NCT07712159

Brief Summary

This multi-center, double-blind study, randomized controlled trial aims to evaluate the efficacy and safety of Temporal Interference transcranial Alternating Current Stimulation (TI-tACS) in patients with major depressive disorder (MDD) Participants with major depressive disorder will be randomized to receive high-frequency TI-tACS(130 Hz), low-frequency TI-tACS(2Hz), or sham stimulation targeting the right amygdala. The intervention consists of 20 stimulation sessions administered over 2 weeks (twice a day for 5 consecutive days, followed by a 2-day break, and another 5 consecutive days). Clinical assessments will be conducted at baseline, during treatment, and at multiple follow-up time points up to 6 months. The primary outcome for MDD is the change from baseline in the Hamilton Depression Rating Scale (HAMD-17) at week 2. Secondary outcomes include changes in clinical symptoms, cognitive function, and safety profiles.

Trial Health

65
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Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
102

participants targeted

Target at P50-P75 for not_applicable

Timeline
20mo left

Started Sep 2026

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Progress3%
Sep 2026Jun 2028

First Submitted

Initial submission to the registry

June 9, 2026

Completed
1 month until next milestone

First Posted

Study publicly available on registry

July 17, 2026

Completed
2 months until next milestone

Study Start

First participant enrolled

September 15, 2026

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2027

Expected
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2028

Last Updated

September 10, 2026

Status Verified

September 1, 2026

Enrollment Period

1.2 years

First QC Date

June 9, 2026

Last Update Submit

September 6, 2026

Conditions

Major Depressive Disorder (MDD)

Keywords

Major Depressive DisorderTemporal Interference Transcranial Alternating Current StimulationMulti-centerRandomized Controlled TrialNon-invasive brain stimulationNeuromodulationdouble-blind

Outcome Measures

Primary Outcomes (1)

  • Change from baseline in the Hamilton Depression Rating Scale(HAMD-17) scores at week 2.

    The 17-item Hamilton Depression Rating Scale (HAMD-17) is a clinician-administered instrument used to assess the severity of depressive symptoms. The scale consists of 17 items with a total score ranging from 0 to 52. Higher scores indicate more severe depressive symptoms. The primary outcome for MDD participants will be calculated as the change in HAMD-17 score from baseline to Week 2.

    2 weeks(from baseline)

Secondary Outcomes (15)

  • Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Score

    Baseline to month 2 follow-up

  • Adverse Events Related to treatment

    Baseline to month 2 follow-up

  • Change in Patient Health Questionnaire-9 (PHQ-9)

    Baseline to month 2 follow-up

  • Change in the Hamilton Anxiety Rating Scale (HAMA) Score

    Baseline to month 2 follow-up

  • Change in Young Mania Rating Scale (YMRS) Score

    Baseline to month 2 follow-up

  • +10 more secondary outcomes

Study Arms (3)

High-frequency TI-tACS

EXPERIMENTAL

Participants in the High-frequency TI-tACS group receive 20-minute temporal interference transcranial alternating current stimulation (130Hz) twice a day, delivered via two pairs of transcranial electrodes, targeting the right amygdala. The stimulation is administered in 2 weeks, consisting of 5 consecutive treatment days, followed by a 2-day break, and then another 5 consecutive treatment days.

Device: Temporal Interference transcranial Alternating Current Stimulation (TI-tACS)

Low-frequency TI-tACS

EXPERIMENTAL

Participants in the Low-frequency TI-tACS group receive 20-minute temporal interference transcranial alternating current stimulation (2 Hz) twice a day, delivered via two pairs of transcranial electrodes, targeting the right amygdala. The stimulation is administered in 2 weeks, consisting of 5 consecutive treatment days, followed by a 2-day break, and then another 5 consecutive treatment days.

Device: Temporal Interference transcranial Alternating Current Stimulation (TI-tACS)

Sham TI-tACS

SHAM COMPARATOR

Participants in the Sham TI-tACS group receive 20-minute sham stimulation of the same device twice a day for 5 consecutive treatment days, followed by a 2-day break, and then another 5 consecutive treatment days.

