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.
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) .
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
32
Continuously motion-modulated stimulation delivered by a vestibular implant already implanted under a prior study protocol (Labyrinth Devices MVI™ Multichannel Vestibular Implant System)
Johns Hopkins School of Medicine
Baltimore, Maryland, United States
RECRUITINGPM1.1: 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.
DGI comprises 8 gait tasks scored by an examiner: walking on a level surface, changing gait speed, walking during horizontal head turns, walking during vertical head turns, pivoting, stepping over an obstacle, stepping around obstacles, and waling up and down stairs. Each task is scored (0-3 points, 3 is best). Raw DGI score is the sum of the eight subtest scores and ranges from 0 to 24, with higher scores meaning better outcome and minimally important difference 3.2 points.
Time frame: 4 years post-implantation up to 5 years post-enrollment
PM1.2: Gain (VHITG) of the vestibulo-ocular reflex (VOR), as measured using the video head impulse test (vHIT)
During video head impulse testing (vHIT), rotational eye and head movement are measured by a goggle-mounted camera and motion sensor during brief, fast \~10 degree head rotations about the axis of a semicircular canal being tested. Performance is quantified by vestibulo-ocular reflex (VOR) gain, which a ratio of eye movement to head movement (in this case the integral of eye velocity relative to the head and the additive inverse of the integral of head velocity, respectively). VHITG, the average vHIT VOR gain for each of the three semicircular canals of the implanted ear, typically ranges from 0 to 1, with higher numbers indicating better performance.
Time frame: 4 years post-implantation up to 5 years post-enrollment
EM1.1: Vestibular Implant Composite Outcome (VICO) score
Vestibular Implant Composite Outcome (VICO) score incorporates changes in vestibulo-ocular reflex gain during video head impulse testing, postural stability, gait, dizziness handicap, and health-related quality of life at 4 years post-implantation, relative to pre-operative baseline. VICO (t=6months post-op) score is the sum of changes, from preoperative baseline to 4 years post-implantation, in vestibulo-ocular reflex gain during passive head impulse rotation (VHITG); postural stability as quantified by the Bruininks-Oseretsky Test of Motor Proficiency, 2nd Edition Balance Subtest 5 (BOT); gait stability as quantified by Dynamic Gait Index (DGI); Dizziness Handicap Inventory (DHI); and SF6D health utility (SF6DU); with each component's contribution scaled to the corresponding test's minimally important difference (MID). Score 0-100, higher scores indicate better outcomes.
Time frame: 4 years post-implantation up to 5 years post-enrollment
EM1.2: Bruininks-Oseretsky Test of Motor Proficiency 2nd Edition Balance Subtest 5 (BOT) score.
BOT comprises 9 postural tasks scored by an examiner: standing with both feet on a line, standing on one leg, tandem walking, walking on a line with eyes open and eyes closed, and standing on a balance beam. Each task is performed twice and scored (0-4 points, 4 is best). The BOT score is the sum of the best scores for each task. It ranges from 0 to 36 points, with higher scores meaning better outcome and minimally important difference 4.5 points.
Time frame: 4 years post-implantation up to 5 years post-enrollment
EM1.3: Dizziness Handicap Inventory (DHI)
Dizziness Handicap Inventory (DHI) is a 25-question survey designed to quantify self-rated disability due to dizziness and unsteadiness, with scores ranging from 0 (least disabled, best outcome) to 100 (worst outcome). The minimally important difference is 18 points.
Time frame: 4 years post-implantation up to 5 years post-enrollment
EM1.4: SF6D utility (SF6DU) score
SF6DU is a unitless health utility score computed from patient-reported replies to the SF6 health-related quality of life survey and ranging from 0 to 1, with higher scores meaning better outcome and minimally important difference 0.03 points.
