Multichannel Vestibular Implant Early Feasibility Study

Vestibular Diseases Clinical Trial

Official title:

First-in-Human Early Feasibility Study of Safety, Tolerability and Efficacy for a Multichannel Vestibular Implant in Individuals With Bilateral Severe-to-Profound Loss of Vestibular Sensation

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02725463
• Other study ID #: NA_00051349
• Secondary ID: R01DC013536JHU80
• Status: Active, not recruiting
• Phase: N/A
• Start date: April 2016
• Est. completion date: March 31, 2026

Study information

• Verified date: March 2024
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Although cochlear implants can restore hearing to individuals who have lost cochlear hair cell function, there is no adequately effective treatment for individuals suffering chronic imbalance, postural instability and unsteady vision due to loss of vestibular hair cell function. Preclinical studies have demonstrated that electrical stimulation of the vestibular nerve via a chronically implanted multichannel vestibular prosthesis can partially restore vestibular reflexes that maintain steady posture and vision. This pilot clinical feasibility study of a multichannel vestibular implant system will evaluate this approach in up to ten human subjects with bilateral vestibular deficiency due to gentamicin ototoxicity or other causes of inner ear dysfunction.

Description:

The system used in this study is the (MVI)™ Multichannel Vestibular Implant System produced by Labyrinth Devices, LLC. It is similar to commercially available cochlear implants in that it includes an implanted stimulator powered and controlled by an external unit, which communicate with the implant across the skin via an inductive link. Unlike a cochlear implant, the implanted stimulator's electrode array is designed for implantation near the ends of the vestibular nerve. The implanted stimulator also includes additional magnets to help facilitate retention of the external unit on the scalp over the implant. The external unit includes a head-worn unit (for sensing head motion and delivering power and signals to the implanted stimulator) and a power and control unit containing a battery and microprocessor. Participants in this trial who meet candidacy criteria and who choose to proceed with implantation surgery, device activation and device deactivation will be asked to participate in a series of post-operative monitoring visits over a ≥1 year period.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 30
• Est. completion date: March 31, 2026
• Est. primary completion date: March 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 22 Years to 90 Years

Eligibility

Inclusion Criteria:

1. Adults age 22.0-90 with bilateral vestibular deficiency not responsive to vestibular rehabilitation as determined by pre-inclusion history, vestibular testing and clinical examination

2. Hearing status: (1) Hearing in the candidate ear for implantation is equivalent to or worse than that in the contralateral ear; and (2) hearing in the contralateral ear is good enough to allow functional communication in case hearing in the implanted ear is lost after implantation. Specifically, the contralateral ear must satisfy all of the following criteria:

1. 0.5/1/2/4 kHz pure-tone-average threshold (PTA) hearing better than (i.e., less than) 70 dB HL; and

2. ear-specific sentence recognition score using the recorded AzBio Sentence Test presented at 60 dB SPL-A in quiet must be >60% when tested under either the unaided condition or, if 0.5/1/2/4 kHz PTA>50 dB, the best-aided condition; and

3. ear-specific word recognition score using the recorded Consonant-Nucleus-Consonant (CNC) Word Recognition Test presented at 60 dBHL in quiet must be >60% when tested under either the unaided condition or, if 0.5/1/2/4 kHz PTA>50 dB, the best-aided condition

3. Caloric responses consistent with severe or profound bilateral loss of labyrinthine function, as indicated by one or more of the following: (a) summed speed of caloric responses to warm and cool supine caloric stimuli totaling <10°/sec per ear for each of both ears; (b) summed speed of ice water caloric responses during supine and prone head orientation tests totaling <10°/sec per ear for each of both ears; or (c) speed of ice water caloric responses during supine head orientation tests <5°/sec per ear for each of both ears, with a lack of nystagmus reversal on quickly flipping from supine to prone

4. Prior MRI imaging of the brain, internal auditory canals and cerebellopontine (CP) angle showing a patent labyrinth, present vestibular nerve, patent cochlea, present cochlear nerve, and absence of internal auditory canal/cerebellopontine angle tumors or other central causes of vestibulo-ocular reflex dysfunction or sensorineural hearing loss

5. Prior CT imaging of the temporal bones showing a facial nerve canal with normal caliber and course, middle ear without evidence of chronic otitis media or tympani membrane perforation or cholesteatoma, a mastoid cavity with adequate aeration for surgical access to each semicircular canal, skull thickness =3 mm at the planned well site, and scalp soft tissue thickness =7 mm. This criterion may be satisfied without additional imaging if an existing head CT or MRI already demonstrates those findings

