Clinical trial NCT06821893: Vagus Auricular Stimulation for Tinnitus
Official title: Vagus Auricular Stimulation for Tinnitus
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Tinnitus
Keywords: Audiology
Otolaryngology
Mindfulness Based Stress Reduction (MBSR)
auricular branch of vagus nerve
neuromodulation
transcutaneous stimulation
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2025-02-12
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This pilot study is a randomized, double-blinded controlled trial of adult participants with chronic, moderate to severe bothersome subjective tinnitus.
Primary purpose: TREATMENT

Brief summary: This pilot study is a randomized, double-blinded controlled trial of adult participants with chronic, moderate to severe bothersome subjective tinnitus. Participants will be randomly assigned to either an active auricular stimulation device group or a sham-control group.Both groups will also undergo virtual Mindfulness-Based Stress Reduction(MBSR) over 8 weeks to promote tinnitus bother reduction, and general well-being. Outcome measures will be assessed at baseline, end of intervention, and at 1-month post-intervention.

Detailed description: Adults experiencing moderate to severe tinnitus have significant impairment in their quality of life. While Cognitive Behavioral Therapy (CBT) is the most effective treatment for tinnitus, its accessibility is limited. Alternative treatment options such as masking pose significant risks and have varying success rates in achieving tinnitus cessation. Given these limitations and risks, there is a need to explore alternative treatment options for tinnitus that are both effective and easily accessible. Transcutaneous electrical stimulation of the vagus nerve has been explored as a treatment option for tinnitus using different study designs with varying response rate. In contrary, this pilot study will provide valuable insights and preliminary evidence for the effectiveness of transcutaneous stimulation of the auricular branch of the vagus nerve (TABVN-stim) utilizing a novel device that produces vibrational stimulation mimicking physiological sensory input to the ABVN. This research provides preliminary evidence for a potentially safe, non-invasive, and easily applicable treatment option for those suffering from chronic bothersome tinnitus, ultimately improving their quality of life.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18
* Ability to read, write, speak, and understand English
* Bothersome tinnitus with initial TSSF score greater than 40 on screening
* Available for the entire period of the study including one month follow-up after completion of 8-week intervention period
* Access to internet-connected device(s) such as phone, tablet, or laptop with a camera

Exclusion Criteria:

* Age\>70
* Pregnant or planning to become pregnant during the study period
* Previous participation in an auricular stimulation trial
* Currently on active treatment for tinnitus
* Have cochlear implant or other device that impedes usage of auricular stimulation device
* Tinnitus related to ear surgery, Meniere's disease, ear infections, or other ear pathology
* Substance abuse
* Unstable psychiatric disorders
* Patient Health Questionnaire (PHQ-9) score greater than 9 History of brain surgery
* History of traumatic brain injury
* History of bradycardia or bradyarythmias

Primary outcomes:
measure: Responder proportion
timeFrame: Week 9
Secondary outcomes:
measure: Proportion of adequate device users
timeFrame: Week 9
measure: Adverse events
timeFrame: Week 9, and 13
measure: Proportion of participants reporting improvement on CGI-I
timeFrame: Week 9 and 13
measure: Change in CGI-S
timeFrame: Week 9, and 13
measure: Responder proportion at 4weeks post-intervention follow up
timeFrame: Week 13
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Jay F Piccirillo, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Batts S, Stankovic KM. Tinnitus prevalence, associated characteristics, and related healthcare use in the United States: a population-level analysis. Lancet Reg Health Am. 2024 Jan 6;29:100659. doi: 10.1016/j.lana.2023.100659. eCollection 2024 Jan.
citation: Tang D, Li H, Chen L. Advances in Understanding, Diagnosis, and Treatment of Tinnitus. Adv Exp Med Biol. 2019;1130:109-128. doi: 10.1007/978-981-13-6123-4_7.
citation: Beukes EW, Andersson G, Allen PM, Manchaiah V, Baguley DM. Effectiveness of Guided Internet-Based Cognitive Behavioral Therapy vs Face-to-Face Clinical Care for Treatment of Tinnitus: A Randomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. 2018 Dec 1;144(12):1126-1133. doi: 10.1001/jamaoto.2018.2238.
