Clinical trial NCT06500975: Long Term Outcomes After Vestibular Implantation
Official title: Long Term Outcomes After Vestibular Implantation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Bilateral Vestibular Hypofunction
Bilateral Vestibular Deficiency
Bilateral Vestibulopathy
Gentamicin Ototoxicity
Aminoglycoside Toxicity
Vestibular Diseases
Sensation Disorders
Labyrinth Diseases
Other Disorders of Vestibular Function
Keywords: Vestibular
Implant
Prosthesis
Labyrinth
Ototoxicity
Gentamicin
Oscillopsia
Disequilibrium
Dizziness
Vestibulopathy
Inner Ear
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
name: National Institute on Deafness and Other Communication Disorders (NIDCD)
name: Labyrinth Devices, LLC
First posted: 2024-07-15
Enrollment: 32
Sex: ALL
Minimum age (years): 22
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Although cochlear implants can restore hearing to individuals who have lost cochlear hair cell function, there is no widely available, adequately effective treatment for individuals suffering chronic imbalance, postural instability and unsteady vision due to bilateral vestibular hypofunction. Prior research focused on ototoxic cases has demonstrated that electrical stimulation of the vestibular nerve via a chronically implanted multichannel vestibular implant can partially restore vestibular reflexes that normally maintain steady posture and vision; improve performance on objective measures of postural stability and gait; and improve patient-reported disability and health-related quality of life. This single-arm open-label study extends that research to evaluate outcomes for up to 8 individuals with non-ototoxic bilateral vestibular hypofunction, yielding a total of fifteen adults (age 22-90 years at time of enrollment) divided as equally as possible between ototoxic and non-ototoxic cases.

Detailed description: There is no widely available, adequately effective treatment for individuals suffering chronic imbalance, postural instability and unsteady vision due to loss of semicircular canal function despite vestibular rehabilitation exercises. The experience of 15 adults with bilateral vestibular hypofunction who underwent unilateral surgical placement of a vestibular implant and have received continuously motion-modulated electrical stimulation of the vestibular nerve for \>6 months revealed vestibular implantation (VI) and motion-modulated stimulation can partially restore vestibular sensation and reflexes that normally maintain steady posture and vision. This study will examine long-term outcomes after vestibular implantation. Within constraints on power and/or minimum detectable effect size due to limits on the number of study participants permitted under IDE G150198, the study will test the following hypotheses regarding unilateral vestibular implantation, activation and long-term (≥3 years) continuous/daily use:

1. It is safe, as determined by incidence of serious unanticipated adverse device-related events and as further quantified by proportions of:

   1. implanted ears with preservation of 4-frequency pure tone average for 0.5,1,2,4 kHz air-conducted audiometric detection thresholds ≤ 50 decibel (dB) HL and ear-specific speech discrimination ≥50% (consistent with Class A or B per American Academy of Otolaryngology-Head and Neck Surgery 1995 guidelines 13 ) or ≤ 30 dB change from preoperative baseline (if preoperative baseline is ≥20 dBHL) and ear-specific speech discrimination ≤30% worse than preoperative baseline (if preoperative baseline is ≤80%)
   2. participants with preservation of useful sound-field hearing by the above criteria, and
   3. implanted ears with preservation of otolith endorgan function, if present pre-operatively
2. It is tolerable, as quantified by duration of compliance with use.
3. It is efficacious, as defined by nonzero improvement with respect to preoperative baseline gait stability as quantified by Dynamic Gait Index (DGI) and vestibulo-ocular reflex gain during passive head impulse rotation (VHITG) .

Eligibility criteria: Inclusion Criteria

* Adults older than 22 years old who
* have previously been enrolled in Johns Hopkins University Institutional Review Board protocol NA_00051349, IRB00335294 or IRB00346924 and
* have previously been implanted with a vestibular implant under FDA IDE G150198

