Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00594061 |
| Other study ID # |
200710716 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
December 2007 |
| Est. completion date |
September 2016 |
Study information
| Verified date |
May 2018 |
| Source |
University of Iowa |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The purpose of this study is to evaluate whether the Iowa/Nucleus 10/10 mm in one ear, in
conjunction with a Nucleus Freedom implant in the other ear can provide useful binaural
hearing in pediatric subjects who have bilateral severe to profound hearing loss and meet the
criteria for cochlear implantation. The Iowa/Nucleus 10/10 mm cochlear implant has a short,
10 mm electrode array that it is inserted only into the more basal region of the cochlea.
Unlike a conventional cochlear implant, the Iowa/Nucleus 10/10 mm is expected to preserve the
regions of the cochlear partition that are apical to the electrode, thus leaving them
available for possible future advances in the field of otolaryngology and hearing devices,
such as mammalian hair cell regeneration techniques or improved implantable hearing devices.
The Iowa/Nucleus 10/10 mm will be implanted in the contralateral ear from the Nucleus Freedom
electrode array as a means of providing bilateral stimulation of auditory pathways while
preserving the middle and apical regions of the scala media.
Description:
The study will be conducted as a repeated-measure , single-subject experiment. A single-
subject research design (in which each participant serves as his or her own control) is
appropriate because it accommodates the heterogeneity that characterizes hearing- impaired
population s. Blinding or masking procedures are not included in the design, as it is not
possible to conceal the presence or absence of a cochlear implant from device recipients
and/or clinical investigators.
Preoperatively , candidates will be assessed with their current amplification to evaluate
their appropriateness for entrance into the study. The candidates' audiometric configuration
must meet the above inclusion criteria. That is, the candidate must have a severe-to-profound
sensorineural hearing loss from 250 to 8000 Hz. Prior to testing, the appropriateness of the
hearing aid fitting will be assessed and adjustments made if necessary. In cases where
amplification has not been used for more than one year, new hearing aids will be fit, worn
for a minimum three-month trial and the participants re- evaluated to confirm continuance
with the study.
Participants will receive one standard Nucleus Freedom electrode array and an Iowa/Nucleus
10/ 10 mm electrode array on the contralateral side. Half will be implanted with the 10 mm
electrode array on their right side and half will be implanted with the 10 mm electrode array
on their left side. We will alternate every other subject between the right and left ears.
Postoperatively, Iowa/Nucleus 10110 mm electrode alone, standard Freedom electrode alone, and
bilateral listening (i.e., Iowa/Nucleus 10/ 10 mm and standard electrodes together) modes
will be compared with repeated testing through five years of age of the child. These
comparisons will help to evaluate the effects of bilateral stimulation using different
cochlear implant devices while possibly preserving the scala media, organ of Corti, and
supporting cells for future advances in the ear receiving the Iowa/Nucleus 10/ 10 mm
electrode device. In addition, we will attempt to compare these results with age-matched
unilaterally implanted children tested on the same speech perception and speech/language
measures. In addition, if possible, we will attempt to compare speech perception and
speech/language measures on age-matched children with bilateral standard long electrode
arrays in both ears. The following defines the various modes referenced throughout the course
of this text:
Iowa/Nucleus 10/10 mm Electrode Array: The Iowa/Nucleus 10/ 10 mm electrode array was
designed to reduce the incidence of intracochlear injury and developed by the Iowa Cochlear
Implant Team and Cochlear Americas. This array was designed to preserve the scala media,
organ of Corti and supporting cells of the implanted ear for future advances in molecular
and/or genetic treatments of the inner ear. This investigational device is very
similar to the Nucleus Hybrid-6 (formerly known as CI24RE Hybrid), the subject ofIDE No.
0990155. See ATTACHMENT 1 for a letter from the Sponsor ofIDE No. 0990155 authorizing the FDA
to review the information in IDE No. 0990155 for purposes of the current IDE application.
Like the Hybrid-6, the Iowa/Nucleus 10/ 10 mm cochlear implant is 0.2 mm x 0.4 mm in diameter
and has a short, 10 mm electrode array that it is inserted only into the more basal region of
the cochlea. In comparison to the Hybrid-6, the Iowa/Nucleus 10/ 10 mm cochlear implant has a
total of 10 contacts, or 4 more than the 6 contacts/channels present on the Hybrid-6. The
contacts are spaced closer together and occupy approximately 6 mm of the apical segment of
the 10 mm array.