Time frame: 4 years post-implantation up to 5 years post-enrollment
EM2.1: Vestibular Implant Composite Outcome (VICO) score
Vestibular Implant Composite Outcome (VICO) score incorporates changes in vestibulo-ocular reflex gain during video head impulse testing, postural stability, gait, dizziness handicap, and health-related quality of life at 4 years post-implantation, relative to pre-operative baseline. VICO (t=6months post-op) score is the sum of changes, from preoperative baseline to 4 years post-implantation, in vestibulo-ocular reflex gain during passive head impulse rotation (VHITG); postural stability as quantified by the Bruininks-Oseretsky Test of Motor Proficiency, 2nd Edition Balance Subtest 5 (BOT); gait stability as quantified by Dynamic Gait Index (DGI); Dizziness Handicap Inventory (DHI); and SF6D health utility (SF6DU); with each component's contribution scaled to the corresponding test's minimally important difference (MID). Score 0-100, higher scores indicate better outcomes.
Time frame: 4 years post-implantation up to 5 years post-enrollment
EM2.2: Bruininks-Oseretsky Test of Motor Proficiency 2nd Edition Balance Subtest 5 (BOT)
BOT includes 9 postural tasks scored by an examiner: standing with both feet on a line, standing on one leg, tandem walking, walking on a line with eyes open and eyes closed, and standing on a balance beam. Each task is performed twice and scored (0-4 points). The BOT score is the sum of the best scores for each task. It ranges from 0 to 36 points, with higher scores meaning better outcome and minimally important difference 4.5 points.
Time frame: 4 years post-implantation up to 5 years post-enrollment
EM2.3: Dizziness Handicap Inventory (DHI)
Dizziness Handicap Inventory (DHI) is a 25-question survey designed to quantify self-rated disability due to dizziness and unsteadiness, with scores ranging from 0 (least disabled, best outcome) to 100 (worst outcome). The minimally important difference is 18 points.
Time frame: 4 years post-implantation up to 5 years post-enrollment
EM2.4: SF6D utility (SF6DU) score
SF6DU is a unitless health utility score computed from patient-reported replies to the SF6 health-related quality of life survey and ranging from 0 to 1, with higher scores meaning better outcome and minimally important difference 0.03 points.
Time frame: 4 years post-implantation up to 5 years post-enrollment
EM2.5: Dynamic Gait Index (DGI)
DGI comprises 8 gait tasks scored by an examiner: walking on a level surface, changing gait speed, walking during horizontal head turns, walking during vertical head turns, pivoting, stepping over an obstacle, stepping around obstacles, and waling up and down stairs. Each task is scored (0-3 points, 3 is best). Raw DGI score is the sum of the eight subtest scores and ranges from 0 to 24, with higher scores meaning better outcome and minimally important difference 3.2 points.
Time frame: 4 years post-implantation up to 5 years post-enrollment
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
During video head impulse testing (vHIT), rotational eye and head movement are measured by a goggle-mounted camera and motion sensor during brief, fast \~10 degree head rotations about the axis of a semicircular canal being tested. Performance is quantified by vestibulo-ocular reflex (VOR) gain, which a ratio of eye movement to head movement (in this case the integral of eye velocity relative to the head and the additive inverse of the integral of head velocity, respectively). VHITG, the average vHIT VOR gain for each of the three semicircular canals of the implanted ear, typically ranges from 0 to 1, with higher numbers indicating better performance.
Time frame: 4 years post-implantation up to 5 years post-enrollment
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.
Vestibular Implant Composite Outcome (VICO) score incorporates changes in vestibulo-ocular reflex gain during video head impulse testing, postural stability, gait, dizziness handicap, and health-related quality of life at 4 years post-implantation, relative to pre-operative baseline. VICO (t=6months post-op) score is the sum of changes, from preoperative baseline to 4 years post-implantation, in vestibulo-ocular reflex gain during passive head impulse rotation (VHITG); postural stability as quantified by the Bruininks-Oseretsky Test of Motor Proficiency, 2nd Edition Balance Subtest 5 (BOT); gait stability as quantified by Dynamic Gait Index (DGI); Dizziness Handicap Inventory (DHI); and SF6D health utility (SF6DU); with each component's contribution scaled to the corresponding test's minimally important difference (MID). Score 0-100, higher scores indicate better outcomes.