Primary outcomes:
measure: PM1.1: Dynamic Gait Index (DGI)18 during motion-modulated implant stimulation at 4 years post-implantation, relative to pre-operative baseline, aggregated across all implant users.
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: PM1.2: Gain (VHITG) of the vestibulo-ocular reflex (VOR), as measured using the video head impulse test (vHIT)
timeFrame: 4 years post-implantation up to 5 years post-enrollment
Secondary outcomes:
measure: EM1.1: Vestibular Implant Composite Outcome (VICO) score
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: EM1.2: Bruininks-Oseretsky Test of Motor Proficiency 2nd Edition Balance Subtest 5 (BOT) score.
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: EM1.3: Dizziness Handicap Inventory (DHI)
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: EM1.4: SF6D utility (SF6DU) score
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: EM2.1: Vestibular Implant Composite Outcome (VICO) score
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: EM2.2: Bruininks-Oseretsky Test of Motor Proficiency 2nd Edition Balance Subtest 5 (BOT)
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: EM2.3: Dizziness Handicap Inventory (DHI)
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: EM2.4: SF6D utility (SF6DU) score
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: EM2.5: Dynamic Gait Index (DGI)
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: EM2.6: Gain (VHITG) of the vestibulo-ocular reflex (VOR), as measured using the video head impulse test (vHIT) and averaged for the three implanted semicircular canals
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: EM3.1: Vestibular Implant Composite Outcome (VICO) score at 4 years post-implantation, relative to pre-operative baseline, for the subgroup of participants who have ototoxic adult-onset BVH.
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: EM3.2: Bruininks-Oseretsky Test of Motor Proficiency 2nd Edition Balance Subtest 5 (BOT) score 4 years post-implantation, relative to pre-operative baseline, for the subgroup of participants who have ototoxic adult-onset BVH.
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: EM3.3: Dizziness Handicap Inventory (DHI) score at 4 years post-implantation, relative to pre-operative baseline, for the subgroup of participants who have ototoxic adult-onset BVH.
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: EM3.4: SF6D utility (SF6DU) score at 4 years post-implantation, relative to pre-operative baseline, for the subgroup of participants who have ototoxic adult-onset BVH.
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: EM3.5: Dynamic Gait Index (DGI) score at 4 years post-implantation, relative to pre-operative.baseline, for the subgroup of participants who have ototoxic adult-onset BVH.
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: EM3.6: Gain (VHITG) of the vestibulo-ocular reflex, measured using the video head impulse test.averaged for the three implanted semicircular canals, relative to pre-operative baseline, for the subgroup of participants who have ototoxic adult-onset BVH.
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: SM0: Type, incidence and severity of unanticipated adverse device effects as of 4 years post-implantation
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: SM1.1: implant-side bone-conduction 4-frequency (0.5, 1, 2, 4 kHz) pure tone average detection threshold (BonePTAi)
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: SM1.2: implant-side air-conduction 4-frequency pure tone average detection threshold (AirPTAi)
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: SM1.3: implant-side consonant-nucleus-consonant word discrimination score (CNCWi)
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: SM1.4: sound-field Arizona Biology (AzBios)27 sentences-in-noise discrimination score
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: SM1.5: Proportion of implanted ears that maintain American Academy of Otolaryngology - Head & Neck Surgery (AAO-HNS) 1995 Class A or B hearing13 or ≤ 30 dB change from preoperative baseline (if preoperative baseline is ≥20 dBHL) and ear-specific speech
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: SM1.6: Proportion of implanted participants who maintain AAO-HNS 1995 Class A or B hearing or ≤ 30 dB change from preoperative baseline (if preoperative baseline is ≥20 dBHL) and ear-specific speech discrimination ≤30% worse than preoperative baseline
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: SM1.7: implant-side distortion-product otoacoustic emissions
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: SM1.8: Ear canal acoustic admittance as assessed by implant-side tympanometry
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: SM1.9: Tinnitus Handicap Inventory (THI)
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: SM1.10: Autophony Index (AI)
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: SM1.11: cervical vestibular-evoked myogenic potential (cVEMP) response amplitude
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: SM1.12: ocular vestibular-evoked myogenic potential (oVEMP) response amplitude
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: SM1.13: subjective visual vertical (SVV) as assessed using the Bucket Test
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: SM1.14: scalp thickness at the location of implanted magnets (Tscalp)
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: SM1.15: all adverse events, including but not limited to events related to the surgical procedure, device and device systems
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: TM1: Proportion of all implanted participants who continue to use the MVI system daily at 4 years post-implantation
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: TM2: Proportion of implanted participants with non-ototoxic/non-central adult-onset BVH who continue to use the MVI system daily at 4 years post-implantation
