Efficacy and Safety of Task-specific, Biomarker-driven, HD-ctACS inTRD.

September 14, 2025 updated by: Ruijin Hospital

Efficacy and Safety of Task-specific, Biomarker-driven, High-definition, Closed-loop Transcranial Alternating Current Stimulation (HD-ctACS) in Treatment-Resistant Depression (TRD): A Randomized, Double-blind, Sham-controlled, Crossover Trial.

This is a single-center, randomized, double-blind, sham-controlled, crossover exploratory clinical trial designed to evaluate the therapeutic effects of task-specific, biomarker-driven HD-ctACS on treatment-resistant depression (TRD). The study will enroll 10 patients diagnosed with TRD. Each participant will, in a randomized order, undergo a 4-week active HD-ctACS treatment period and a 4-week sham stimulation (delayed HD-ctACS) period, separated by an 8-week washout period. The primary objective is to assess the efficacy of HD-ctACS in improving core depressive symptoms, with the primary outcome being the difference in the Hamilton Depression Rating Scale (HAMD) total score between the end of the two intervention periods. Secondary objectives include evaluating the safety of the therapy, its effects on other symptom dimensions, and exploring its modulatory effects on neurobiological markers of emotional processing (e.g., NAc gamma power). The total participation time for each subject is approximately 16 weeks.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
10

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China, 200025
        • Ruijin Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria Age between 18 and 65 years, any gender.

Meets DSM-5 diagnostic criteria for Major Depressive Disorder (MDD), currently in a moderate to severe episode (total HAMD score ≥ 17).

Meets the definition of Treatment-Resistant Depression (TRD): failure to respond to or intolerance of at least two antidepressant medications from different mechanistic classes, administered at an adequate dose and duration (e.g., 6-8 weeks) during the current depressive episode.

Agrees to maintain a stable dosage of their current antidepressant medication regimen (if taking any) throughout the study period.

Able to comprehend the study procedures and voluntarily provide written informed consent.

Has intracranial deep brain electrodes implanted for research purposes, with electrodes located in the target brain regions (e.g., NAc, BNST).

Exclusion Criteria History of other severe psychiatric disorders such as schizophrenia or bipolar disorder.

Current severe suicide risk.

History of alcohol or substance abuse/dependence (within the last year).

History of epilepsy or has intracranial metal implants (other than the research electrodes).

Presence of any unstable and significant somatic illness.

Women who are pregnant or breastfeeding.

Currently participating in another clinical trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: active stimulation and crossover to sham stimulation
Device: HD ctACS
Participants received High-Definition closed-loop transcranial Alternating Current Stimulation (HD-ctACS) for 30 minutes daily, 5 days per week. A 4x1 ring electrode montage was used, with the center electrode placed over the bilateral temporal cortices. Stimulation was delivered as a sinusoidal alternating current at a 2 mA peak amplitude, with the frequency individualized for each participant based on their baseline EEG. The stimulation was administered in a closed-loop, task-specific manner: a 500 ms burst of stimulation was triggered only when a subliminal negative facial stimulus was presented and the participant's real-time Nucleus Accumbens gamma power exceeded their baseline by two standard deviations.
Device: HD ctACS sham
Participants received High-Definition transcranial Alternating Current Stimulation (HD-tACS) in 30-minute sessions once daily, 5 days per week. A 4x1 ring electrode layout was used to target the bilateral temporal cortices. The stimulation consisted of a sinusoidal alternating current with a 2 mA peak intensity, delivered at an individualized gamma frequency determined from a baseline EEG. The intervention was administered using a closed-loop, task-specific paradigm: upon presentation of a subliminal negative facial stimulus while the real-time Nucleus Accumbens gamma power exceeded a baseline threshold of +2 SD, a 500 ms stimulation was delivered following a random delay of 1000-2000 ms.
Active Comparator: sham stimulation and crossover to active stimulation
Device: HD ctACS
Participants received High-Definition closed-loop transcranial Alternating Current Stimulation (HD-ctACS) for 30 minutes daily, 5 days per week. A 4x1 ring electrode montage was used, with the center electrode placed over the bilateral temporal cortices. Stimulation was delivered as a sinusoidal alternating current at a 2 mA peak amplitude, with the frequency individualized for each participant based on their baseline EEG. The stimulation was administered in a closed-loop, task-specific manner: a 500 ms burst of stimulation was triggered only when a subliminal negative facial stimulus was presented and the participant's real-time Nucleus Accumbens gamma power exceeded their baseline by two standard deviations.
Device: HD ctACS sham
Participants received High-Definition transcranial Alternating Current Stimulation (HD-tACS) in 30-minute sessions once daily, 5 days per week. A 4x1 ring electrode layout was used to target the bilateral temporal cortices. The stimulation consisted of a sinusoidal alternating current with a 2 mA peak intensity, delivered at an individualized gamma frequency determined from a baseline EEG. The intervention was administered using a closed-loop, task-specific paradigm: upon presentation of a subliminal negative facial stimulus while the real-time Nucleus Accumbens gamma power exceeded a baseline threshold of +2 SD, a 500 ms stimulation was delivered following a random delay of 1000-2000 ms.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change from Baseline in Hamilton Depression Rating Scale 17-item (HAMD-17) Score
Time Frame: Baseline, Week 2, and Week 4 (End of Intervention).
The 17-item Hamilton Depression Rating Scale (HAMD-17) is a clinician-rated scale used to assess the severity of depression. The total score ranges from 0 to 52. A higher score indicates a worse outcome (i.e., greater depression severity).
Baseline, Week 2, and Week 4 (End of Intervention).

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Change from Baseline in Nucleus Accumbens (NAc) Gamma Power
Time Frame: Baseline, day1, day2, day3 day4, day5, day6, day7, day8, day9, day10, day11, day12, day13, day14, day15.
Baseline, day1, day2, day3 day4, day5, day6, day7, day8, day9, day10, day11, day12, day13, day14, day15.
Amplitude of Event-Related Potential (ERP) in Response to Facial Stimuli
Time Frame: Baseline, day1, day2, day3 day4, day5, day6, day7, day8, day9, day10, day11, day12, day13, day14, day15.
Baseline, day1, day2, day3 day4, day5, day6, day7, day8, day9, day10, day11, day12, day13, day14, day15.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ruijin Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 14, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 4, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 14, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 22, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 22, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 14, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HD-ctACS for MDD

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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