Transcutaneous Auricular Vagus Nerve Stimulation for Poor Weight-Loss Response to Lifestyle Intervention

June 1, 2026 updated by: Yan Bi, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Transcutaneous Auricular Vagus Nerve Stimulation as an Adjunctive Treatment for Overweight/Obese Patients With Poor Weight Loss Response to Lifestyle Intervention: A Single-Center, Randomized, Sham-Controlled Pilot Study

This single-center, randomized, single-blind, sham-controlled pilot study aims to evaluate the adjunctive effect of transcutaneous auricular vagus nerve stimulation (taVNS) in overweight/obese patients who show a poor weight loss response to lifestyle intervention. Participants who achieve no more than 5% weight loss after 12 weeks of lifestyle intervention will be randomized to receive either taVNS plus lifestyle intervention or sham stimulation plus lifestyle intervention for an additional 12 weeks. The primary objective is to compare the percent change in body weight from baseline between the two groups after 12 weeks of intervention. Secondary objectives include evaluation of changes in body composition and fat distribution, autonomic function, liver-related parameters, and glycemic and lipid-related metabolic parameters.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Obesity is a chronic metabolic disease with substantial health consequences, and lifestyle intervention remains the foundation of weight management. However, a considerable proportion of overweight or obese individuals fail to achieve clinically meaningful weight loss after structured lifestyle intervention. In this study, patients with poor response to lifestyle intervention are defined as those who have completed 12 weeks of lifestyle intervention with weight loss of 5% or less.

Transcutaneous auricular vagus nerve stimulation (taVNS) is a noninvasive neuromodulation technique that stimulates the auricular branch of the vagus nerve and may improve autonomic balance, appetite regulation, and energy metabolism. This study is designed to investigate whether taVNS can enhance weight loss and improve metabolic outcomes when used as an adjunct to lifestyle intervention in overweight/obese patients with poor early response.

A total of 24 participants will be enrolled at a single center and randomized in a 1:1 ratio to either the taVNS plus lifestyle intervention group or the sham stimulation plus lifestyle intervention group. The intervention period will last 12 weeks. All participants will receive standardized lifestyle guidance including dietary management and exercise management. Dietary intervention will be individualized based on basal metabolic rate measured by InBody and guided by the Dietary Guidelines for Chinese Residents, with an intended daily energy deficit of approximately 500 kcal. Exercise management will require at least 3 days of moderate-to-high intensity physical activity per week, with a total duration of at least 150 minutes, monitored by a wearable device.

Participants in the active treatment group will receive taVNS applied to the left cymba conchae using an intermittent electrical stimulation pattern (15 seconds on, 5 seconds off), frequency of 20 Hz, pulse width of 0.2 ms, and intensity gradually increased to a tolerable mild tingling sensation, usually 1.0-2.5 mA. Stimulation will be administered twice daily for 30 minutes each time, 5 times per week, for 12 weeks. Participants in the control group will receive sham stimulation at the left tail of the helix, with the same stimulation schedule and device settings.

Assessments will be performed at baseline and after 12 weeks of intervention, including anthropometric measurements, body composition analysis, autonomic function testing, laboratory testing, and evaluation of hepatic steatosis and fibrosis using FibroTouch and liver MRI. The primary endpoint is percent change in body weight from baseline at week 12. Secondary endpoints include changes in body composition and fat distribution, autonomic function, liver-related parameters, and glycemic and lipid-related metabolic parameters.

Study Type

Interventional

Enrollment (Estimated)

24

Phase

  • 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 Contact

Study Contact Backup

Study Locations

  • China
    • Jiangsu
      • Nanjing, Jiangsu, China, 210008
        • Recruiting
        • Department of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University Medical School
        • Contact:
          • Tian Wei Gu, MD, PhD
          • Phone Number: (86) 25-831066 (86) 25-83106666
          • Email: gtw0235@163.com
        • Contact:

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

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Completed 12 weeks of lifestyle intervention treatment with ≤5% weight loss during the treatment period;
  2. Completed 12 weeks of lifestyle intervention, with less than 1 month since completion, and achieved ≤5% weight loss during the intervention period;
  3. Current body mass index (BMI) ≥28 kg/m², or BMI ≥24 kg/m² with at least one weight-related comorbidity (e.g., hypertension or fatty liver disease);
  4. Willingness to provide written informed consent.

Exclusion Criteria:

  1. Presence of diseases that may substantially affect body weight homeostasis, including Cushing's syndrome, uncontrolled thyroid disease (thyroid-stimulating hormone >6.0 mIU/L or <0.4 mIU/L), malignancy, or similar conditions;
  2. Use within the past 3 months of medications that may significantly affect body weight, including glucocorticoids and antipsychotic agents;
  3. Skin infection or damage involving the auricular area;
  4. Women planning pregnancy in the near future;
  5. Inability to complete the 12-week intervention period for practical reasons, such as frequent business travel or planned travel.

