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

NCT07619989 | Recruiting

• 1 other identifier: 2026-0518-01
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, randomized, participant-blinded, sham-controlled pilot 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.

Conditions

Obesity & Overweight

Keywords

Obesity & Overweight; Transcutaneous Auricular Vagus Nerve Stimulation; Incretin Receptor Agonists; Non-responders

Outcome Measures

Primary Outcomes (1)

• Percent Change in Body Weight From Baseline

  Percent change in body weight from baseline to week 12 will be compared between the taVNS plus tirzepatide group and the sham stimulation plus tirzepatide group to evaluate the adjunctive effect of taVNS on weight reduction.

  Baseline, 4 weeks, 8 weeks, 12 weeks

Secondary Outcomes (15)

• Change in Waist Circumference

  Baseline, Week 4, Week 8, Week 12

• Change in Body Composition and Fat Distribution

  Baseline, ,Week 4, Week 8, Week 12

• Change in blood glucose

  Baseline, Week 12

• Change in Hip Circumference

  Baseline, Week 4, Week 8, Week 12

• Change in Visceral Fat Area

  Baseline, Week 4, Week 8, Week 12

Other Outcomes (1)

• Change in Brain Biotype

  Baseline, Week 12

Study Arms (2)

taVNS Plus Tirzepatide 5 mg

EXPERIMENTAL

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, usually 1.0-2.5 mA. Stimulation will be administered twice daily for 30 minutes per session, 5 days per week, for 12 weeks. Tirzepatide will be administered as a subcutaneous injection once weekly.

Device: transcutaneous auricular vagus nerve stimulation

Sham Stimulation Plus Tirzepatide 5 mg

SHAM COMPARATOR

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, 5 days per week, for 12 weeks. Tirzepatide will be administered as a subcutaneous injection once weekly.

Device: Sham

Interventions

transcutaneous auricular vagus nerve stimulation DEVICE

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, usually 1.0-2.5 mA. Stimulation will be administered twice daily for 30 minutes per session, 5 days per week, for 12 weeks. Tirzepatide will be administered as a subcutaneous injection once weekly.

Also known as: tirzepatide 5 mg

taVNS Plus Tirzepatide 5 mg

Sham DEVICE

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, 5 days per week, for 12 weeks. Tirzepatide will be administered as a subcutaneous injection once weekly.

Also known as: tirzepatide 5 mg

Sham Stimulation Plus Tirzepatide 5 mg

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Individuals with obesity, or overweight accompanied by at least one weight-related comorbidity (e.g., hypertension or fatty liver disease), who have been receiving incretin receptor agonist therapy for at least 6 months and have achieved ≤10% weight loss during treatment;
• Willingness to provide written informed consent.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School: lead

Study Sites (1)

Department of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University Medical School

Nanjing, Jiangsu, 210008, China

RECRUITING

MeSH Terms

Conditions

Obesity; Overweight

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Yan Bi, MD, PhD

  Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University

  STUDY DIRECTOR

Central Study Contacts

Yan Bi, MD, PhD

CONTACT

6-25-83-105302; biyan@nju.edu.cn

Tian Wei Gu, MD, PhD

CONTACT

(86) 25-83106666; gtw0235@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Only participants are masked in this trial. Participants are randomly assigned to active taVNS plus tirzepatide 5 mg or sham stimulation plus tirzepatide 5 mg. To maintain masking, sham stimulation uses the same device, similar stimulation procedures, and the same treatment schedule as active stimulation, but is applied to a non-vagal auricular site (the left tail of the helix). Randomization codes are generated by an independent unblinded team and allocation is concealed using sealed, opaque envelopes. Emergency unblinding materials are prepared and securely retained.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: May 18, 2026
• First Posted: June 2, 2026
• Study Start: April 21, 2026
• Primary Completion (Estimated): July 14, 2026
• Study Completion (Estimated): July 21, 2026
• Last Updated: June 2, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)