Efficacy Analysis of Transcutaneous Auricular Vagus Nerve Stimulation Combined With Tailor-Made Notched Music Therapy in the Treatment of Chronic Subjective Tinnitus

Efficacy Analysis of Transcutaneous Auricular Vagus Nerve Stimulation Combined With Tailor-Made Notched Music Therapy in the Treatment of Chronic Subjective Tinnitus: A Multicenter, Randomized, Double-Blind Controlled Clinical Trial

The goal of this multicenter, randomized, double-blind clinical trial is to compare two treatments for adults with chronic subjective tinnitus. Researchers will determine whether transcutaneous auricular vagus nerve stimulation (taVNS) plus Tailor-Made Notched Music therapy (TMNMT) provides greater relief than the same music therapy combined with sham taVNS.

A total of 444 participants aged 18 to 70 years will be enrolled at multiple study centers. Participants will be randomly assigned in a 1:1 ratio to receive taVNS plus TMNMT or sham taVNS plus the same TMNMT. The treatment period will last 3 months.

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Subjective Tinnitus
• Intervention / Treatment: Device: taVNS Combined With TMNMT; Device: Sham taVNS Combined With TMNMT

• Study Type: Interventional
• Enrollment (Estimated): 444
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yuexin Cai, Doctor; Phone Number: 86+13825063663; Email: caiyx25@mail.sysu.edu.cn
• Study Contact Backup: Name: Qianhui Xu, MD; Phone Number: 86+13719908396; Email: xuqh9@mail2.sysu.edu.cn

Study Locations

• China
  • Shanghai, China
    • Eye & ENT Hospital, Fudan University
    • Contact: Shan Sun; Phone Number: 86+18917786102; Email: Shansun@fudan.edu.cn
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
      • Contact: Qianhui Xu, MD; Phone Number: 13719908396; Email: xuqh9@mail2.sysu.edu.cn
    • Huizhou, Guangdong, China
      • Huizhou First People's Hospital
      • Contact: Jia Fu; Phone Number: +86 15820715830; Email: Jiaggfu1985@163.com
    • Jieyang, Guangdong, China
      • Jieyang People's Hospital
      • Contact: Jiongcong Yuan; Phone Number: +86 13480311910; Email: jiongcongyuan@126.com
    • Zhongshan, Guangdong, China
      • Zhongshan City People's Hospital
      • Contact: Guoping Chen; Phone Number: 86+15019918918; Email: cgping345@163.com
    • Zhuhai, Guangdong, China, 519000
      • Zhuhai Integrated Traditional Chinese and Western Medicine Hospital
      • Contact: Binbin Xiong; Phone Number: 86+13926935096; Email: xiongbb2015@126.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria

1. Patients with tinnitus as the primary chief complaint and the reason for seeking medical consultation.
2. Patients with chronic subjective tinnitus duration of 6 months or longer.
3. Age between 18 and 70 years.
4. Tinnitus frequency within the range of 125-8000 Hz.
5. Hearing threshold ≤ 70 dB HL.
6. Tinnitus Handicap Inventory (THI) score ≥ 38.

