Multi-scenario Clinical Application of Precision Closed-loop Brain-Computer Interface Neuromodulation in Treatment-Resistant Major Depressive Disorder
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 70
- 主要终点
- Change in 17-item Hamilton Rating Scale for Depression (HAMD-17) score
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 to 70 years, regardless of sex.
- •At least primary school education and able to understand the content of the assessment scales.
- •Meet the diagnostic criteria for depressive disorders according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).
- •Have a history of depression lasting at least 24 months and have received adequate-dose and adequate-duration treatment with at least 2 antidepressants for 8 weeks or longer, including electroconvulsive therapy without anesthesia, with a reduction rate in the HAMD-17 score of 20% or less after treatment.
- •Have a HAMD-17 score greater than 17 at baseline.
- •Have been on a stable regimen of the current antidepressant medication for at least 1 month before enrollment.
- •Meet at least one of the following three criteria:
- •Depression with onset before 18 years of age.
- •The age at first depressive episode was younger than 18 years, confirmed by a psychiatrist at the attending physician level or above according to the DSM-5 or International Classification of Diseases, 11th Revision (ICD-11) diagnostic criteria for depressive disorders.
- •The age at onset can be supported by at least one of the following sources: the participant's medical history report, previous medical records, or information about age at onset provided by a guardian.
- •If the onset age is unclear, confirmation requires consistency between at least two independent sources of information.
- •A clear history of self-injurious or suicidal behavior:
- •As confirmed by a guardian or through review of previous medical records, the participant has had clinically significant self-injurious behavior, such as cutting, burning, hitting oneself, involving intentional self-harm without the intent to die; or suicidal behavior or tendencies, such as recurrent suicidal ideation, suicidal planning, or a suicide attempt.
- •Such behavior or tendencies must be documented in, but not limited to, outpatient or inpatient medical records, psychological assessment records, or school or community referral records. Alternatively, they may be clearly described by a guardian and documented and confirmed in writing by the investigator.
- •A clear history of traumatic stress:
- •As confirmed by a guardian or through review of previous medical records, before the onset or worsening of depression, the participant experienced a situation meeting the DSM-5 definition of traumatic events, including but not limited to: actual or threatened death; serious injury; sexual violence; abuse; neglect; bullying; major accidents; war; natural disasters; intimate partner violence.
- •The traumatic event must have a clearly documented time of occurrence, type of event, and temporal relationship with the onset or worsening of depressive symptoms.
- •Standardized instruments such as life event questionnaires may be used as supplementary assessments. However, final eligibility determination must be made by the investigator based on comprehensive evaluation of: information provided by the legal guardian; previous medical records; clinical judgment.
- •Participants or their legal guardians must voluntarily sign the informed consent form and must be capable of completing follow-up assessments;
- •Participants assigned to the DBS group must pass preoperative evaluation for DBS surgery and must have no contraindications for neurosurgical procedures;
- •Participants assigned to the taVNS group must pass taVNS eligibility assessment, including: no recent facial or auricular injuries; no metallic implants in the head or heart; no active gastrointestinal symptoms; no acute exacerbation of respiratory disorders; no personal or family history of epilepsy; no frequent or severe headaches.
排除标准
- •Previous diagnosis of: schizophrenia; schizoaffective disorder; substance dependence or drug addiction; mental disorders secondary to other medical conditions; or presence of significant psychotic symptoms, including delusions and hallucinations.
- •Presence of severe or unstable disorders involving the: central nervous system; cardiovascular system; respiratory system; liver; kidney; endocrine system; hematological system; or other major organ systems, which, in the investigator's judgment, make the participant unsuitable for enrollment.
- •Female participants who are: pregnant; breastfeeding; planning pregnancy during the study period or within 8 weeks after the last medication administration; or male participants with plans for reproduction during the study period.
- •Participation in another clinical trial within the previous 3 months.
- •Inability to undergo MRI examination.
- •MRI findings indicating any of the following: more than two lacunar infarcts; regional infarction lesions with a volume >1 cm³; significant white matter lesions; a total Fazekas score of
- •Severe aphasia, visual impairment, hearing impairment, or other conditions preventing completion of study procedures.
