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Tinnitus, SubjectiveNCT05417711

Efficacy of Transcutaneous Vagus Nerve Stimulation Paired With Tailor-Made Notched Music Therapy Versus Tailor-made Notched Music Training for Chronic Subjective Tinnitus

A study testing Transcutaneous Vagus Nerve Stimulation Paired with Tailor-Made Notched Music Therapy and Tailor-made Notched Music Training in people with Tinnitus, Subjective and Vagus Nerve Stimulation, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This clinical study is a prospective, multicenter, randomized, controlled, double-blind clinical study. Sun Yat Sen Memorial Hospital of Sun Yat sen University was the central unit, and Nanjing First Hospital, Sun Yat Sen people's Hospital, Guanfzhou Panyu central Hospital and Zhuhai integrated traditional Chinese and… Read more about this study

Who is it for?
Ages 18 to 60 years
What is being tested?
Transcutaneous Vagus Nerve Stimulation Paired with Tailor-Made Notched Music Therapy and Tailor-made Notched Music Training
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
388 participants
Where
No sites listed yet
Study dates
23 Nov 2023to 1 Sep 2026
Phase
Interventional
Are there results?
None posted in the registry

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 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Patients with tinnitus as the main complaint: the patients subjectively feel the sound in the ear or deep part of the head without internal or external sound stimulation, and therefore seek medical treatment
  • Chronic (≥ 6 months) and tonal tinnitus
  • Age 18-60
  • Tinnitus frequency is 125-8000 Hz
  • Hearing threshold at each frequency shall not exceed 70 dB HL

Who cannot join

  • Patients with conductive deafness, history of middle ear surgery, pulsatile tinnitus caused by vascular distortion and tinnitus caused by Meniere disease
  • History of head trauma, central nervous system diseases, mental diseases and drug abuse

Trial locations and contacts

No sites are listed yet.

Yuexin Cai Cai, Doctor contact

+8613825063663

panada810456@126.com

Zhaopeng Tong Tong, bachelor contact

tongzhp@mail2.sysu.edu.cn

About this study

Official title: Efficacy of Transcutaneous Vagus Nerve Stimulation Paired With Tailor-Made Notched Music Therapy Versus Tailor-made Notched Music Training for Chronic Subjective Tinnitus: A Multicenter, Randomized, Double-blind, Controlled Clinical Trial

This clinical study is a prospective, multicenter, randomized, controlled, double-blind clinical study. Sun Yat Sen Memorial Hospital of Sun Yat sen University was the central unit, and Nanjing First Hospital, Sun Yat Sen people's Hospital, Guanfzhou Panyu central Hospital and Zhuhai integrated traditional Chinese and Western medicine hospital were the cooperative units. In this study, 388 patients with chronic subjective tinnitus were recruited. In view of chronic subjective tinnitus, a common ear disease, the study gave the patients three months of treatment with transcutaneous vagus nerve stimulation paired with tailor-made notched music therapy or tailor-made notched music training alone. By comparing the changes of subjective scale scores related to tinnitus before and after treatment in patients receiving two different therapies, such as THI, VAS, BAI, BDI, PSQI, to evaluate the efficacy of the two therapies, so as to judge whether transcutaneous vagus nerve stimulation paired with tailor-made notched music therapy is better than tailor-made notched music training alone. In addition, the study will continue to follow up the patients after the treatment for one year to observe the difference in the long-term sustained efficacy of the two therapies. This clinical study will also evaluate the two therapies from the perspective of compliance and safety, and explore the factors that affect the efficacy of the two therapies.

Read the detailed description

Unified rules for filling in case report forms：

  • All case report forms must be completed by designated and trained researchers.
  • Two data managers independently input and proofread the data in duplicate.
  • The data manager will modify, confirm and enter the data according to the scales written by participant.
  • The locked data file will not be changed.
  • Use medical terms / concepts to record AES . The type, degree, occurrence time, duration, treatment measures and treatment process shall be recorded in detail.