6. Vaccinations as recommended per Johns Hopkins Listening Center protocols to reduce the risk of meningitis in subjects undergoing cochlear implantation, as described at this site: http://www.hopkinsmedicine.org/otolaryngology/specialty_areas/listencenter/vaccine.htm l

7. Motivated to travel to the study center, to undergo testing and examinations required for the investigational study, and to participate actively in a vestibular rehabilitation exercise regimen

8. The participant must agree 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 duration of participation in the study and until at least 1 month after final deactivation of the MVI Implant

Exclusion Criteria:

1. Inability to understand the procedures and the potential risks involved as determined by study staff

2. Inability to participate in study procedures due to blindness, = ±10° neck range of motion, cervical spine instability, ear canal stenosis or malformation sufficient to prevent caloric testing

3. Diagnosis of acoustic neuroma/vestibular schwannoma, chronic middle ear disease, cholesteatoma, or central nervous system causes of vestibulo-ocular reflex dysfunction, including chronic and continuing use of medications, drugs or alcohol at doses sufficiently great to interfere with vestibular compensation

4. Vestibular dysfunction known to be caused by reasons other than labyrinthine injury due to ototoxicity, ischemia, trauma, infection, Meniere's disease, or genetic defects known to act on hair cells

5. Lack of labyrinth patency or vestibular nerve as determined by MRI of the brain with attention to the internal acoustic meatus

6. Any contraindication to the planned surgery, anesthesia, device activation and deactivation, or participation in study assessments, as determined by the surgeon, anesthesiologist, or designee, including known intolerance of any materials used in any component of the investigational devices that will come in contact with the subject

7. History of myocardial infarction, coronary bypass surgery, or any percutaneous coronary intervention (PCI) within 6 months prior to screening

8. Orthopedic, neurologic or other nonvestibular pathologic conditions of sufficient severity to confound posture and gait testing or other tests used in the study to assay vestibular function.

9. Subjects with estimated glomerular filtration rate (GFR) < 30 ml/min (MDRD formula) at screening

10. Subjects with heart failure NYHA class III or IV

11. Subjects with Child-Pugh class C cirrhosis

12. A psychiatric disease or substance abuse history likely to interfere with protocol compliance

13. Contraindications to scleral coil eye movement testing, including monocular blindness and a history of fainting vagal reactions to prior eye manipulations would exclude subjects from eye coil testing

14. Inability to tolerate baseline testing protocols

15. Recent corneal injury

16. A history of cervical spine disease preventing head rotation

17. A history of fainting or vagal reactions prior to eye manipulations that would preclude 3D eye movement coil testing

18. Pregnancy, positive urine or serum pregnancy test at any time during study participation,

19. Ability to become pregnant combined with failure or refusal to consistently use a highly effective method of contraception from at least 1 month prior to implantation to not before 1 month after both device deactivation and conclusion of study participation. Highly effective contraception methods include:

Total abstinence. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post ovulation methods) and withdrawal are not acceptable methods of contraception for purposes of defining exclusion criteria for this study

Female sterilization (surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before entering the study. A woman who has undergone oophorectomy without hysterectomy may participate in the study only after her reproductive status has been confirmed by subsequent hormone level assessment

For female subjects of child-bearing potential, study participation is not excluded if the study candidate's male partner is the sole partner of the study candidate and has been vasectomized.

Combination of any two of the following:

Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example, hormone vaginal ring or transdermal hormone contraception

Placement of an intrauterine device (IUD) or intrauterine system (IUS)

Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository In case of use of oral contraception, women should have been stabile on the same pill for a minimum of 3 months before taking study treatment.

20. Women who are nursing/lactating

21. Any medical condition, judged by the investigator team, that is likely to interfere with a study candidate's participation in the study or likely to cause serious adverse events during the study.

