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Active, Not Recruiting

NCT Number: NCT07184697

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

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Major Depression Depressive Disorder Depressive Disorder, Major Mental Disorders Mood Disorders

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Ruijin Hospital

Shanghai, Shanghai Municipality, 200025, China

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

HD ctACS

Device

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.

HD ctACS sham

Device

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.

Primary outcomes

  1. 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).

Secondary outcomes

  1. 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.

  2. 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.

Sponsors and collaborators

Lead sponsor

Ruijin Hospital

Other

Registry information

Official study title

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.

Important dates

Study start
2025
Primary completion
2025
Study completion
2026
First posted
Sep 22, 2025
Registry last updated
Sep 22, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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