Cochlear Promontory Stimulation for Treatment of Tinnitus

Cochlear Promontory Stimulation for Treatment of Tinnitus: Towards Developing an Implantable Device

Tinnitus is the perception of sound when no external noise is present. The Center for Disease Control (CDC) estimates over 50 million - nearly 15% of the general public -experience some form of tinnitus. Roughly 20 million people struggle with burdensome chronic tinnitus, with 2 million experiencing extreme and debilitating symptoms.

The 2014 Clinical Practice Guideline on tinnitus from the American Academy of Otolaryngology - Head and Neck Surgery summarized the existing state of tinnitus management by stating "A cure for primary tinnitus does not yet exist, and despite claims to the contrary, no method has been proven to provide long-term suppression of tinnitus."

The purpose of this study is to look at the safety and efficacy of cochlear promontory stimulation in the short term relief of tinnitus. The secondary goal of the study is to determine the optimum region(s) of the cochlear promontory in planning for an implantable electrical device for long term tinnitus suppression.

Study Overview

• Status: Suspended
• Conditions: Tinnitus
• Intervention / Treatment: Device: Cochlear promontory stimulation

Detailed Description

Candidate subjects will undergo a temporal bone Computed Tomography (CT) scan, contrast enhanced head Magnetic Resonance Imaging (MRI), audiogram with immittance testing, pitch and level matching of tinnitus, Distortion Product Otoacoustic Emissions (DPOAE) and Auditory Brainstem Response (ABR) testing prior to promontory stimulation. Head MRI, DPOAE, audiogram and immittance testing are considered clinically routine for assessment of asymmetric tinnitus. Temporal bone CT, ABR, tinnitus pitch, level matching, masking levels and residual inhibition testing are not standard clinical assessments for asymmetric tinnitus. In addition, subjects will complete the Tinnitus Handicap Inventory (THI), Tinnitus Functional Index (TFI) and Visual Analog Scale (VAS) questionnaires three separate times within the week prior to promontory stimulation testing. Additional testing for comorbid anxiety and depressive conditions will be a screening Generalized Anxiety Disorder (GAD7), Patient Health Questionnaire (PHQ8), and short Health Anxiety Inventory (HAI-S). The NEO Personality Inventory (NEO PI) will be administered to provide baseline information. The initial session of promontory stimulation will define optimal stimulation parameters (i.e., location, current level, pulse-width, phase polarity), where maximal tinnitus suppression occurs with minimal or no auditory percept. After these parameters are established, the patient will complete the THI, TFI, and VAS immediately prior to stimulation, during stimulation, and following completion of stimulation at 10-minutes, 1-hour, 24-hours, 48-hours, and 1-week following completion of stimulation. In addition, pitch and level matching of tinnitus will be completed immediately upon completion of each promontory stimulation session. Each patient will undergo three successive treatments separated by 1-week. Prior to each treatment, the patient will receive an audiogram and DPOAE testing to document interval safety. At the conclusion of the study, subjects will be asked about their willingness to undergo surgical implantation of a device capable of long-term scheduled or on-demand electrical stimulation for tinnitus suppression

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Normal to moderate sensorineural hearing loss (based on pure tone audiometry (PTA) of 500, 1000 and 2000 Hz) and a word recognition score greater than 75%
2. Asymmetric subjective tonal tinnitus

3. Tinnitus that is disruptive

   1. Determined by THI score (in the severe range i.e. >56/100)
   2. TFI (in the severe range i.e. >52/100)
   3. VAS (> 5/10 )
4. Tinnitus that is intractable, and has not been ameliorated by conventional measures such as a hearing aid or masking
5. Normal contrast-enhanced MRI of the head

Exclusion Criteria:

1. Tinnitus present less than 6 months or longer than 3 years
2. History of brain or major ear surgery
3. Prior major head trauma

4. History of depression or anxiety

   1. Determined by screening using the GAD 7, PHQ8, and HAI-S

      • GAD7 > 9 (indicates clinically significant anxiety)
      • PHQ > 9 (indicates clinically significant depression)
      • HAI-S > 25 (hypochondriacal level illness anxiety)
   2. Inability to assess, continue or complete trial
5. Currently on antidepressants, anxiolytics or antipsychotics
6. Active use of other tinnitus treatments
7. MRI Incompatible Devices
8. Known pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Testing Arm; There will only be one arm. The patient and investigator will initially be blinded to the "on-off" status of the electrode. The patient will thus serve as an internal control for testing. Once device integrity and possible benefit is confirmed, the patients will undergo non-tactile electrical stimulation to the bone of the inner ear (cochlear promontory) for short term relief of tinnitus via Cochlear promontory stimulation.

