Multichannel Vestibular Implant Early Feasibility Study

Study Overview
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Brief Summary
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Although cochlear implants can restore hearing to individuals who have lost cochlear hair cell function, there is no adequately effective treatment for individuals suffering chronic imbalance, postural instability and unsteady vision due to loss of vestibular hair cell function. Preclinical studies have demonstrated that electrical stimulation of the vestibular nerve via a chronically implanted multichannel vestibular prosthesis can partially restore vestibular reflexes that maintain steady posture and vision. This pilot clinical feasibility study of a multichannel vestibular implant system will evaluate this approach in up to ten human subjects with bilateral vestibular deficiency due to gentamicin ototoxicity or other causes of inner ear dysfunction.

Detailed Description
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The system used in this study is the (MVI)™ Multichannel Vestibular Implant System produced by Labyrinth Devices, LLC. It is similar to commercially available cochlear implants in that it includes an implanted stimulator powered and controlled by an external unit, which communicate with the implant across the skin via an inductive link. Unlike a cochlear implant, the implanted stimulator's electrode array is designed for implantation near the ends of the vestibular nerve. The implanted stimulator also includes additional magnets to help facilitate retention of the external unit on the scalp over the implant. The external unit includes a head-worn unit (for sensing head motion and delivering power and signals to the implanted stimulator) and a power and control unit containing a battery and microprocessor. Participants in this trial who meet candidacy criteria and who choose to proceed with implantation surgery, device activation and device deactivation will be asked to participate in a series of post-operative monitoring visits over a ≥1 year period.

Official Title
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First-in-Human Early Feasibility Study of Safety, Tolerability and Efficacy for a Multichannel Vestibular Implant in Individuals With Bilateral Severe-to-Profound Loss of Vestibular Sensation

Conditions
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Other Disorders of Vestibular Function, Bilateral, Bilateral Vestibular Deficiency (BVD), Gentamicin Ototoxicity, Labyrinth Diseases, Vestibular Diseases, Sensation Disorders

