Chronic Subjective TinnitusNCT07469969
Transcutaneous Auricular Vagus Nerve Stimulation Combined With Tailor-Made Notched Music Training Therapy for Chronic Subjective Tinnitus
A study testing transcutaneous auricular vagus nerve stimulation combined with tailor-made notched music training therapy and tinnitus retraining therapy in people with Chronic Subjective Tinnitus, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University at 1 site in China.
Trial summary
This study is a prospective, multicenter, randomized, controlled, open-label clinical trial designed to evaluate the superiority of transauricular vagus nerve microcurrent stimulation (taVNS) combined with Tailor-Made Notched Music Training (TMNMT) compared with Tinnitus Retraining Therapy (TRT) in patients with… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Chronic Subjective Tinnitus
- What is being tested?
- transcutaneous auricular vagus nerve stimulation combined with tailor-made notched music training therapy and tinnitus retraining therapy
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 386 participants
- Where
- 1 siteChina
- Study dates
- 1 Apr 2026to 31 Mar 2030
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients whose primary complaint is tinnitus and who seek medical care for this reason
- Patients diagnosed with chronic tinnitus for more than 6 months
- Age between 18 and 70 years
- Tinnitus frequency within the range of 125-8000 Hz
- Hearing threshold not exceeding 70 dB HL
- Tinnitus Handicap Inventory (THI) score ≥ 38 points.
Who cannot join
- Patients with conductive hearing loss, history of middle ear surgery, pulsatile tinnitus due to vascular malformations, or tinnitus associated with Meniere's disease
- History of head trauma, central nervous system disorders, psychiatric disorders, or substance abuse/dependence
- Patients unwilling or unable to comply with the study protocol requirements
- Patients with space-occupying lesions in the peripheral auditory pathway or central nervous system (e.g., acoustic neuroma, middle ear cholesteatoma, meningioma) as identified by imaging studies.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
Guangzhou, Guangdong, 510120
About this study
Official title: Transcutaneous Auricular Vagus Nerve Stimulation Combined With Tailor-Made Notched Music Training Therapy for Chronic Subjective Tinnitus: A Multicenter, Randomized, Controlled, Open-label Trial
This study is a prospective, multicenter, randomized, controlled, open-label clinical trial designed to evaluate the superiority of transauricular vagus nerve microcurrent stimulation (taVNS) combined with Tailor-Made Notched Music Training (TMNMT) compared with Tinnitus Retraining Therapy (TRT) in patients with chronic subjective tinnitus. A total of 386 participants aged 18-70 years with a tinnitus duration of at least 6 months and a Tinnitus Handicap Inventory (THI) score ≥38 will be enrolled, excluding individuals with severe hearing loss, organic cranial diseases, or other contraindications. Eligible participants will be randomly assigned in a 1:1 ratio to either the experimental group or the control group. The control group will receive standardized TRT, including habituation sound therapy and structured educational counseling, while the experimental group will receive TMNMT combined with taVNS (0.1 Hz pulse-train stimulation, sub-pain threshold intensity of 0.5-10 mA). Although the trial is open-label, outcome assessors and statisticians will remain blinded to group allocation. Baseline and follow-up assessments include THI, visual analog scale (VAS), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), Pittsburgh Sleep Quality Index (PSQI), audiological evaluations, and multimodal neuroimaging using EEG and fMRI. The primary outcome is the tinnitus improvement response rate at 3 months after treatment initiation, defined as a reduction of more than 7 points in the THI score from baseline. Secondary outcomes include treatment response rates at 6 and 12 months, changes in tinnitus severity and tinnitus-related comorbid symptoms, and neuroplasticity-related changes in central neural mechanisms.
- Conditions
- Chronic Subjective Tinnitus
- Being tested
- transcutaneous auricular vagus nerve stimulation combined with tailor-made notched music training therapy, tinnitus retraining therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
transcutaneous auricular vagus nerve stimulation combined with tailor-made notched music training therapyDevice
This group receives combined transcutaneous auricular vagus nerve stimulation (taVNS) and tailor-made notched music training (TMNMT) delivered through a single, registered Class II medical device. The device synchronously administers taVNS (0.1 Hz, pulse train, 0.5-10 mA, titrated below individual pain threshold) and delivers TMNMT via integrated, phase-synchronized algorithms. The notched music is centered at the patient's tinnitus frequency with a ½-octave bandwidth. Treatment consists of 30-minute sessions, four times daily for 3 months.