Device: Cochlear promontory stimulation; Promontory stimulation is an established otologic procedure that was initially developed as a diagnostic tool to assess patient candidacy for cochlear implantation. Promontory stimulation is most commonly performed in the outpatient setting on an awake patient by placing a single insulated probe through a topically anesthetized tympanic membrane and applying monopolar current for several seconds to minutes. The initial session of promontory stimulation will define optimal stimulation parameters (i.e., location, current level, pulse-width, phase polarity), where maximal tinnitus suppression occurs with minimal or no auditory percept. Additional stimulation testing visits will confirm these findings.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Short Term Relief of Tinnitus as Measured by the Tinnitus Handicap Inventory	The Tinnitus Handicap Inventory (THI) has 25 questions with possible answers of Yes (4 points), Sometimes (2 points), and No (0 points). Scores categories are (1-16: Slight or no handicap - Grade 1), (18-36: Mild handicap - Grade 2), (38-56: Moderate handicap - Grade 3), (58-76: Severe handicap - Grade 4), (78-100: Catastrophic handicap - Grade 5).	7 days after electrical stimulation procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Optimal Location of Tinnitus Relief	Location on the cochlear promontory where highest perceived benefit from electrical stimulation	Immediately after electrical stimulation procedure (approximately 1 min after stimulation)
Auditory Feedback	Perception of hearing the electrical stimulus (if at all)	Immediately after electrical stimulation procedure (approximately 1 min after stimulation)
Tactile Feedback	Perception of hearing the electrical stimulus (if at all)	Immediately after electrical stimulation procedure (approximately 1 min after stimulation)
Short Term Relief of Tinnitus as Measured by the Tinnitus Functional Index	The Tinnitus Functional Index (TFI) contains eight subscales (domains), of which seven contain 3 items and one contains 4. The possible responses for each item range from 0 (did not interfere) to 10 (completely interfered). The total score is transformed to a scale ranging from 0 (no interference) to 100 (completely interfered with activities).	7 days after electrical stimulation procedure
Short Term Relief of Tinnitus as Measured by the Visual Analog Scale	The Visual Analog Scale (VAS) for Numeric Pain Distress was used for this outcome. The VAS has pre-set marks between the extremes of 0 (no pain) and 10 (unbearable pain).	7 days after electrical stimulation procedure

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Matthew L Carlson, Mayo Clinic

Publications and helpful links

General Publications

• Zeman F, Koller M, Figueiredo R, Aazevedo A, Rates M, Coelho C, Kleinjung T, de Ridder D, Langguth B, Landgrebe M. Tinnitus handicap inventory for evaluating treatment effects: which changes are clinically relevant? Otolaryngol Head Neck Surg. 2011 Aug;145(2):282-7. doi: 10.1177/0194599811403882.
• Tunkel DE, Bauer CA, Sun GH, Rosenfeld RM, Chandrasekhar SS, Cunningham ER Jr, Archer SM, Blakley BW, Carter JM, Granieri EC, Henry JA, Hollingsworth D, Khan FA, Mitchell S, Monfared A, Newman CW, Omole FS, Phillips CD, Robinson SK, Taw MB, Tyler RS, Waguespack R, Whamond EJ. Clinical practice guideline: tinnitus. Otolaryngol Head Neck Surg. 2014 Oct;151(2 Suppl):S1-S40. doi: 10.1177/0194599814545325.
• Tsai BS, Sweetow RW, Cheung SW. Audiometric asymmetry and tinnitus laterality. Laryngoscope. 2012 May;122(5):1148-53. doi: 10.1002/lary.23242. Epub 2012 Mar 23.
• Perez R, Shaul C, Vardi M, Muhanna N, Kileny PR, Sichel JY. Multiple electrostimulation treatments to the promontory for tinnitus. Otol Neurotol. 2015 Feb;36(2):366-72. doi: 10.1097/MAO.0000000000000309.
• Rubinstein JT, Tyler RS, Johnson A, Brown CJ. Electrical suppression of tinnitus with high-rate pulse trains. Otol Neurotol. 2003 May;24(3):478-85. doi: 10.1097/00129492-200305000-00021.
• Watanabe K, Okawara D, Baba S, Yagi T. Electrocochleographic analysis of the suppression of tinnitus by electrical promontory stimulation. Audiology. 1997 May-Jun;36(3):147-54. doi: 10.3109/00206099709071968.
• Steenerson RL, Cronin GW. Treatment of tinnitus with electrical stimulation. Otolaryngol Head Neck Surg. 1999 Nov;121(5):511-3. doi: 10.1016/S0194-5998(99)70048-3.
• Mertens G, De Bodt M, Van de Heyning P. Cochlear implantation as a long-term treatment for ipsilateral incapacitating tinnitus in subjects with unilateral hearing loss up to 10 years. Hear Res. 2016 Jan;331:1-6. doi: 10.1016/j.heares.2015.09.016. Epub 2015 Oct 24.
• Tyler RS. Patient preferences and willingness to pay for tinnitus treatments. J Am Acad Audiol. 2012 Feb;23(2):115-25. doi: 10.3766/jaaa.23.2.6.
• Arts RA, George EL, Stokroos RJ, Vermeire K. Review: cochlear implants as a treatment of tinnitus in single-sided deafness. Curr Opin Otolaryngol Head Neck Surg. 2012 Oct;20(5):398-403. doi: 10.1097/MOO.0b013e3283577b66.
• Arts RA, George EL, Chenault MN, Stokroos RJ. Optimizing intracochlear electrical stimulation to suppress tinnitus. Ear Hear. 2015 Jan;36(1):125-35. doi: 10.1097/AUD.0000000000000090.
• Topf MC, Hsu DW, Adams DR, Zhan T, Pelosi S, Willcox TO, McGettigan B, Fisher KW. Rate of tympanic membrane perforation after intratympanic steroid injection. Am J Otolaryngol. 2017 Jan-Feb;38(1):21-25. doi: 10.1016/j.amjoto.2016.09.004. Epub 2016 Sep 28.
• Marinelli JP, Anzalone CL, Prummer CM, Poling GL, Staab JP, Tombers NM, Lohse CM, Carlson ML. Electrical stimulation of the cochlea for treatment of chronic disabling tinnitus: an open-label trial towards the development of an implantable device. J Transl Med. 2022 Jan 29;20(1):56. doi: 10.1186/s12967-022-03271-4.

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2018
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: November 30, 2017
• First Submitted That Met QC Criteria: November 28, 2018
• First Posted (Actual): November 30, 2018

Study Record Updates

• Last Update Posted (Actual): July 13, 2023
• Last Update Submitted That Met QC Criteria: July 12, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Otorhinolaryngologic Diseases; Ear Diseases; Sensation Disorders; Hearing Disorders; Tinnitus
• Other Study ID Numbers: 17-004832

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes