Efficacy and Safety of Transcranial Temporal Interference Stimulation for Depression

May 27, 2026 updated by: Yonggui Yuan

The goal of this clinical trial is to learn whether transcranial temporal interference stimulation (tTIS) can help treat major depressive disorder (MDD) in adults. The study will also learn about the safety of tTIS and explore how it may affect brain structure and brain function.

The main questions it aims to answer are whether active tTIS lowers depression symptom scores more than sham stimulation after treatment, and what medical problems or side effects participants have during or after tTIS.

Researchers will compare active tTIS targeting the left anterior limb of the internal capsule, active tTIS targeting the left subgenual anterior cingulate cortex, and sham stimulation. Sham stimulation is designed to feel similar to real stimulation but does not provide the same active treatment.

Participants with MDD will be randomly assigned to one of the three groups. They will receive two 20-minute treatment sessions each day for 5 days. They will complete depression, anxiety, pleasure, psychosomatic symptom, and safety assessments before treatment, after treatment, and during follow-up. They will also have brain magnetic resonance imaging scans before and after treatment.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Major depressive disorder (MDD) is a common and disabling mental disorder. Although medication, psychotherapy, and established brain stimulation methods can help many people with MDD, some participants still have insufficient improvement. Transcranial temporal interference stimulation (tTIS) is a non-invasive brain stimulation technique that may allow modulation of deeper brain regions or pathways. This study is designed to evaluate whether tTIS can improve depressive symptoms in adults with MDD, assess its safety, and explore potential neuroimaging mechanisms.

This is a single-center, randomized, double-blind, sham-controlled clinical trial conducted at Zhongda Hospital, Southeast University. Eligible participants with MDD will be randomly assigned in a 1:1:1 ratio to one of three groups: active tTIS targeting the left anterior limb of the internal capsule (ALIC), active tTIS targeting the left subgenual anterior cingulate cortex (sgACC), or sham tTIS. The sham stimulation will be designed to provide sensory feedback similar to active stimulation while maintaining blinding.

Participants with MDD will receive 10 treatment sessions over 5 consecutive days, with two 20-minute sessions each day. Clinical symptoms and safety will be assessed at baseline, after treatment, and during follow-up. The main clinical outcome is the change in the 24-item Hamilton Depression Rating Scale (HAMD-24) total score from baseline to after treatment. Secondary outcomes include follow-up changes in depressive symptoms, response and remission rates, anxiety symptoms, anhedonia, psychosomatic symptoms, side effects, and adverse events.

Multimodal 5.0T brain magnetic resonance imaging (MRI) will be collected from participants with MDD before and after treatment. MRI measures will include structural imaging, resting-state functional imaging, and diffusion imaging. These data will be used to explore changes in brain structure, functional connectivity, and diffusion-related measures after tTIS, and to identify potential imaging biomarkers related to treatment response.

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • 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

  • Name: Yue Zhou, MD Candidate
  • Phone Number: +86 15651003002
  • Email: 2725106172@qq.com

Study Contact Backup

  • Name: Yubo Zhang, MD Candidate
  • Phone Number: +86 18651617808
  • Email: 1301053461@qq.com

Study Locations

  • China
    • Jiangsu
      • Nanjing, Jiangsu, China, 210009
        • Zhongda Hospital Southeast University
        • Contact:
        • Contact:
        • Principal Investigator:
          • Yonggui Yuan, PhD

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

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Diagnosed with major depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), by two independent psychiatrists
  • 24-item Hamilton Depression Rating Scale (HAMD-24) total score greater than 20 at baseline
  • Aged 18 to 65 years
  • Right-handed
  • Able to understand the study procedures and willing to provide written informed consent

Exclusion Criteria:

  • History of epilepsy, brain tumor, or brain trauma
  • Receipt of transcranial magnetic stimulation, transcranial electrical stimulation, or electroconvulsive therapy within the past 3 months
  • Presence of metal implants or other contraindications to transcranial electrical stimulation or magnetic resonance imaging
  • Acute or severe suicidal ideation
  • Any other condition judged by the investigators to make participation unsuitable for this study

