Effect of Transcutaneous Auricular Vagus Nerve Stimulation on Postoperative Delirium and Negative Emotions in Patients Undergoing Cardiac Surgery

March 12, 2026 updated by: Weidong Mi, Chinese PLA General Hospital

Effect of Intraoperative Transcutaneous Auricular Vagus Nerve Stimulation on Postoperative Delirium and Negative Emotional States in Patients Undergoing Cardiac Surgery: A Multicenter, Randomized, Double-Blind, Sham-Controlled Trial

A multicenter, randomized, double-blind, sham-controlled trial to investigate the effects of intraoperative transcutaneous auricular vagus nerve stimulation (taVNS) on the incidence of postoperative delirium and negative emotional states (anxiety, depression) in patients undergoing elective cardiac surgery.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Cardiac surgery is associated with a high risk of postoperative neurocognitive disorders, including delirium and negative emotional states such as anxiety and depression, which significantly impact patient recovery and long-term outcomes. This study aims to evaluate whether intraoperative taVNS, a non-invasive neuromodulation technique, can reduce the incidence and severity of these complications. Patients will be randomized to receive either active taVNS or sham stimulation during surgery. Outcomes including delirium, anxiety, depression, pain, sleep quality, recovery quality, and relevant biomarkers will be assessed postoperatively.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
270

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Beijing, China
        • First Medical Center of Chinese PLA General Hospital, Beijing, China.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Aged 18 to 85 years. Scheduled for elective cardiac surgery (e.g., CABG, valve replacement/repair). NYHA cardiac function class I-III. Willing and able to provide informed consent. Expected surgery duration ≥ 2 hours.

Exclusion Criteria:

  • Preoperative MMSE score < 24; severe communication barriers. History of diagnosed delirium, 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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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. The current is gradually increased from 10mA to a level slightly below the individual's "prickling" sensation threshold (20-60mA). Stimulation is applied to the left auricular concha for 30 minutes after anesthesia induction and for another 30 minutes after cardiopulmonary bypass weaning.
Sham Comparator: Sham taVNS Group
Patients receiving sham (placebo) stimulation with an identical device during surgery.
Device: Sham taVNS Group
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 at the same time points as the active group (30 minutes after induction and 30 minutes after CPB weaning).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Incidence of Postoperative Delirium
Time Frame: Within 7 days after surgery
Postoperative delirium will be assessed using the 3-Minute Diagnostic Interview for CAM (3D-CAM) for general ward patients and the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) for ICU patients, from postoperative day 1 to day 7. Diagnosis requires the presence of acute onset/fluctuating course and inattention, plus either disorganized thinking or altered level of consciousness.
Within 7 days after surgery

