Amygdala-Targeted Transcranial Temporal Interference Stimulation for Major Depressive Disorder: A Randomized Sham-Controlled Trial of Clinical Efficacy and Neurobiological Mechanisms

NCT07829575 · tracked via the Priya Life Science China tracker

Sponsor

Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University

Phase

Not applicable

Started

2026-10-20

Last updated

2026-09-21

Condition(s) studied

Major Depressive Disorder (MDD

Investigational drug(s) / intervention(s)

Transcranial Temporal Interference StimulationSham Transcranial Temporal Interference Stimulation

Transcranial Temporal Interference Stimulation: Active transcranial temporal interference stimulation (tTIS) will be delivered using two pairs of scalp electrodes. Two high-frequency alternating currents with slightly different carrier frequencies will be applied to generate a low-frequency temporal interference envelope within the targeted amygdala region. Electrode placement and stimulation parameters will be determined according to the study protocol and individualized electric-field modeling when applicable. Participants assigned to the active group will receive 10 stimulation sessions, with each session lasting 30 minutes, according to the predefined treatment schedule.

Sham Transcranial Temporal Interference Stimulation: Participants assigned to the sham group will undergo the same electrode placement and treatment procedures as the active stimulation group. Sham stimulation will include brief ramp-up and ramp-down periods to mimic the initial sensory experience of active stimulation, without delivering continuous therapeutic stimulation during the remainder of the session.

Study summary

This randomized, sham-controlled clinical trial aims to evaluate the efficacy and safety of amygdala-targeted transcranial temporal interference stimulation (tTIS) in adults with major depressive disorder (MDD) and to explore its potential neurobiological mechanisms.

The main questions this study aims to answer are:

Whether active amygdala-targeted tTIS reduces depressive symptoms compared with sham stimulation.

Whether tTIS produces changes in amygdala-related neural activity and functional brain networks that are associated with clinical improvement.

Participants will be randomly assigned to receive either active tTIS or sham stimulation. They will complete a course of stimulation sessions and undergo clinical assessments before and after the intervention. Neuroimaging assessments will also be performed to investigate treatment-related changes in the amygdala and associated brain networks.

Eligibility

Sex

ALL

Min age

18 Years

Max age

55 Years

Healthy volunteers

Inclusion Criteria: 1. Aged 18 to 55 years, inclusive, with no restriction on sex. 2. Diagnosed with Major Depressive Disorder (MDD) according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), as determined by a study physician. 3. A 17-item Hamilton Depression Rating Scale (HAMD-17) score ≥17 at screening/baseline. 4. The antidepressant medication regimen must remain stable from at least 30 days before signing the informed consent form through the study period. 5. In the judgment of the investigator, the participant or their legally authorized representative is able to understand the purpose and procedures of the study, comply with the study protocol, and provide written informed consent. Exclusion Criteria: 1. A history of other psychiatric disorders, neurological disorders, or substance abuse that, in the investigator's judgment, may interfere with the assessment of treatment efficacy. 2. A history of epilepsy, seizures, or convulsive episodes. 3. Presence of intracranial metallic foreign bodies or metallic implants in or near the heart. 4. Presence of organic brain disease, or a history of severe head injury or cranial surgery. 5. Receipt of electroconvulsive therapy (ECT) or other physical treatments, such as transcranial magnetic stimulation (TMS), within the 30 days before enrollment. 6. An unstable psychiatric condition or significant suicide risk, as assessed by the investigator. 7. Women who are pregnant or breastfeeding. 8. Current participation in another interventional clinical trial. 9. Any other condition that, in the investigator's judgment, makes the participant unsuitable for participation in this study.

Primary outcome measure(s)

Change in 17-item Hamilton Depression Rating Scale (HAMD-17) Total Score — Baseline; after 10 stimulation sessions (30 minutes per session; end of Week 2)
The 17-item Hamilton Depression Rating Scale (HAMD-17) is a clinician-rated scale used to assess the severity of depressive symptoms. Total scores range from 0 to 52, with higher scores indicating greater depressive symptom severity. The primary outcome is the change in HAMD-17 total score from baseline to the end of the 10-session intervention.

Trial sites (1)

Facility	City	Region	Status
Shanghai Pudong New Area Mental Health Center	Shanghai	Shanghai Municipality

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Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT07829575 on ClinicalTrials.gov ↗ ← All trials in China