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

N/ANot Yet RecruitingNCT07829575

Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University60 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Major Depressive Disorder (MDD

Interventions

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 StimulationDEVICE

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Change in 17-item Hamilton Depression Rating Scale (HAMD-17) Total Score

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.

Time frame: Baseline; after 10 stimulation sessions (30 minutes per session; end of Week 2)

Secondary Outcomes

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

The Montgomery-Åsberg Depression Rating Scale (MADRS) is a clinician-rated scale used to assess the severity of depressive symptoms. Total scores range from 0 to 60, with higher scores indicating greater depressive symptom severity. Changes in MADRS total score from baseline will be assessed following treatment and during follow-up.

Time frame: Baseline,after 5 stimulation sessions (30 minutes per session; end of Week 1); after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 1 week and 4 weeks after completion of the 10-session intervention.

Change in 17-item Hamilton Depression Rating Scale (HAMD-17) Total Score Across Treatment and Follow-up

Change in Hamilton Anxiety Rating Scale (HAMA) Total Score

The Hamilton Anxiety Rating Scale (HAMA) is a clinician-rated scale used to assess the severity of anxiety symptoms. Total scores range from 0 to 56, with higher scores indicating greater anxiety severity. Changes in HAMA total score from baseline will be assessed following treatment and during follow-up.

Change in Snaith-Hamilton Pleasure Scale (SHAPS) Score

The Snaith-Hamilton Pleasure Scale (SHAPS) is used to assess anhedonia and reduced capacity to experience pleasure. Changes in SHAPS score from baseline will be used to evaluate treatment-related changes in hedonic functioning.

Time frame: Baseline,after 5 stimulation sessions (30 minutes per session; end of Week 1); after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 4 weeks after completion of the 10-session intervention.

Change in Pittsburgh Sleep Quality Index (PSQI) Global Score

The Pittsburgh Sleep Quality Index (PSQI) is a self-reported measure of sleep quality and sleep disturbances. The global score ranges from 0 to 21, with higher scores indicating poorer sleep quality. Changes in PSQI global score from baseline will be assessed following treatment and during follow-up.

Change in World Health Organization Quality of Life-BREF (WHOQOL-BREF) Domain Scores

The WHOQOL-BREF is a self-reported measure of quality of life across physical health, psychological health, social relationships, and environmental domains. Higher domain scores indicate better perceived quality of life. Changes in domain scores from baseline will be assessed after treatment and during follow-up.

Time frame: Baseline,after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 4 weeks after completion of the 10-session intervention.

Change in Generalized Anxiety Disorder-7 (GAD-7) Score

The Generalized Anxiety Disorder-7 (GAD-7) is a self-reported measure of anxiety symptoms. Total scores range from 0 to 21, with higher scores indicating greater anxiety symptom severity. Changes in GAD-7 score from baseline will be assessed following treatment and during follow-up.

Change in Patient Health Questionnaire-9 (PHQ-9) Total Score

The Patient Health Questionnaire-9 (PHQ-9) is a 9-item self-reported measure used to assess the severity of depressive symptoms. Total scores range from 0 to 27, with higher scores indicating greater depressive symptom severity. Changes in PHQ-9 total score from baseline will be assessed following treatment and during follow-up.

Change in Cognitive Performance Assessed by the THINC-integrated Tool (THINC-it)

The THINC-integrated Tool (THINC-it) is a computerized cognitive assessment designed to evaluate subjective and objective cognitive functioning, including attention, processing speed, working memory, and executive function. Changes in THINC-it performance from baseline will be assessed following treatment and during follow-up.

Change in Temporal Experience of Pleasure Scale (TEPS) Score

The Temporal Experience of Pleasure Scale (TEPS) is a self-reported measure of anticipatory and consummatory pleasure. Changes in TEPS scores from baseline will be explored to assess treatment-related changes in reward-related emotional experience.

Time frame: Baseline,after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 4 weeks after completion of the 10-session intervention.

Change in Emotion Regulation Questionnaire (ERQ) Score

The Emotion Regulation Questionnaire (ERQ) assesses habitual use of cognitive reappraisal and expressive suppression as emotion regulation strategies. Changes in ERQ scores from baseline will be explored following treatment and during follow-up.

Time frame: Baseline,after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 4 weeks after completion of the 10-session intervention.

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts