Temporal Interference Transcranial Alternating Current Stimulation for Major Depressive Disorder

A Double-Blind, Randomized, Sham-Controlled Clinical Trial of Temporal Interference Transcranial Alternating Current Stimulation for the Treatment of Major Depressive Disorder

Status

Not yet recruiting

Phases

Unknown

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT07712159

Enrollment

102

Registered

2026-07-17

Start date

2026-09-15

Completion date

2028-06-01

Last updated

2026-09-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Major Depressive Disorder (MDD)

Keywords

Major Depressive Disorder, Temporal Interference Transcranial Alternating Current Stimulation, Multi-center, Randomized Controlled Trial, Non-invasive brain stimulation, Neuromodulation, double-blind

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.

Detailed description

Major depressive disorder (MDD) is a highly prevalent psychiatric disorder associated with substantial disability and impaired quality of life. Neuroimaging studies have demonstrated abnormalities in distributed cortical-subcortical circuits, particularly involving the amygdala, which plays a central role in emotional processing and symptom regulation. Although several neuromodulation techniques have shown therapeutic potential, currently available approaches have limited ability to selectively modulate deep brain structures without invasive procedures. Temporal interference transcranial alternating current stimulation (TI-tACS) is a novel non-invasive neuromodulation technique that delivers two high-frequency alternating currents with slightly different frequencies to generate a low-frequency envelope within deep brain regions. This approach enables selective modulation of deep neural structures, such as the amygdala, while minimizing stimulation of the overlying cortex. This is a multicenter, randomized, triple-blind, sham-controlled clinical trial designed to evaluate the efficacy, safety, and neurobiological mechanisms of TI-tACS in participants with MDD. Participants will be enrolled randomized to receive active or sham TI-tACS according to the study protocol. Approximately 102 participants will be recruited. Following written informed consent, participants will undergo baseline assessments and subsequent study evaluations according to the protocol. Study assessments include clinical evaluations, neurocognitive testing, electroencephalography (EEG), magnetic resonance imaging (MRI), and biological sample collection. TI-tACS treatment consists of 20 stimulation sessions administered over two weeks (two sessions per day for five consecutive days, followed by a two-day break, and another five consecutive treatment days). Participants will also complete scheduled post-treatment follow-up assessments to evaluate the persistence of treatment effects and the long-term safety of TI-tACS.

Interventions

DEVICETemporal Interference transcranial Alternating Current Stimulation (TI-tACS)

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.

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

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

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Outcomes Assessor)

Masking description

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.

Intervention model description

Participants with major depressive disorder will be randomized to receive high-frequency TI-tACS(130 Hz), low-frequency TI-tACS(2Hz), or sham stimulation.

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

Healthy volunteers

Inclusion criteria

1. Age between 18 and 55 years (inclusive), any gender; 2. 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; 3. HAMD-17 score ≥14; inadequate response to stable, regular antidepressant medication for at least 1 month at an adequate dose; 4. Education level: junior high school or above; adequate cognitive and language ability to understand and complete study assessments; 5. Voluntary participation with signed informed consent; ability to comply with study visits, treatment schedules, laboratory tests, and other study procedures.

Exclusion criteria

1. History of psychiatric disorders other than MDD; 2. Pregnancy or lactation; 3. Neurologic disorders or serious systemic diseases (e.g., thyroid disease, lupus erythematosus, diabetes, hepatic or renal impairment, active infection, major trauma); 4. History of significant head injury or coma 5. Receipt of physical therapies such as electroconvulsive therapy or rTMS within the past six months before enrollment 6. Suspected or confirmed history of alcohol or substance dependence; 7. Current severe suicidal ideation or recent suicide attempt; 8. Current participation in another clinical trial or recent use of prohibited psychotropic medications; 9. Positive urine drug screening or abnormal thyroid function tests; 10. Contraindications to magnetic resonance imaging (MRI) or electroencephalography (EEG); 11. Inability to provide fully informed consent.

Design outcomes

Primary

Measure	Time frame	Description
Change from baseline in the Hamilton Depression Rating Scale(HAMD-17) scores at week 2.	2 weeks(from baseline)	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.

