An interventional study of Temporal Interference transcranial Alternating Current Stimulation (TI-tACS) and Sham Temporal Interference transcranial Alternating Current Stimulation (TI-tACS) in Major Depressive Disorder (MDD), sponsored by Central South University. Not yet recruiting. Open to participants aged 18 Years to 55 Years. Per ClinicalTrials.gov, last updated 2026-10-21.
Sponsored by Central South University · Not applicable, Interventional, and Treatment
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.
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, double-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 and 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.
3,041 studies on the registry are indexed under Depressive Disorder, Major; 588 are open to participants now.
This study's planned enrollment of 102 is above the median of 79 across 2,530 interventional studies indexed under Depressive Disorder, Major.
Browse Depressive Disorder, Major studies →Central South University is the lead sponsor of 134 studies on the registry; 32 are open to participants now.
Counted across the registry records on this site, refreshed daily.
The criteria were revised on the registry on Oct 7, 2026. See what changed
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants in the High-frequency TI-tACS group receive 20-minute temporal interference transcranial alternating current stimulation (130Hz) twice a day, delivered via two pairs of transcranial electrodes, targeting the right amygdala. The stimulation is administered in 2 weeks, consisting of 5 consecutive treatment days, followed by a 2-day break, and then another 5 consecutive treatment days.
Device: Temporal Interference transcranial Alternating Current Stimulation (TI-tACS)
Participants in the Low-frequency TI-tACS group receive 20-minute temporal interference transcranial alternating current stimulation (2 Hz) twice a day, delivered via two pairs of transcranial electrodes, targeting the right amygdala. The stimulation is administered in 2 weeks, consisting of 5 consecutive treatment days, followed by a 2-day break, and then another 5 consecutive treatment days.
Device: Temporal Interference transcranial Alternating Current Stimulation (TI-tACS)
Participants in the Sham TI-tACS group receive 20-minute sham stimulation of the same device twice a day for 5 consecutive treatment days, followed by a 2-day break, and then another 5 consecutive treatment days.
Device: Sham Temporal Interference transcranial Alternating Current Stimulation (TI-tACS)
Temporal Interference transcranial Alternating Current Stimulation (TI-tACS) is a non-invasive neuromodulation technique that generates a 130Hz envelope field in deep brain regions, particularly the right amygdala, through the interaction of two currents (2000 Hz, 2130Hz).
Also known as: Temporal Interference Stimulation (TIS), Transcranial Temporal Interference Stimulation (tTIS)
Sham Temporal Interference transcranial Alternating Current Stimulation will mimic the sensory experience of active stimulation without delivering effective current.
Temporal Interference transcranial Alternating Current Stimulation (TI-tACS) is a non-invasive neuromodulation technique that generates a 2Hz envelope field in deep brain regions, particularly the right amygdala, through the interaction of two currents (2000 Hz, 2002Hz).
Also known as: Temporal Interference Stimulation (TIS), Transcranial Temporal Interference Stimulation (tTIS)
Change from baseline in the Hamilton Depression Rating Scale(HAMD-17) scores at week 2.
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.
Time frame: Baseline and Week 2
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Score
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. The outcome will be calculated as the change in Montgomery-Åsberg Depression Rating Scale scores from baseline to each post-baseline assessment time point.
Time frame: Baseline, Week 1, Week 2, Week 4 and Week 8
Adverse Events Related to treatment
Incidence, type, and severity of adverse events related to the transcranial temporal interference stimulation, assessed using a standardized Neuromodulation Adverse Effects Questionnaire.
Time frame: Week 1, Week 2, Week 4 and Week 8
Change in Patient Health Questionnaire-9 (PHQ-9)
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. The outcome will be calculated as the change in PHQ-9 score from baseline to each post-baseline assessment time point.
Time frame: Baseline, Week 1, Week 2, Week 4 and Week 8
Change in the Hamilton Anxiety Rating Scale (HAMA) Score
Anxiety symptom severity will be assessed using the Hamilton Anxiety Rating Scale (HAMA), a 14-item clinician-administered scale with a total score range of 0 to 56. Higher scores indicate greater anxiety symptom severity, which represents a worse outcome. The outcome will be calculated as the change in HAMA total score from baseline to each post-baseline assessment time point.
Time frame: Baseline, Week 1, Week 2, Week 4, and Week 8
Change in Young Mania Rating Scale (YMRS) Score
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. The outcome will be calculated as the change in YMRS total score from baseline to each post-baseline assessment time point.
Time frame: Baseline, Week 1, Week 2, Week 4, and Week 8
Change in Pittsburgh Sleep Quality Index (PSQI) Score
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. The outcome will be calculated as the change in PSQI score from baseline to each post-baseline assessment time point.
Time frame: Baseline, Week 1, Week 2, Week 4 and Week 8
Change in Beck Scale for Suicide Ideation (BSI) Score
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. The outcome will be calculated as the change in BSI total score from baseline to each post-baseline assessment time point.
Time frame: Baseline, Week 1, Week 2, Week 4 and Week 8
Change in 10-item Connor-Davidson Resilience Scale (CD-RISC-10) Score
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. The outcome will be calculated as the change in CD-RISC-10 total score from baseline to each post-baseline assessment time point.
Time frame: Baseline, Week 2 and Week 8
Change in Chinese Version of the Cognitive Emotion Regulation Questionnaire (CERQ-C) Score
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. The outcome will be calculated as the change in CERQ-C total score from baseline to each post-baseline assessment time point.
