Clinical trial NCT04918745: VertiGO! - Get up and GO! With the Vestibular Implant
Official title: VertiGO! - Get up and GO! With the Vestibular Implant
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Bilateral Vestibular Loss
Keywords: Vestibular Implant
Cochlear vestibular implant
Bilateral vestibulopathy
Bilateral vestibular hypofunction
Bilateral vestibular loss
Cochlear implant
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: University Hospital, Geneva
name: MED-EL Elektromedizinische Geräte GesmbH
name: Health Holland
name: Heinsius-Houbolt Fund
name: Radboud University Medical Center
First posted: 2021-06-09
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Controlled clinical trial with a randomized single-blind 3-treatment 3-period crossover design
Primary purpose: DEVICE_FEASIBILITY

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety of vestibular stimulation via the CVI
timeFrame: Through full trial period, up to 5 years postoperatively
measure: The feasibility of vestibular stimulation improving Dynamic Visual Acuity during walking
timeFrame: Through each 4-day VI stimulation period, within 2 years after implantation
measure: The feasibility of vestibular stimulation improving Dynamic Visual Acuity during passive head movements
timeFrame: Through each 4-day VI stimulation period, within 2 years after implantation
measure: The feasibility of vestibular stimulation restoring the high-frequency vestibulo-ocular reflex
timeFrame: Through each 4-day VI stimulation period, within 2 years after implantation
measure: The feasibility of vestibular stimulation restoring the low-frequency vestibulo-ocular reflex
timeFrame: Through each 4-day VI stimulation period, within 2 years after implantation
measure: The feasibility of vestibular stimulation improving the self-movement perception in dark
timeFrame: Through each 4-day VI stimulation period, within 2 years after implantation
measure: The feasibility of vestibular stimulation improving gait stability and balance based on motion capture data
timeFrame: Through each 4-day VI stimulation period, within 2 years after implantation
measure: The feasibility of vestibular stimulation improving balance based on clinical evaluation
timeFrame: Through each 4-day VI stimulation period, within 2 years after implantation
measure: Speech perception with CVI in quiet without simultaneous vestibular stimulation
timeFrame: Through the full trial period, until 5 years after implantation
measure: Interaction between vestibular and cochlear stimulation on speech perception in quiet
timeFrame: Through each 4-day VI stimulation period, within 2 years after implantation
measure: Speech perception with CVI in noise without simultaneous vestibular stimulation
timeFrame: Through the full trial period, until 5 years after implantation
measure: Change in otolith function due to CVI implantation
timeFrame: preoperatively and 1 month postoperatively
measure: Vestibular and cochlear electrode location
timeFrame: Through the full trial period, until 5 years after implantation
Secondary outcomes:
measure: Characterization of study population on perceived dizziness
timeFrame: Measured pre-operatively and directly before the start of the VI stimulation period
measure: Characterization of study population on perceived risk of falling
timeFrame: Measured pre-operatively and directly before the start of the VI stimulation period
measure: Characterization of study population on perceived severity of oscillopsia
timeFrame: Measured pre-operatively and directly before the start of the VI stimulation period
measure: Subjective hearing performance of the CVI
timeFrame: Yearly evaluation through the full trial period, until 5 years after implantation
measure: Effect of CVI implantation on tinnitus burden
timeFrame: Pre-operatively and 1 month postoperatively
measure: Characterization of study population on perceived health-related quality of life
timeFrame: Measured pre-operatively and directly before the start of the VI stimulation period
measure: Evaluating the influence of receiving and using a CVI on quality of life
timeFrame: Through the full trial period, until 5 years after implantation
measure: Evaluating the influence of receiving and using a CVI on capabilities in life
timeFrame: Through the full trial period, until 5 years after implantation
measure: Evaluating the influence of receiving and using a CVI on anxiety and depression
timeFrame: Through the full trial period, until 5 years after implantation
measure: Evaluating the daily experience with vestibular stimulation
timeFrame: Through each 4-day VI stimulation period, within 2 years after implantation
measure: Characterizing the participant's experience with vestibular stimulation
timeFrame: Through each 4-day VI stimulation period, within 2 years after implantation
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht UMC+
state: Limburg
Study officials:
affiliation: Maastricht UMC
name: Raymond van de Berg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wall C 3rd, Kos MI, Guyot JP. Eye movements in response to electric stimulation of the human posterior ampullary nerve. Ann Otol Rhinol Laryngol. 2007 May;116(5):369-74. doi: 10.1177/000348940711600509.
citation: van de Berg R, Guinand N, Stokroos RJ, Guyot JP, Kingma H. The vestibular implant: quo vadis? Front Neurol. 2011 Aug 11;2:47. doi: 10.3389/fneur.2011.00047. eCollection 2011.