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
Intervention / Treatment
Active Comparator: Active tTIS Targeting Left ALIC
Participants in this arm will receive active transcranial temporal interference stimulation (tTIS) targeting the left anterior limb of the internal capsule (ALIC). Treatment will be delivered twice daily for 5 consecutive days, with each session lasting 20 minutes and a 30-minute interval between sessions.
Device: Active Transcranial Temporal Interference Stimulation Targeting Left ALIC
Participants in this arm will receive active transcranial temporal interference stimulation (tTIS) targeting the left anterior limb of the internal capsule (ALIC). The stimulation target will be individualized based on each participant's magnetic resonance imaging data. The difference frequency will be 130 Hz. Each session will last 20 minutes, twice daily for 5 consecutive days, with a 30-minute interval between sessions.
Other Names:
  • Active tTIS Targeting Left ALIC
Active Comparator: Active tTIS Targeting Left sgACC
Participants in this arm will receive active transcranial temporal interference stimulation (tTIS) targeting the left subgenual anterior cingulate cortex (sgACC). Treatment will be delivered twice daily for 5 consecutive days, with each session lasting 20 minutes and a 30-minute interval between sessions.
Device: Active Transcranial Temporal Interference Stimulation Targeting Left sgACC
Participants in this arm will receive active transcranial temporal interference stimulation (tTIS) targeting the left subgenual anterior cingulate cortex (sgACC). The stimulation target will be individualized based on each participant's magnetic resonance imaging data. The difference frequency will be 130 Hz. Each session will last 20 minutes, twice daily for 5 consecutive days, with a 30-minute interval between sessions.
Other Names:
  • Active tTIS Targeting Left sgACC
Sham Comparator: Sham tTIS
Participants in this arm will receive sham transcranial temporal interference stimulation (tTIS). Sham stimulation will be delivered using the same type of device and will provide sensory feedback similar to active stimulation, but it will not provide the same active treatment dose. Treatment sessions will follow the same schedule as the active stimulation arms.
Device: Sham Transcranial Temporal Interference Stimulation
Participants in this arm will receive sham transcranial temporal interference stimulation (tTIS) using the same type of device as active stimulation. Sham stimulation will provide sensory feedback similar to active stimulation to help maintain masking, but it will not deliver the same active treatment dose. Each session will last 20 minutes, twice daily for 5 consecutive days, with a 30-minute interval between sessions.
Other Names:
  • Sham tTIS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in 24-item Hamilton Depression Rating Scale (HAMD-24) Total Score From Baseline to Week 1
Time Frame: Baseline and Week 1
The 24-item Hamilton Depression Rating Scale (HAMD-24) will be used to assess the severity of depressive symptoms. The total score ranges from 0 to 76, with higher scores indicating more severe depressive symptoms. The primary outcome is the change in HAMD-24 total score from baseline to Week 1.
Baseline and Week 1