Time frame: 4 years post-implantation up to 5 years post-enrollment
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.
BOT includes 9 postural tasks scored by an examiner: standing with both feet on a line, standing on one leg, tandem walking, walking on a line with eyes open and eyes closed, and standing on a balance beam. Each task is performed twice and scored (0-4 points). The BOT score is the sum of the best scores for each task. It ranges from 0 to 36 points, with higher scores meaning better outcome and minimally important difference 4.5 points.
Time frame: 4 years post-implantation up to 5 years post-enrollment
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.
Dizziness Handicap Inventory (DHI) is a 25-question survey designed to quantify self-rated disability due to dizziness and unsteadiness, with scores ranging from 0 (least disabled, best outcome) to 100 (worst outcome). The minimally important difference is 18 points.
Time frame: 4 years post-implantation up to 5 years post-enrollment
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.
SF6DU is a unitless health utility score computed from patient-reported replies to the SF6 health-related quality of life survey and ranging from 0 to 1, with higher scores meaning better outcome and minimally important difference 0.03 points.
Time frame: 4 years post-implantation up to 5 years post-enrollment
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.
DGI comprises 8 gait tasks scored by an examiner: walking on a level surface, changing gait speed, walking during horizontal head turns, walking during vertical head turns, pivoting, stepping over an obstacle, stepping around obstacles, and waling up and down stairs. Each task is scored (0-3 points, 3 is best). Raw DGI score is the sum of the eight subtest scores and ranges from 0 to 24, with higher scores meaning better outcome and minimally important difference 3.2 points.
Time frame: 4 years post-implantation up to 5 years post-enrollment
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.
During video head impulse testing (vHIT), rotational eye and head movement are measured by a goggle-mounted camera and motion sensor during brief, fast \~10 degree head rotations about the axis of a semicircular canal being tested. Performance is quantified by vestibulo-ocular reflex (VOR) gain, which a ratio of eye movement to head movement (in this case the integral of eye velocity relative to the head and the additive inverse of the integral of head velocity, respectively). VHITG, the average vHIT VOR gain for each of the three semicircular canals of the implanted ear, typically ranges from 0 to 1, with higher numbers indicating better performance.
Time frame: 4 years post-implantation up to 5 years post-enrollment
SM0: Type, incidence and severity of unanticipated adverse device effects as of 4 years post-implantation
Assess safety of the intervention, aggregating data across all implanted participants (diversified across ototoxic and non-ototoxic/non-central adult-onset BVH), as determined by incidence of adverse device-related events from pre-intervention to 4 years post-implantation.
Time frame: 4 years post-implantation up to 5 years post-enrollment
SM1.1: implant-side bone-conduction 4-frequency (0.5, 1, 2, 4 kHz) pure tone average detection threshold (BonePTAi)
BonePTAi is the 4-frequency average of pure tone detection thresholds, in dBHL, for implant-side bone-conduction presentation of pure tones at 0.5, 1, 2 and 4 kHz. Range is -10 to 80 dBHL, with change toward smaller absolute values representing better (closer to normal) outcome.
Time frame: 4 years post-implantation up to 5 years post-enrollment
SM1.2: implant-side air-conduction 4-frequency pure tone average detection threshold (AirPTAi)
AirPTAi is the 4-frequency average of pure tone detection thresholds, in dBHL, for implant-side air-conduction presentation of pure tones at 0.5, 1, 2 and 4 kHz. Range is -10 to 120 dBHL, with change toward smaller absolute values representing better (closer to normal) outcome.
