Efficacy of Transcutaneous Auricular Vagus Nerve Stimulation on Alleviating Major Depressive Disorder in Patients With Acute Coronary Syndrome After Percutaneous Coronary Intervention:A Prospective, Double-Blind,Randomized Controlled Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Change in depressive symptom severity as measured by the 17-item Hamilton Depression Rating Scale (HAMD-17) from baseline (Week 0) to Week 8
研究概览
简要总结
This is a randomized, controlled study. ACS follow- up patients aged 18 to 80 years old with hemodynamic stability, who are 14 days to 1 year after PCI, are screened through the HAMD score and the HAMA score. Patients with a HAMD score greater than 7 points and a HAMD score higher than that of the HAMA, are included in this study.
Patients were allocated to the active taVNS group or sham taVNS group with a 1:1 ratio. Both groups received the stimulation for 20 minutes each time, twice a day with an 8-week treatment and a 8-week follow-up.
All treatments were self-administered by the patients at home after they received training from the hospitals.
The primary observation endpoints include the depression scores of the HAMD. The secondary observation endpoints include the HAMA 、GAD、 response and remission rates of HAMD ，as well as the PCL-C for post-traumatic stress disorder. We also observed the cardiac function indexes measured by echocardiography and the B-type natriuretic peptide .
详细描述
I. Background and Rationale Acute Coronary Syndrome (ACS) is a severe form of coronary artery disease characterized by the rupture or erosion of atherosclerotic plaques, followed by the formation of occlusive or non-occlusive thrombi. Encompassing unstable angina, acute ST-segment elevation myocardial infarction, and non-ST-segment elevation myocardial infarction, ACS remains a leading cause of morbidity and mortality globally. Percutaneous Coronary Intervention (PCI) is a cornerstone therapeutic strategy for ACS, enabling rapid revascularization and myocardial reperfusion. However, as an invasive procedure, combined with patients' concerns regarding postoperative complications, stent longevity, medication side effects, and treatment costs, PCI is frequently associated with significant emotional disturbances in the postoperative period.
Meta-analyses have shown that the prevalence of depression among post-PCI patients ranges from 20% to 82%, while the incidence of anxiety is between 25% and 37%. Notably, the rates of depression and anxiety can surge to 44.7% and 54.7%, respectively, on the first day after PCI. Clinical evidence confirms that post-PCI depression and anxiety substantially reduce treatment adherence and increase the risk of Major Adverse Cardiovascular Events (MACE): patients with anxiety face a 3.742-fold higher risk of MACE compared to those without anxiety, while depressed patients have a 3.087-fold higher risk, and the combined effect of anxiety and depression elevates this risk to 7.303-fold. These emotional disorders are thus recognized as crucial predictors of poor prognosis in post-PCI patients. Nevertheless, conventional antidepressant therapies have inherent limitations: antidepressant medications yield a response rate of only 50%-67%, require at least 4 weeks to exert therapeutic effects, and are associated with common side effects such as nausea, cardiovascular reactions, and sexual dysfunction, leading to poor medication adherence. Cognitive behavioral therapy, on the other hand, is hindered by its complexity and high cost, limiting its accessibility in primary care settings.
Vagus Nerve Stimulation (VNS) is an FDA-approved somatic therapy for treatment-resistant depression (TRD), demonstrating clinically significant antidepressant efficacy. However, invasive VNS (iVNS) is less appealing due to surgical risks, high costs (ranging from $30,000 to $50,000), and potential side effects, resulting in low clinical utilization. To overcome these barriers, non-invasive transcutaneous auricular Vagus Nerve Stimulation (taVNS) has been developed and garnered increasing attention. Anatomical studies have identified the ear as the only body surface region innervated by afferent vagus nerve fibers. Based on the "bottom-up" mechanism of the central nervous system, electrical stimulation propagates retrogradely from peripheral nerves to brainstem and central structures, mimicking the antidepressant effects of conventional VNS without the burden of surgical intervention. Since the first clinical study on taVNS for depression in 2009, a series of trials have validated its efficacy in ameliorating depressive symptoms. However, research on taVNS for treating depression in ACS patients after PCI remains scarce. Therefore, this randomized controlled trial aims to investigate the efficacy and safety of taVNS in this specific population, providing a novel therapeutic option for clinical practice.
II. Study Objectives (A) Primary Objective To evaluate the antidepressant efficacy of transcutaneous auricular Vagus Nerve Stimulation (taVNS) in ACS patients with mild-to-moderate depression after PCI, using the change in Hamilton Depression Rating Scale (HAMD-17) scores from baseline to week 8 as the primary outcome measure.
(B) Secondary Objectives To assess the effects of taVNS on anxiety, post-traumatic stress disorder (PTSD), and quality of life in the study population; To observe the impacts of taVNS on physiological indicators, including heart rate variability (HRV), cardiac function, and inflammatory factors; To verify the clinical safety of taVNS (adverse events, MACE incidence) and relevant efficacy metrics (HAMD response rate, remission rate).