Nucleus Freedom electrode array: The standard electrode array, which is 19 mm in length.
Bilateral Stimulation :The use of the Iowa/Nucleus 10110 mm cochlear implant and the Nucleus
Freedom cochlear implant on contralateral ears.
1.4 Preoperative Procedures: 1.4.1 Informed Consent: A preoperative interview will be
conducted by the surgeon and audiologist to inform the parent(s) or legal guardian of the
child about all aspects of implantation with the Iowa/Nucleus 10/10 mm cochlear implant and
Nucleus Freedom cochlear implant, study expectations, number of visits, surgical procedure,
as well as the postoperative evaluation schedule. The risks of surgery shall be explained to
the parent(s) or guardian as outlined on the Informed Consent Form (Parental Agreement).
These include the normal risks associated with general anesthetic, as well as other risks
such as facial paralysis, dizziness, meningitis, postoperative discomfort, and flap
complications. The potential limitations and advantages of implantation with the Iowa/Nucleus
10/10 mm and Nucleus Freedom cochlear implants shall also be explained. The parent(s) or
guardian will be given adequate time to review the Informed Consent Form and given the
opportunity to ask questions about the Informed Consent and/or the study prior to signing the
Informed Consent Form. The parent(s) or guardian will then be given a copy of the signed
Informed Consent Form.
Note that the Informed Consent Form must be reviewed and signed by the relevant parties prior
to any study evaluation taking place. Any testing,for screening purposes, completed prior to
consent being obtained must be repeated after theparticipant consents toparticipation in the
study.
1.4.2 Hearing History: Information regarding P.articipant' s hearing-history (etiology, onset
of hearing loss, duration of severe-to-profound hearing loss, amplification use) is to be
reported.
1.4.3 Medical/Surgical History: The participant's medical/surgical history is to be reported
and is required in order to determine that the participant is medically suitable for cochlear
implantation .
Information to be collected may include: the participant 's general medical history,
medications, radiological information (i.e. x-rays), otologic history, and otologic surgical
history.
1.4.4 Fitting of Hearing Aids: Lack of benefit from appropriately fit hearing aids will be
determined by the lack of progress in the development of simple auditory skills as defined by
aided and unaided behavioral thresholds; auditory brainstem response testing; otoacoustic
emission testing; steady state evoked potential testing; IT-MAIS and/or the lack of
developmentally appropriate vocal behaviors. Criteria for appropriate vocal behaviors include
achieving the production of canonical babble as defined by production of reduplicated
sequences such as [mamama], [dadadal, or [bababal] (Oller and Eilers 1988). Hearing aid use
will be determined by parental and educator reports.
Bilateral behind-the-ear (BTE) hearing aids will be used during the three month trial period.
Audiometric criteria must be met with the participants using appropriately fit hearing aids.
Ifthe participant has not been appropriately fit with amplification, hearing aids will be fit
prior to the completion of aided audiometric testing to ensure that candidacy criteria are
met.
The National Acoustics Laboratories' (NAL) and Desired Sensation Level (DSL), hearing aid
fitting strategies will be used, depending upon the age of the candidate (Dillon, 1999;
Scollie, et al, 2005) to assess the degree to which real-ear or coupler- predicted targets
are met for each patient. These fitting methods are based on extensive research and clinical
trials with patients with sensorineural hearing loss and are the most widely used fitting
formulas in clinical use.
Real-ear measures or DSL measures will be made to verify that the target of the frequency
response is within 5 dB per octave of the target measure.
For those candidates that wear hearing aids fit based on DSL targets, coupler-predicted
maximum output levels at 90 dB HL will not be exceeded.
1.4.5 Audiological Assessment The degree of hearing loss will be determined by a combination
of electrophysiological and behavioral tests including auditory brainstem response testing;
otoacoustic emission testing; steady state evoked potential testing; behavioral observation
audiometry, visual reinforcement audiometry and/or conditioned play audiometry. Audiological
assessment will include unaided and aided audiometric thresholds.