Secondary

Measure	Time frame	Description
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Score	Baseline to month 2 follow-up	The Montgomery-Åsberg Depression Rating Scale (MADRS) is a clinician-administered instrument used to assess the severity of depressive symptoms and sensitivity to treatment-related changes. The scale consists of 10 items with a total score ranging from 0 to 60. Higher scores indicate more severe depressive symptoms.
Adverse Events Related to treatment	Baseline to month 2 follow-up	Incidence, type, and severity of adverse events related to the transcranial temporal interference stimulation, assessed using a standardized Neuromodulation Adverse Effects Questionnaire.
Change in Patient Health Questionnaire-9 (PHQ-9)	Baseline to month 2 follow-up	A 9-item self-report questionnaire used to assess depressive symptom severity. Total scores range from 0 to 27, with higher scores indicating greater depression severity.
Change in the Hamilton Anxiety Rating Scale (HAMA) Score	Baseline to month 2 follow-up	The Hamilton Depression Rating Scale-17 (HAMD-17) is a 17-item clinician-administered scale used to assess the severity of depressive symptoms. The total score ranges from 0 to 52, with higher scores indicating more severe depressive symptoms.
Change in Young Mania Rating Scale (YMRS) Score	Baseline to month 2 follow-up	The Young Mania Rating Scale (YMRS) is an 11-item clinician-administered instrument used to assess the severity of manic symptoms and to monitor treatment-emergent mania or hypomania. Total scores range from 0 to 60, with higher scores indicating more severe manic symptoms.
Change in Pittsburgh Sleep Quality Index (PSQI) Score	Baseline to month 2 follow-up	The Pittsburgh Sleep Quality Index (PSQI) is a 19-item self-report questionnaire used to assess subjective sleep quality and sleep disturbances over the previous month. The questionnaire generates a global score ranging from 0 to 21, with higher scores indicating poorer sleep quality.
Change in Beck Scale for Suicide Ideation (BSI) Score	Baseline to month 2 follow-up	The Beck Scale for Suicide Ideation (BSI) is a 19-item clinician-administered instrument used to assess the severity of suicidal thoughts, attitudes, and intentions. Total scores range from 0 to 38, with higher scores indicating more severe suicidal ideation.
hange in 10-item Connor-Davidson Resilience Scale (CD-RISC-10) Score	Baseline to month 2 follow-up	The 10-item Connor-Davidson Resilience Scale (CD-RISC-10) is a 10-item self-report questionnaire used to assess psychological resilience and the ability to cope with adversity. Total scores range from 0 to 40, with higher scores indicating greater psychological resilience.
Change in Chinese Version of the Cognitive Emotion Regulation Questionnaire (CERQ-C) Score	Baseline to month 2 follow-up	The Chinese Version of the Cognitive Emotion Regulation Questionnaire (CERQ-C) is a 36-item self-report questionnaire used to assess cognitive emotion regulation strategies in response to stressful or negative life events. Total scores range from 36 to 180, with higher scores indicating greater use of cognitive emotion regulation strategies.
Change in State Anxiety Inventory (S-AI) Score	Baseline to month 2 follow-up	The State Anxiety Inventory (S-AI) is a 20-item self-report questionnaire used to assess transient anxiety experienced at the time of assessment. Total scores range from 20 to 80, with higher scores indicating greater state anxiety.
Change in Generalized Anxiety Disorder-7 (GAD-7) Score	Baseline to month 2 follow-up(post treatment)	A 7-item self-report questionnaire used to assess the severity of generalized anxiety symptoms. Total scores range from 0 to 21, with higher scores indicating greater anxiety severity.
Change in 17-item Hamilton Depression Rating Scale (HAMD-17) Score	Baseline to month 2 follow-up	The 17-item Hamilton Depression Rating Scale (HAMD-17) is a 17-item clinician-administered instrument used to assess the severity of depressive symptoms. Total scores range from 0 to 52, with higher scores indicating more severe depressive symptoms.
Change in Sheehan Disability Scale (SDS) Score	Baseline to month 2 follow-up	he Sheehan Disability Scale (SDS) is a 3-item self-report questionnaire used to assess functional impairment in work/school, social life, and family life/home responsibilities. Total scores range from 0 to 30, with higher scores indicating greater functional impairment.
Change in Snaith-Hamilton Pleasure Scale (SHAPS) Score	Baseline to month 2 follow-up	The Snaith-Hamilton Pleasure Scale (SHAPS) is a 14-item self-report questionnaire used to assess anhedonia, or the ability to experience pleasure. Total scores range from 14 to 56, with higher scores indicating greater anhedonia (reduced ability to experience pleasure).
Change in Ruminative Responses Scale (RRS) Score	Baseline to month 2 follow-up	The Ruminative Responses Scale (RRS) is a 22-item self-report questionnaire used to assess the tendency to engage in repetitive negative thinking in response to depressed mood or distress. Total scores range from 22 to 88, with higher scores indicating greater rumination.

Contacts

CONTACTYumeng Ju( Associate Researcher), PhD

yumeng.ju@csu.edu.cn86+18100731091

CONTACTLingsi Zeng, PhD Candidate

zenglsi@163.com

PRINCIPAL_INVESTIGATORYumeng Ju, PhD

Second Xiangya Hospital of Central South University

STUDY_CHAIRYan Zhang, PhD