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

N/AActive Not RecruitingNCT04918745

Maastricht University Medical Center13 enrolled

Overview

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 firstly make use of this combined stimulation during 3 weeks of prolonged use under direct supervision in a hospital environment. Following this, participants will make use of combined stimulation in a real-life environment (e.g., outside of the hospital setting) for 15 months under indirect supervision. 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.

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 first be assessed using a research processor during 3 weeks (3x4 days, +- 8 hours a day) of prolonged stimulation under direct supervision in the safety of a hospital environment. This is considered the in-hospital part. Following this, a modified research processor will be used during 15 months (13 visits, half and full day) of prolonged stimulation in real-life situations under indirect supervision. This is considered the home-use part of the trial. During the in-hospital part, 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. During the home-use part, the efficacy and safety of prolonged VI stimulation will be evaluated in a home environment using pre-post intervention evaluation. During this part, the stimulation status will alternate between VI-ON and VI-OFF, depending on the phase. The stimulation algorithm will be optimized per patients to best evaluate VI efficacy (optimization phase). Furthermore, safety and efficacy will be further elucidated by maintaining consistent prolonged VI stimulation (persistency phase), using a consistent algorithm with minimal adjustments. Following this, a resting period of at least four weeks (washout phase) will commence, where no VI stimulation will be used. This will allow for comparison between vestibular stimulation (VI-ON) versus without stimulation (VI-OFF), which aligns with the primary comparison used during the in-hospital period. In addition, this phase aims to minimize carry-over effect, ensure adequate resolution of aftereffects and evaluation of changes to quality of life. Finally, evaluation of single blinded preference between stimulation statuses will be assessed (preference phase). Patients will have the option to continue using vestibular stimulation after the preference phase for as long as the trial continues (resume phase). Alongside the periods 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.

Interventions

Cochlear Vestibular Implant (CVI)DEVICE

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. During the in-hospital part, 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 During the home-use part, a preference phase will be included to assess the effects of a "control". Participants will receive two research processors, each with a different vestibular stimulation mode. These modes will be randomized over a 4-week period, each appearing twice (2 treatments appearing twice each x 4 weeks = 6 arms). These stimulation modes are: * 1 - individualized vestibular stimulation * 2 - control vestibular stimulation

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion criteria: 1. Chronic vestibular syndrome being presented by disabling symptoms of postural imbalance and/or impaired image stabilization (e.g. oscillopsia) 2. 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) 3. Onset of bilateral vestibular loss after the age of 2 4. Vestibular dysfunction from a peripheral origin or idiopathic BV 5. Patent vestibular end-organ (judged by CT) 6. 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 7. Meeting CI-candidacy in ear to implant with CVI 8. Agreed to receive a MED-EL CVI implant with MED-EL sound processor 9. Capacitated adults ≥ 18 years 10. Proficient speaker of the Dutch language 11. No contra-indications for CVI surgery 12. 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 13. 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: 1. Signs of central vestibular/cochlear dysfunction or structural vestibular/cochlear nerve pathology (judged by physical examination / MRI) 2. Clear signs of structural nerve pathology or indications of improperly functioning vestibular/cochlear nerves 3. Requirement for electric-acoustic activation of the CI part (e.g. "hybrid" processor) prior to completion of the prolonged VI stimulation period 4. Having received a cochlear implant earlier on the side to implant (e.g. explantation/reimplantation) 5. Having received a cochlear implant from another brand than MED-EL in the other ear (bilateral implantation with different brands is not supported) 6. 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. 7. Pre-lingual onset of bilateral profound deafness (\< 4 years of age) 8. Active participation in another prospective clinical trial 9. Pregnancy or having plans to become pregnant at the time of imaging or during the VI trial 10. Orthopedic, ocular, neurologic or other non-vestibular pathologic conditions of sufficient severity to confound vestibular function tests used in the study 11. Current psychological or psychiatric disorders that could significantly interfere with the use or evaluation of VI stimulation 12. Physical or non-physical contraindications for MRI or CT imaging prior to surgery 13. Making chronic use of psychiatric medication which suppresses VOR responses (e.g. SSRI's, benzodiazepines) 14. Significant dental problems which prohibit the stable use of a 'bite bar' (used as calibration reference for the gyroscope functionality of the CVI) 15. Any medical condition, judged by the research team, that is likely to interfere with a study candidate's participation in the study

Outcomes

Primary Outcomes

Safety of vestibular stimulation via the CVI

Amount of (S)AE's after implantation to determine safety of the device

Time frame: 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 vestibular stimulation will be evaluated through the in-hospital and home-use parts.

Time frame: Through all stimulation periods, within 5 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.