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, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years
- •Meeting the diagnostic criteria for ACS
- •14 days to 12 months after successful PCI, with stable vital signs
- •Meeting the diagnostic criteria for depression according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V)
- •HAMD-17 score ≥7 and <24 (mild-to-moderate depression), with HAMA score <HAMD score;
- •Refusal of psychiatric consultation, antidepressant medication, or psychological therapy by the patient or their legal representative after full informed consent
- •Voluntary participation in the study and signing of the informed consent form
排除标准
- •Severe heart failure (New York Heart Association [NYHA] class ≥III)
- •Uncontrolled hypertension (systolic blood pressure ≥180 mmHg and diastolic blood pressure ≥110 mmHg)
- •Electrocardiographic abnormalities (first-degree atrioventricular block with PR interval ≥0.20 s, second-degree type II or third-degree atrioventricular block at any time, 24-hour average heart rate ≤50 beats per minute, RR interval ≥3 s) or a history of syncope unrelated to the current ACS
- •Dialysis-dependent patients
- •Previous renal sympathetic denervation or vagal ganglion ablation
- •Expected survival time <4 months
- •Pre-PCI diagnosis of severe mental illnesses, including schizophrenia, severe intellectual disability, or substance abuse
- •Current use of antipsychotic medications
- •High suicide risk
- •Pregnant or lactating women
- •Left ear diseases, acute exacerbation of asthma or chronic obstructive pulmonary disease, or other conditions precluding taVNS treatment
- •Implanted cardiac pacemaker, implantable cardioverter-defibrillator (ICD), or other implantable stimulators (e.g., vagus nerve stimulator, deep brain stimulator)
研究组 & 干预措施
Transcutaneous Auricular Vagus Nerve Stimulation Intervention (taVNS)
Participants in this arm receive the active transcutaneous auricular vagus nerve stimulation (taVNS) intervention as defined in the corresponding Intervention section. The intervention is administered twice daily for 20 minutes per session, continuously for 8 weeks, with weekly follow-up visits to assess depressive symptoms and stimulation safety.
干预措施: Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) Intervention (Device)
Sham Transcutaneous Auricular Vagus Nerve Stimulation Control(sham taVNS)
Participants in this arm receive the sham transcutaneous auricular vagus nerve stimulation (sham taVNS) intervention as defined in the corresponding Intervention section. The sham intervention is delivered twice daily for 20 minutes per session over 8 weeks, matching the active group in procedure duration and frequency to maintain participant blinding, with weekly follow-up assessments identical to the active arm.
干预措施: sham Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) Control (Device)
结局指标
主要结局
Change in depressive symptom severity as measured by the 17-item Hamilton Depression Rating Scale (HAMD-17) from baseline (Week 0) to Week 8
时间窗: from baseline (Week 0) to Week 8
The primary outcome is the change in total HAMD-17 scores from baseline (Week 0, prior to the initiation of transcutaneous auricular vagus nerve stimulation \[taVNS\] intervention) to the end of the 8-week taVNS intervention (Week 8). HAMD-17 scores range from 0 to 52, with higher scores indicating more severe depressive symptoms; a negative change score reflects a reduction in depressive symptom severity and clinical improvement. All assessments are conducted by trained clinicians who are masked to the participants' study group allocation (active taVNS vs. sham taVNS).
次要结局
- Change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels from baseline (Week 0) to Week 8(Baseline (Week 0, pre-intervention), Week 8 (end of intervention))
- Change in 17-item Hamilton Depression Rating Scale (HAMD-17) scores at multiple time points from baseline (Week 0) to Week 16(From baseline to week 16 (every 4 weeks))
- Change in Hamilton Anxiety Rating Scale (HAMA) scores from baseline (Week 0) to Week 16(From baseline to week 16 (every 4 weeks))
- Change in Generalized Anxiety Disorder 7-item (GAD-7) scale scores from baseline (Week 0) to Week 16(From baseline to week 16 (every 4 weeks))
- Change in Beck Depression Inventory (BDI) scores from baseline (Week 0) to Week 16(From baseline to week 16 (every 4 weeks))
- Change in Posttraumatic Stress Disorder Checklist (PCL) scores from baseline (Week 0) to Week 16(From baseline to week 16 (every 4 weeks))
- Response rate based on the 17-item Hamilton Depression Rating Scale (HAMD-17)(From baseline to week 16 (every 4 weeks))
- Remission rate based on the 17-item Hamilton Depression Rating Scale (HAMD-17)(From baseline to week 16 (every 4 weeks))
- Change in Heart Rate Variability (HRV) parameters from baseline (Week 0) to Week 8(Baseline (Week 0, pre-intervention), Week 8 (end of intervention))
- Change in peripheral inflammatory cytokine levels from baseline (Week 0) to Week 8(Baseline (Week 0, pre-intervention), Week 8 (end of intervention))
- Left Ventricular Ejection Fraction (LVEF) Measured by Echocardiography(Week 0 (baseline), Week 8)
- Left Ventricular End-Diastolic Diameter (LVEDD) Measured by Echocardiography(Week 0 (baseline), Week 8)
- Left Ventricular End-Systolic Diameter (LVESD) Measured by Echocardiography(Week 0 (baseline), Week 8)
- Occurrence of Major Adverse Cardiovascular Events (MACE) from baseline (Week 0) to Week 16(From baseline to week 16 (every 4 weeks))
- Quality of Life Score Measured by the 36-Item Short Form Health Survey (SF-36)(From baseline to week 16 (every 4 weeks))
研究者
Jing Han
Principal Investigator, Department of Cardiology, Tang-Du Hospital
Tang-Du Hospital