Skip to main content
OpenTrials
Not Yet Recruiting

NCT Number: NCT07612501

Efficacy and Safety of Transcranial Temporal Interference Stimulation for Depression

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.

Not Yet Recruiting

Trial opening soon.

Get Notified

Key information

Conditions

Major Depressive Disorder (MDD) Depressive Disorder Depressive Disorder, Major Mental Disorders Mood Disorders

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Active Transcranial Temporal Interference Stimulation Targeting Left ALIC

Device

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 Transcranial Temporal Interference Stimulation Targeting Left sgACC

Device

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 Transcranial Temporal Interference Stimulation

Device

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

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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.

  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.

  3. 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.

  4. 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.

  5. 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.

  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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

Other outcomes

  1. 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.

  2. 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.

  3. 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Yubo Zhang, MD Candidate

CONTACT

[email protected]

+86 18651617808

Yue Zhou, MD Candidate

CONTACT

[email protected]

+86 15651003002

Sponsors and collaborators

Lead sponsor

Yonggui Yuan

Other

Registry information

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
May 28, 2026
Registry last updated
May 28, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.