tinnitus retraining therapyDevice
This group receives standard Tinnitus Retraining Therapy (TRT) using the same device platform, but without active microcurrent output. Therapy includes structured counseling and sound therapy, where broadband natural sounds are delivered at a individually set "mixing" level via the device. Daily sound exposure totals 2 hours over 3 months, supported by initial education and follow-up counseling sessions focused on habituation and cognitive restructuring.
| Study group | Role | What they receive |
|---|---|---|
| taVNS + TMNMT | Experimental | transcutaneous auricular vagus nerve stimulation combined with tailor-made notched music training therapy Receives: Device: transcutaneous auricular vagus nerve stimulation combined with tailor-made notched music training therapy |
| TRT | Active comparator | Tinnitus Retraining Therapy Receives: Device: tinnitus retraining therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tinnitus Improvement Response Rate
The Tinnitus Improvement Response Rate is evaluated based on the change in Tinnitus Handicap Inventory (THI) scores. A higher score indicates greater interference of tinnitus with quality of life. Treatment response is defined as a reduction in the THI score of >7 points from the baseline assessment after 3 months of treatment, based on the internationally recognized Minimal Clinically Important Difference (MCID) threshold. Calculation Formula: Tinnitus Improvement Response Rate (%) = (Number of Responders / Total Number of Cases in the Corresponding Group) × 100%
Measured: Before treatment and at the end of the 3-month treatment period
Secondary outcomes (11)
Change in Self-Perceived Tinnitus Loudness assessed by Visual Analogue Scale (VAS) Score
Patients rate their current perception of tinnitus loudness on a Visual Analogue Scale (VAS) ranging from 0 to 10. A score of 0 represents "extremely faint/imperceptible" tinnitus, and 10 represents "extremely loud/intolerable" tinnitus. The outcome is reported as the change in score from Baseline.
Measured: Baseline, Month 3, Month 6, Month 12
Change in Tinnitus Loudness Matching Threshold
Based on the pitch characteristics described by the patient, a test stimulus (pure tone or narrow-band noise, 0.125-8.0 kHz) is selected. Using a bracketing procedure with 2 dB steps, the loudness is matched to the patient's tinnitus perception. The outcome is measured in decibels sensation level (dB SL/HL) relative to the patient's hearing threshold.
Measured: Baseline, Month 3, Month 6, Month 12
Number of Participants with Treatment-Related Adverse Events
Total number of participants who experience treatment-related adverse events. Events include auditory system-related reactions (e.g., burns, earache, hearing deterioration, worsening tinnitus) and non-auditory reactions (e.g., dizziness, headache, palpitations, vomiting) deemed related to the intervention.
Measured: From Baseline through Month 3
Change in Beck Anxiety Inventory (BAI) Standardized Score
The BAI requires patients to rate 21 anxiety symptoms. The raw score is converted to a standardized score using the formula Y = int(1.19x). Scores range from 0 to 63, with higher scores indicating more severe anxiety. The outcome is reported as the change in standardized score from Baseline.
Measured: Baseline, Month 3, Month 6, Month 12
Change in Beck Depression Inventory (BDI) Total Score
The BDI consists of 21 groups of items. Scores are summed to obtain a total score ranging from 0 to 63. Higher scores indicate a more severe degree of depression. The outcome is reported as the change in total score from Baseline.
Measured: Baseline, Month 3, Month 6, Month 12
Change in Pittsburgh Sleep Quality Index (PSQI) Global Score
The PSQI assesses sleep quality. The Global Score ranges from 0 to 21, where a higher score indicates poorer sleep quality. The outcome is reported as the change in Global Score from Baseline.
Measured: Baseline, Month 3, Month 6, Month 12
Percentage of Participants Achieving Minimal Clinically Important Difference in THI Score
Evaluated based on the Tinnitus Handicap Inventory (THI). A "Responder" is defined as a participant showing a reduction in THI score of >7 points from baseline (the Minimal Clinically Important Difference). Reported as the percentage of participants in each group who meet this criterion.
Measured: Month 6, Month 12
Change in Quantitative EEG (qEEG) Spectral and Connectivity Metrics (0.5-100 Hz)
Resting-state EEG data will be recorded and analyzed across the broad frequency spectrum (0.5-100 Hz). The outcome measures include: 1) Power Spectral Density (PSD) across global and local regions; 2) Functional connectivity metrics (e.g., Coherence, Phase Lag Index); and 3) Neural network synchronization. Analysis will be performed to assess changes in cortical activity and inhibition/excitation balance.