Intervention / Treatment
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* Device: Labyrinth Devices MVI™ Multichannel Vestibular Implant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults age 22.0-90 with bilateral vestibular deficiency not responsive to vestibular rehabilitation as determined by pre-inclusion history, vestibular testing and clinical examination Hearing status: (1) Hearing in the candidate ear for implantation is equivalent to or worse than that in the contralateral ear; and (2) hearing in the contralateral ear is good enough to allow functional communication in case hearing in the implanted ear is lost after implantation. Specifically, the contralateral ear must satisfy all of the following criteria: 0.5/1/2/4 kHz pure-tone-average threshold (PTA) hearing better than (i.e., less than) 70 dB HL; and ear-specific sentence recognition score using the recorded AzBio Sentence Test presented at 60 dB SPL-A in quiet must be >60% when tested under either the unaided condition or, if 0.5/1/2/4 kHz PTA>50 dB, the best-aided condition; and ear-specific word recognition score using the recorded Consonant-Nucleus-Consonant (CNC) Word Recognition Test presented at 60 dBHL in quiet must be >60% when tested under either the unaided condition or, if 0.5/1/2/4 kHz PTA>50 dB, the best-aided condition Caloric responses consistent with severe or profound bilateral loss of labyrinthine function, as indicated by one or more of the following: (a) summed speed of caloric responses to warm and cool supine caloric stimuli totaling <10°/sec per ear for each of both ears; (b) summed speed of ice water caloric responses during supine and prone head orientation tests totaling <10°/sec per ear for each of both ears; or (c) speed of ice water caloric responses during supine head orientation tests <5°/sec per ear for each of both ears, with a lack of nystagmus reversal on quickly flipping from supine to prone Prior MRI imaging of the brain, internal auditory canals and cerebellopontine (CP) angle showing a patent labyrinth, present vestibular nerve, patent cochlea, present cochlear nerve, and absence of internal auditory canal/cerebellopontine angle tumors or other central causes of vestibulo-ocular reflex dysfunction or sensorineural hearing loss Prior CT imaging of the temporal bones showing a facial nerve canal with normal caliber and course, middle ear without evidence of chronic otitis media or tympani membrane perforation or cholesteatoma, a mastoid cavity with adequate aeration for surgical access to each semicircular canal, skull thickness ≥3 mm at the planned well site, and scalp soft tissue thickness ≤7 mm. This criterion may be satisfied without additional imaging if an existing head CT or MRI already demonstrates those findings Vaccinations as recommended per Johns Hopkins Listening Center protocols to reduce the risk of meningitis in subjects undergoing cochlear implantation, as described at this site: http://www.hopkinsmedicine.org/otolaryngology/specialty_areas/listencenter/vaccine.html Motivated to travel to the study center, to undergo testing and examinations required for the investigational study, and to participate actively in a vestibular rehabilitation exercise regimen The participant must agree not to swim or to use or operate vehicles, heavy machinery, powered tools or other devices that could pose a threat to the participant, to others, or to property throughout the duration of participation in the study and until at least 1 month after final deactivation of the MVI Implant Exclusion Criteria: Inability to understand the procedures and the potential risks involved as determined by study staff Inability to participate in study procedures due to blindness, ≤ ±10° neck range of motion, cervical spine instability, ear canal stenosis or malformation sufficient to prevent caloric testing Diagnosis of acoustic neuroma/vestibular schwannoma, chronic middle ear disease, cholesteatoma, or central nervous system causes of vestibulo-ocular reflex dysfunction, including chronic and continuing use of medications, drugs or alcohol at doses sufficiently great to interfere with vestibular compensation Vestibular dysfunction known to be caused by reasons other than labyrinthine injury due to ototoxicity, ischemia, trauma, infection, Meniere's disease, or genetic defects known to act on hair cells Lack of labyrinth patency or vestibular nerve as determined by MRI of the brain with attention to the internal acoustic meatus Any contraindication to the planned surgery, anesthesia, device activation and deactivation, or participation in study assessments, as determined by the surgeon, anesthesiologist, or designee, including known intolerance of any materials used in any component of the investigational devices that will come in contact with the subject History of myocardial infarction, coronary bypass surgery, or any percutaneous coronary intervention (PCI) within 6 months prior to screening Orthopedic, neurologic or other nonvestibular pathologic conditions of sufficient severity to confound posture and gait testing or other tests used in the study to assay vestibular function. Subjects with estimated glomerular filtration rate (GFR) < 30 ml/min (MDRD formula) at screening Subjects with heart failure NYHA class III or IV Subjects with Child-Pugh class C cirrhosis A psychiatric disease or substance abuse history likely to interfere with protocol compliance Contraindications to scleral coil eye movement testing, including monocular blindness and a history of fainting vagal reactions to prior eye manipulations would exclude subjects from eye coil testing Inability to tolerate baseline testing protocols Recent corneal injury A history of cervical spine disease preventing head rotation A history of fainting or vagal reactions prior to eye manipulations that would preclude 3D eye movement coil testing Pregnancy, positive urine or serum pregnancy test at any time during study participation, Ability to become pregnant combined with failure or refusal to consistently use a highly effective method of contraception from at least 1 month prior to implantation to not before 1 month after both device deactivation and conclusion of study participation. Highly effective contraception methods include: Total abstinence. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post ovulation methods) and withdrawal are not acceptable methods of contraception for purposes of defining exclusion criteria for this study Female sterilization (surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before entering the study. A woman who has undergone oophorectomy without hysterectomy may participate in the study only after her reproductive status has been confirmed by subsequent hormone level assessment For female subjects of child-bearing potential, study participation is not excluded if the study candidate's male partner is the sole partner of the study candidate and has been vasectomized. Combination of any two of the following: Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example, hormone vaginal ring or transdermal hormone contraception Placement of an intrauterine device (IUD) or intrauterine system (IUS) Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository In case of use of oral contraception, women should have been stabile on the same pill for a minimum of 3 months before taking study treatment. Women who are nursing/lactating Any medical condition, judged by the investigator team, that is likely to interfere with a study candidate's participation in the study or likely to cause serious adverse events during the study.