Related Conditions & MeSH terms

• Bilateral Vestibular Deficiency (BVD)
• Bilateral Vestibulopathy
• Gentamicin Ototoxicity
• Labyrinth Diseases
• Labyrinthitis
• Other Disorders of Vestibular Function, Bilateral
• Ototoxicity
• Sensation Disorders
• Vestibular Diseases

Intervention

Device:
• Labyrinth Devices MVI™ Multichannel Vestibular Implant

Locations

Country	Name	City	State
United States	Johns Hopkins School of Medicine	Baltimore	Maryland

Sponsors (3)

Lead Sponsor	Collaborator
Johns Hopkins University	Labyrinth Devices, LLC, National Institute on Deafness and Other Communication Disorders (NIDCD)

Country where clinical trial is conducted

United States, 

References & Publications (18)

Boutros PJ, Schoo DP, Rahman M, Valentin NS, Chow MR, Ayiotis AI, Morris BJ, Hofner A, Rascon AM, Marx A, Deas R, Fridman GY, Davidovics NS, Ward BK, Trevino C, Bowditch SP, Roberts DC, Lane KE, Gimmon Y, Schubert MC, Carey JP, Jaeger A, Della Santina CC. — View Citation

Chow MR, Ayiotis AI, Schoo DP, Gimmon Y, Lane KE, Morris BJ, Rahman MA, Valentin NS, Boutros PJ, Bowditch SP, Ward BK, Sun DQ, Trevino Guajardo C, Schubert MC, Carey JP, Della Santina CC. Posture, Gait, Quality of Life, and Hearing with a Vestibular Implant. N Engl J Med. 2021 Feb 11;384(6):521-532. doi: 10.1056/NEJMoa2020457. — View Citation

Dai C, Fridman GY, Chiang B, Davidovics NS, Melvin TA, Cullen KE, Della Santina CC. Cross-axis adaptation improves 3D vestibulo-ocular reflex alignment during chronic stimulation via a head-mounted multichannel vestibular prosthesis. Exp Brain Res. 2011 May;210(3-4):595-606. doi: 10.1007/s00221-011-2591-5. Epub 2011 Mar 4. — View Citation

Dai C, Fridman GY, Chiang B, Rahman MA, Ahn JH, Davidovics NS, Della Santina CC. Directional plasticity rapidly improves 3D vestibulo-ocular reflex alignment in monkeys using a multichannel vestibular prosthesis. J Assoc Res Otolaryngol. 2013 Dec;14(6):863-77. doi: 10.1007/s10162-013-0413-0. Epub 2013 Sep 8. — View Citation

Dai C, Fridman GY, Davidovics NS, Chiang B, Ahn JH, Della Santina CC. Restoration of 3D vestibular sensation in rhesus monkeys using a multichannel vestibular prosthesis. Hear Res. 2011 Nov;281(1-2):74-83. doi: 10.1016/j.heares.2011.08.008. Epub 2011 Aug 26. — View Citation

Dai C, Fridman GY, Della Santina CC. Effects of vestibular prosthesis electrode implantation and stimulation on hearing in rhesus monkeys. Hear Res. 2011 Jul;277(1-2):204-10. doi: 10.1016/j.heares.2010.12.021. Epub 2010 Dec 31. — View Citation

Davidovics NS, Rahman MA, Dai C, Ahn J, Fridman GY, Della Santina CC. Multichannel vestibular prosthesis employing modulation of pulse rate and current with alignment precompensation elicits improved VOR performance in monkeys. J Assoc Res Otolaryngol. 2013 Apr;14(2):233-48. doi: 10.1007/s10162-013-0370-7. Epub 2013 Jan 26. — View Citation

Della Santina CC, Migliaccio AA, Patel AH. A multichannel semicircular canal neural prosthesis using electrical stimulation to restore 3-d vestibular sensation. IEEE Trans Biomed Eng. 2007 Jun;54(6 Pt 1):1016-30. doi: 10.1109/TBME.2007.894629. — View Citation

Della Santina CC. Regaining balance with bionic ears. Sci Am. 2010 Apr;302(4):68-71. doi: 10.1038/scientificamerican0410-68. No abstract available. — View Citation

Fridman GY, Davidovics NS, Dai C, Migliaccio AA, Della Santina CC. Vestibulo-ocular reflex responses to a multichannel vestibular prosthesis incorporating a 3D coordinate transformation for correction of misalignment. J Assoc Res Otolaryngol. 2010 Sep;11(3):367-81. doi: 10.1007/s10162-010-0208-5. Epub 2010 Feb 23. — View Citation

Fridman GY, Della Santina CC. Progress toward development of a multichannel vestibular prosthesis for treatment of bilateral vestibular deficiency. Anat Rec (Hoboken). 2012 Nov;295(11):2010-29. doi: 10.1002/ar.22581. Epub 2012 Oct 8. — View Citation