Time frame: Baseline, Week 2 and Week 8
Change in State Anxiety Inventory (S-AI) Score
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. The outcome will be calculated as the change in the S-AI total score from baseline to each post-baseline assessment time point.
Time frame: Baseline, Week 1, Week 2, Week 4 and Week 8
Change in Generalized Anxiety Disorder-7 (GAD-7) Score
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. The outcome will be calculated as the change in the GAD-7 total score from baseline to each post-baseline assessment time point.
Time frame: Baseline, Week 1, Week 2, Week 4 and Week 8
Change in 17-item Hamilton Depression Rating Scale (HAMD-17) Score
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. The outcome will be calculated as the change in HAMD-17 total score from baseline to each post-baseline assessment time point.
Time frame: Baseline, Week 1, Week 4 and Week 8
Change in Sheehan Disability Scale (SDS) Score
The 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. The outcome will be calculated as the change in SDS total score from baseline to each post-baseline assessment time point.
Time frame: Baseline, Week 2, Week 4, and Week 8
Change in Snaith-Hamilton Pleasure Scale (SHAPS) Score
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). The outcome will be calculated as the change in SHAPS total score from baseline to each post-baseline assessment time point.
Time frame: Baseline, Week 2 and Week 8
Change in Ruminative Responses Scale (RRS) Score
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. The outcome will be calculated as the change in RRS total score from baseline to each post-baseline assessment time point.
Time frame: Baseline, Week 2 and Week 8
Change in Magnetic Resonance Imaging Measures
Brain structural and/or functional measures will be assessed using magnetic resonance imaging. The specific values and ranges depend on the imaging modality and derived measure, such as structural, functional connectivity, or brain network metrics. Interpretation will depend on the specific magnetic resonance imaging measure analyzed. The outcome will be calculated as the change in magnetic resonance imaging measures from baseline to each post-baseline assessment time point.
Time frame: Baseline, Week 1, Week 2 and Week 8
Change in Electroencephalography Measures
Brain electrophysiological activity will be assessed using electroencephalography (EEG). EEG-derived measures may include spectral power within predefined frequency bands, functional connectivity, synchronization, and other electrophysiological features. The specific values and ranges depend on the EEG-derived measure analyzed. Interpretation will depend on the specific EEG measure, with changes from baseline reflecting alterations in brain electrophysiological activity following the intervention. The outcome will be calculated as the change in EEG measures from baseline to each post-baseline assessment time point.
Time frame: Baseline, Week 1, Week 2 and Week 8
Change in Blood-Based Biomarkers
Peripheral blood samples will be collected for the assessment of blood-based biomarkers. The specific biomarkers, values, and reference ranges may vary depending on the laboratory assay and biological measure analyzed, such as inflammatory, metabolic, neuroendocrine, proteomic, metabolomic, transcriptomic, or other molecular profiles. Interpretation will depend on the specific biomarker assessed. The outcome will be calculated as the change in blood-based biomarkers from baseline to each post-baseline assessment time point.
Time frame: Baseline, Week 2, Week 4 and Week 8
Change in Anxiety and Depression Visual Analogue Scale Scores
Subjective anxiety and depression severity will be assessed using visual analogue scale ratings for anxiety and depression. Each visual analogue scale score ranges from 0 to 10, with higher scores indicating greater subjective symptom severity, which represents a worse outcome. The outcome will be calculated as the change in visual analogue scale scores from baseline to each post-baseline assessment time point.
Time frame: Baseline, Week 1, Week 2, Week 4 and Week 8
Change in Perceived Stress Scale (PSS) Total Score
Perceived stress will be assessed using the 10-item Perceived Stress Scale (PSS), a self-report questionnaire with a total score range of 0 to 40. Higher scores indicate greater perceived stress, which represents a worse outcome. The outcome will be calculated as the change in the PSS total score from baseline to each post-baseline assessment time point.
Time frame: Baseline, Week 2, and Week 8
Change in Cognitive Test Performance
Cognitive function will be assessed using neurocognitive tests administered in this study. The score range depends on the specific cognitive test or task. For accuracy-based cognitive measures, higher scores indicate better cognitive performance, which represents a better outcome; for time-based measures such as reaction time, higher values indicate slower performance, which represents a worse outcome. The outcome will be calculated as the change in cognitive test performance from baseline to each post-baseline assessment time point.
Time frame: Baseline, Week 1, Week 2, and Week 8
No study locations are listed for this record.
Plan to share: No — Individual participant data will not be shared because the dataset includes sensitive neuroimaging and biological data that may compromise participant confidentiality.
No publications or documents are linked to this record.
Start is estimated for Oct 2026; primary completion for Dec 2027, 14 months later.
Of 647 non-industry interventional studies with no phase under Depressive Disorder, Major, half reached primary completion within 35 months of starting (the median), counting those still running; a quarter within 19 and three quarters within 55. This study's planned 14 months is below that.
Counting every sponsor, half of 687 studies reached it within 33 months; a quarter within 17 and three quarters within 55.
Start moved once since we started tracking on Sep 25, 2026: Sep 2026 → Oct 2026, on Oct 7, 2026.
Earlier changes are on the record history on ClinicalTrials.gov ↗
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is not yet recruiting, as verified in Oct 2026. You cannot join it, but the record below documents what was studied.
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