Multichannel Vestibular Implant Early Feasibility Study

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.

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.