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

NCT05417711 | Not Yet Recruiting

• 1 other identifier: 2022-KY-074
• Study Type: interventional
• Target: 388
• Locations: 0 countries
• Sites: N/A

Brief 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 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.

Conditions

Tinnitus, Subjective; Vagus Nerve Stimulation; Music Therapy; Double-Blind Method; Female; Male; Humans; Treatment Outcome

Keywords

Chronic subjective tinnitus; Tailor-made notched music training; Vagus nerve stimulation; Electroencephalogram; Clinical trial

Outcome Measures

Primary Outcomes (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).

  From baseline to 3-month follow-up visit

Secondary Outcomes (14)

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

  From baseline to 3-month follow-up visit

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

  From baseline to 3-month follow-up visit

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

  From baseline to 3-month follow-up visit

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

  From baseline to 3-month follow-up visit

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

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

Other Outcomes (1)

• Incidence of treatment-related adverse events

  From baseline to 12-month follow-up visit

Study Arms (2)

Transcutaneous Vagus Nerve Stimulation Paired with Tailor-Made Notched Music Therapy

EXPERIMENTAL

The 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.

Device: Transcutaneous Vagus Nerve Stimulation Paired with Tailor-Made Notched Music Therapy

Tailor-made Notched Music Training

ACTIVE COMPARATOR

Similarly, 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.

Device: Tailor-made Notched Music Training

Interventions

Transcutaneous Vagus Nerve Stimulation Paired with Tailor-Made Notched Music Therapy DEVICE

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.

Transcutaneous Vagus Nerve Stimulation Paired with Tailor-Made Notched Music Therapy

Tailor-made Notched Music Training DEVICE

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.

Tailor-made Notched Music Training

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead
• The First Affiliated Hospital with Nanjing Medical University: collaborator
• Zhongshan People's Hospital, Guangdong, China: collaborator
• Affiliated Zhuhai Hospital of Southern Medical University: collaborator
• Guangzhou Panyu Central Hospital: collaborator
• Shenshan Medical Center, Memorial Hospital of Sun Yat-sen University: collaborator
• Eighth Affiliated Hospital, Sun Yat-sen University: collaborator
• Second Affiliated Hospital of Guangzhou Medical University: collaborator
• Southern Medical University, China: collaborator

Related Publications (16)

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

  PMID: 32176246 BACKGROUND

• 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.

  PMID: 28830503 BACKGROUND

• 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.

  PMID: 32362561 BACKGROUND

• 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.

  PMID: 30044727 BACKGROUND

• 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

  BACKGROUND

• 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.

  PMID: 25441152 BACKGROUND

• 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.

  PMID: 20080545 BACKGROUND

• 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.

  PMID: 28931943 BACKGROUND

• 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.

  PMID: 30015361 BACKGROUND

• 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.

  PMID: 25164906 BACKGROUND

• 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.

  PMID: 32410932 BACKGROUND

• 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.

  BACKGROUND

• 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.

  PMID: 26771015 BACKGROUND

• 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.

  PMID: 34122002 BACKGROUND

• 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.

  PMID: 26987755 BACKGROUND

• 蔡跃新, 孙映凤, 杨海弟, et al. 个性化切迹音乐治疗主观性耳鸣的初步观察 [J]. 中华耳科学杂志, 2017, 15(04): 465-70.

  BACKGROUND

MeSH Terms

Conditions

Tinnitus

Condition Hierarchy (Ancestors)

Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Yuexin Cai Cai

  Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yuexin Cai Cai, Doctor

CONTACT

+8613825063663; panada810456@126.com

Zhaopeng Tong Tong, bachelor

CONTACT

tongzhp@mail2.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: In the whole clinical research process, the subjects and researchers participating in the efficacy and safety evaluation should be in a blind state, that is, neither of them knows the specific intervention measures given to the subjects. For participant, the treatment equipment is exactly the same between the two groups. Also, 10 seconds sham stimulation at the beginning of treatment is set in the control group for minimizing risk of participants being able to guess treatment allocation. The randomized allocation is completed by a unified randomization center. Therefore, the investigators in each center just know "A" or "B" for the allocation information of each participant. For outcomes assessors, they are only responsible for baseline and follow-up assessment during the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: June 6, 2022
• First Posted: June 14, 2022
• Study Start: November 23, 2023
• Primary Completion: January 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: November 27, 2023

Record last verified: 2023-11