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Device Feasibility
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: vestibular implant<br>Up to 30 participants will undergo implantation, activation and deactivation of a Labyrinth Devices MVI™ Multichannel Vestibular Implant System | Device: Labyrinth Devices MVI™ Multichannel Vestibular Implant<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identified adverse events to assess the safety and tolerability of the Labyrinth Devices Multichannel Vestibular Implant (MVI™) | Number of participants with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events v4.3 (CTCAE v4.3) | Through study completion, an average of 1 year, that is: in visits 0 through 10 | 
| Assess the feasibility of the MVI, as determined by changes in 3-dimensional vestibulo-ocular reflex (3D VOR) gain and alignment compared to pre-intervention values and published data from subjects with normal vestibular function | 3D VOR gain (eye velocity / -head velocity) | Through study completion, an average of 1 year, that is: in visits 0, and 3 through 10 | 
| Assess the preliminary efficacy of the MVI, as determined by changes in 3-dimensional vestibulo-ocular reflex (3D VOR) gain and alignment compared to pre-intervention values and published data from subjects with normal vestibular function | 3D VOR gain (eye velocity / -head velocity) | Through study completion, an average of 1 year, that is: in visits 0, and 3 through 10 | 
| Assess the effects of MVI implantation on cochlear function, as indicated by changes in pure tone audiometry | Pure tone audiometry (decibels [dB]) | through study completion, an average of 1 year, that is: in visits 0, and 3 through 10 | 
| Assess the effects of MVI use on cochlear function, as indicated by changes in pure tone audiometry | Pure tone audiometry (decibels [dB]) | through study completion, an average of 1 year, that is: in visits 0, and 3 through 10 | 
| Assess the effects of MVI implantation on cochlear function, as indicated by changes in Consonant-vowel nucleus-consonant (CNC) speech recognition scores | CNC speech recognition score (0-100% correct), higher scores means better outcome | through study completion, an average of 1 year, that is: in visits 0, and 3 through 10 | 
| Assess the effects of MVI use on cochlear function, as indicated by changes in Consonant-vowel nucleus-consonant (CNC) speech recognition scores | CNC speech recognition score (0-100% correct), higher scores means better outcome | through study completion, an average of 1 year, that is: in visits 0, and 3 through 10 | 
| Assess the effects of MVI implantation on cochlear function, as indicated by changes in Arizona Biomedical (AzBio) sentence recognition scores | AzBio sentence recognition score (0-100% correct), higher scores means better outcome | through study completion, an average of 1 year, that is: in visits 0, and 3 through 10 | 
| Assess the effects of MVI use on cochlear function, as indicated by changes in Arizona Biomedical (AzBio) sentence recognition scores | AzBio sentence recognition score (0-100% correct), higher scores means better outcome | through study completion, an average of 1 year, that is: in visits 0, and 3 through 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Vestibulo-ocular reflex (VOR) three-dimensional (3D) alignment to assess the preliminary efficacy of the MVI | Measured in degrees | In a period of up to 24 weeks, in visits 0, and 3 through 10 | 
| Change in Ocular Vestibular Evoked Myogenic Potentials (oVEMP) to assess the effects of MVI implantation and use on utricular function | oVEMP peak-to-peak amplitude in microvolts | In a period of up to 24 weeks, in visits 0, and 3 through 10 | 
| Change in Cervical Vestibular Evoked Myogenic Potentials (cVEMP) to assess the effects of MVI implantation and use on saccular function | cVEMP peak-to-peak amplitude in microvolts | In a period of up to 24 weeks, in visits 0, and 3 through 10 | 
| Changes in utility scores on 36-Item Short Form Health Survey (SF-36) to assess the effects of MVI implantation and use on activities of daily living and quality of life | SF-36 Utility (No scale) | In a period of up to 24 weeks, in visits 0, 6, 8, and 10 | 
| Changes in scores on Tinnitus Handicap Inventory (THI) to assess the effects of MVI implantation and use on activities of daily living and quality of life | THI score (0-100), higher scores means worse outcome | In a period of up to 24 weeks, in visits 0, 6, 8, and 10 | 
| Changes in scores on Dizziness Handicap Inventory (DHI) to assess the effects of MVI implantation and use on activities of daily living and quality of life | DHI score (0-100), higher scores means worse outcome | In a period of up to 24 weeks, in visits 0, 6, 8, and 10 | 
| Changes in scores on the Health Utilities Index 3 (HUI3) to assess the effects of MVI implantation and use on activities of daily living and quality of life | HUI3 scores (0-1), higher scores means better outcome | In a period of up to 24 weeks, in visits 0, 6, 8, and 10 | 
| Changes in scores on the Vestibular Activities of Daily Living (VADL) to assess the effects of MVI implantation and use on activities of daily living and quality of life | VADL score (1-10), higher scores means worse outcome | In a period of up to 24 weeks, in visits 0, 6, 8, and 10 | 
| Changes in scores on the Autophony Index (AI) to assess the effects of MVI implantation and use on activities of daily living and quality of life | AI score (0-104), higher scores means worse outcome | In a period of up to 24 weeks, in visits 0, 6, 8, and 10 | 
| Changes in scores on the bilateral vestibular deficiency BVD-case definition subset of questions to assess the effects of MVI™ implantation and use on activities of daily living and quality of life | BVD-case definition subset of questions from the National Health Interview Survey 2008 Balance Questions (NHIS) score (no scale) | In a period of up to 24 weeks, in visits 0, 6, 8, and 10 | 
| Change in Dynamic visual acuity (DVA) to assess the feasibility and preliminary efficacy of the MVI | DVA test score in log10 of the Minimum Angle Resolvable (LogMAR) units, as the difference between raw DVA LogMAR and static visual acuity LogMAR | In a period of up to 24 weeks, in visits 0 and 3 through 10 | 
| Change in Bruininks-Oseretsky test of motor proficiency- balance subtest 2 (BOT2) score | BOT2 score (0-36), higher scores means better outcome | In a period of up to 24 weeks, in visits 0, and 3 through 10 | 
| Change in Dynamic Gait Index (DGI) | DGI score (0-24), higher scores means better outcome | In a period of up to 24 weeks, in visits 0, and 3 through 10 | 
| Change in gait characteristics using the GaitRite™ system | Gait speed analysis in meters per second | In a period of up to 24 weeks, in visits 0, and 3 through 10 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vestibular, implant, prosthesis, labyrinth, ototoxicity, gentamicin, oscillopsia, disequilibrium, dizziness, vestibulopathy, inner ear