Device: Sham Temporal Interference transcranial Alternating Current Stimulation (TI-tACS)

Interventions

Temporal Interference transcranial Alternating Current Stimulation (TI-tACS)DEVICE

Temporal Interference transcranial Alternating Current Stimulation (TI-tACS) is a non-invasive neuromodulation technique that generates a low-frequency （130HZ or 2HZ) envelope field in deep brain regions, particularly the right amygdala, through the interaction of two high-frequency currents.

Also known as: Temporal Interference Stimulation (TIS), Transcranial Temporal Interference Stimulation (tTIS)
High-frequency TI-tACSLow-frequency TI-tACS
Sham Temporal Interference transcranial Alternating Current Stimulation (TI-tACS)DEVICE

Sham Temporal Interference transcranial Alternating Current Stimulation will mimic the sensory experience of active stimulation without delivering effective current.

Sham TI-tACS

Eligibility Criteria

Age18 Years - 55 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Age between 18 and 55 years (inclusive), any gender;
  • Diagnosis of a single or recurrent episode of Major Depressive Disorder (MDD) according to DSM-5 criteria, assessed by trained researchers using the Structured Clinical Interview for DSM-5 (SCID), without psychotic features;
  • HAMD-17 score ≥14; inadequate response to stable, regular antidepressant medication for at least 1 month at an adequate dose;
  • Education level: junior high school or above; adequate cognitive and language ability to understand and complete study assessments;
  • Voluntary participation with signed informed consent; ability to comply with study visits, treatment schedules, laboratory tests, and other study procedures.

You may not qualify if:

  • History of psychiatric disorders other than MDD;
  • Pregnancy or lactation;
  • Neurologic disorders or serious systemic diseases (e.g., thyroid disease, lupus erythematosus, diabetes, hepatic or renal impairment, active infection, major trauma);
  • History of significant head injury or coma
  • Receipt of physical therapies such as electroconvulsive therapy or rTMS within the past six months before enrollment
  • Suspected or confirmed history of alcohol or substance dependence;
  • Current severe suicidal ideation or recent suicide attempt;
  • Current participation in another clinical trial or recent use of prohibited psychotropic medications;
  • Positive urine drug screening or abnormal thyroid function tests;
  • Contraindications to magnetic resonance imaging (MRI) or electroencephalography (EEG);
  • Inability to provide fully informed consent.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive DisorderMood DisordersMental Disorders

Study Officials

  • Yumeng Ju, PhD

    Second Xiangya Hospital of Central South University

    PRINCIPAL INVESTIGATOR

  • Yan Zhang, PhD

    Second Xiangya Hospital of Central South University

    STUDY CHAIR

Central Study Contacts

Yumeng Ju( Associate Researcher), PhD

CONTACT

86+18100731091yumeng.ju@csu.edu.cn

Lingsi Zeng, PhD Candidate

CONTACT

zenglsi@163.com

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Masking Details
This study is conducted using a double-blind design. Participants and outcome assessors are blinded to group assignment. Randomization codes are generated and maintained by an independent researcher who is not involved in participant assessment or data analysis. Participants assigned to the active stimulation groups receive temporal interference transcranial alternating current stimulation with different stimulation frequencies targeting the right amygdala. Participants in the sham stimulation group undergo identical electrode placement and stimulation procedures. In the sham condition, the stimulation current is ramped up for 15 seconds and then discontinued, followed by a 15-second ramp-down after 20 minutes, without delivering effective stimulation. The stimulation setup, procedures, and device appearance are identical across groups to maintain blinding.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Participants with major depressive disorder will be randomized to receive high-frequency TI-tACS(130 Hz), low-frequency TI-tACS(2Hz), or sham stimulation.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Investigator

Study Record Dates

First Submitted

June 9, 2026

First Posted

July 17, 2026

Study Start

September 15, 2026

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

June 1, 2028

Last Updated

September 10, 2026

Record last verified: 2026-09

Data Sharing

IPD Sharing
Will not share

Individual participant data will not be shared because the dataset includes sensitive neuroimaging and biological data that may compromise participant confidentiality.