citation: Miller L. Cognitive behavioral therapy for patients suffering with tinnitus distress. JAAPA. 2023 Sep 1;36(9):13-16. doi: 10.1097/01.JAA.0000947036.33633.84.
citation: Butt MF, Albusoda A, Farmer AD, Aziz Q. The anatomical basis for transcutaneous auricular vagus nerve stimulation. J Anat. 2020 Apr;236(4):588-611. doi: 10.1111/joa.13122. Epub 2019 Nov 19.
citation: Hilz MJ. Transcutaneous vagus nerve stimulation - A brief introduction and overview. Auton Neurosci. 2022 Dec;243:103038. doi: 10.1016/j.autneu.2022.103038. Epub 2022 Sep 27.
citation: Kim AY, Marduy A, de Melo PS, Gianlorenco AC, Kim CK, Choi H, Song JJ, Fregni F. Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. Sci Rep. 2022 Dec 21;12(1):22055. doi: 10.1038/s41598-022-25864-1.
citation: Byun YJ, Lee JA, Nguyen SA, Rizk HG, Meyer TA, Lambert PR. Transcutaneous Electrical Nerve Stimulation for Treatment of Tinnitus: A Systematic Review and Meta-analysis. Otol Neurotol. 2020 Aug;41(7):e767-e775. doi: 10.1097/MAO.0000000000002712.
citation: Meikle MB, Henry JA, Griest SE, Stewart BJ, Abrams HB, McArdle R, Myers PJ, Newman CW, Sandridge S, Turk DC, Folmer RL, Frederick EJ, House JW, Jacobson GP, Kinney SE, Martin WH, Nagler SM, Reich GE, Searchfield G, Sweetow R, Vernon JA. The tinnitus functional index: development of a new clinical measure for chronic, intrusive tinnitus. Ear Hear. 2012 Mar-Apr;33(2):153-76. doi: 10.1097/AUD.0b013e31822f67c0.
citation: Langguth B, De Ridder D. Minimal Clinically Important Difference of Tinnitus Outcome Measurement Instruments-A Scoping Review. J Clin Med. 2023 Nov 15;12(22):7117. doi: 10.3390/jcm12227117.
citation: Frumkin MR, Kallogjeri D, Piccirillo JF, Beukes EW, Manchaiah V, Andersson G, Rodebaugh TL. Development and Preliminary Evaluation of the Tinnitus Severity Short Form. Am J Audiol. 2021 Jun 14;30(2):404-415. doi: 10.1044/2021_AJA-20-00164. Epub 2021 May 24.
citation: Natarajan N, Batts S, Stankovic KM. Noise-Induced Hearing Loss. J Clin Med. 2023 Mar 17;12(6):2347. doi: 10.3390/jcm12062347.
citation: Kang HJ, Kang DW, Kim SS, Oh TI, Kim SH, Yeo SG. Analysis of Chronic Tinnitus in Noise-Induced Hearing Loss and Presbycusis. J Clin Med. 2021 Apr 19;10(8):1779. doi: 10.3390/jcm10081779.
citation: Saeed S, Khan QU. The Pathological Mechanisms and Treatments of Tinnitus. Discoveries (Craiova). 2021 Sep 30;9(3):e137. doi: 10.15190/d.2021.16. eCollection 2021 Jul-Sep.
citation: Dehaene S, Kerszberg M, Changeux JP. A neuronal model of a global workspace in effortful cognitive tasks. Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14529-34. doi: 10.1073/pnas.95.24.14529.
citation: Hinkley LBN, Larson PS, Henderson Sabes J, Mizuiri D, Demopoulos C, Adams ME, Neylan TC, Hess CP, Nagarajan SS, Cheung SW. Striatal networks for tinnitus treatment targeting. Hum Brain Mapp. 2022 Feb 1;43(2):633-646. doi: 10.1002/hbm.25676. Epub 2021 Oct 5.