Measured: Baseline, Month 3, Month 6
Change in Functional MRI (fMRI) BOLD Signal and Network Connectivity
Assessed using resting-state fMRI. Metrics include: 1) Amplitude of Low-Frequency Fluctuations (ALFF) and Regional Homogeneity (ReHo) to reflect local spontaneous brain activity; and 2) Functional Connectivity (FC) strength (z-transformed correlation coefficients) within auditory and non-auditory networks (e.g., Limbic system, Salience network, Default Mode Network).
Measured: Baseline, Month 3, Month 6
Change in Structural MRI Morphometry (Gray Matter Volume and Cortical Thickness)
Structural MRI data (T1-weighted images) will be analyzed using Voxel-Based Morphometry (VBM) and surface-based methods. Key metrics include changes in regional Gray Matter Volume (GMV) and Cortical Thickness in tinnitus-related regions (e.g., auditory cortex, prefrontal cortex, hippocampus).
Measured: Baseline, Month 3, Month 6
Change in Diffusion MRI Metrics and Glymphatic System Activity (DTI-ALPS)
Diffusion Tensor Imaging (DTI) will be used to assess white matter integrity and glymphatic function. Metrics include: 1) Fractional Anisotropy (FA) and Mean Diffusivity (MD) of auditory pathways; and 2) The DTI-ALPS (Analysis along the Perivascular Space) index, used as a proxy for measuring glymphatic system activity and waste clearance efficiency.
Measured: Baseline, Month 3, Month 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2026
- Study start1 Apr 2026 (estimated)
- Primary completion31 Mar 2030 (estimated)
- Study completion31 Mar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Subjective TinnitusStudies of the same condition, open and under way.
- More trials run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 386 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yuexin Cai, Study chair, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07469969
- Sponsor's protocol ID
- SYS-5010-202601
- Status last verified
- Mar 2026
- First submitted
- 20 Jan 2026
- Last updated
- 13 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data (IPD) from this study will not be shared due to privacy concerns and ethical restrictions related to patient confidentiality.
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transcutaneous Auricular Vagus Nerve Stimulation Combined With Tailor-Made Notched Music Training Therapy for Chronic Subjective Tinnitus: A Multicenter, Randomized, Controlled, Open-label Trial
- ClinicalTrials.gov ID
- NCT07469969
- Acronym / sponsor ID
- SYS-5010-202601
- Conditions
- Chronic Subjective Tinnitus
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 386 participants (estimated)
- Lead sponsor
- Sun Yat-Sen Memorial Hospital of Sun Yat-Sen UniversityUniversity, hospital or other
- Study start
- 1 Apr 2026 (estimated)
- Primary completion
- 31 Mar 2030 (estimated)
- Study completion
- 31 Mar 2030 (estimated)
- First posted
- 13 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a prospective, multicenter, randomized, controlled, open-label clinical trial designed to evaluate the superiority of transauricular vagus nerve microcurrent stimulation (taVNS) combined with Tailor-Made Notched Music Training (TMNMT) compared with Tinnitus Retraining Therapy (TRT) in patients with chronic subjective tinnitus. A total of 386 participants aged 18-70 years with a tinnitus duration of at least 6 months and a Tinnitus Handicap Inventory (THI) score ≥38 will be enrolled, excluding individuals with severe hearing loss, organic cranial diseases, or other contraindications. Eligible participants will be randomly assigned in a 1:1 ratio to either the experimental group or the control group. The control group will receive standardized TRT, including habituation sound therapy and structured educational counseling, while the experimental group will receive TMNMT combined with taVNS (0.1 Hz pulse-train stimulation, sub-pain threshold intensity of 0.5-10 mA). Although the trial is open-label, outcome assessors and statisticians will remain blinded to group allocation. Baseline and follow-up assessments include THI, visual analog scale (VAS), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), Pittsburgh Sleep Quality Index (PSQI), audiological evaluations, and multimodal neuroimaging using EEG and fMRI. The primary outcome is the tinnitus improvement response rate at 3 months after treatment initiation, defined as a reduction of more than 7 points in the THI score from baseline. Secondary outcomes include treatment response rates at 6 and 12 months, changes in tinnitus severity and tinnitus-related comorbid symptoms, and neuroplasticity-related changes in central neural mechanisms.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| taVNS + TMNMT | Experimental | Device: transcutaneous auricular vagus nerve stimulation combined with tailor-made notched music training therapytranscutaneous auricular vagus nerve stimulation combined with tailor-made notched music training therapy |