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Incidence and Severity of Postoperative Depression
Time Frame: Preoperative day, Postoperative day 1, 2, 3, 7, and 30
Postoperative Anxiety Incidence and Severity: HADS-D (Hospital Anxiety and Depression Scale - Anxiety Subscale) Score.Higher score indicates greater depression severity. A score ≥ 8 is considered clinically significant for depression (per standard cutoff).
Preoperative day, Postoperative day 1, 2, 3, 7, and 30
Incidence and Severity of Postoperative Anxiety
Time Frame: Preoperative day, Postoperative day 1, 2, 3, 7, and 30
Postoperative Anxiety Incidence and Severity: HADS-A (Hospital Anxiety and Depression Scale - Anxiety Subscale) Score. Higher score indicates greater anxiety severity. A score ≥ 8 is considered clinically significant for anxiety (per standard cutoff).
Preoperative day, Postoperative day 1, 2, 3, 7, and 30
Incidence and Severity of Postoperative Depression
Time Frame: Preoperative day, Postoperative day 1, 2, 3, 7, and 30
Assessed using Hamilton Depression Rating Scale (HAMD-17). Scores above standard cut-offs indicate depressive states.
Preoperative day, Postoperative day 1, 2, 3, 7, and 30
Incidence and Severity of Postoperative Anxiety (HADS-A)
Time Frame: Preoperative day, Postoperative day 1, 2, 3, 7, and 30
Assessed using the anxiety subscale of the Hospital Anxiety and Depression Scale (HADS-A) at specified time points. Scores above standard cut-offs indicate anxiety states.
Preoperative day, Postoperative day 1, 2, 3, 7, and 30
Postoperative Agitation Score
Time Frame: At the time of extubation (within 24 hours post-surgery)
Assessed using the Riker Sedation-Agitation Scale (SAS) at the time of extubation.
At the time of extubation (within 24 hours post-surgery)
Postoperative Nausea and Vomiting (PONV)
Time Frame: Within 3 days after extubation
Assessed using a Visual Analogue Scale (VAS, 0-10) within 3 days after extubation.
Within 3 days after extubation
Postoperative Pain Score
Time Frame: Postoperative day 1, 2, 3, 7, and 30
Assessed using the Numerical Rating Scale (NRS, 0-10).
Postoperative day 1, 2, 3, 7, and 30
Postoperative Sleep Quality
Time Frame: Postoperative day 1, 2, 3, 7, and 30
Assessed using the Insomnia Severity Index (ISI, score 0-28).
Postoperative day 1, 2, 3, 7, and 30
Postoperative Recovery Quality
Time Frame: Postoperative day 7 and 30
Assessed using the Quality of Recovery-15 or QoR-40 scale.
Postoperative day 7 and 30
Incidence and Severity of Postoperative Anxiety (GAD-7)
Time Frame: Preoperative day, Postoperative day 1, 2, 3, 7, and 30
Assessed using the Generalized Anxiety Disorder-7 (GAD-7) at specified time points. Scores above standard cut-offs indicate anxiety states.
Preoperative day, Postoperative day 1, 2, 3, 7, and 30
Incidence and Severity of Postoperative Anxiety (SAS)
Time Frame: Preoperative day, Postoperative day 1, 2, 3, 7, and 30
Assessed using the Self-Rating Anxiety Scale (SAS) at specified time points. Scores above standard cut-offs indicate anxiety states.
Preoperative day, Postoperative day 1, 2, 3, 7, and 30

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Postoperative Complications
Time Frame: From surgery completion to hospital discharge or up to 30 days postoperatively
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
Time Frame: Preoperative day, end of surgery, postoperative day 1
Perioperative Serum Biomarker: C-Reactive Protein (CRP) Levels
Preoperative day, end of surgery, postoperative day 1
Arterial Blood Pressure
Time Frame: Perioperative period
Perioperative Arterial Blood Pressure
Perioperative period
Perioperative Electroencephalogram (EEG) Data
Time Frame: Intraoperative period
Including Ai (0-100), EMG index, BSR, SEF95, α/β/γ band power.
Intraoperative period
Heart Rate
Time Frame: Perioperative period
Perioperative Heart Rate
Perioperative period
Postoperative Quality of Life
Time Frame: Postoperative day 7 and 30
Assessed using the EQ-5D-5L scale.
Postoperative day 7 and 30
Length of Hospital Stay
Time Frame: The duration is calculated from the date of admission (Day 0) until the date of discharge. The assessment period was censored at 100 days, meaning if patients were not discharged by then, they were considered censored at that point.
Length of Hospital Stay
The duration is calculated from the date of admission (Day 0) until the date of discharge. The assessment period was censored at 100 days, meaning if patients were not discharged by then, they were considered censored at that point.
Adverse Events Related to taVNS
Time Frame: From stimulation start to postoperative day 3
Including skin reactions, dizziness, nausea, etc.
From stimulation start to postoperative day 3
IL-6
Time Frame: Preoperative day, end of surgery, postoperative day 1
Interleukin-6 (IL-6) Levels
Preoperative day, end of surgery, postoperative day 1
S100β
Time Frame: Preoperative day, end of surgery, postoperative day 1
S100β Protein Levels
Preoperative day, end of surgery, postoperative day 1
BDNF
Time Frame: Preoperative day, end of surgery, postoperative day 1
Brain-Derived Neurotrophic Factor (BDNF) Levels
Preoperative day, end of surgery, postoperative day 1
IL-10
Time Frame: Preoperative day, end of surgery, postoperative day 1
Interleukin-10 (IL-10) Levels
Preoperative day, end of surgery, postoperative day 1

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Chinese PLA General Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
The Sixth Medical Center of Chinese PLA General Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 28, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 28, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 28, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 26, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 12, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 17, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 17, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 12, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PLAGH-RCT-taVNS-Cardiac

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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