VertiGO! - Get up and GO! With the Vestibular Implant

Study Overview
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Brief Summary
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In the VertiGO! trial 13 participants with bilateral vestibulopathy (BV) and severe sensory neural hearing loss in the ear to be implanted will receive a combined cochlear (CI) and vestibular implant (VI), capable of stimulating both the cochlear and vestibular nerves (CVI). The participants will make use of this combined stimulation during 3 weeks of prolonged use under supervision in a hospital environment. This trial will serve as a proof-of-concept for restoring vestibular function in patients with BV, an as-of-yet untreatable disorder causing severe impairment and discomfort. The aims of this trial are to investigate efficacy and safety of prolonged vestibular stimulation, to identify the influence of different stimulation algorithms, to assess the feasibility of the combined VI/CI device, to develop a VI rehabilitation program and to further build on the fundamental knowledge of vestibular organ stimulation while also taking into account the patient perspective.

Detailed Description
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The vestibular sensory organ is essential for balance and image stabilization. Patients with severe function loss of both vestibular organs present themselves with serious day-to-day disabilities such as strong balance disturbances, higher risk of falling, visual symptoms (oscillopsia) and a loss of autonomy. Up until now no effective treatment is available for these patients to restore vestibular function. In the past years experimental electric stimulation of the vestibular nerve in humans by means of a VI has shown to be able to partly restore balance and gaze functionality in test situations. To evaluate combined prolonged stimulation of both the vestibular organ and the cochlea, participants will be implanted with a CVI. This modified CI also consists of 3 vestibular electrodes, each placed in individual electrode leads for insertion into the three semicircular canals. Therefore the CVI is capable of stimulating both the cochlear and vestibular nerves. Hearing rehabilitation with the CI part of the device will follow the standard clinical protocol, with the participant using a standard CI processor. Functionality of prolonged combined vestibular and cochlear stimulation will be assessed using a research processor during 3 weeks (3x4 days, +- 8 hours a day) of prolonged stimulation under supervision in the safety of a hospital environment. During each identical period of 4 days a different stimulation algorithm will be used for vestibular stimulation, with the order being randomized and single-blinded. The stimulation algorithms which will be used are (1) baseline stimulation without motion modulation, (2) baseline stimulation with motion modulation, and (3) reduced baseline stimulation with motion modulation. Alongside the 3 weeks of prolonged stimulation, the participant will make yearly visits to our clinic up to 5 years after implantation for evaluation of long-term response to acute vestibular stimulation and general CI performance.

Official Title
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VertiGO! - Get up and GO! With the Vestibular Implant

Conditions
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Bilateral Vestibular Loss

Intervention / Treatment
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* Device: Cochlear Vestibular Implant (CVI)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Chronic vestibular syndrome being presented by disabling symptoms of postural imbalance and/or impaired image stabilization (e.g. oscillopsia) Reduced or absent bilateral VOR function based on at least one of the tests below meeting criteria A, with the other tests meeting criteria B: Criteria A: Caloric response: Each side ≤6°/sec, vHIT gain: Bilateral horizontal SCC ≤ 0.6 AND Bilateral vertical SCC <0.7, Rotatory chair gain: ≤ 0.1 (0.1 Hz) Criteria B: Caloric response: Each side <10°/sec, vHIT gain: 2 Bilateral SCC <0.7, Rotatory chair gain: ≤ 0.2 (0.1 Hz) Onset of bilateral vestibular loss after the age of 2 Vestibular dysfunction from a peripheral origin or idiopathic BV Patent vestibular end-organ (judged by CT) Vestibular function and symptoms have not recovered beyond inclusion criteria within 6 months from onset of symptoms including a 3 month rehabilitation program off vestibular suppressant medications Meeting CI-candidacy in ear to implant with CVI Agreed to receive a MED-EL CVI implant with MED-EL sound processor Capacitated adults ≥ 18 years Proficient speaker of the Dutch language No contra-indications for CVI surgery Active participation in the trial related procedures such as regular testing, the VI fitting period, the baseline testing day and three weeks of intensive VI rehabilitation and testing in the study center (MUMC+) including an exercise regimen Agreed 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 period of VI activation and until at least 1 day after VI deactivation Remark: Patients who qualify to receive a regular CI as part of standard clinical care will have a