| TRT | Active comparator | Device: tinnitus retraining therapyTinnitus Retraining Therapy |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients whose primary complaint is tinnitus and who seek medical care for this reason
- Patients diagnosed with chronic tinnitus for more than 6 months
- Age between 18 and 70 years
- Tinnitus frequency within the range of 125-8000 Hz
- Hearing threshold not exceeding 70 dB HL
Key exclusion criteria (4 listed)
- Patients with conductive hearing loss, history of middle ear surgery, pulsatile tinnitus due to vascular malformations, or tinnitus associated with Meniere's disease
- History of head trauma, central nervous system disorders, psychiatric disorders, or substance abuse/dependence
- Patients unwilling or unable to comply with the study protocol requirements
- Patients with space-occupying lesions in the peripheral auditory pathway or central nervous system (e.g., acoustic neuroma, middle ear cholesteatoma, meningioma) as identified by imaging studies.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| transcutaneous auricular vagus nerve stimulation combined with tailor-made notched music training therapyThis group receives combined transcutaneous auricular vagus nerve stimulation (taVNS) and tailor-made notched music training (TMNMT) delivered through a single, registered Class II medical device. The device synchronously administers taVNS (0.1 Hz, pulse train, 0.5-10 mA, titrated below individual pain threshold) and delivers TMNMT via integrated, phase-synchronized algorithms. The notched music is centered at the patient's tinnitus frequency with a ½-octave bandwidth. Treatment consists of 30-minute sessions, four times daily for 3 months. | Device | taVNS + TMNMT |
| tinnitus retraining therapyThis group receives standard Tinnitus Retraining Therapy (TRT) using the same device platform, but without active microcurrent output. Therapy includes structured counseling and sound therapy, where broadband natural sounds are delivered at a individually set "mixing" level via the device. Daily sound exposure totals 2 hours over 3 months, supported by initial education and follow-up counseling sessions focused on habituation and cognitive restructuring. | Device | TRT |
Primary outcome
Tinnitus Improvement Response Rate
Time frame: Before treatment and at the end of the 3-month treatment period
The Tinnitus Improvement Response Rate is evaluated based on the change in Tinnitus Handicap Inventory (THI) scores. A higher score indicates greater interference of tinnitus with quality of life. Treatment response is defined as a reduction in the THI score of >7 points from the baseline assessment after 3 months of treatment, based on the internationally recognized Minimal Clinically Important Difference (MCID) threshold. Calculation Formula: Tinnitus Improvement Response Rate (%) = (Number of Responders / Total Number of Cases in the Corresponding Group) × 100%
11 secondary outcomes
Change in Self-Perceived Tinnitus Loudness assessed by Visual Analogue Scale (VAS) Score
Time frame: Baseline, Month 3, Month 6, Month 12
Change in Tinnitus Loudness Matching Threshold
Time frame: Baseline, Month 3, Month 6, Month 12
Number of Participants with Treatment-Related Adverse Events
Time frame: From Baseline through Month 3
Change in Beck Anxiety Inventory (BAI) Standardized Score
Time frame: Baseline, Month 3, Month 6, Month 12
Change in Beck Depression Inventory (BDI) Total Score
Time frame: Baseline, Month 3, Month 6, Month 12
Change in Pittsburgh Sleep Quality Index (PSQI) Global Score
Time frame: Baseline, Month 3, Month 6, Month 12
Percentage of Participants Achieving Minimal Clinically Important Difference in THI Score
Time frame: Month 6, Month 12
Change in Quantitative EEG (qEEG) Spectral and Connectivity Metrics (0.5-100 Hz)
Time frame: Baseline, Month 3, Month 6
Change in Functional MRI (fMRI) BOLD Signal and Network Connectivity
Time frame: Baseline, Month 3, Month 6
Change in Structural MRI Morphometry (Gray Matter Volume and Cortical Thickness)
Time frame: Baseline, Month 3, Month 6
Change in Diffusion MRI Metrics and Glymphatic System Activity (DTI-ALPS)
Time frame: Baseline, Month 3, Month 6
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2026.
- Individual participant dataSharing planned: No. Individual participant data (IPD) from this study will not be shared due to privacy concerns and ethical restrictions related to patient confidentiality.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Yuexin Cai study chair
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing transcutaneous auricular vagus nerve stimulation combined with tailor-made notched music training therapy and tinnitus retraining therapy in people with Chronic Subjective Tinnitus, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 13 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yuexin Cai (86+13825063663, caiyx25@mail.sysu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tinnitus Improvement Response Rate (time frame: Before treatment and at the end of the 3-month treatment period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2026.