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

NCT07184697 | Active Not Recruiting

• 1 other identifier: HD-ctACS for MDD
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Major Depression

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in Hamilton Depression Rating Scale 17-item (HAMD-17) Score

  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 Outcomes (2)

• Change from Baseline in Nucleus Accumbens (NAc) Gamma Power

  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

  Baseline, day1, day2, day3 day4, day5, day6, day7, day8, day9, day10, day11, day12, day13, day14, day15.

Study Arms (2)

active stimulation and crossover to sham stimulation

ACTIVE COMPARATOR

Device: HD ctACS; Device: HD ctACS sham

sham stimulation and crossover to active stimulation

ACTIVE COMPARATOR

Device: HD ctACS; Device: HD ctACS sham

Interventions

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.

active stimulation and crossover to sham stimulation; sham stimulation and crossover to active stimulation

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.

active stimulation and crossover to sham stimulation; sham stimulation and crossover to active stimulation

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

Ruijin Hospital

Shanghai, Shanghai Municipality, 200025, China

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2025
• First Posted: September 22, 2025
• Study Start: August 14, 2025
• Primary Completion: November 1, 2025
• Study Completion: January 1, 2026
• Last Updated: September 22, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)