Hedjoudje A, Schoo DP, Ward BK, Carey JP, Della Santina CC, Pearl M. Vestibular Implant Imaging. AJNR Am J Neuroradiol. 2021 Jan;42(2):370-376. doi: 10.3174/ajnr.A6991. Epub 2020 Dec 24. — View Citation

Mitchell DE, Dai C, Rahman MA, Ahn JH, Della Santina CC, Cullen KE. Head movements evoked in alert rhesus monkey by vestibular prosthesis stimulation: implications for postural and gaze stabilization. PLoS One. 2013 Oct 17;8(10):e78767. doi: 10.1371/journal.pone.0078767. eCollection 2013. — View Citation

Rahman MA, Dai C, Fridman GY, Davidovics NS, Chiang B, Ahn J, Hayden R, Melvin TA, Sun DQ, Hedjoudje A, Della Santina CC. Restoring the 3D vestibulo-ocular reflex via electrical stimulation: the Johns Hopkins multichannel vestibular prosthesis project. Annu Int Conf IEEE Eng Med Biol Soc. 2011;2011:3142-5. doi: 10.1109/IEMBS.2011.6090857. — View Citation

Sun DQ, Lehar M, Dai C, Swarthout L, Lauer AM, Carey JP, Mitchell DE, Cullen KE, Della Santina CC. Histopathologic Changes of the Inner ear in Rhesus Monkeys After Intratympanic Gentamicin Injection and Vestibular Prosthesis Electrode Array Implantation. J Assoc Res Otolaryngol. 2015 Jun;16(3):373-87. doi: 10.1007/s10162-015-0515-y. Epub 2015 Mar 20. — View Citation

Sun DQ, Ward BK, Semenov YR, Carey JP, Della Santina CC. Bilateral Vestibular Deficiency: Quality of Life and Economic Implications. JAMA Otolaryngol Head Neck Surg. 2014 Jun;140(6):527-34. doi: 10.1001/jamaoto.2014.490. — View Citation

Valentin NS, Hageman KN, Dai C, Della Santina CC, Fridman GY. Development of a multichannel vestibular prosthesis prototype by modification of a commercially available cochlear implant. IEEE Trans Neural Syst Rehabil Eng. 2013 Sep;21(5):830-9. doi: 10.1109/TNSRE.2013.2259261. Epub 2013 May 1. — View Citation