Sample size estimation:

  • △ THI≥ 7 points in the comparison between groups indicates that the difference in efficacy has clinical significance, the superiority margin is established.
  • The pre-test results showed that △ THI = -10.2 points, SD = 10.0 points in the two groups after the treatment.
  • According to unilateral inspection standard α= 0.025, inspection efficacy 1- β= 0.80, using two sample t-test to estimate the sample size, the results show that at least 155 subjects are included in each group.
  • Further estimation was made according to the loss of follow-up rate of 20%. Finally, at least 194 subjects (388 persons in total) should be included in each group.
  • PASS 21.0.03 (NCSs, LLC, Kaysville, Utah, USA) is adopted for the above calculation.

Plan for missing data：

  • If the subject uses the drugs, treatment or surgery prohibited in the protocol, the subject will no longer meet the conditions of the clinical study and will be deemed to have withdrawn from the study.
  • If the event occurs before 3 months of treatment, the subject's data will no longer be used for statistical analysis of subsequent data.
  • If the event occurs in the follow-up period after the completion of treatment, the data of the subject before and after treatment shall be retained. The data in the follow-up period shall be regarded as missing data and filled with corresponding methods for full analysis set analysis.
  • For the missing data caused by the loss of follow-up, this study will use the method of multiple imputation to estimate the missing value.
  • The research subjects who failed in screening will provide corresponding treatment according to their own conditions and clinical guidelines. These subjects will not be included in the clinical study.

Statistical analysis plan:

When considering the influence of baseline, the continuous variables were analyzed by covariance analysis, and the qualitative indicators were tested by CMH test or logistic regression.

Primary analysis： Using covariance analysis to compare the different changes of THI scores between two groups after 3-month treatment, controlled for age and baseline THI.

Secondary analysis： Using covariance analysis to compare the different changes of VAS, BAI, BDI, PSQI scores between two groups after 3-month treatment, controlled for age and baseline values corresponding to each scale.

Using a repeated measure ANOVA to compare the different changes of THI, VAS, BAI, BDI, PSQI between two groups at 3, 6 and 12 follow-up visits.

Using Chi square test or Fisher exact test to compare the different efficient rate between two groups after 3-month treatment.

Exploratory analysis:

Using multiple linear regression analysis to explore the factors affecting the short-term and long -term efficacy of the two treatments, such as age, hearing loss threshold, tinnitus loudness, tinnitus frequency and so on.

Using Independent two sample t-test or nonparametric analysis to compare the differences in EEG- or fMRI-related indicators between two groups.

Safety analysis:

Using Pearson's chi-square test to compare the difference of adverse event incidence rate between two groups.

Being tested
Transcutaneous Vagus Nerve Stimulation Paired with Tailor-Made Notched Music Therapy, Tailor-made Notched Music Training
Keywords
Chronic subjective tinnitus, Tailor-made notched music training, Vagus nerve stimulation, Electroencephalogram, Clinical trial
Medical subject headings
Tinnitus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Transcutaneous Vagus Nerve Stimulation Paired with Tailor-Made Notched Music TherapyDevice

    The pulse frequency of vagus nerve stimulation is 25 Hz, the pulse width is 200 US, and the intensity is 1-10 mA. Tailor-made notched music is produced by filtering a frequency band of 1/2 octave width centered at the individual tinnitus frequency. When two sides of tinnitus frequencies are different, each side of music are filtered respectively, according to the different tinnitus frequency. When only have unilateral tinnitus or bilateral tinnitus in the same central frequency, both sides of music are filtered with the same tinnitus frequency. The tVNS and TMNM begin at the same time during treatment.

  • Tailor-made Notched Music TrainingDevice

    Tailor-made notched music is produced by filtering a frequency band of 1/2 octave width centered at the individual tinnitus frequency. When two sides of tinnitus frequencies are different, each side of music are filtered respectively, according to the different tinnitus frequency. When only have unilateral tinnitus or bilateral tinnitus in the same central frequency, both sides of music are filtered with the same tinnitus frequency. At the beginning of TMNMT, 10 seconds sham vagus nerve stimulation is output, whose parameters are as same as experimental group.