Exclusion Criteria

1. Patients with conductive hearing loss, history of middle ear surgery, pulsatile tinnitus due to vascular malformations, or Meniere's disease-related tinnitus.
2. History of head trauma, central nervous system disorders, or substance abuse/dependence. Patients with severe primary psychiatric disorders or acute episodes of severe psychological disturbances requiring priority specialist intervention. Patients with severe anxiety symptoms (Beck Anxiety Inventory [BAI] score ≥26), severe depressive symptoms (Beck Depression Inventory [BDI] score ≥29), or suicidal ideation identified during clinical interview will be excluded.
3. Patients unwilling or unable to comply with study protocol requirements.
4. Patients with peripheral auditory pathway or central space-occupying lesions identified by imaging, such as acoustic neuroma, middle ear cholesteatoma, or meningioma.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: taVNS + TMNMT Group; Participants receive active transcutaneous auricular vagus nerve stimulation (taVNS) combined with Tailor-Made Notched Music therapy (TMNMT) for 3 months. taVNS is administered at 0.1 Hz, with a pulse width of 250-1000 ms and an intensity of 0-0.5 mA.	Device: taVNS Combined With TMNMT; Participants receive transcutaneous auricular vagus nerve stimulation (taVNS) combined with Tailor-Made Notched Music Therapy (TMNMT) for 3 months. taVNS is administered at 0.1 Hz, with a pulse width of 250-1000 ms and an intensity of 0-0.5 mA.
Sham Comparator: Sham taVNS + TMNMT Group; Participants receive sham transcutaneous auricular vagus nerve stimulation (taVNS) combined with the same Tailor-Made Notched Music therapy (TMNMT) as the experimental arm for 3 months. The initial sham stimulation parameters are 0.1 Hz, a pulse width of 250-1000 ms, and an intensity of 0-0.5 mA.	Device: Sham taVNS Combined With TMNMT; Participants receive sham transcutaneous auricular vagus nerve stimulation (sham taVNS) combined with Tailor-Made Notched Music Therapy (TMNMT) for 3 months. The initial sham stimulation parameters are 0.1 Hz, a pulse width of 250-1000 ms, and an intensity of 0-0.5 mA.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effective Rate of Tinnitus Improvement at 3 Months	Treatment response was defined as a reduction of ≥7 points in the THI score from baseline after 3 months of treatment (based on the internationally recognized minimal clinically important difference threshold). Effective rate (%) = (Number of responders / Total number of patients in the corresponding group) x 100%.	Baseline and 3 months after treatment initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effective Rate of Tinnitus Improvement at 6 and 12 Months	Treatment response was defined as a reduction of ≥7 points in the THI score from baseline after 6 and 12 months of treatment (based on the internationally recognized minimal clinically important difference threshold). Effective rate (%) = (Number of responders / Total number of patients in the corresponding group) x 100%.	Baseline, 6 months, and 12 months after treatment initiation
Change in Visual Analog Scale (VAS) Score for Tinnitus Loudness	Change in tinnitus loudness assessed using a 10-point Visual Analog Scale (VAS), ranging from 0 (barely perceptible) to 10 (unbearably loud). The change score (ΔVAS) is calculated as the difference between post-treatment/follow-up scores and baseline. Higher scores indicate greater perceived loudness; a decrease in VAS score indicates improvement in loudness perception.	Baseline, 3 months, 6 months, and 12 months after treatment initiation
Change in Acoustic Tinnitus Match Loudness	Change in acoustic tinnitus match loudness assessed using a calibrated audiometer in a standard sound-proof environment. The change in loudness threshold is calculated relative to baseline. Assessment method: audiologist-assessed.	Baseline, 3 months, 6 months, and 12 months after treatment initiation
Change in Beck Anxiety Inventory (BAI) Score	Change in anxiety symptoms assessed using the Beck Anxiety Inventory (BAI), a 21-item self-reported questionnaire measuring the severity of anxiety symptoms over the past week. Higher scores indicate greater anxiety severity. The change score (ΔBAI) is calculated as the difference between post-treatment/follow-up scores and baseline. Assessment method: self-reported.	Baseline, 3 months, 6 months, and 12 months after treatment initiation
Change in Beck Depression Inventory (BDI) Score	Change in depressive symptoms assessed using the Beck Depression Inventory (BDI). The change score (ΔBDI) is calculated as the difference between post-treatment/follow-up scores and baseline.	Baseline, 3 months, 6 months, and 12 months after treatment initiation
Change in Pittsburgh Sleep Quality Index (PSQI) Score	Change in sleep quality assessed using the Pittsburgh Sleep Quality Index (PSQI). The change score (ΔPSQI) is calculated as the difference between post-treatment/follow-up scores and baseline. Assessment method: self-reported.	Baseline, 3 months, 6 months, and 12 months after treatment initiation
Change in Resting-State EEG Features	Change in resting-state EEG features, including power spectrum entropy and oscillatory characteristics, from baseline to post-treatment and follow-up.	Baseline, 3 months, and 6 months after treatment initiation
Change in MRI Features	Change in MRI features from baseline to post-treatment and follow-up.	Baseline, 3 months, and 6 months after treatment initiation
Safety Outcomes: Incidence of Treatment-Related Adverse Events	Incidence of treatment-related adverse events, including auditory system-related events (e.g., ear canal or auricle burns, otalgia, hearing loss, tinnitus worsening) and non-auditory system-related events (e.g., dizziness, headache, palpitations, vomiting) occurring during the treatment period. Adverse event rate (%) = (Number of patients experiencing treatment-related adverse events / Total number of patients receiving treatment) × 100%.	From treatment initiation through 3 months (end of treatment)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Gut Microbiome Shannon Diversity Index	Gut microbial alpha diversity will be assessed using the Shannon diversity index in stool samples collected at baseline, 3 months, and 6 months.	Baseline, 3 months, and 6 months after treatment initiation
Change From Baseline in Blood Metabolite Abundance	Blood metabolite abundance will be assessed at baseline, 3 months, and 6 months using metabolomic profiling.	Baseline, 3 months, and 6 months after treatment initiation
Change From Baseline in Blood Protein Abundance	Blood protein abundance will be assessed at baseline, 3 months, and 6 months using proteomic profiling.	Baseline, 3 months, and 6 months after treatment initiation

Collaborators and Investigators

• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Investigators: Study Chair: Yuexin Cai, Doctor, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): October 30, 2030
• Study Completion (Estimated): December 30, 2030

Study Registration Dates

• First Submitted: August 25, 2026
• First Submitted That Met QC Criteria: August 28, 2026
• First Posted (Actual): August 31, 2026

Study Record Updates

• Last Update Posted (Actual): August 31, 2026
• Last Update Submitted That Met QC Criteria: August 28, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: SYSKY-2025-917-02

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