Ward BK, Agrawal Y, Hoffman HJ, Carey JP, Della Santina CC. Prevalence and impact of bilateral vestibular hypofunction: results from the 2008 US National Health Interview Survey. JAMA Otolaryngol Head Neck Surg. 2013 Aug 1;139(8):803-10. doi: 10.1001/jamaoto.2013.3913. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Identified adverse events to assess the safety and tolerability of the Labyrinth Devices Multichannel Vestibular Implant (MVI™)	Number of participants with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events v4.3 (CTCAE v4.3)	Through study completion, an average of 1 year, that is: in visits 0 through 10
Primary	Assess the feasibility of the MVI, as determined by changes in 3-dimensional vestibulo-ocular reflex (3D VOR) gain and alignment compared to pre-intervention values and published data from subjects with normal vestibular function	3D VOR gain (eye velocity / -head velocity)	Through study completion, an average of 1 year, that is: in visits 0, and 3 through 10
Primary	Assess the preliminary efficacy of the MVI, as determined by changes in 3-dimensional vestibulo-ocular reflex (3D VOR) gain and alignment compared to pre-intervention values and published data from subjects with normal vestibular function	3D VOR gain (eye velocity / -head velocity)	Through study completion, an average of 1 year, that is: in visits 0, and 3 through 10
Primary	Assess the effects of MVI implantation on cochlear function, as indicated by changes in pure tone audiometry	Pure tone audiometry (decibels [dB])	through study completion, an average of 1 year, that is: in visits 0, and 3 through 10
Primary	Assess the effects of MVI use on cochlear function, as indicated by changes in pure tone audiometry	Pure tone audiometry (decibels [dB])	through study completion, an average of 1 year, that is: in visits 0, and 3 through 10
Primary	Assess the effects of MVI implantation on cochlear function, as indicated by changes in Consonant-vowel nucleus-consonant (CNC) speech recognition scores	CNC speech recognition score (0-100% correct), higher scores means better outcome	through study completion, an average of 1 year, that is: in visits 0, and 3 through 10
Primary	Assess the effects of MVI use on cochlear function, as indicated by changes in Consonant-vowel nucleus-consonant (CNC) speech recognition scores	CNC speech recognition score (0-100% correct), higher scores means better outcome	through study completion, an average of 1 year, that is: in visits 0, and 3 through 10
Primary	Assess the effects of MVI implantation on cochlear function, as indicated by changes in Arizona Biomedical (AzBio) sentence recognition scores	AzBio sentence recognition score (0-100% correct), higher scores means better outcome	through study completion, an average of 1 year, that is: in visits 0, and 3 through 10
Primary	Assess the effects of MVI use on cochlear function, as indicated by changes in Arizona Biomedical (AzBio) sentence recognition scores	AzBio sentence recognition score (0-100% correct), higher scores means better outcome	through study completion, an average of 1 year, that is: in visits 0, and 3 through 10
Secondary	Change in Vestibulo-ocular reflex (VOR) three-dimensional (3D) alignment to assess the preliminary efficacy of the MVI	Measured in degrees	In a period of up to 24 weeks, in visits 0, and 3 through 10
Secondary	Change in Ocular Vestibular Evoked Myogenic Potentials (oVEMP) to assess the effects of MVI implantation and use on utricular function	oVEMP peak-to-peak amplitude in microvolts	In a period of up to 24 weeks, in visits 0, and 3 through 10
Secondary	Change in Cervical Vestibular Evoked Myogenic Potentials (cVEMP) to assess the effects of MVI implantation and use on saccular function	cVEMP peak-to-peak amplitude in microvolts	In a period of up to 24 weeks, in visits 0, and 3 through 10
Secondary	Changes in utility scores on 36-Item Short Form Health Survey (SF-36) to assess the effects of MVI implantation and use on activities of daily living and quality of life	SF-36 Utility (No scale)	In a period of up to 24 weeks, in visits 0, 6, 8, and 10
Secondary	Changes in scores on Tinnitus Handicap Inventory (THI) to assess the effects of MVI implantation and use on activities of daily living and quality of life	THI score (0-100), higher scores means worse outcome	In a period of up to 24 weeks, in visits 0, 6, 8, and 10
Secondary	Changes in scores on Dizziness Handicap Inventory (DHI) to assess the effects of MVI implantation and use on activities of daily living and quality of life	DHI score (0-100), higher scores means worse outcome	In a period of up to 24 weeks, in visits 0, 6, 8, and 10
Secondary	Changes in scores on the Health Utilities Index 3 (HUI3) to assess the effects of MVI implantation and use on activities of daily living and quality of life	HUI3 scores (0-1), higher scores means better outcome	In a period of up to 24 weeks, in visits 0, 6, 8, and 10
Secondary	Changes in scores on the Vestibular Activities of Daily Living (VADL) to assess the effects of MVI implantation and use on activities of daily living and quality of life	VADL score (1-10), higher scores means worse outcome	In a period of up to 24 weeks, in visits 0, 6, 8, and 10
Secondary	Changes in scores on the Autophony Index (AI) to assess the effects of MVI implantation and use on activities of daily living and quality of life	AI score (0-104), higher scores means worse outcome	In a period of up to 24 weeks, in visits 0, 6, 8, and 10
Secondary	Changes in scores on the bilateral vestibular deficiency BVD-case definition subset of questions to assess the effects of MVI™ implantation and use on activities of daily living and quality of life	BVD-case definition subset of questions from the National Health Interview Survey 2008 Balance Questions (NHIS) score (no scale)	In a period of up to 24 weeks, in visits 0, 6, 8, and 10
Secondary	Change in Dynamic visual acuity (DVA) to assess the feasibility and preliminary efficacy of the MVI	DVA test score in log10 of the Minimum Angle Resolvable (LogMAR) units, as the difference between raw DVA LogMAR and static visual acuity LogMAR	In a period of up to 24 weeks, in visits 0 and 3 through 10
Secondary	Change in Bruininks-Oseretsky test of motor proficiency- balance subtest 2 (BOT2) score	BOT2 score (0-36), higher scores means better outcome	In a period of up to 24 weeks, in visits 0, and 3 through 10
Secondary	Change in Dynamic Gait Index (DGI)	DGI score (0-24), higher scores means better outcome	In a period of up to 24 weeks, in visits 0, and 3 through 10
Secondary	Change in gait characteristics using the GaitRite™ system	Gait speed analysis in meters per second	In a period of up to 24 weeks, in visits 0, and 3 through 10

External Links

•   Trial-related news updates and links to application