citation: Guyot JP, Sigrist A, Pelizzone M, Kos MI. Adaptation to steady-state electrical stimulation of the vestibular system in humans. Ann Otol Rhinol Laryngol. 2011 Mar;120(3):143-9. doi: 10.1177/000348941112000301.
citation: van de Berg R, Guinand N, Guyot JP, Kingma H, Stokroos RJ. The modified ampullar approach for vestibular implant surgery: feasibility and its first application in a human with a long-term vestibular loss. Front Neurol. 2012 Feb 20;3:18. doi: 10.3389/fneur.2012.00018. eCollection 2012.
citation: Perez Fornos A, Guinand N, van de Berg R, Stokroos R, Micera S, Kingma H, Pelizzone M, Guyot JP. Artificial balance: restoration of the vestibulo-ocular reflex in humans with a prototype vestibular neuroprosthesis. Front Neurol. 2014 Apr 29;5:66. doi: 10.3389/fneur.2014.00066. eCollection 2014.
citation: Nguyen TA, Ranieri M, DiGiovanna J, Peter O, Genovese V, Perez Fornos A, Micera S. A real-time research platform to study vestibular implants with gyroscopic inputs in vestibular deficient subjects. IEEE Trans Biomed Circuits Syst. 2014 Aug;8(4):474-84. doi: 10.1109/TBCAS.2013.2290089.
citation: Pelizzone M, Fornos AP, Guinand N, van de Berg R, Kos I, Stokroos R, Kingma H, Guyot JP. First functional rehabilitation via vestibular implants. Cochlear Implants Int. 2014 May;15 Suppl 1:S62-4. doi: 10.1179/1467010014Z.000000000165. No abstract available.
citation: van de Berg R, van Tilburg M, Kingma H. Bilateral Vestibular Hypofunction: Challenges in Establishing the Diagnosis in Adults. ORL J Otorhinolaryngol Relat Spec. 2015;77(4):197-218. doi: 10.1159/000433549. Epub 2015 Sep 15.
citation: van de Berg R, Guinand N, Nguyen TA, Ranieri M, Cavuscens S, Guyot JP, Stokroos R, Kingma H, Perez-Fornos A. The vestibular implant: frequency-dependency of the electrically evoked vestibulo-ocular reflex in humans. Front Syst Neurosci. 2015 Jan 20;8:255. doi: 10.3389/fnsys.2014.00255. eCollection 2014.
citation: Guinand N, van de Berg R, Cavuscens S, Stokroos RJ, Ranieri M, Pelizzone M, Kingma H, Guyot JP, Perez-Fornos A. Vestibular Implants: 8 Years of Experience with Electrical Stimulation of the Vestibular Nerve in 11 Patients with Bilateral Vestibular Loss. ORL J Otorhinolaryngol Relat Spec. 2015;77(4):227-240. doi: 10.1159/000433554. Epub 2015 Sep 15.
citation: Guinand N, van de Berg R, Ranieri M, Cavuscens S, DiGiovanna J, Nguyen TA, Micera S, Stokroos R, Kingma H, Guyot JP, Perez Fornos A. Vestibular implants: Hope for improving the quality of life of patients with bilateral vestibular loss. Annu Int Conf IEEE Eng Med Biol Soc. 2015;2015:7192-5. doi: 10.1109/EMBC.2015.7320051.
citation: Nguyen TA, DiGiovanna J, Cavuscens S, Ranieri M, Guinand N, van de Berg R, Carpaneto J, Kingma H, Guyot JP, Micera S, Fornos AP. Characterization of pulse amplitude and pulse rate modulation for a human vestibular implant during acute electrical stimulation. J Neural Eng. 2016 Aug;13(4):046023. doi: 10.1088/1741-2560/13/4/046023. Epub 2016 Jul 11.
citation: DiGiovanna J, Nguyen TA, Guinand N, Perez-Fornos A, Micera S. Neural Network Model of Vestibular Nuclei Reaction to Onset of Vestibular Prosthetic Stimulation. Front Bioeng Biotechnol. 2016 Apr 20;4:34. doi: 10.3389/fbioe.2016.00034. eCollection 2016.
citation: Guyot JP, Perez Fornos A, Guinand N, van de Berg R, Stokroos R, Kingma H. Vestibular assistance systems: promises and challenges. J Neurol. 2016 Apr;263 Suppl 1:S30-5. doi: 10.1007/s00415-015-7922-1. Epub 2016 Apr 15.
citation: Guinand N, Van de Berg R, Cavuscens S, Stokroos R, Ranieri M, Pelizzone M, Kingma H, Guyot JP, Perez Fornos A. Restoring Visual Acuity in Dynamic Conditions with a Vestibular Implant. Front Neurosci. 2016 Dec 22;10:577. doi: 10.3389/fnins.2016.00577. eCollection 2016.
