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

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

10

Phase

  • 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

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
Intervention / Treatment
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

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

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

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)

August 14, 2025

Primary Completion (Estimated)

November 1, 2025

Study Completion (Estimated)

January 1, 2026

Study Registration Dates

First Submitted

September 4, 2025

First Submitted That Met QC Criteria

September 14, 2025

First Posted (Actual)

September 22, 2025

Study Record Updates

Last Update Posted (Actual)

September 22, 2025

Last Update Submitted That Met QC Criteria

September 14, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID 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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