Study groups in NCT05417711
Study groupRoleWhat they receive
Transcutaneous Vagus Nerve Stimulation Paired with Tailor-Made Notched Music TherapyExperimentalThe participants receive 30 minutes / time, 4 times / day, continuous 3 months of auditory tVNS combined with TMNMT. The stimulation intensity used in each course was set to the highest level that the patient could tolerate. The participants listen to the tailor-made notched music at the same time.
Receives: Device: Transcutaneous Vagus Nerve Stimulation Paired with Tailor-Made Notched Music Therapy
Tailor-made Notched Music TrainingActive comparatorSimilarly, 30 minutes / time, 4 times / day, continuous 3 months of TMNMT is received every day. The setting of parameters and the selection of music were the same as those in the experimental group. At the beginning of TMNMT, 10 s of sham stimulation set according to the standard of the experimental group is given.
Receives: Device: Tailor-made Notched Music Training

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Changes in Tinnitus Handicap Inventory (THI) scores for short-term efficacy assessment

    Difference in the change of THI scores between two groups after 3-month treatment. The THI evaluates the severity of tinnitus in terms of emotion and function. The global scores of THI range from 0 (no disability) to 100 (serve disability).

    Measured: From baseline to 3-month follow-up visit

Secondary outcomes (14)

  1. Changes in scores of Visual Analog Scale (VAS) for short-term efficacy assessment

    Difference in the change of VAS scores between two groups after 3-month treatment. The total VAS scores range from 0 (negligible) to 10 (too nosiy to tolerate), reflecting the loudness of tinnitus patients feel.

    Measured: From baseline to 3-month follow-up visit

  2. Changes in scores of Beck Anxiety Inventory (BAI) for short-term efficacy assessment

    Difference in the change of BAI scores between two groups after 3-month treatment. The total BAI scores range from 0 (normal) to 63 (serve anxiety), reflecting the degree of anxiety.

    Measured: From baseline to 3-month follow-up visit

  3. Changes in scores of Beck Depression Inventory (BDI) for short-term efficacy assessment

    Difference in the change of BDI scores between two groups after 3-month treatment. The total BDI scores range from 0 (normal) to 63 (serve depression), reflecting the degree of depression.

    Measured: From baseline to 3-month follow-up visit

  4. Changes in scores of Pittsburgh sleep quality index (PSQI) for short-term efficacy assessment

    Difference in the change of PSQI scores between two groups after 3-month treatment. The total PSQI scores range from 0 (sleep well) to 21 (quite poor sleep), reflecting the sleep quality.

    Measured: From baseline to 3-month follow-up visit

  5. Changes of Tinnitus Handicap Inventory (THI) scores in the two groups for long-term efficacy assessment

    Difference in changes of THI between two groups from 3-month follow-up visit to 12-month follow-up visit. The THI evaluates the severity of tinnitus in terms of emotion and function. The global scores of THI range from 0 (no disability) to 100 (serve disability).

    Measured: From 3-month follow-up visit to 12-month follow-up visit

  6. Changes of Visual Analog Scale (VAS) scores in the two groups for long-term efficacy assessment

    Difference in changes of VAS between two groups from 3-month follow-up visit to 12-month follow-up visit. The total VAS scores range from 0 (negligible) to 10 (too nosiy to tolerate), reflecting the loudness of tinnitus patients feel.

    Measured: From 3-month follow-up visit to 12-month follow-up visit

  7. Changes of Beck Anxiety Inventory (BAI) scores in the two groups for long-term efficacy assessment

    Difference in changes of BAI between two groups from 3-month follow-up visit to 12-month follow-up visit. The total BAI scores range from 0 (normal) to 63 (serve anxiety), reflecting the degree of anxiety.

    Measured: From 3-month follow-up visit to 12-month follow-up visit

  8. Changes of Beck Depression Inventory (BDI) scores in the two groups for long-term efficacy assessment

    Difference in changes of PSQI between two groups from 3-month follow-up visit to 12-month follow-up visit. The total BDI scores range from 0 (normal) to 63 (serve depression), reflecting the degree of depression.

    Measured: From 3-month follow-up visit to 12-month follow-up visit

  9. Changes of Pittsburgh sleep quality index (PSQI) scores in the two groups for long-term efficacy assessment

    Difference in changes of PSQI between two groups from 3-month follow-up visit to 12-month follow-up visit. The total PSQI scores range from 0 (sleep well) to 21 (quite poor sleep), reflecting the sleep quality.