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: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: taVNS Plus Lifestyle Intervention
Participants will receive active transcutaneous auricular vagus nerve stimulation in addition to lifestyle intervention for 12 weeks.
Device: transcutaneous auricular vagus nerve stimulation
Participants will receive active transcutaneous auricular vagus nerve stimulation in addition to lifestyle Intervention for 12 weeks. Active stimulation will be delivered to the left cymba conchae using an intermittent waveform (15 seconds on, 5 seconds off) at 20 Hz with a pulse width of 0.2 ms. Stimulation intensity will be titrated from 0 mA to a level that produces mild tingling without obvious discomfort, usually 1.0-2.5 mA. Stimulation will be administered twice daily for 30 minutes per session, 5 days per week, for 12 weeks.
Other Names:
  • Lifestyle Intervention
Sham Comparator: Sham Stimulation plus Lifestyle Intervention
Participants will receive sham stimulation in addition to standardized lifestyle intervention for 12 weeks
Device: Sham
Participants will receive sham stimulation in addition to lifestyle Intervention for 12 weeks. Sham stimulation will be applied to the left tail of the helix using the same waveform parameters, stimulation intensity titration, and treatment schedule as the active group, namely twice daily for 30 minutes per session, 5 days per week, for 12 weeks.
Other Names:
  • Lifestyle Intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent Change in Body Weight From Baseline
Time Frame: Baseline, 4 weeks, 8 weeks, 12 weeks
Percent change in body weight from baseline to week 12 will be compared between the taVNS plus lifestyle intervention group and the sham stimulation plus lifestyle intervention group to evaluate the adjunctive effect of taVNS on weight reduction.
Baseline, 4 weeks, 8 weeks, 12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in blood glucose
Time Frame: Baseline, Week 12
Change in fasting blood glucose from baseline to Week 12 will be assessed using laboratory testing.
Baseline, Week 12
Change in Glycated Hemoglobin
Time Frame: Baseline, Week 12
Change in glycated hemoglobin (HbA1c) from baseline to Week 12 will be assessed using laboratory testing.
Baseline, Week 12
Change in High-Density Lipoprotein Cholesterol
Time Frame: Baseline, Week 12
Change in high-density lipoprotein cholesterol (HDL-C) from baseline to Week 12 will be assessed using laboratory testing.
Baseline, Week 12
Change in Low-Density Lipoprotein Cholesterol
Time Frame: Baseline, Week 12
Change in low-density lipoprotein cholesterol (LDL-C) from baseline to Week 12 will be assessed using laboratory testing.
Baseline, Week 12
Change in Triglycerides
Time Frame: Baseline, Week 12
Change in triglycerides from baseline to Week 12 will be assessed using laboratory testing.
Baseline, Week 12
Change in Controlled Attenuation Parameter
Time Frame: Baseline, Week 12
Change in controlled attenuation parameter (CAP) from baseline to Week 12 will be assessed using transient elastography.
Baseline, Week 12
Change in Liver Stiffness Measurement
Time Frame: Baseline, Week 12
Change in liver stiffness measurement (LSM) from baseline to Week 12 will be assessed using transient elastography.
Baseline, Week 12
Change in Liver Function
Time Frame: Baseline, Week 12
Change in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) from baseline to Week 12 will be assessed using laboratory testing.
Baseline, Week 12
Change in Heart Rate Variability
Time Frame: Baseline, Week 12
Change in heart rate variability from baseline to Week 12 will be assessed using time-domain and/or frequency-domain heart rate variability analysis.
Baseline, Week 12
Change in Cardiovascular Autonomic Reflex Test Result
Time Frame: Baseline, Week 12
Change in cardiovascular autonomic reflex function from baseline to Week 12 will be assessed using standardized cardiovascular autonomic reflex testing.
Baseline, Week 12
Change in Waist Circumference
Time Frame: Baseline, ,Week 4, Week 8, Week 12

Change in waist circumference from baseline to Week 4, Week 8, and Week 12 will be assessed using standardized Change in waist circumference from baseline to Week 4, Week 8, and Week 12 will be assessed using standardized anthropometric measurement.

Change in waist circumference from baseline to Week 4, Week 8, and Week 12 will be assessed using standardized anthropometric measurement.
Baseline, ,Week 4, Week 8, Week 12
Change in Body Composition and Fat Distribution
Time Frame: Baseline, ,Week 4, Week 8, Week 12
Changes in body composition and fat distribution will be assessed by body fat percentage using anthropometric measurements and body composition analysis
Baseline, ,Week 4, Week 8, Week 12
Change in Visceral Fat Area
Time Frame: Baseline, ,Week 4, Week 8, Week 12
Change in visceral fat area from baseline to Week 4, Week 8, and Week 12 will be assessed using body composition analysis.
Baseline, ,Week 4, Week 8, Week 12
Change in Hip Circumference
Time Frame: Baseline, ,Week 4, Week 8, Week 12
Change in hip circumference from baseline to Week 4, Week 8, and Week 12 will be assessed using standardized anthropometric measurement.
Baseline, ,Week 4, Week 8, Week 12
Change in Insulin Resistance
Time Frame: Baseline, Week 12
Change in insulin resistance from baseline to Week 12 will be assessed using the homeostatic model assessment of insulin resistance (HOMA-IR), calculated from fasting glucose and fasting insulin levels.
Baseline, Week 12

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Brain Biotype
Time Frame: Baseline, Week 12
Changes in brain biotype after 12 weeks of intervention will be explored using brain MRI-based analyses. Brain biotype will be assessed at baseline and Week 12 using brain MRI-based analyses. Brain biotype will be defined as an MRI-derived classification based on pre-specified brain imaging features, such as resting-state functional connectivity patterns. Participants will be assigned to a brain biotype category according to the pre-specified MRI analysis algorithm.
Baseline, Week 12

Collaborators and Investigators

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

Sponsor

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

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 (Actual)

May 8, 2026

Primary Completion (Estimated)

July 31, 2026

Study Completion (Estimated)

March 31, 2027

Study Registration Dates

First Submitted

May 19, 2026

First Submitted That Met QC Criteria

June 1, 2026

First Posted (Actual)

June 5, 2026

Study Record Updates

Last Update Posted (Actual)

June 5, 2026

Last Update Submitted That Met QC Criteria

June 1, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2026-0518-02

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

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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