Time frame: 4 years post-implantation up to 5 years post-enrollment
SM1.3: implant-side consonant-nucleus-consonant word discrimination score (CNCWi)
CNCWi is the percentage of monosyllabic consonant-nucleus-consonant words correctly repeated when presented via an earphone speaker on the implanted side in a sound-isolation booth while a masking noise is played to the contralateral ear at 40 dB above its bone-conduction 4-frequency pure tone detection threshold if that threshold is at least 10 dB better than that of the ear being tested. CNCWi ranges from 0-100% correct, with higher score meaning better outcome.
Time frame: 4 years post-implantation up to 5 years post-enrollment
SM1.4: sound-field Arizona Biology (AzBios)27 sentences-in-noise discrimination score
AzBios is the percentage of words correctly repeated when a set of 20 Arizona Biology sentences (randomly chosen without repeats from 15 sets) is presented at a moderate level (60 dB SPL) along with masking noise (simultaneous presentation of ten sentences from another set at aggregate sound level 55 dBSPL) to both ears via a sound field speaker in a sound-isolation booth. Scores range from 0-100% correct, with higher score meaning better outcome.
Time frame: 4 years post-implantation up to 5 years post-enrollment
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
For ClassABCNCW, AAO-HNS (American Academy of Otolaryngology - Head \& Neck Surgery) 1995 Class A or B hearing is defined as AirPTAi not worse than 50 dBHL and CNCWi not worse than 50%. ClassABCNCW proportion ranges from 0-100%, with higher values meaning better outcomes.
Time frame: 4 years post-implantation up to 5 years post-enrollment
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
For ClassABAzBio, AAO-HNS (American Academy of Otolaryngology - Head \& Neck Surgery) 1995 Class A or B hearing is defined as AirPTAi not worse than 50 dBHL and sound-field-presentation Arizona Biology sentences-in-noise discrimination score (AzBios) not worse than 50%. ClassABAzBio proportion ranges from 0-100%, with higher values meaning better outcomes.
Time frame: 4 years post-implantation up to 5 years post-enrollment
SM1.7: implant-side distortion-product otoacoustic emissions
Distortion-product otoacoustic emissions (DPOAE) are sounds generated by a normal cochlea and detectable using a microphone in the ear canal when pairs of pure tones (centered on 0.75, 1, 1.5, 2, 3, 4, 6 and 8 kHz) are presented to the ear. DPOAE signals (and 8-valued vector for responses to stimuli centered on 0.75, 1, 1.5, 2, 3, 4, 6 and 8 kHz) are quantified in dB relative to the frequency-specific noise floor recorded by the same microphone before onset of stimulation. Response range is 0-15 dB, with higher values meaning better outcome.
Time frame: 4 years post-implantation up to 5 years post-enrollment
SM1.8: Ear canal acoustic admittance as assessed by implant-side tympanometry
Tympanometry involves using an ear canal microphone to measure ear canal acoustic admittance (conventionally reported in units of mL) and volume (in mL) by sensing reflection of a 226 Hz tone presented via a speaker in the ear canal while ear canal pressure is slowly varied from -400 to 200 decaPascals. Negative bias pressures pull the ear drum outward, positive bias pressures push the ear drum inward, and acoustic admittance is greatest when the ear drum is in a neutral anatomic position, neither retracted inward nor ballooned outward. Results are conventionally represented graphically then summarized by a three-valued vector comprising peak compliance (range 0-2 milliliters (mL), values closer to normal range of 0.3-1.4 mL meaning more normal outcome), pressure at which compliance peaks (range -400 to 200 decaPascal, values closer to 0 meaning more normal outcome), and ear canal volume (range 0-3 mL, values closer to normal adult range of 0.6-1.4 meaning more normal outcome).
Time frame: 4 years post-implantation up to 5 years post-enrollment
SM1.9: Tinnitus Handicap Inventory (THI)
The Tinnitus Handicap Inventory (THI) survey is set of questions designed to quantify self-perceived handicap due to tinnitus. THI score ranges from 0-100. Higher scores mean worse outcome.