    Measured: From 3-month follow-up visit to 12-month follow-up visit

  10. The effective rate of relieving chronic subjective tinnitus in the two groups

    Group effective rate = number of patients in each group who completed 3 months of treatment and whose THI score decreased by ≥ 7 points / number of patients in each group who completed 3 months of treatment.

    Measured: From baseline to 3-month follow-up visit

  11. The difference of functional connectivity based on resting state electroencephalogram (EEG) between the two groups

    The difference of functional connectivity based on resting state electroencephalogram (EEG) in the two groups from baseline to 12-month follow-up visit. The functional connectivity is defined as the correlation between two different brain regions based on coherence or phase synchronization.

    Measured: From baseline to 12-month follow-up visit

  12. The difference of effective connectivity based on resting state electroencephalogram (EEG) between the two groups

    The difference of effective connectivity based on resting state electroencephalogram (EEG) in the two groups from baseline to 12-month follow-up visit. The effective connectivity is defined as the directed functional connectivity between two brain regions based on granger causality analysis.

    Measured: From baseline to 12-month follow-up visit

  13. The difference of functional connectivity based on functional magnetic resonance imaging (fMRI) between the two groups

    The difference of functional connectivity based on functional magnetic resonance imaging (fMRI) in the two groups from baseline to 12-month follow-up visit. The functional connectivity is defined as the Pearson's correlation between two different brain regions.

    Measured: From baseline to 12-month follow-up visit

  14. The difference of effective connectivity based on functional magnetic resonance imaging (fMRI) between the two groups

    The difference of effective connectivity based on functional magnetic resonance imaging (fMRI) in the two groups from baseline to 12-month follow-up visit. The effective connectivity is defined as the directed functional connectivity between two brain regions based on granger causality analysis.

    Measured: From baseline to 12-month follow-up visit

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jun 2022
  2. Study start23 Nov 2023 (estimated)
  3. Primary completion1 Jan 2026 (estimated)
  4. Study completion1 Sep 2026 (estimated)

Resources

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
Model description
The subjects included in the study are randomized by a unified randomization center. The randomization center will number the subjects with the random number table generated by the computer, and then arrange them in the order of number. The subjects will be randomly divided into groups in turn, and the subjects in the groups will be numbered with the random number table. The first half of the subjects with a larger number in the groups will be divided into the experimental group (tVNS paired with TMNMT), and the rest into the control group (TMNMT).
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
388 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05417711
Sponsor's protocol ID
2022-KY-074
Status last verified
Nov 2023
First submitted
6 Jun 2022
Last updated
27 Nov 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Piccirillo JF, Rodebaugh TL, Lenze EJ. Tinnitus. JAMA. 2020 Apr 21;323(15):1497-1498. doi: 10.1001/jama.2020.0697. No abstract available.

    PubMed 32176246

  • Stockdale D, McFerran D, Brazier P, Pritchard C, Kay T, Dowrick C, Hoare DJ. An economic evaluation of the healthcare cost of tinnitus management in the UK. BMC Health Serv Res. 2017 Aug 22;17(1):577. doi: 10.1186/s12913-017-2527-2.

    PubMed 28830503

  • Henry JA, Reavis KM, Griest SE, Thielman EJ, Theodoroff SM, Grush LD, Carlson KF. Tinnitus: An Epidemiologic Perspective. Otolaryngol Clin North Am. 2020 Aug;53(4):481-499. doi: 10.1016/j.otc.2020.03.002. Epub 2020 Apr 30.

    PubMed 32362561

  • Langguth B, Elgoyhen AB, Cederroth CR. Therapeutic Approaches to the Treatment of Tinnitus. Annu Rev Pharmacol Toxicol. 2019 Jan 6;59:291-313. doi: 10.1146/annurev-pharmtox-010818-021556. Epub 2018 Jul 25.

    PubMed 30044727

  • 龚树生 贺 王. 解读美国《耳鸣临床应用指南》 [J]. 中华耳科学杂志, 2016, 14(2): 4

  • Stein A, Engell A, Junghoefer M, Wunderlich R, Lau P, Wollbrink A, Rudack C, Pantev C. Inhibition-induced plasticity in tinnitus patients after repetitive exposure to tailor-made notched music. Clin Neurophysiol. 2015 May;126(5):1007-15. doi: 10.1016/j.clinph.2014.08.017. Epub 2014 Sep 6.