- •Any condition that, in the investigator's opinion, makes the participant unsuitable for participation in this study.
- •Contraindications to DBS surgery or chronic vagus nerve stimulation (VNS).
- •High suicide risk determined using the Columbia-Suicide Severity Rating Scale (C-SSRS). Participants will be excluded if any of the following criteria are met:
- •A suicide attempt within the previous 3 months;
- •Persistent active suicidal ideation with intent to act, as indicated by the C-SSRS assessment;
- •Emergency department visit or hospitalization due to suicide risk within 1 month prior to enrollment;
- •Baseline C-SSRS assessment indicates non-persistent active suicidal ideation, but the investigator determines, based on the intensity of suicidal intent score (C-SSRS Item 5) and clinical evaluation, that the participant has severely impaired impulse control and immediate suicide risk, confirmed by a psychiatric specialist.
研究组 & 干预措施
Active DBS
Participants will receive active closed-loop deep brain stimulation (DBS). After DBS implantation surgery, stimulation will be activated 7-14 days after surgery. Participants will receive closed-loop DBS treatment and undergo clinical follow-up assessments for 8 weeks to evaluate changes in depressive symptoms, cognitive function, and safety outcomes.
干预措施: Closed-loop Deep Brain Stimulation (DBS) (Device)
Sham DB
Participants will receive sham deep brain stimulation (DBS) during the blinded comparison period. After DBS implantation surgery, stimulation will remain inactive until 8 weeks after surgery. Participants will undergo the same clinical follow-up assessments as the active DBS group during the study period.
干预措施: Closed-loop Deep Brain Stimulation (DBS) (Device)
Active taVNS
Participants will receive active transcutaneous auricular vagus nerve stimulation (taVNS). Electrical stimulation will be delivered through electrodes placed at the auricular stimulation sites. Participants will receive taVNS treatment and undergo clinical follow-up assessments for 8 weeks to evaluate changes in depressive symptoms, cognitive function, and safety outcomes.
干预措施: Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) (Device)
Sham taVNS
Participants will receive sham transcutaneous auricular vagus nerve stimulation (taVNS). The electrodes will be placed at the same auricular sites as active stimulation, but no therapeutic electrical stimulation will be delivered. Participants will undergo the same clinical follow-up assessments as the active taVNS group.
干预措施: Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) (Device)
结局指标
主要结局
Change in 17-item Hamilton Rating Scale for Depression (HAMD-17) score
时间窗: Baseline to Week 8
The primary efficacy outcome is the change in the 17-item Hamilton Depression Rating Scale (HAMD-17) score from baseline to week 8 after intervention. The HAMD-17 is used to assess the severity of depressive symptoms, with higher scores indicating greater severity of depressive symptoms. A decrease in HAMD-17 score indicates improvement in depressive symptoms.
次要结局
- Change in Hamilton Anxiety Rating Scale (HAMA) score(Baseline to Week 8)
- Change in Montreal Cognitive Assessment scale (MoCA) score(Baseline to Week 8)
- Change in Montgomery-Asberg Depression Rating Scale (MADRS) score(Baseline to Week 8)
- Change in Patient Health Questionnaire-9 (PHQ-9) score(Baseline to Week 8)
- Change in Generalized Anxiety Disorder-7 (GAD-7) score(Baseline to Week 8)
- Change in Clinical Global Impression-Improvement (CGI) score, using Clinical Global Impression-Severity (CGI-S)(Baseline to Week 8)
- Change in Clinical Global Impression-Improvement (CGI) score, using Clinical Global Impression-Improvement (CGI-I).(Baseline to Week 8)
- Change in Personal and Social Performance Scale (PSP) score(Baseline to Weeks 1, 2, 4, 6, and 8)
- Change in Social Functioning Rating Scale (SFRS) score(Baseline to Week 8)
- EEG Delta, Theta, Alpha, and Beta Band Power and Theta/Beta Power Ratio(Baseline to Week 8)
- Changes in neuroimaging measures assessed by magnetic resonance imaging (MRI)(Baseline to Week 8)
- Number and percentage of participants with adverse events or serious adverse events(Baseline to Week 8)
研究者
Lin SUN
Principal Investigator
Shanghai Mental Health Center