VertiGO! - Get up and GO! with the vestibular implant

The vestibular sensory organ is essential for balance and image stabilization.
It drives the eyes to keep the image of the environment stable. Severe function
loss of both vestibular organs is referred to as bilateral vestibulopathy (BV).
Patients with BV 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. It has been conservatively estimated that
more than 200.000 people in Europe and 2.1 million people worldwide are
affected. Up until now no effective treatment is available for these patients.
In the past years experimental electric stimulation of the vestibular nerve in
humans by means of a vestibular implant (VI) has shown to be able to partly
restore balance and gaze functionality in test situations. After showing
feasibility of vestibular stimulation in humans in previous trials
(NL36777.068.11, NL31405.068.10), the current step in this trial will be to
show that prolonged daily stimulation is effective and safe.

The primary objective of the VertiGO! trial is to assess the feasibility of
restoring vestibular function by making use of prolonged VI stimulation. This
will be done using a combined VI and CI device: The CVI. To achieve this
objective, patients will use the wearable CVI device during three weeks within
the safety of a hospital environment. This trial will serve as a
proof-of-concept for restoring functional, long-term vestibular function to
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,
and to further build on the fundamental knowledge of vestibular organ
stimulation while also taking into account the patient perspective.

1. Primary
a. To investigate the efficacy of prolonged daily VI stimulation
b. To investigate the safety of prolonged daily VI stimulation
c. To investigate the efficacy of three different types of stimulation:
baseline stimulation without motion modulation, baseline stimulation with
motion modulation, reduced baseline stimulation with motion modulation

2. Secondary
a. To develop a rehabilitation program for VI recipients
b. To evaluate the interaction between vestibular and cochlear nerve stimulation
c. To evaluate acute VI performance across several years

Controlled clinical trial with a randomized single-blind cross-over design

To evaluate combined prolonged stimulation of both the vestibular organ and the
cochlea, subjects will be implanted with the cochlear-vestibular implant (CVI).
This extended CI also incorporates a vestibular component (VI) in order to
restore both hearing and vestibular function. Once the prosthesis is implanted,
the patient will pay scheduled visits to our clinic. Hearing rehabilitation
with the CI will follow the standard clinical protocol. Evaluation of the VI
functionality will include a CBCT scan 1 week post-op, 1 hour extra testing at
the end of the CI rehabilitation period, a VI fitting period (4 days), a day of
baseline testing, 3 periods of 4 days prolonged VI stimulation and tests
conducted during regular CI follow-up visits until 5 years after implantation,
including 3 CBCT scans (12 hours extra during standard visits). An overview of
the trial schedule is given in figure 1 of the reasearch protocol. More
detailed overviews can be found in chapter 3 of the research protocol. During
the fitting period and the prolonged stimulation period the patients will be
staying in a hotel next to the hospital. During the prolonged stimulation
period, subjects will follow a vestibular rehabilitation program and the
outcomes will be evaluated using a set of vestibular tests (including
video-oculography (VOG), perception tests and test of gait), auditory tests,
semi-structured qualitative interviews and questionnaires.

The main burden associated with participation is significant time investment.
Patients will undergo both CI inclusion testing (2 visits) and VI inclusion
testing (1 visit) and be admitted for surgery (2 days). After surgery, patients
will visit the hospital for the regular CI visits and for trial-specific
visits. The trial specific visits include a VI fitting period (4 days),
baseline testing (1 day) and the prolonged stimulation period (3*4 days).
During a number of the regular CI visits extra tests will be conducted
specifically for the trial (see table 1, chapter 4 of the research protocol).
During the fitting period and the prolonged stimulation period, patients will
be staying in a hotel next to the hospital to reduce the burden of travel on
the patients. During the visits, rehabilitation exercises, vestibular tests,
hearing tests and interviews will be executed. All of these activities are
associated with a low physical and psychological burden. Personal limits of
patients will explicitly be taken into account.
The most substantial risks involved with receiving a CVI is damage to the
neural structures within the cochlea and the vestibular system. Therefore, we
apply stringent inclusion criteria and will only implant patients with
disabling symptoms of BV and severe SNHL in the ear to be implanted, to
minimize the amount of potential damage that can be done. Alongside this,
outside of the research setting, the CVI implant will function as a regular CI,
restoring hearing in the ear to be implanted and compensating for the loss in
natural hearing potentially occurring by inserting the electrodes into the
inner ear. Other risks associated with implantation of the CVI are estimated to
be minimal based on previous CVI implantations performed in our clinic
(NL36777.068.11, NL31405.068.10) and similar to risks associated with
implanting and using a regular CI.
Risks of vestibular stimulation via the CVI include dizziness, nausea and a
risk of falling. The risks of dizziness and nausea will most likely subside as
the patient gets more used to vestibular stimulation, and can always be negated
by stopping the vestibular stimulation. The risk of falling, alongside any
unforeseen risks, are minimalized by taking care and time to let the patient
get used to vestibular stimulation and by only applying vestibular stimulation
while the patient is in the hospital under supervision by a member of the
research team. While the patient receives vestibular stimulation via the CVI,
the performance of the CI-part of the implant might be reduced.
The benefit for the patient is that via the CI functionality of the CVI their
hearing will most likely improve, analogous to a regular CI. The VI
functionality of the CVI can only be used within a research setting, and will
therefore not result in a direct patient benefit outside off trial related
activities under supervision in the hospital.
Concerning group relatedness, BV represents a major handicap with strong
balance disturbances, higher risk of falling, visual symptoms (oscillopsia) and
a loss of autonomy. There is no therapeutic strategy at the moment.
Development of a vestibular prosthesis could help this group of patients to
have a better quality of life. With this study we hope to answer crucial
research questions (see chapter 1.4 of the research protocol) and bring
essential knowledge towards the development and refining of a vestibular
prosthesis. This trial is part of a larger plan to develop the concept of a VI
which can be adopted into clinics. As described in chapter 1.4, substantial
research has been conducted with VI stimulation in the past. This trial serves
as the next step in this process. If this trial succeeds in proving the safety
and efficacy of prolonged vestibular stimulation, future trials with a larger
patient cohort are in the pipeline to build on the knowledge gathered in this
trial.