citation: De Ridder D, Vanneste S, Congedo M. The distressed brain: a group blind source separation analysis on tinnitus. PLoS One. 2011;6(10):e24273. doi: 10.1371/journal.pone.0024273. Epub 2011 Oct 6.
citation: Moller AR. Sensorineural Tinnitus: Its Pathology and Probable Therapies. Int J Otolaryngol. 2016;2016:2830157. doi: 10.1155/2016/2830157. Epub 2016 Feb 8.
citation: Rademaker MM, Stegeman I, Ho-Kang-You KE, Stokroos RJ, Smit AL. The Effect of Mindfulness-Based Interventions on Tinnitus Distress. A Systematic Review. Front Neurol. 2019 Nov 1;10:1135. doi: 10.3389/fneur.2019.01135. eCollection 2019.
citation: Noble W. Treatments for tinnitus. Trends Amplif. 2008 Sep;12(3):236-41. doi: 10.1177/1084713808320552. Epub 2008 Jul 17.
citation: Garin P, Gilain C, Van Damme JP, de Fays K, Jamart J, Ossemann M, Vandermeeren Y. Short- and long-lasting tinnitus relief induced by transcranial direct current stimulation. J Neurol. 2011 Nov;258(11):1940-8. doi: 10.1007/s00415-011-6037-6. Epub 2011 Apr 21.
citation: Lee HY. Adjunctive Role of Bifrontal Transcranial Direct Current Stimulation in Distressed Patients with Severe Tinnitus. J Korean Med Sci. 2019 Jan 4;34(3):e19. doi: 10.3346/jkms.2019.34.e19. eCollection 2019 Jan 21.
citation: Cheung SW, Racine CA, Henderson-Sabes J, Demopoulos C, Molinaro AM, Heath S, Nagarajan SS, Bourne AL, Rietcheck JE, Wang SS, Larson PS. Phase I trial of caudate deep brain stimulation for treatment-resistant tinnitus. J Neurosurg. 2019 Sep 24;133(4):992-1001. doi: 10.3171/2019.4.JNS19347. Print 2020 Oct 1.
citation: Hesser H, Weise C, Westin VZ, Andersson G. A systematic review and meta-analysis of randomized controlled trials of cognitive-behavioral therapy for tinnitus distress. Clin Psychol Rev. 2011 Jun;31(4):545-53. doi: 10.1016/j.cpr.2010.12.006. Epub 2010 Dec 23.
citation: Fuller T, Cima R, Langguth B, Mazurek B, Vlaeyen JW, Hoare DJ. Cognitive behavioural therapy for tinnitus. Cochrane Database Syst Rev. 2020 Jan 8;1(1):CD012614. doi: 10.1002/14651858.CD012614.pub2.
citation: Rodrigo H, Beukes EW, Andersson G, Manchaiah V. Internet-based cognitive-behavioural therapy for tinnitus: secondary analysis to examine predictors of outcomes. BMJ Open. 2021 Aug 20;11(8):e049384. doi: 10.1136/bmjopen-2021-049384.
citation: Landry EC, Sandoval XCR, Simeone CN, Tidball G, Lea J, Westerberg BD. Systematic Review and Network Meta-analysis of Cognitive and/or Behavioral Therapies (CBT) for Tinnitus. Otol Neurotol. 2020 Feb;41(2):153-166. doi: 10.1097/MAO.0000000000002472.
citation: Mueller L, Kallogjeri D, Frumkin MR, Dizdar K, Shin J, Rodebaugh T, Piccirillo JF. Predictors of Response to Cognitive Behavioral Therapy in Patients With Tinnitus. JAMA Otolaryngol Head Neck Surg. 2024 Sep 1;150(9):819-826. doi: 10.1001/jamaoto.2024.2264.
citation: Kaldo V, Cars S, Rahnert M, Larsen HC, Andersson G. Use of a self-help book with weekly therapist contact to reduce tinnitus distress: a randomized controlled trial. J Psychosom Res. 2007 Aug;63(2):195-202. doi: 10.1016/j.jpsychores.2007.04.007.
