Auditory Brainstem Implant (ABI) in Pediatric Non-Neurofibromatosis Type 2 Subjects (ABI)

Study of the Nucleus 24 and ABI541 Auditory Brainstem Implants in Pediatric Non-Neurofibromatosis Type 2

The purpose of this research study is to determine whether Auditory Brainstem Implant (ABI) can improve hearing in children who are deaf and cannot receive a cochlear implants.

Study Overview

• Status: Terminated
• Conditions: Bilateral Hearing Loss for Causes Other Than Tumors
• Intervention / Treatment: Device: Nucleus 24 (discontinued) and ABI541 Auditory Brainstem Implants (ABI)

Detailed Description

The goal of this MEEI Auditory Brainstem Implant (ABI) research study is to find new ways to improve hearing in children who are deaf and cannot receive a cochlear implant. The ABI is a surgically placed bionic implant that converts sounds into electrical signals that are directly transmitted to the cochlear nucleus, the first auditory center of the brain. For many years, ABIs have improved the hearing of patients who are deaf due to brain tumors associated with a genetic syndrome called Neurofibromatosis Type 2 (NF2). However, a number of recent studies suggest that deaf patients who do not have NF2 and are not eligible for a cochlear implant may also benefit from placement of an ABI. These preliminary studies suggest that these non-NF2 or "nontumor" patients may actually have better outcomes after ABI surgery than patients suffering from NF2. Children appear to be particularly good candidates because of their developmental plasticity and in many studies, outcomes are more favorable in children that adults. Patients who do not have NF2 and are deaf due to abnormalities in their hearing nerves or inner ears from congenital malformations, infection, disease, or injury are not cochlear implant candidates and there are no other options to improve hearing in these cases except for the ABI. Thus, the purpose of our study is to carefully analyze whether ABI surgery improves the hearing and quality of life of non-NF2 children based on subjective and objective measures of their hearing before and after ABI surgery. In particular, we plan to study ABI outcomes in non-NF2 pediatric patients, characterize the parameters used on their devices, and determine the safety profile of ABIs in these patients.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts Eye and Ear Infirmary

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Pre-linguistic hearing loss (birth-5 yrs.; age at ABI implantation 18 months-5yrs) with both:

   1. MRI +/- CT evidence of one of the following:

      • Cochlear nerve deficiency
      • Cochlear aplasia or severe hypoplasia
      • Severe inner ear malformation
      • Post-meningitis ossification

   2. When a cochlea is present or patent with a normally appearing cochlear nerve, lack of significant benefit from CI despite consistent use (>6 mo.)

      • No or limited speech perception ability (limited to pattern perception on closed set testing materials using the CI)
      • Lack of progress in auditory skills development

2. Post-linguistic hearing loss (<18 yrs. of age) with both:

   1. Loss or lack of benefit from appropriate CI without the possibility for revision or contralateral implantation. Examples might include:

      • Post-meningitis ossification
      • Bilateral temporal bone fractures with cochlear nerve avulsion
      • Failed revision CI without benefit
   2. Previously developed open set speech perception and auditory-oral language skills
3. No medical contraindications
4. Willing to receive the appropriate meningitis vaccinations
5. No or limited cognitive/developmental delays which would be expected to interfere with the child's ability to cooperate in testing and/or programming of the device, in developing speech and oral language, or which would make an implant and subsequent emphasis on aural/oral communication not in the child's best interest
6. Strong family support including language proficiency of the parent(s) in the child's primary mode of communication as well as written and spoken English.

7. Reasonable expectations from parents including a thorough understanding:

   • of potential benefits and limitations of ABI
   • of parental role in rehabilitation
   • that the child may not develop spoken language as a primary communication mode or even sufficient spoken language to make significant academic progress in an aural/oral environment
8. Involvement in an educational program that emphasizes development of auditory skills with or without the use of supplementary visual communication.
9. Able to comply with study requirements including travel to investigation sites and clinic visits.
10. Informed consent for the procedure from the child's parents.

Exclusion Criteria:

1. Pre- or post-linguistic child currently making significant progress with CI - This will be considered if a child is progressing along the expected speech reception hierarchy (SRI-Q) as detailed by Wang et al (50). Even for the very young children (18 months of age with 6 months of use), nearly all children with a good auditory signal from their CI will have reached ceiling effects on the IT-MAIS and have pattern perception beyond chance using the ESP (50). Moreover, there will evidence of improvement in these metrics over time.

2. MRI evidence of one of the following:

   • normal cochlea and cochlear nerves or NF2
   • brainstem or cortical anomaly that makes implantation unfeasible
3. Clear surgical reason for poor CI performance that can be remediated with revision CI or contralateral surgery rather than ABI.
4. Intractable seizures or progressive, deteriorating neurological disorder
5. Unable to participate in behavioral testing and mapping with their CI. If this appears to be an age effect, ABI will be delayed until we can be assured that the child will be able to participate, as reliable objective measures of mapping are currently not available for mapping these devices.