Unaided audiometric thresholds will be obtained for each ear, using insert earphones when
possible. Thresholds will also be obtained using the standard audiometric technique
conditioned play audiometric (CPA) techniques, visual reinforcement audiometric (VRA) and/or
behavioral observation (BOA) techniques for pure-tone air-conduction. The most appropriate
testing technique will be used according to the child's age. Bone conduction testing will be
completed using the above techniques. Aided audiometric thresholds will be obtained, using
narrowband noise, for each ear in the sound-field using standard audiometric techniques, CPA,
VRA or BOA with the speakers positioned at 45°-azimuth relative to the participant's head.
Results for unaided testing must be reported for the frequencies of 250, 500, 1000, 2000,
4000, 6000, and 8000 Hz. Results for aided testing needs to be reported for the frequencies
of 250, 500, 1000, 2000 and 4000 Hz.
A candidate is not considered enrolled until a properly executed Informed Consent form has
been obtained and along with the results of the preoperative candidacy evaluation and
reviewed and approved by the University of Iowa.
1.4.6 Baseline Speech Perception and Speech/Language Testing
In order to establish a baseline level of auditory function, auditory function will be
evaluated in the best aided condition using the following battery of speech language
production and subjective measures:
- The Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS) is a parent
questionnaire that consists of ten questions regarding a young infant or toddler's
auditory behavior , e.g. "Does the child spontaneously respond to his/her name in quiet
with auditory cues?" Each question is scored on a five point scale: O=never, 1=rarely,
2=occasionally, 3=frequently, and 4=always . The aim of this tool is to assess the
benefit of the child's personal amplification device(s). This questionnaire is generally
used during the cochlear implant work-up to assess hearing aid benefit. It is also used
post-cochlear implantation to chart the progress the child is making with his/her
cochlear implant when other formalized speech perception tests are not appropriate.
- Vocalizations/speech sample protocol: The samples will be elicited by presenting the
child with a set of age-appropriate toys with lexical labels that have phonemes
representing early consonant productions and the entire vowel quadrilateral.
Additionally, for children who are beginning to combine consonant and vowel productions
and likely to be between 18 and 29 months of age, we will use the assessment words
included in previous research conducted by Preisser, Hodson and Paden (1988). This word
list assesses 20 consonants, and all classes of phonemes, plus 10 consonant clusters.
The words will be elicited by objects or questions. Elicited productions will be
transcribed using broad International Phonetic Alphabet transcription. A number of
analyses will be completed in order to describe the patterns of speech acquisition. We
will use independent analyses (Stoel-Gammon & Dunn, 1985), allowing us to describe the
sounds and syllable structures produced by each child.
Specifically, we will analyze each participant's phonemic inventory in the initial and final
position with respect to place and manner of production rather than phonemic target. We will
also use relational analyses, from the point at which we obtain 90 different words. We will
then compare the child's production with the standard adult phonemic target. Speech
development will be assessed using the Percent Phoneme Correct and Percent Vowel Correct (PPC
or PVC ) {Shriberg and Kwiatkowski, 1982). When developmentally appropriate, phoneme
production skills will also be assessed using the Goldman-Fristoe Test o(Articulation-2
(Goldman & Fristoe, 2000). This measure has norms based on the performance of normal-hearing
children from age 2 years to 21 years.
- MacArthur Communicative Developmental Inventories (CD!) and the Minnesota Child
Development Inventor y (MinnCDI, Ireton & Thwing, 1974) are parent report measures that
provide an index of growth from birth to 30 months of age. The CD!has a ceiling on the
Wordsand Sentences version of 30 months of age; however the MinnCDI assesses development
up to 6 years of age. The CD!also has two forms: Gestures and Words for children aged 8-
to
16-months-old and Words and Sentences for children aged 17- to 30-months- old. In order
to create a single scale for these two measures, an item analysis using item response
theory (Drasgow, & Parsons, 1983) will be performed and the scores will be transformed
to a Rasch ability scale that provides a single equal-ability-interval scale suitable
for growth curve analysis.
- The Preschool Languag e Scale-3 (PLS-3) (Zimmerman, Steiner, & Pond 1992) is a
standardized language test that is used to measure the language development of children
with normal hearing aged 0 months to 83 months. The test evaluates "Expressive
Communication" and "Auditory Comprehension" and is designed to evaluate skills in a
variety of areas: vocal development, social communication , attention, semantics
(content), structure (form), and integrative thinking skills.