preferential position to be included in the trial. Exclusion Criteria: Signs of central vestibular/cochlear dysfunction or structural vestibular/cochlear nerve pathology (judged by physical examination / MRI) Clear signs of structural nerve pathology or indications of improperly functioning vestibular/cochlear nerves Requirement for electric-acoustic activation of the CI part (e.g. hybrid processor) prior to completion of the prolonged VI stimulation period Having received a cochlear implant earlier on the side to implant (e.g. explantation/reimplantation) Having received a cochlear implant from another brand than MED-EL in the other ear (bilateral implantation with different brands is not supported) Unwillingness to stop the use of antihistamines which might suppress VOR responses (e.g. cinnarizine) in the period of 1 month before until after each measurement point. Pre-lingual onset of bilateral profound deafness (< 4 years of age) Active participation in another prospective clinical trial Pregnancy or having plans to become pregnant at the time of imaging or during the VI trial Orthopedic, ocular, neurologic or other non-vestibular pathologic conditions of sufficient severity to confound vestibular function tests used in the study Current psychological or psychiatric disorders that could significantly interfere with the use or evaluation of VI stimulation Physical or non-physical contraindications for MRI or CT imaging prior to surgery Making chronic use of psychiatric medication which suppresses VOR responses (e.g. SSRI's, benzodiazepines) Significant dental problems which prohibit the stable use of a 'bite bar' (used as calibration reference for the gyroscope functionality of the CVI) Any medical condition, judged by the research team, that is likely to interfere with a study candidate's participation in the study

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Controlled clinical trial with a randomized single-blind 3-treatment 3-period crossover design
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: ABC<br>A = Baseline stimulation, no modulation B = Baseline stimulation, modulation stimulation C = Reduced baseline stimulation, modulation stimulation | Device: Cochlear Vestibular Implant (CVI)<br>* The Cochlear Vestibular Implant (CVI) is a modified cochlear implant (CI) which also incorporates a vestibular component (VI) in order to restore both hearing and vestibular function. Three vestibular stimulation algorithms will be compared in a randomized order (3 treatments x 3 periods, = 6 arms). These stimulation algorithms are: A - Baseline stimulation, no modulation stimulation B - Baseline stimulation, modulated stimulation C - Reduced baseline stimulation, modulated stimulation<br>|
| Other: ACB<br>A = Baseline stimulation, no modulation C = Reduced baseline stimulation, modulation stimulation B = Baseline stimulation, modulation stimulation | Device: Cochlear Vestibular Implant (CVI)<br>* The Cochlear Vestibular Implant (CVI) is a modified cochlear implant (CI) which also incorporates a vestibular component (VI) in order to restore both hearing and vestibular function. Three vestibular stimulation algorithms will be compared in a randomized order (3 treatments x 3 periods, = 6 arms). These stimulation algorithms are: A - Baseline stimulation, no modulation stimulation B - Baseline stimulation, modulated stimulation C - Reduced baseline stimulation, modulated stimulation<br>|
| Other: BAC<br>B = Baseline stimulation, modulation stimulation A = Baseline stimulation, no modulation C = Reduced baseline stimulation, modulation stimulation | Device: Cochlear Vestibular Implant (CVI)<br>* The Cochlear Vestibular Implant (CVI) is a modified cochlear implant (CI) which also incorporates a vestibular component (VI) in order to restore both hearing and vestibular function. Three vestibular stimulation algorithms will be compared in a randomized order (3 treatments x 3 periods, = 6 arms). These stimulation algorithms are: A - Baseline stimulation, no modulation stimulation B - Baseline stimulation, modulated stimulation C - Reduced baseline stimulation, modulated stimulation<br>|
| Other: BCA<br>B = Baseline stimulation, modulation stimulation C = Reduced baseline stimulation, modulation stimulation A = Baseline stimulation, no modulation | Device: Cochlear Vestibular Implant (CVI)<br>* The Cochlear Vestibular Implant (CVI) is a modified cochlear implant (CI) which also incorporates a vestibular component (VI) in order to restore both hearing and vestibular function. Three vestibular stimulation algorithms will be compared in a randomized order (3 treatments x 3 periods, = 6 arms). These stimulation algorithms are: A - Baseline stimulation, no modulation stimulation B - Baseline stimulation, modulated stimulation C - Reduced baseline stimulation, modulated stimulation<br>|
| Other: CAB<br>C = Reduced baseline stimulation, modulation stimulation A = Baseline stimulation, no modulation B = Baseline stimulation, modulation stimulation | Device: Cochlear Vestibular Implant (CVI)<br>* The Cochlear Vestibular Implant (CVI) is a modified cochlear implant (CI) which also incorporates a vestibular component (VI) in order to restore both hearing and vestibular function. Three vestibular stimulation algorithms will be compared in a randomized order (3 treatments x 3 periods, = 6 arms). These stimulation algorithms are: A - Baseline stimulation, no modulation stimulation B - Baseline stimulation, modulated stimulation C - Reduced baseline stimulation, modulated stimulation<br>|