citation: Zenner HP, Vonthein R, Zenner B, Leuchtweis R, Plontke SK, Torka W, Pogge S, Birbaumer N. Standardized tinnitus-specific individual cognitive-behavioral therapy: a controlled outcome study with 286 tinnitus patients. Hear Res. 2013 Apr;298:117-25. doi: 10.1016/j.heares.2012.11.013. Epub 2012 Dec 31.
citation: McKenna L, Marks EM, Hallsworth CA, Schaette R. Mindfulness-Based Cognitive Therapy as a Treatment for Chronic Tinnitus: A Randomized Controlled Trial. Psychother Psychosom. 2017;86(6):351-361. doi: 10.1159/000478267. Epub 2017 Nov 3.
citation: McKenna L, Marks EM, Vogt F. Mindfulness-Based Cognitive Therapy for Chronic Tinnitus: Evaluation of Benefits in a Large Sample of Patients Attending a Tinnitus Clinic. Ear Hear. 2018 Mar/Apr;39(2):359-366. doi: 10.1097/AUD.0000000000000491.
citation: Kreuzer PM, Goetz M, Holl M, Schecklmann M, Landgrebe M, Staudinger S, Langguth B. Mindfulness-and body-psychotherapy-based group treatment of chronic tinnitus: a randomized controlled pilot study. BMC Complement Altern Med. 2012 Nov 28;12:235. doi: 10.1186/1472-6882-12-235.
citation: Vernon JA, Meikle MB. Masking devices and alprazolam treatment for tinnitus. Otolaryngol Clin North Am. 2003 Apr;36(2):307-20, vii. doi: 10.1016/s0030-6665(02)00163-9.
citation: Bahmad F Jr, Carasek N, Lamounier P. Cochlear implant in tinnitus management. Curr Opin Otolaryngol Head Neck Surg. 2023 Apr 1;31(2):155-157. doi: 10.1097/MOO.0000000000000874. Epub 2023 Jan 31.
citation: Rufener KS, Wienke C, Salanje A, Haghikia A, Zaehle T. Effects of transcutaneous auricular vagus nerve stimulation paired with tones on electrophysiological markers of auditory perception. Brain Stimul. 2023 Jul-Aug;16(4):982-989. doi: 10.1016/j.brs.2023.06.006. Epub 2023 Jun 17.
citation: Vanneste S, Plazier M, Van de Heyning P, De Ridder D. Transcutaneous electrical nerve stimulation (TENS) of upper cervical nerve (C2) for the treatment of somatic tinnitus. Exp Brain Res. 2010 Jul;204(2):283-7. doi: 10.1007/s00221-010-2304-5. Epub 2010 May 28.
citation: Botha C, Farmer AD, Nilsson M, Brock C, Gavrila AD, Drewes AM, Knowles CH, Aziz Q. Preliminary report: modulation of parasympathetic nervous system tone influences oesophageal pain hypersensitivity. Gut. 2015 Apr;64(4):611-7. doi: 10.1136/gutjnl-2013-306698. Epub 2014 May 28.
citation: Cutsforth-Gregory JK, Benarroch EE. Nucleus of the solitary tract, medullary reflexes, and clinical implications. Neurology. 2017 Mar 21;88(12):1187-1196. doi: 10.1212/WNL.0000000000003751. Epub 2017 Feb 15. No abstract available.
citation: Steenerson RL, Cronin GW. Tinnitus reduction using transcutaneous electrical stimulation. Otolaryngol Clin North Am. 2003 Apr;36(2):337-44. doi: 10.1016/s0030-6665(02)00164-0.
citation: Yakunina N, Kim SS, Nam EC. BOLD fMRI effects of transcutaneous vagus nerve stimulation in patients with chronic tinnitus. PLoS One. 2018 Nov 28;13(11):e0207281. doi: 10.1371/journal.pone.0207281. eCollection 2018.
citation: 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.