6. Lack of potential for spoken language development. This will be considered the case when evidence of the following exist:

   • Severe psychomotor retardation, autism, cerebral palsy, or developmental delays beyond speech that would preclude usage of the device and oral educational development. Autism is a special case where there is the potential for delayed presentation. When early signs are considered present, we will request a comprehensive developmental assessment for further evaluation prior to considering routine evaluation.
7. Unable to tolerate general anesthesia (cardiac, pulmonary, bleeding diathesis, etc.).
8. Need for brainstem irradiation
9. Unrealistic expectations on the part of the subject/family regarding the possible benefits, risks and limitations that are inherent to the procedure and prosthetic device.
10. Unwilling to sign the informed consent.
11. Unwilling to make necessary follow-up appointments.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Non-NF2 ABI surgery; All subjects will be part of a single arm involving placement of the ABI541 Auditory Brainstem Implant (ABI) device. The Nucleus 24 was discontinued and is no longer available.	Device: Nucleus 24 (discontinued) and ABI541 Auditory Brainstem Implants (ABI); Nucleus ABI541 Auditory Brainstem Implant (ABI) surgery followed by device activation, testing, and clinical assessment for five years following surgery.; Other Names: ABI, Nucleus 24, ABI541, Nucleus Profile, Cochlear Americas

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Major or Minor ABI Complications	We will track any major and minor complications peri-operatively and post-operatively in all study participants. Major complications include mortality, cerebellar contusion, facial palsy, meningitis, lower cranial neuropathy, hydrocephalus, pseudomeningocele and CSF leak. Minor complications include transient hydrocephalus, wound seroma, minor infections, balance problems, transient nerve palsies, transient dysphonia or difficulty swallowing, headache, flap problems, and non-auditory side effects. These complications will be tracked through serial clinical exams as well as patient recorded questionnaires to determine the safety profile of ABI surgery.	1 year from date of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Pure Tone Threshold (dB HL) Using the ABI	We will complete audiometric threshold testing and speech based tests to determine performance before and after ABI surgery. The measure data value was calculated as mean threshold shift in dB HL from pre-surgery (or baseline) to postoperatively (following activation of the ABI) across subjects analyzed. Only those subjects that had auditory perception abilities were included. 2/9 subjects did not have auditory perception and are not using their devices. The outcome measure time frame varies across subjects based on available followup data as this study was stopped early. Audiometric testing will include: • Behavioral pure tone threshold average (PTA) in both aided (with ABI) and unaided (without ABI)	1-4 years from date of surgery
Number of Participants With Similar eABR Morphology on the Day of ABI Activation Compared to Intraoperative Responses	We will measure and record the specific programmed parameters of the ABI device. Intraoperatively, evoked Auditory Brainstem Response (eABRs) will be recorded and saved. These tracings and data will be compared to the settings on activation to determine whether the same electrodes are appropriately positioned. By following these measures, we will be able to capture how electrophysiologic parameters vary (if at all) over time. The outcome measure data are the number of subjects whose eABR morphology was similar on the day of activation (4 to 8 weeks following surgery) as recorded intraoperatively during ABI surgery.	4 to 8 weeks after surgery (day of activation under anesthesia)

Collaborators and Investigators

• Sponsor: Massachusetts Eye and Ear Infirmary
• Investigators: Principal Investigator: Daniel J Lee, MD FACS, MEEI/MGH

Publications and helpful links

General Publications

• Colletti V, Shannon RV, Carner M, Veronese S, Colletti L. Complications in auditory brainstem implant surgery in adults and children. Otol Neurotol. 2010 Jun;31(4):558-64. doi: 10.1097/MAO.0b013e3181db7055.
• Sennaroglu L, Ziyal I, Atas A, Sennaroglu G, Yucel E, Sevinc S, Ekin MC, Sarac S, Atay G, Ozgen B, Ozcan OE, Belgin E, Colletti V, Turan E. Preliminary results of auditory brainstem implantation in prelingually deaf children with inner ear malformations including severe stenosis of the cochlear aperture and aplasia of the cochlear nerve. Otol Neurotol. 2009 Sep;30(6):708-15. doi: 10.1097/MAO.0b013e3181b07d41.
• Choi JY, Song MH, Jeon JH, Lee WS, Chang JW. Early surgical results of auditory brainstem implantation in nontumor patients. Laryngoscope. 2011 Dec;121(12):2610-8. doi: 10.1002/lary.22137.
• Colletti V, Shannon R, Carner M, Veronese S, Colletti L. Outcomes in nontumor adults fitted with the auditory brainstem implant: 10 years' experience. Otol Neurotol. 2009 Aug;30(5):614-8. doi: 10.1097/MAO.0b013e3181a864f2.
• Colletti V, Carner M, Miorelli V, Guida M, Colletti L, Fiorino F. Auditory brainstem implant (ABI): new frontiers in adults and children. Otolaryngol Head Neck Surg. 2005 Jul;133(1):126-38. doi: 10.1016/j.otohns.2005.03.022.
• Colletti V. Auditory outcomes in tumor vs. nontumor patients fitted with auditory brainstem implants. Adv Otorhinolaryngol. 2006;64:167-185. doi: 10.1159/000094651.
• Colletti L, Zoccante L. Nonverbal cognitive abilities and auditory performance in children fitted with auditory brainstem implants: preliminary report. Laryngoscope. 2008 Aug;118(8):1443-8. doi: 10.1097/MLG.0b013e318173a011.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2013
• Primary Completion (Actual): April 25, 2019
• Study Completion (Actual): April 25, 2019

Study Registration Dates

• First Submitted: May 22, 2013
• First Submitted That Met QC Criteria: May 24, 2013
• First Posted (Estimate): May 29, 2013

Study Record Updates

• Last Update Posted (Actual): June 2, 2020
• Last Update Submitted That Met QC Criteria: May 22, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Pediatric; Hearing loss; Auditory Brainstem Implant; ABI; Nucleus 24; Deafness; Non-tumor; Non-NF2; ABI541
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Otorhinolaryngologic Diseases; Ear Diseases; Sensation Disorders; Hearing Disorders; Hearing Loss; Deafness; Hearing Loss, Bilateral
• Other Study ID Numbers: 13-028H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No