| Other: CBA<br>C = Reduced baseline stimulation, modulation stimulation B = Baseline stimulation, modulation stimulation A = Baseline stimulation, no modulation | Device: Cochlear Vestibular Implant (CVI)<br>* The Cochlear Vestibular Implant (CVI) is a modified cochlear implant (CI) which also incorporates a vestibular component (VI) in order to restore both hearing and vestibular function. Three vestibular stimulation algorithms will be compared in a randomized order (3 treatments x 3 periods, = 6 arms). These stimulation algorithms are: A - Baseline stimulation, no modulation stimulation B - Baseline stimulation, modulated stimulation C - Reduced baseline stimulation, modulated stimulation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of vestibular stimulation via the CVI | Amount of (S)AE's after implantation to determine safety of the device | Through full trial period, up to 5 years postoperatively | 
| The feasibility of vestibular stimulation improving Dynamic Visual Acuity during walking | Quantifying vestibulo-ocular reflex restoration on a functional level by evaluating the capacity of vestibular stimulation (via the CVI) to improve dynamic visual acuity while walking. Adaptation to stimulation will be evaluated through each 4-day stimulation period with each stimulation algorithm being evaluated separately. | Through each 4-day VI stimulation period, within 2 years after implantation | 
| The feasibility of vestibular stimulation improving Dynamic Visual Acuity during passive head movements | Quantifying vestibulo-ocular reflex restoration on a functional level by evaluating the capacity of vestibular stimulation (via the CVI) to improve dynamic visual acuity during fast passive head movements measured with the functional Head Impulse Test. Adaptation to stimulation will be evaluated through each 4-day stimulation period with each stimulation algorithm being evaluated separately. | Through each 4-day VI stimulation period, within 2 years after implantation | 
| The feasibility of vestibular stimulation restoring the high-frequency vestibulo-ocular reflex | Evaluating the capacity of vestibular stimulation (via the CVI) to increase vestibulo-ocular reflex gain during fast passive head movements in the LHRH, RALP and LARP planes measured with the video Head Impulse Test. Adaptation to stimulation will be evaluated through each 4-day stimulation period with each stimulation algorithm being evaluated separately. | Through each 4-day VI stimulation period, within 2 years after implantation | 
| The feasibility of vestibular stimulation restoring the low-frequency vestibulo-ocular reflex | Evaluating the capacity of vestibular stimulation (via the CVI) to increase vestibulo-ocular reflex gain during slow, passive, full body rotations measured with the Torsion Swing test. Adaptation to stimulation will be evaluated through each 4-day stimulation period with each stimulation algorithm being evaluated separately. | Through each 4-day VI stimulation period, within 2 years after implantation | 
| The feasibility of vestibular stimulation improving the self-movement perception in dark | Evaluating whether vestibular stimulation (via the CVI) can improve self-motion perception measured by controlled motion stimuli delivered by a moving platform. Adaptation to stimulation will be evaluated through each 4-day stimulation period with each stimulation algorithm being evaluated separately. | Through each 4-day VI stimulation period, within 2 years after implantation | 
| The feasibility of vestibular stimulation improving gait stability and balance based on motion capture data | Evaluating the influence of vestibular stimulation (via the CVI) on walking patterns and stability based on motion capture data. Adaptation to stimulation will be evaluated through each 4-day stimulation period with each stimulation algorithm being evaluated separately. | Through each 4-day VI stimulation period, within 2 years after implantation | 
| The feasibility of vestibular stimulation improving balance based on clinical evaluation | Clinical evaluation of the influence of vestibular stimulation (via the CVI) on balance measured with the MiniBESTest. Adaptation to stimulation will be evaluated through each 4-day stimulation period with each stimulation algorithm being evaluated separately. | Through each 4-day VI stimulation period, within 2 years after implantation | 
| Speech perception with CVI in quiet without simultaneous vestibular stimulation | Evaluating hearing performance with the CVI based on speech perception in quiet measured with an aided consonant-nucleus-consonant word test, without simultaneous vestibular stimulation | Through the full trial period, until 5 years after implantation | 