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in 24-item Hamilton Depression Rating Scale (HAMD-24) Total Score From Baseline to Week 2
Time Frame: Baseline and Week 2
The 24-item Hamilton Depression Rating Scale (HAMD-24) will be used to assess depressive symptoms. The total score ranges from 0 to 76, with higher scores indicating more severe depressive symptoms. This outcome measures the change in HAMD-24 total score from baseline to Week 2.
Baseline and Week 2
Change in 24-item Hamilton Depression Rating Scale (HAMD-24) Total Score From Baseline to Week 6
Time Frame: Baseline and Week 6
The 24-item Hamilton Depression Rating Scale (HAMD-24) will be used to assess depressive symptoms. The total score ranges from 0 to 76, with higher scores indicating more severe depressive symptoms. This outcome measures the change in HAMD-24 total score from baseline to Week 6.
Baseline and Week 6
Remission Rate Based on the 24-item Hamilton Depression Rating Scale (HAMD-24) at Week 1
Time Frame: Week 1
Remission is defined as a 24-item Hamilton Depression Rating Scale (HAMD-24) total score of 9 or lower. This outcome measures the proportion of participants who meet the remission criterion at Week 1.
Week 1
Remission Rate Based on the 24-item Hamilton Depression Rating Scale (HAMD-24) at Week 2
Time Frame: Week 2
Remission is defined as a 24-item Hamilton Depression Rating Scale (HAMD-24) total score of 9 or lower. This outcome measures the proportion of participants who meet the remission criterion at Week 2.
Week 2
Remission Rate Based on the 24-item Hamilton Depression Rating Scale (HAMD-24) at Week 6
Time Frame: Week 6
Remission is defined as a 24-item Hamilton Depression Rating Scale (HAMD-24) total score of 9 or lower. This outcome measures the proportion of participants who meet the remission criterion at Week 6.
Week 6
Response Rate Based on the 24-item Hamilton Depression Rating Scale (HAMD-24) at Week 1
Time Frame: Baseline and Week 1
Response is defined as a reduction of at least 50% in the 24-item Hamilton Depression Rating Scale (HAMD-24) total score from baseline. This outcome measures the proportion of participants who meet the response criterion at Week 1.
Baseline and Week 1
Response Rate Based on the 24-item Hamilton Depression Rating Scale (HAMD-24) at Week 2
Time Frame: Baseline and Week 2
Response is defined as a reduction of at least 50% in the 24-item Hamilton Depression Rating Scale (HAMD-24) total score from baseline. This outcome measures the proportion of participants who meet the response criterion at Week 2.
Baseline and Week 2
Response Rate Based on the 24-item Hamilton Depression Rating Scale (HAMD-24) at Week 6
Time Frame: Baseline and Week 6
Response is defined as a reduction of at least 50% in the 24-item Hamilton Depression Rating Scale (HAMD-24) total score from baseline. This outcome measures the proportion of participants who meet the response criterion at Week 6.
Baseline and Week 6
Change in Hamilton Anxiety Rating Scale (HAMA) Total Score From Baseline to Week 1
Time Frame: Baseline and Week 1
The Hamilton Anxiety Rating Scale (HAMA) will be used to assess anxiety symptoms. The total score ranges from 0 to 56, with higher scores indicating more severe anxiety symptoms. This outcome measures the change in HAMA total score from baseline to Week 1.
Baseline and Week 1
Change in Hamilton Anxiety Rating Scale (HAMA) Total Score From Baseline to Week 2
Time Frame: Baseline and Week 2
The Hamilton Anxiety Rating Scale (HAMA) will be used to assess anxiety symptoms. The total score ranges from 0 to 56, with higher scores indicating more severe anxiety symptoms. This outcome measures the change in HAMA total score from baseline to Week 2.
Baseline and Week 2
Change in Hamilton Anxiety Rating Scale (HAMA) Total Score From Baseline to Week 6
Time Frame: Baseline and Week 6
The Hamilton Anxiety Rating Scale (HAMA) will be used to assess anxiety symptoms. The total score ranges from 0 to 56, with higher scores indicating more severe anxiety symptoms. This outcome measures the change in HAMA total score from baseline to Week 6.
Baseline and Week 6
Change in Snaith-Hamilton Pleasure Scale (SHAPS) Total Score From Baseline to Week 1
Time Frame: Baseline and Week 1
The Snaith-Hamilton Pleasure Scale (SHAPS) will be used to assess anhedonia. The total score ranges from 0 to 14, with higher scores indicating more severe anhedonia. This outcome measures the change in SHAPS total score from baseline to Week 1.
Baseline and Week 1
Change in Snaith-Hamilton Pleasure Scale (SHAPS) Total Score From Baseline to Week 2
Time Frame: Baseline and Week 2
The Snaith-Hamilton Pleasure Scale (SHAPS) will be used to assess anhedonia. The total score ranges from 0 to 14, with higher scores indicating more severe anhedonia. This outcome measures the change in SHAPS total score from baseline to Week 2.
Baseline and Week 2
Change in Snaith-Hamilton Pleasure Scale (SHAPS) Total Score From Baseline to Week 6
Time Frame: Baseline and Week 6
The Snaith-Hamilton Pleasure Scale (SHAPS) will be used to assess anhedonia. The total score ranges from 0 to 14, with higher scores indicating more severe anhedonia. This outcome measures the change in SHAPS total score from baseline to Week 6.
Baseline and Week 6
Change in Psychosomatic Symptoms Scale (PSSS) Total Score From Baseline to Week 1
Time Frame: Baseline and Week 1
The Psychosomatic Symptoms Scale (PSSS) will be used to assess psychosomatic symptoms. Higher scores indicate more severe psychosomatic symptoms. This outcome measures the change in PSSS total score from baseline to Week 1.
Baseline and Week 1
Change in Psychosomatic Symptoms Scale (PSSS) Total Score From Baseline to Week 2
Time Frame: Baseline and Week 2
The Psychosomatic Symptoms Scale (PSSS) will be used to assess psychosomatic symptoms. Higher scores indicate more severe psychosomatic symptoms. This outcome measures the change in PSSS total score from baseline to Week 2.
Baseline and Week 2
Change in Psychosomatic Symptoms Scale (PSSS) Total Score From Baseline to Week 6
Time Frame: Baseline and Week 6
The Psychosomatic Symptoms Scale (PSSS) will be used to assess psychosomatic symptoms. Higher scores indicate more severe psychosomatic symptoms. This outcome measures the change in PSSS total score from baseline to Week 6.
Baseline and Week 6
Incidence of Adverse Events
Time Frame: From Day 1 through Week 6
Adverse events will be recorded throughout the treatment and follow-up period. The number and proportion of participants experiencing adverse events will be summarized. The type, severity, duration, outcome, and relationship of adverse events to the intervention will be recorded.
From Day 1 through Week 6

