Effect of Transcutaneous Auricular Vagus Nerve Stimulation on Perioperative Negative Emotions in Breast Cancer Surgery Patients

Effect of Intraoperative Transcutaneous Auricular Vagus Nerve Stimulation on Perioperative Negative Emotions in Patients Undergoing Breast Cancer Surgery: A Multicenter, Randomized, Double-Blind, Sham-Controlled Trial

A multicenter, randomized, double-blind, sham-controlled trial to investigate the effects of a single session of intraoperative transcutaneous auricular vagus nerve stimulation (taVNS) on perioperative negative emotions (anxiety and depression), pain, nausea, sleep, and recovery in patients undergoing elective breast cancer surgery.

Study Overview

• Status: Not yet recruiting
• Conditions: Depression; Breast Surgery; Anxiety; Postoperative
• Intervention / Treatment: Device: Active taVNS; Device: Sham taVNS

Detailed Description

Patients undergoing breast cancer surgery frequently experience perioperative anxiety and depression, which can adversely affect recovery and quality of life. This study evaluates the efficacy of a single 30-minute intraoperative taVNS session in mitigating these negative emotions and improving postoperative outcomes. Patients will be randomized to receive either active taVNS or sham stimulation after anesthesia induction. The primary outcome is the incidence of depressive symptoms within 3 days postoperatively. Secondary outcomes include anxiety, pain, PONV, sleep quality, and recovery parameters.

• Study Type: Interventional
• Enrollment (Estimated): 232
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Weidong Mi; Phone Number: 13381082966; Email: wwdd1962@163.com

Study Locations

• China
  • Beijing, China
    • Beijing Tiantan Hospital
    • Contact: Yishuang Wu; Phone Number: +8615600950688; Email: zznyx@outlook.com
  • Beijing, China
    • First Medical Center of Chinese PLA General Hospital, Beijing, China.
    • Contact: Weidong Mi; Phone Number: 13381082966; Email: wwdd1962@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged ≥18 years. Scheduled for elective breast cancer surgery. ASA physical status I-III. Willing and able to provide informed consent.

Exclusion Criteria:

• Preoperative MMSE score < 24; severe communication barriers. History of diagnosed dementia, Parkinson's disease, schizophrenia, bipolar disorder, major depressive disorder, or long-term use of psychotropic drugs.

Skin lesions, infection, or deformity of bilateral ears; history of ear surgery or nerve injury; allergy to electrode materials.

Severe arrhythmia; implanted electronic devices (e.g., pacemaker, ICD). Participation in another interventional trial within 3 months. Other conditions deemed unsuitable by investigators.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active taVNS Group; Patients receiving active transcutaneous auricular vagus nerve stimulation during surgery.	Device: Active taVNS; Stimulation parameters: Amplitude 20 (mA), Frequency 20Hz, Pulse width 200μs, asymmetric biphasic square wave. A single 30-minute stimulation session is applied to the left auricular concha after anesthesia induction.
Sham Comparator: Sham taVNS Group; Patients receiving sham (placebo) stimulation with an identical device during surgery.	Device: Sham taVNS; The sham device is identical in appearance, weight, indicator lights, and operation sounds to the active device but delivers no effective electrical current. It is applied to the left auricular concha for 30 minutes after anesthesia induction.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Postoperative Depressive Symptoms	Assessed using the Patient Health Questionnaire-9 (PHQ-9), Hamilton Depression Rating Scale (HAMD-17), and the depression subscale of the Hospital Anxiety and Depression Scale (HADS-D). A score above the standard cut-off on any of these scales indicates the presence of depressive symptoms.	Within 3 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Postoperative Anxiety Symptoms	Assessed using the anxiety subscale of the Hospital Anxiety and Depression Scale (HADS-A), the Generalized Anxiety Disorder-7 (GAD-7), and the Self-Rating Anxiety Scale (SAS).	Within 3 days, 7 days, and at 30 days after surgery
Incidence of Depressive Symptoms	Assessed using the Patient Health Questionnaire-9 (PHQ-9), Hamilton Depression Rating Scale (HAMD-17), and the depression subscale of the Hospital Anxiety and Depression Scale (HADS-D). A score above the standard cut-off on any of these scales indicates the presence of depressive symptoms.Higher scores indicate greater severity of depression.	Postoperative day 7 and 30
Postoperative Nausea and Vomiting (PONV)	Assessed using a Visual Analogue Scale (VAS, 0-10)	Within 3 days after surgery
Postoperative Pain Score	Assessed using the Numerical Rating Scale (NRS, 0-10).	Postoperative day 3, 7, and 30
Postoperative Sleep Quality	Assessed using the Insomnia Severity Index (ISI, score 0-28).	Postoperative day 3, 7, and 30
Time to First Postoperative Flatus and Defecation	Time to First Postoperative Flatus and Defecation	From end of surgery until first occurrence, assessed up to 7 days
Postoperative Recovery Quality	Assessed using the Quality of Recovery-15 or QoR-40 scale.	Postoperative day 3, 7, and 30
Postoperative Quality of Life	Assessed using the EQ-5D-5L scale.	Postoperative day 3, 7, and 30

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of Hospital Stay	Length of Hospital Stay	From admission day (Day 0) to discharge day (the time range for calculating Length of Hospital Stay is from the admission day to the discharge day)
Postoperative Complications	Incidence of complications such as respiratory failure, stroke, acute kidney injury, etc.	From surgery completion to hospital discharge or up to 30 days postoperatively
CRP	Perioperative Serum Biomarker: C-Reactive Protein (CRP) Levels	Preoperative day, end of surgery, postoperative day 1
IL-6	Perioperative Serum Biomarker: Interleukin-6 (IL-6) Levels	Preoperative day, end of surgery, postoperative day 1
S100β	Perioperative Serum Biomarker: S100β Protein Levels	Preoperative day, end of surgery, postoperative day 1
BDNF	Perioperative Serum Biomarker: Brain-Derived Neurotrophic Factor (BDNF) Levels	Preoperative day, end of surgery, postoperative day 1
IL-10	Perioperative Inflammatory Cytokine: Interleukin-10 (IL-10) Levels	Preoperative day, end of surgery, postoperative day 1
Adverse Events Related to taVNS	Adverse Events Related to taVNS	From stimulation start to postoperative day 3
Postoperative Mortality	Postoperative Mortality	7 days and 30 days after surgery
Arterial Blood Pressure	Perioperative Arterial Blood Pressure	Perioperative period
Perioperative Electroencephalogram (EEG) Data	Including Ai (0-100), EMG index, BSR, SEF95, α/β/γ band power.	Intraoperative period
Heart Rate	Perioperative Heart Rate	Perioperative period

Collaborators and Investigators

• Sponsor: Chinese PLA General Hospital
• Collaborators: Beijing Tiantan Hospital; Peking University Shougang Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): February 28, 2026
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): February 28, 2027

Study Registration Dates

• First Submitted: February 26, 2026
• First Submitted That Met QC Criteria: March 4, 2026
• First Posted (Actual): March 9, 2026

Study Record Updates

• Last Update Posted (Actual): March 9, 2026
• Last Update Submitted That Met QC Criteria: March 4, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Depression; Anxiety; Randomized Controlled Trial; Transcutaneous Vagus Nerve Stimulation; Breast Cancer Surgery
• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Behavior; Anxiety Disorders; Depression
• Other Study ID Numbers: PLAGH-RCT-taVNS-BreastCancer

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No