| Interaction between vestibular and cochlear stimulation on speech perception in quiet | Evaluating hearing performance with the CVI based on speech perception in quiet while simultaneously providing vestibular stimulation, measured with an aided consonant-nucleus-consonant word test. The influence of each vestibular stimulation algorithm will be evaluated separately. | Through each 4-day VI stimulation period, within 2 years after implantation | 
| Speech perception with CVI in noise without simultaneous vestibular stimulation | Evaluating hearing performance with the CVI based on speech perception in noise measured with a sentence speech In noise test, without simultaneous vestibular stimulation | Through the full trial period, until 5 years after implantation | 
| Change in otolith function due to CVI implantation | Evaluating the influence of CVI implantation on otolith function based on cVEMP and oVEMP responses post-operatively, comparing with the pre-operative situation. | preoperatively and 1 month postoperatively | 
| Vestibular and cochlear electrode location | Evaluating the location and potential migration of the vestibular and cochlear electrodes of the CVI with cone-beam CT scans- of the mastoid. | Through the full trial period, until 5 years after implantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterization of study population on perceived dizziness | Characterizing the study population based on their perceived dizziness and the related handicap measured with the Dizziness Handicap Inventory. | Measured pre-operatively and directly before the start of the VI stimulation period | 
| Characterization of study population on perceived risk of falling | Characterizing the study population based on their perceived risk of falling measured with the Falls Efficacy Scale-International | Measured pre-operatively and directly before the start of the VI stimulation period | 
| Characterization of study population on perceived severity of oscillopsia | Characterizing the study population based on their perceived severity of oscillopsia measured with the Oscillopsia Severity Questionnaire | Measured pre-operatively and directly before the start of the VI stimulation period | 
| Subjective hearing performance of the CVI | Evaluating the subjective hearing performance of the CVI measured with the Speech and Spatial Qualities of hearing scale-12 | Yearly evaluation through the full trial period, until 5 years after implantation | 
| Effect of CVI implantation on tinnitus burden | Evaluating the influence of CVI implantation on the subjective severity and burden of tinnitus measured with the Tinnitus Questionnaire | Pre-operatively and 1 month postoperatively | 
| Characterization of study population on perceived health-related quality of life | Characterizing the study population based on their perceived health-related quality of life measured with the Health Utility Index - 3 | Measured pre-operatively and directly before the start of the VI stimulation period | 
| Evaluating the influence of receiving and using a CVI on quality of life | Evaluating the influence of the different stages of receiving and using a CVI on quality of life measured with the EuroQOL 5 Dimensional questionnaire. Aimed at separating CI-only use and full CVI use throughout the trial to get an accurate assessment of the influence vestibulo-cochlear electrical stimulation (via the CVI) can have on quality of life | Through the full trial period, until 5 years after implantation | 
| Evaluating the influence of receiving and using a CVI on capabilities in life | Evaluating the influence of the different stages of receiving and using a CVI on capabilities in life measured with the ICEPOP Capability measure for adults. Aimed at separating CI-only use and full CVI use throughout the trial to get an accurate assessment of the influence vestibulo-cochlear electrical stimulation (via the CVI) can have on quality of life. | Through the full trial period, until 5 years after implantation | 
| Evaluating the influence of receiving and using a CVI on anxiety and depression | Evaluating the influence of the different stages of receiving and using a CVI on anxiety and depression measured with the Hospital Anxiety and Depression Scale. Aimed at separating CI-only use and full CVI use throughout the trial to get an accurate assessment of the influence vestibulo-cochlear electrical stimulation (via the CVI) can have on these aspects. | Through the full trial period, until 5 years after implantation | 
| Evaluating the daily experience with vestibular stimulation | A self-developed visual-analog scale-based list of questions for evaluating the participant's experience with the CVI on a daily basis during the prolonged stimulation period. | Through each 4-day VI stimulation period, within 2 years after implantation | 
| Characterizing the participant's experience with vestibular stimulation | Semi-standardized interviews for in-depth qualitative analysis of the participant's experience with receiving vestibular stimulation (via the CVI) | Through each 4-day VI stimulation period, within 2 years after implantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vestibular Implant, Cochlear vestibular implant, Bilateral vestibulopathy, Bilateral vestibular hypofunction, Bilateral vestibular loss, Cochlear implant