Transcutaneous Auricular Vagus Nerve Stimulation for Poor Weight-Loss Response to Incretin Receptor Agonists

Official title

Adjunctive Transcutaneous Auricular Vagus Nerve Stimulation in Overweight or Obese Patients With a Suboptimal Weight-Loss Response to Incretin Receptor Agonists: A Single-Center, Randomized, Sham-Controlled Study

Overview

This is a single-center, randomized, participant-blinded, sham-controlled trial designed to evaluate the adjunctive effect of transcutaneous auricular vagus nerve stimulation (taVNS) in overweight or obese patients who show a suboptimal weight-loss response to incretin receptor agonist therapy. A total of 24 participants will be randomly assigned to receive either taVNS plus tirzepatide 5 mg or sham stimulation plus tirzepatide 5 mg for 12 weeks. The primary objective is to compare the percent change in body weight from baseline to week 12 between the two groups.

Detailed description

This is a prospective, single-center, randomized, participant-blinded, sham-controlled, parallel-group study conducted at the Department of Endocrinology, Nanjing Drum Tower Hospital. The study will enroll 24 overweight or obese participants with a suboptimal weight-loss response, defined as a body weight reduction of no more than 10% after at least 12 weeks of tirzepatide treatment. Eligible participants will be randomized in a 1:1 ratio to the taVNS plus tirzepatide 5 mg group or the sham stimulation plus tirzepatide 5 mg group for 12 weeks.

Before and after intervention, all participants will undergo standardized assessments, including lifestyle questionnaires, anthropometric measurements, body composition analysis, autonomic function evaluation, laboratory testing, and assessment of hepatic steatosis and fibrosis. Autonomic function assessment will include heart rate variability, cardiovascular autonomic reflex tests, sudomotor function, and brain MRI. Liver-related assessments will include FibroTouch and liver MRI. During follow-up, body weight will be monitored weekly by telephone or WeChat, waist circumference, hip circumference, and body composition will be reassessed every 4 weeks, and device use will be monitored through an app to ensure adherence and protocol consistency.

The primary endpoint is the between-group difference in percent change in body weight from baseline to week 12. Secondary endpoints include changes in body composition and fat distribution, glucose- and lipid-related metabolic parameters, liver function and hepatic steatosis/fibrosis-related parameters, and autonomic function measures. Exploratory analyses will evaluate changes in brain imaging phenotypes after 12 weeks of intervention.

Interventions

• Device transcutaneous auricular vagus nerve stimulation
  Participants will receive active transcutaneous auricular vagus nerve stimulation plus tirzepatide 5 mg for 12 weeks. Active stimulation will be delivered to the bilateral cymba conchae, an auricular region innervated by the auricular branch of the vagus nerve. Stimulation will use an intermittent waveform of 15 seconds on and 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, u
• Device Sham
  Participants will receive sham stimulation in addition to tirzepatide 5 mg for 12 weeks. Sham stimulation will be applied to the bilateral tail of the helix, an auricular site without vagus nerve distribution, whereas active taVNS targets the cymba conchae, which is innervated by the auricular branch of the vagus nerve. The sham group will use the same waveform parameters, stimulation intensity titration, and treatment schedule as the active group, namely twice daily for 30 minutes per session,

Primary outcome measures

• Percent Change in Body Weight From Baseline [Time frame: Baseline, 4 weeks, 8 weeks, 12 weeks]

Secondary outcome measures (12)

• Change in Waist Circumference [Time frame: Baseline, Week 4, Week 8, Week 12]
• Change in Body Composition and Fat Distribution [Time frame: Baseline, ,Week 4, Week 8, Week 12]
• Change in blood glucose [Time frame: Baseline, Week 12]
• Change in Hip Circumference [Time frame: Baseline, Week 4, Week 8, Week 12]
• Change in Visceral Fat Area [Time frame: Baseline, Week 4, Week 8, Week 12]
• Change in Glycated Hemoglobin [Time frame: Baseline, Week 12]
• Change in High-Density Lipoprotein Cholesterol [Time frame: Baseline, Week 12]
• Change in Low-Density Lipoprotein Cholesterol [Time frame: Baseline, Week 12]
• Change in Triglycerides [Time frame: Baseline, Week 12]
• Change in Controlled Attenuation Parameter [Time frame: Baseline, Week 12]
• Change in Liver Stiffness Measurement [Time frame: Baseline, Week 12]
• Change in Liver Function [Time frame: Baseline, Week 12]

Eligibility criteria

Inclusion criteria

• Individuals with obesity, or overweight accompanied by at least one weight-related comorbidity (e.g., hypertension or fatty liver disease), who have been receiving tirzepatide therapy for at least 12 weeks and have achieved ≤10% weight loss during treatment;
• Willingness to provide written informed consent.

Exclusion criteria

• 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;
• Use within the past 3 months of medications, other than incretin receptor agonists, that may significantly affect body weight, including glucocorticoids and antipsychotic agents;
• Skin infection or damage involving the auricular area;
• Women planning pregnancy in the near future;
• Contraindications to MRI, such as metallic prostheses or claustrophobia;
• Diagnosis of diabetes mellitus; Inability to complete the 12-week intervention period for practical reasons, such as frequent business travel or planned travel.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 1 center

• Department of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University Medi — Nanjing

Identifiers

NCT: NCT07619989 · 2026-0518-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