1.4.7 Surgical Procedure: The surgical procedure for the Iowa/Nucleus 10/ 10 mm cochlear
implant is different from the Nucleus Freedom cochlear implant. The surgical procedure for
the Iowa/Nucleus l 0/10 mm requires care to prevent inner ear damage. The cochleostomy is
smaller (approximately 0.5 mm in diameter compares to > 1.0 mm for the Nucleus Freedom
electrode). Soft surgery techniques will be used on both. The cochleostomy will be made in a
similar position for both devices. Creation of the cochleostomy requires control of bleeding
and removal of bone over the scala tympany exposing the endosteum. The endosteum is removed
with a .02 mm hook. No suctioning of perilymph is allowed. The devices are then advanced
slowly into the cochlea. For the Iowa/Nucleus 10/ 10 mm cochlear implant, the array is
inserted 10 mm into the scala tympani and 19 mm for the Nucleus Freedom cochlear implant.
Intraoperative impedance telemetry measurements will beperformed using CG,MPJ , MP2 and MP1+2
modes. The postoperative hospital stay is usually <23 hours.
1.5 Postoperative Procedures: 1.5.1 Device Activation The participants will be fit with
Freedom speech processors using a behind-the-ear (BTE) controller or body level controller.
Speech processing strategies used with this device will include ACE (RE), ACE, CIS (RE), CIS
or SPEAK, which are all FDA approved for children . Threshold (T) and comfort (C) values will
be measured for the electrical stimulation for each of the channels (10 on the Iowa/Nucleus
10/ 10 mm and 24 on the Nucleus Freedom). Impedance telemetry results using common ground
(CG) and monopolar (MPI , MP2 and MP 1+2) stimulation modes will also be recorded . This
information will be used to program the speech processor and also to monitor the device for
possible degradation of function and/or damage to neural elements.
The process of adjusting the speech processor programs takes place over a period of several
months for young children. Techniques used for programming speech processors of young
children are standard audiological techniques for children in this age group and require two
audiologists to perform . Play audiometry techniques will be used, as appropriate for the
child's developmental level, to determine electrical threshold levels for the channels in a
child's program. Behavioral observation or visual reinforcement
audiometry will be used for children who are unable to perform play audiometry.
Electrophysiological data will verify levels obtained behaviorally or in those instances when
behavioral information is limited. Electrical comfort levels will be set conservatively on
initial programs to ensure a comfortable listening level for the child. Levels will be
increased gradually at home and over several programming sessions during the first year of
implant use. This approach is necessary in order to ensure comfortable listening levels are
not exceeded in children who are unable to give us direct input as to how loud sounds are
through the cochlear implant.
Parents and professionals working with the children will receive extensive counseling
regarding how the equipment functions, maintenance and troubleshooting of the device, and
progression of auditory skills of children who cochlear implants. This is accomplished during
visits to the center and through in-service training offered locally via the fiberoptic
teleconferences.
1.5.2 Programming Follow-up Following surgical implantation of the device and an adequate
healing period, the implants will be activated (usually 4 to 6 weeks after surgery) and
programmed. Thereafter, prior to the 4-month post-operative evaluation, three additional
programming follow-up sessions will be scheduled at 2 weeks, 1 month, and 2 months as it is
not unusual for threshold and comfort levels to change during the initial postactivation
period. The follow-up sessions will allow the participant 's T- and C-levels to be checked as
well as any programming adjustments to be made based on the participant's initial experience
with the device. Electrical impedance measures also will be obtained.
Additional programming at additional postactivation intervals will be assessed and conducted
as needed.
1.5.3 Listening conditions
The following describes the listening modes used by the child during each speech perception
or speech/language measure:
- Iowa/Nucleus 10/10 mm electrode array only (unilateral),
- Nucleus Freedom electrode array only (unilateral),
- Iowa/Nucleus 10/ 10 mm and Nucleus Freedom electrodes together (bilateral).
1.5.4 Speech Perception and Speech/Language Testing: Speech perception and speech/language
development will be assessed longitudinally at 4, 8, 12, 18, 24 months, and annually
thereafter through five years of age. The tests or questionnaires will be administered age
appropriately.
1.5.4.1 Speech Perception
- The Infant-Toddler Meaningful Auditor y Integration Scale {!T-MAIS) or Meaningful
Auditory Integration Scale (MAIS) is a parent questionnaire that consists of ten
questions regarding a young infant or toddler's auditory behavior, e.g. "Does the child
spontaneously respond to his/her name in quiet with auditory cues?" Each question is
scored on a five point scale: O=never,
1. rarely , 2=occasionally, 3=frequently, and 4=always. The aim of this tool is to
assess the benefit of the child's personal amplification device(s). This
questionnaire is generally used during the cochlear implant work-up to assess
hearing aid benefit. It is also used post-cochlear implantation to chart the
progress the child is making with his/her cochlear implant when other formalized
speech perception tests are not appropriate.