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: TM3: Proportion of implanted participants with ototoxic adult-onset BVH who continue to use the MVI system daily at 4 years post-implantation
timeFrame: 4 years post-implantation up to 5 years post-enrollment
Other outcomes:
measure: XM1.1 (A,B,C): VOR latency during VHIT
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: XM1.2 (A,B,C): saccade latency during VHIT
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: XM2.1 (A,B,C): VOR gain-time constant product during whole-body yaw rotary chair velocity step rotations toward the implanted ear
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: XM2.2 (A,B,C): VOR frequency response during whole-body yaw rotary chair sinusoidal rotations
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: XM3.1: electrically-evoked vestibulo-ocular reflex (eeVOR) response peak magnitude for largest response on each electrode
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: XM3.2: electrically-evoked vestibulo-ocular reflex (eeVOR) response 3D misalignment for largest response on each electrode
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: XM4 (A,B,C): time to failure on Modified Romberg Test with Eyes Closed on Foam
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: XM5.1 (A,B,C): slope of change in treadmill dynamic visual acuity with increasing walking speed (LogMAR/mph)
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: XM5.2 (A,B,C): maximum treadmill velocity achieved during (mph)
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: XM6.1 (A,B,C): gait speed when walking in well-light hall
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: XM6.2 (A,B,C): gait speed when walking in dim light
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: XM7.1 (A,B,C): TUG when walking in well-light hall
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: XM7.2 (A,B,C): TUG when walking in dim light
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: XM8.1 (A,B,C): gait speed when walking during dual task/cognitive distraction (Serial 7s downward counting)
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: XM8.2 (A,B,C): TUG during dual task/cognitive distraction (Serial 7s)
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: XM9 (A,B,C): Serial 7s downward counting while standing with eyes open
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: XM10.1 (A,B,C): time to complete the Trail Making Test Part B (TMT)
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: XM10.2 (A,B,C): performance on the Triangle Completion Test (TCT)
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: XM11: electrode impedance
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: XM12: electrode location distance, as determined by post-implantation computed tomography (CT) imaging
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: XM13: vestibular evoked compound action potential (veCAP)24 amplitude
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: XM14.1: scalp thickness over the implant, measured on post-operative CT imaging
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: XM14.2: inductively-measured intercoil distance between implant antenna coil and external processor antenna coil
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: XM15.1: Bilateral Vestibulopathy Questionnaire score (BVQ)
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: XM15.2: Number of Audio/video recording of structured interviews
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: XM16: Vestibular Activities of Daily Living score (VADL)
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: XM17 (A,B,C): Oscillopsia Visual Analog Scale score (oVAS)
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: XM18: Activities-specific Balance Confidence Scale score (ABC)
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: XM19.1: Vertigo Symptom Scale score (VSS)
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: XM19.2: Vertigo Visual Analogue Scale score (VAS)
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: XM20.1: Health Utilities Index Mark 3 (HUI)
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: XM20.2: EuroQol 5 Dimension (EQ-5D)
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: XM21: Tinnitus Handicap Inventory (THI)
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: XM22: Autophony Index (AI)
timeFrame: 4 years post-implantation up to 5 years post-enrollment
measure: XM23.1: OTOSCOPE genetic testing panel (or equivalent panel from another Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory, such as Invitae Corpl) for participants who agree to genetic testing
timeFrame: Preoperative baseline
measure: XM23.2: Presence or absence of Mitochondrially Encoded 12S RRNA (MTRNR1) gene abnormality as assessed by genetic test panel (or equivalent) for participants with known ototoxic exposure who agree to genetic testing
timeFrame: Preoperative baseline
measure: XM23.3: RFC1 presence or absence of an MTRNR1 gene abnormality as assessed by Ataxia/CANVAS genetic testing panel (or equivalent) for participants suspected to have CANVAS or demonstrate potential CANVAS related symptoms
timeFrame: Preoperative baseline
measure: XM24.1: Number of intraoperative video recordings of electrode implantation
timeFrame: Intraoperatively
measure: XM24.2: Number of post-implantation temporal bone CT imagings
timeFrame: 3 weeks post-implantation
measure: XM25: Study visit duration (days) by activity/test/assessment
timeFrame: 4 years post-implantation up to 3 years post-enrollment
measure: XM26: Number of audio/video recording of participants' descriptions of motion percepts during eeVOR testing
timeFrame: 4 years post-implantation up to 3 years post-enrollment
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins School of Medicine
state: Maryland
Study officials:
affiliation: Johns Hopkins School of Medicine
name: John P Carey, MD
role: PRINCIPAL_INVESTIGATOR
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