Time frame: 4 years post-implantation up to 5 years post-enrollment
SM1.10: Autophony Index (AI)
The Autophony Index (AI) survey is set of questions designed to quantify self-perceived autophony (hearing one's voice or other internally-generated body sounds). AI score ranges from 0-104. Higher scores mean worse outcomes.
Time frame: 4 years post-implantation up to 5 years post-enrollment
SM1.11: cervical vestibular-evoked myogenic potential (cVEMP) response amplitude
Cervical vestibular-evoked myogenic potentials (cVEMPs) are a measure of saccule-mediated inhibition of sternocleidomastoid muscle electromyographic (EMG) activity during presentation of loud tones to the ipsilateral ear. After normalizing to average rectified EMG activity (in microvolts) prior to sound stimulation, cVEMP amplitudes (in microvolts) are unitless. Values range from 0 to \~10, with larger values suggesting increased saccule activity and generally indicating better outcomes, except that values above 3.0 suggest abnormally high saccule sensitivity to sound.
Time frame: 4 years post-implantation up to 5 years post-enrollment
SM1.12: ocular vestibular-evoked myogenic potential (oVEMP) response amplitude
Ocular vestibular-evoked myogenic potentials (oVEMPs) are a measure of utricle-mediated electromyographic (EMG) activity of inferior oblique and inferior rectus extraocular muscles during presentation of loud tones to the contralateral ear. Amplitude ranges from 0 to \~50 microvolts, with larger values generally suggesting increased utricle activity and better outcomes but values above 17 microvolts suggesting abnormally high utricle sensitivity to sound.
Time frame: 4 years post-implantation up to 5 years post-enrollment
SM1.13: subjective visual vertical (SVV) as assessed using the Bucket Test
A participant's vision is occluded by a bucket oriented so that its axis aligns with the participant's nasooccipital axis. The examiner rotates the bucket about the axis to a new orientation, the participant reorients it until a line drawn on the floor of the bucket is judges by the participant to be Earth-vertical and deviation of that line from true vertical is recorded. Values range over -15 to 15 degrees, with smaller absolute values meaning more normal outcomes.
Time frame: 4 years post-implantation up to 5 years post-enrollment
SM1.14: scalp thickness at the location of implanted magnets (Tscalp)
Scalp thickness at the location of implanted magnets (Tscalp) is measured in mm using a magnetic sensor. Range is 0 to 10 mm, with values closer to the range 3-7mm indicating better outcomes.
Time frame: 4 years post-implantation up to 5 years post-enrollment
SM1.15: all adverse events, including but not limited to events related to the surgical procedure, device and device systems
Assess safety of the intervention, aggregating data across all implanted participants (diversified across ototoxic and non-ototoxic/non-central adult-onset BVH), as determined by changes in hearing and otolith endorgan function indicated by changes in all adverse events, including but not limited to events related to the surgical procedure, device and device systems.
Time frame: 4 years post-implantation up to 5 years post-enrollment
TM1: Proportion of all implanted participants who continue to use the MVI system daily at 4 years post-implantation
Assess tolerance of the intervention, aggregating data across all implanted participants, as determined by the proportion of all implant recipients who continue to use the MVI system daily at 4 years post-implantation.
Time frame: 4 years post-implantation up to 5 years post-enrollment
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
Assess tolerance of the intervention, for the subgroup of participants who have non-ototoxic/non-central adult-onset BVH, as determined by the 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.
Time frame: 4 years post-implantation up to 5 years post-enrollment
TM3: Proportion of implanted participants with ototoxic adult-onset BVH who continue to use the MVI system daily at 4 years post-implantation
Assess tolerance of the intervention, for the subgroup of participants who have ototoxic adult-onset BVH, as determined by the proportion of implanted participants with ototoxic adult-onset BVH who continue to use the MVI system daily at 4 years post-implantation.
Time frame: 4 years post-implantation up to 5 years post-enrollment
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