Precision Closed-loop Brain-Computer Interface Neuromodulation for Treatment-Resistant Depression

Summary

The goal of this clinical trial is to evaluate whether precision closed-loop neuromodulation treatments can improve depressive symptoms and daily functioning in people with treatment-resistant major depressive disorder (TRD). The study will assess the effectiveness and safety of two neuromodulation approaches: closed-loop deep brain stimulation (DBS) and transcutaneous auricular vagus nerve stimulation (taVNS).

Treatment-resistant major depressive disorder refers to depression that does not improve sufficiently after adequate treatment with standard antidepressant therapies. This study focuses on people with TRD, including individuals with early-onset depression, a history of self-harm or suicidal thoughts, or depression associated with traumatic experiences.

This study aims to answer whether closed-loop DBS and taVNS can reduce depressive symptoms compared with sham stimulation, whether these treatments are safe and well tolerated, and whether changes in brain activity are associated with clinical improvement.

This is a multicenter, prospective clinical study conducted at Shanghai Mental Health Center, Beijing Anding Hospital, and Xuanwu Hospital. Eligible participants with TRD will receive either DBS or taVNS according to patient preference. Within each intervention group, participants will be randomly assigned to active stimulation or sham stimulation groups to assess treatment effects.

During the study, participants will receive neuromodulation treatment and complete regular follow-up assessments. These assessments will include evaluation of depressive symptoms, anxiety symptoms, cognitive function, social functioning, brain electrical activity using electroencephalography (EEG), brain imaging using magnetic resonance imaging (MRI), and monitoring of adverse events.

The study will compare changes in clinical symptoms, brain-related measures, and safety outcomes between active and sham stimulation groups. The findings may help determine whether precision neuromodulation approaches can provide a new treatment option for people with treatment-resistant major depressive disorder.

Conditions

• Treatment-Resistant Major Depressive Disorder
• Major Depressive Disorder

Interventions

DEVICE

Closed-loop Deep Brain Stimulation (DBS)

Closed-loop deep brain stimulation (DBS) is an implanted neuromodulation intervention that delivers electrical stimulation based on real-time neural signals. Participants assigned to the DBS pathway will undergo implantation of a DBS system and receive either active or delayed stimulation according to the randomized study assignment. Clinical outcomes, cognitive function, brain activity, and safety outcomes will be assessed during follow-up.

DEVICE

Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)

Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation intervention that delivers electrical stimulation through electrodes placed on auricular sites associated with the vagus nerve. Participants assigned to the taVNS pathway will receive either active or sham stimulation according to the randomized study assignment. Clinical outcomes, cognitive function, brain activity, and safety outcomes will be assessed during follow-up.

Sponsors & Collaborators

• Xuanwu Hospital, Beijing

  collaborator OTHER

• Anding Hospital, Beijing

  collaborator UNKNOWN

• Shanghai Mental Health Center

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2027-01-01

Primary Completion

2028-12-31

Completion

2028-12-31