citation: Nguyen TAK, Cavuscens S, Ranieri M, Schwarz K, Guinand N, van de Berg R, van den Boogert T, Lucieer F, van Hoof M, Guyot JP, Kingma H, Micera S, Perez Fornos A. Characterization of Cochlear, Vestibular and Cochlear-Vestibular Electrically Evoked Compound Action Potentials in Patients with a Vestibulo-Cochlear Implant. Front Neurosci. 2017 Nov 21;11:645. doi: 10.3389/fnins.2017.00645. eCollection 2017.
citation: Guinand N, Van de Berg R, Cavuscens S, Ranieri M, Schneider E, Lucieer F, Kingma H, Guyot JP, Perez Fornos A. The Video Head Impulse Test to Assess the Efficacy of Vestibular Implants in Humans. Front Neurol. 2017 Nov 14;8:600. doi: 10.3389/fneur.2017.00600. eCollection 2017.
citation: van de Berg R, Guinand N, Ranieri M, Cavuscens S, Khoa Nguyen TA, Guyot JP, Lucieer F, Starkov D, Kingma H, van Hoof M, Perez-Fornos A. The Vestibular Implant Input Interacts with Residual Natural Function. Front Neurol. 2017 Dec 14;8:644. doi: 10.3389/fneur.2017.00644. eCollection 2017.
citation: Perez Fornos A, Cavuscens S, Ranieri M, van de Berg R, Stokroos R, Kingma H, Guyot JP, Guinand N. The vestibular implant: A probe in orbit around the human balance system. J Vestib Res. 2017;27(1):51-61. doi: 10.3233/VES-170604.
citation: van de Berg R, Lucieer F, Guinand N, van Tongeren J, George E, Guyot JP, Kingma H, van Hoof M, Temel Y, van Overbeeke J, Perez-Fornos A, Stokroos R. The Vestibular Implant: Hearing Preservation during Intralabyrinthine Electrode Insertion-A Case Report. Front Neurol. 2017 Apr 10;8:137. doi: 10.3389/fneur.2017.00137. eCollection 2017.
citation: Fornos AP, van de Berg R, Armand S, Cavuscens S, Ranieri M, Cretallaz C, Kingma H, Guyot JP, Guinand N. Cervical myogenic potentials and controlled postural responses elicited by a prototype vestibular implant. J Neurol. 2019 Sep;266(Suppl 1):33-41. doi: 10.1007/s00415-019-09491-x. Epub 2019 Aug 8.
citation: Guyot JP, Perez Fornos A. Milestones in the development of a vestibular implant. Curr Opin Neurol. 2019 Feb;32(1):145-153. doi: 10.1097/WCO.0000000000000639.
citation: Starkov D, Guinand N, Lucieer F, Ranieri M, Cavuscens S, Pleshkov M, Guyot JP, Kingma H, Ramat S, Perez-Fornos A, van de Berg R. Restoring the High-Frequency Dynamic Visual Acuity with a Vestibular Implant Prototype in Humans. Audiol Neurootol. 2020;25(1-2):91-95. doi: 10.1159/000503677. Epub 2019 Oct 29.
citation: Seppen BF, van Hoof M, Stultiens JJA, van den Boogert T, Guinand N, Guyot JP, Kingma H, Fornos AP, Handschuh S, Glueckert R, Jacobi L, Schrott-Fischer A, Johnson Chacko L, van de Berg R. Drafting a Surgical Procedure Using a Computational Anatomy Driven Approach for Precise, Robust, and Safe Vestibular Neuroprosthesis Placement-When One Size Does Not Fit All. Otol Neurotol. 2019 Jun;40(5S Suppl 1):S51-S58. doi: 10.1097/MAO.0000000000002211.
citation: Stultiens JJA, Postma AA, Guinand N, Perez Fornos A, Kingma H, van de Berg R. Vestibular Implantation and the Feasibility of Fluoroscopy-Guided Electrode Insertion. Otolaryngol Clin North Am. 2020 Feb;53(1):115-126. doi: 10.1016/j.otc.2019.09.006. Epub 2019 Oct 31.
citation: Cretallaz C, Boutabla A, Cavuscens S, Ranieri M, Nguyen TAK, Kingma H, Van De Berg R, Guinand N, Perez Fornos A. Influence of systematic variations of the stimulation profile on responses evoked with a vestibular implant prototype in humans. J Neural Eng. 2020 Jun 12;17(3):036027. doi: 10.1088/1741-2552/ab8342.
citation: van de Berg R, Ramos A, van Rompaey V, Bisdorff A, Perez-Fornos A, Rubinstein JT, Phillips JO, Strupp M, Della Santina CC, Guinand N. The vestibular implant: Opinion statement on implantation criteria for research. J Vestib Res. 2020;30(3):213-223. doi: 10.3233/VES-200701.