two dimensions of cognitive flexibility: Alternatives (13 items) and Control (7 items). Total scores range from 20 to 100, with higher scores indicating greater cognitive flexibility (better outcomes). Alternatives reflects the ability to generate multiple explanations and solutions to difficult situations, whereas Control reflects the tendency to perceive difficult situations as controllable.
Baseline, Week 1, Week 2, Week 4.

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.
Tianjin Medical University General Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Tianjin Anding Hospital
Fuzhou Neuropsychiatric Hospital Affiliated to Fujian Medical University

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 (Actual)

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.
March 11, 2025

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.
June 15, 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.
June 15, 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).
November 3, 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.
November 6, 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.
November 9, 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.
November 9, 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.
November 6, 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.
November 1, 2026

More Information

Terms related to this study

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.
  • XY1895

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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.

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