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Brain Structural Imaging Metrics From 5.0T Magnetic Resonance Imaging
Time Frame: Baseline and Day 6
Brain structural imaging metrics will be derived from 5.0T structural magnetic resonance imaging. This outcome explores changes in brain structural imaging metrics from baseline to post-treatment.
Baseline and Day 6
Change in Resting-state Functional Connectivity From 5.0T Functional Magnetic Resonance Imaging
Time Frame: Baseline and Day 6
Resting-state functional connectivity will be derived from 5.0T resting-state functional magnetic resonance imaging. This outcome explores changes in resting-state functional connectivity from baseline to post-treatment.
Baseline and Day 6
Change in Diffusion Imaging Metrics From 5.0T Magnetic Resonance Imaging
Time Frame: Baseline and Day 6
Diffusion imaging metrics will be derived from 5.0T diffusion magnetic resonance imaging. This outcome explores changes in diffusion imaging metrics from baseline to post-treatment.
Baseline and Day 6

Collaborators and Investigators

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

Sponsor

Yonggui Yuan

Investigators

  • Principal Investigator: Yonggui Yuan, PhD, Zhongda Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

May 30, 2026

Primary Completion (Estimated)

May 30, 2027

Study Completion (Estimated)

May 30, 2027

Study Registration Dates

First Submitted

May 20, 2026

First Submitted That Met QC Criteria

May 27, 2026

First Posted (Actual)

May 28, 2026

Study Record Updates

Last Update Posted (Actual)

May 28, 2026

Last Update Submitted That Met QC Criteria

May 27, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MR-32-25-078202
  • 82271570 (Other Grant/Funding Number: National Natural Science Foundation of China)
  • BF2025611 (Other Grant/Funding Number: Jiangsu Province Frontier Technology Research and Development Program (Health Sector))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual participant data will not be publicly shared because the study involves sensitive mental health information and neuroimaging data. Data sharing may increase the risk of participant identification. De-identified data may be made available from the principal investigator upon reasonable request and with approval from the ethics committee, when permitted by applicable regulations and the informed consent.

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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