citation: Qureshi IS, Datta-Chaudhuri T, Tracey KJ, Pavlov VA, Chen ACH. Auricular neural stimulation as a new non-invasive treatment for opioid detoxification. Bioelectron Med. 2020 Mar 30;6:7. doi: 10.1186/s42234-020-00044-6. eCollection 2020.
citation: Lee SK, Chung H, Chung JH, Yeo SG, Park MS, Byun JY. Effectiveness of transcutaneous electrical stimulation for chronic tinnitus. Acta Otolaryngol. 2014 Feb;134(2):159-67. doi: 10.3109/00016489.2013.844854. Epub 2013 Nov 11.
citation: Engelberg M, Bauer W. Transcutaneous electrical stimulation for tinnitus. Laryngoscope. 1985 Oct;95(10):1167-73. doi: 10.1288/00005537-198510000-00003.
citation: Aydemir G, Tezer MS, Borman P, Bodur H, Unal A. Treatment of tinnitus with transcutaneous electrical nerve stimulation improves patients' quality of life. J Laryngol Otol. 2006 Jun;120(6):442-5. doi: 10.1017/S0022215106000910. Epub 2006 Mar 24.
citation: Tan G, Adams J, Donovan K, Demarest P, Willie JT, Brunner P, Gorlewicz JL, Leuthardt EC. Does vibrotactile stimulation of the auricular vagus nerve enhance working memory? A behavioral and physiological investigation. Brain Stimul. 2024 Mar-Apr;17(2):460-468. doi: 10.1016/j.brs.2024.04.002. Epub 2024 Apr 7.
citation: Addorisio ME, Imperato GH, de Vos AF, Forti S, Goldstein RS, Pavlov VA, van der Poll T, Yang H, Diamond B, Tracey KJ, Chavan SS. Investigational treatment of rheumatoid arthritis with a vibrotactile device applied to the external ear. Bioelectron Med. 2019 Apr 17;5:4. doi: 10.1186/s42234-019-0020-4. eCollection 2019.
citation: Gos E, Rajchel JJ, Dziendziel B, Kutyba J, Bienkowska K, Swierniak W, Gocel M, Raj-Koziak D, Skarzynski PH, Skarzynski H. How to Interpret Tinnitus Functional Index Scores: A Proposal for a Grading System Based on a Large Sample of Tinnitus Patients. Ear Hear. 2021 May/Jun;42(3):654-661. doi: 10.1097/AUD.0000000000000967.
citation: Gos E, Sagan A, Skarzynski PH, Skarzynski H. Improved measurement of tinnitus severity: Study of the dimensionality and reliability of the Tinnitus Handicap Inventory. PLoS One. 2020 Aug 25;15(8):e0237778. doi: 10.1371/journal.pone.0237778. eCollection 2020.
citation: Henry JA, Griest S, Thielman E, McMillan G, Kaelin C, Carlson KF. Tinnitus Functional Index: Development, validation, outcomes research, and clinical application. Hear Res. 2016 Apr;334:58-64. doi: 10.1016/j.heares.2015.06.004. Epub 2015 Jun 12.
citation: Kallogjeri D, Spitznagel EL Jr, Piccirillo JF. Importance of Defining and Interpreting a Clinically Meaningful Difference in Clinical Research. JAMA Otolaryngol Head Neck Surg. 2020 Feb 1;146(2):101-102. doi: 10.1001/jamaoto.2019.3744. No abstract available.
citation: Busner J, Targum SD. The clinical global impressions scale: applying a research tool in clinical practice. Psychiatry (Edgmont). 2007 Jul;4(7):28-37.
citation: Polak T, Markulin F, Ehlis AC, Langer JB, Ringel TM, Fallgatter AJ. Far field potentials from brain stem after transcutaneous vagus nerve stimulation: optimization of stimulation and recording parameters. J Neural Transm (Vienna). 2009 Oct;116(10):1237-42. doi: 10.1007/s00702-009-0282-1.
citation: Santorelli, S., Mindfulness-based stress reduction (MBSR): Standards of practice. 2014: Center for Mindfulness in Medicine, Health Care & Society, University of Massachusetts Medical School, 2014