    PubMed 25441152

  • Okamoto H, Stracke H, Stoll W, Pantev C. Listening to tailor-made notched music reduces tinnitus loudness and tinnitus-related auditory cortex activity. Proc Natl Acad Sci U S A. 2010 Jan 19;107(3):1207-10. doi: 10.1073/pnas.0911268107. Epub 2009 Dec 28.

    PubMed 20080545

  • Tyler R, Cacace A, Stocking C, Tarver B, Engineer N, Martin J, Deshpande A, Stecker N, Pereira M, Kilgard M, Burress C, Pierce D, Rennaker R, Vanneste S. Vagus Nerve Stimulation Paired with Tones for the Treatment of Tinnitus: A Prospective Randomized Double-blind Controlled Pilot Study in Humans. Sci Rep. 2017 Sep 20;7(1):11960. doi: 10.1038/s41598-017-12178-w.

    PubMed 28931943

  • Rammo R, Ali R, Pabaney A, Seidman M, Schwalb J. Surgical Neuromodulation of Tinnitus: A Review of Current Therapies and Future Applications. Neuromodulation. 2019 Jun;22(4):380-387. doi: 10.1111/ner.12793. Epub 2018 Jul 17.

    PubMed 30015361

  • Clancy JA, Mary DA, Witte KK, Greenwood JP, Deuchars SA, Deuchars J. Non-invasive vagus nerve stimulation in healthy humans reduces sympathetic nerve activity. Brain Stimul. 2014 Nov-Dec;7(6):871-7. doi: 10.1016/j.brs.2014.07.031. Epub 2014 Jul 16.

    PubMed 25164906

  • Yap JYY, Keatch C, Lambert E, Woods W, Stoddart PR, Kameneva T. Critical Review of Transcutaneous Vagus Nerve Stimulation: Challenges for Translation to Clinical Practice. Front Neurosci. 2020 Apr 28;14:284. doi: 10.3389/fnins.2020.00284. eCollection 2020.

    PubMed 32410932

  • 曾祥丽, 郑可, 岑锦添, et al. 经皮耳迷走神经刺激治疗慢性耳鸣的疗效观察 [J]. 临床耳 鼻咽喉头颈外科杂志, 2021, 35(02): 105-8.

  • Shim HJ, Kwak MY, An YH, Kim DH, Kim YJ, Kim HJ. Feasibility and Safety of Transcutaneous Vagus Nerve Stimulation Paired with Notched Music Therapy for the Treatment of Chronic Tinnitus. J Audiol Otol. 2015 Dec;19(3):159-67. doi: 10.7874/jao.2015.19.3.159. Epub 2015 Dec 18.

    PubMed 26771015

  • Yakunina N, Nam EC. Direct and Transcutaneous Vagus Nerve Stimulation for Treatment of Tinnitus: A Scoping Review. Front Neurosci. 2021 May 28;15:680590. doi: 10.3389/fnins.2021.680590. eCollection 2021.

    PubMed 34122002

  • Stein A, Wunderlich R, Lau P, Engell A, Wollbrink A, Shaykevich A, Kuhn JT, Holling H, Rudack C, Pantev C. Clinical trial on tonal tinnitus with tailor-made notched music training. BMC Neurol. 2016 Mar 17;16:38. doi: 10.1186/s12883-016-0558-7.

    PubMed 26987755

Questions about this trial

What is this clinical trial studying?

A study testing Transcutaneous Vagus Nerve Stimulation Paired with Tailor-Made Notched Music Therapy and Tailor-made Notched Music Training in people with Tinnitus, Subjective and Vagus Nerve Stimulation, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University.

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 5 inclusion and 2 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: status not confirmed, as of the sponsor's last update on 27 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

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?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Yuexin Cai Cai, Doctor (+8613825063663, panada810456@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Changes in Tinnitus Handicap Inventory (THI) scores for short-term efficacy assessment (time frame: From baseline to 3-month follow-up visit). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05417711, which also lists 16 linked publications.

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 27 Nov 2023.

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