- The Glendonald Auditor y Screening Procedure Word Test (GASP) contains 12
single-syllable and multisyllable words. The child will be tested in the bilateral
listening condition. This test is always administered in a live-voice mode. The child is
asked to repeat the word presented by the clinician. The child is encouraged to use sign
if his or her verbal approximations are not clear to the clinician. This test is the
easiest open-set measure in this battery because it includes common vocabulary and the
speaker is familiar. It can be administered to children as young as two years of age.
- Iowa Children's Vowel Test requires the identification of a monosyllabic word from a
closed set of four words (e.g., toe, toy, tie, two) varying only in vowel content (place
and height). Ifthe child performs at 80% or higher, multi-talker babble at a +7 dB-C SIN
will be added. It will be administered in both the unilateral and bilateral listening
conditions at 70 dB C.
- The CID Four Choice Spondee and Monosyllable tests require the identification of a
spondee or monosyllable from a set of four spondees (i.e., French fry, airplane, hotdog,
popcorn) or monosyllables (i.e., ball, book, bird, boat), respectively presented in
quiet. The CID test will be scored as total number of words correct. It will be
administered in both the unilateral and bilateral listening conditions at 70 dB C.
- The CRISP JR. Test will be used to assess speech perception in noise in both the
unilateral and bilateral listening conditions for children ages 2.5-5 years. This test
is designed with 12 monosyllabic and 4 bi-syllabic words that are within the receptive
language and vocabulary of 2.5- to 3.0-year-old children (Garadat & Litovsky, 2007).
This test was developed and is licensed from the University of Wisconsin - Madison .
Speech perception will be measured using a four- alternative forced choice paradigm.
Target speech and background two-talker female babble will be presented from the front
(0 degrees). Speech reception thresholds are measured adaptively using a
three-down/one-up algorithm finding the 79.4% correct level.
- The Multisyllabic Lexical Neighborhood Test (MLNT) and Lexical Neighborhood Test (LNT)
are two open-set word recognition tests. The experimenter gives a list of 24 words and
the participants are expected to repeat the word after each presentation. The MLNT
consists of two parallel lists. The LNT and MLNT are based on the lexical
characteristics of word frequency and neighborhood density, and include words found in
the vocabularies of children age three to five.
1.5.4.2 Speech and Language Testing -all administered in the bilateral listening condition
- Vocalizations/speech samples as described above in baseline/pre-operative testing will
be collected.
- MacArthur Communicative Developmental Inventories (CDI) and the Minnesota Child
Development Inventory (MinnCDI, Ireton & Thwing, 1974) as described above in
baseline/pre-operative testing will be collected.
- The Preschool Language Scale-3 (PLS-3), Zimmerman, Steiner, & Pond, 1992) as described
above in baseline/pre-operative testing will be collected.
- The child's mean length of utterance (MLU) and number of different words (NDW) will be
computed a speech sample of at least 50 utterances and will be based upon 100 utterances
once this level of production is reached.
- Peabod y Picture Vocabulary Development Scale. This is a receptive vocabulary test that
will be administered in an auditory/visual condition. The test provides an index of
receptive vocabulary skill.
- Ex pressive Vocabulary Test. This is an expressive vocabulary test that provides an
index of expressive vocabulary skill.
1.5.5 Psychophysical and Electrical Impedance Measurements: The following psychophysical and
electrical impedance measurements will be attempted at 4, 8, 12, 18, 24 months, and annually
there after through five years of age.
1. Electrical thresholds measured in current level.
2. Electrical maximum comfort levels measured in current level.
3. Impedance telemetry results using common ground (CG) and monopolar (MPI, MP2, MP I +2)
stimulation modes.
Because this is a feasibility study, we will only be implanting up to 10 children. We
recognize that this small number of subjects may not afford us enough statistical power to
adequately answer all questions associated with using an Iowa/Nucleus 10/ 10 mm and a Nucleus
Freedom electrode array in contralateral ears in pediatric subjects who have bilateral severe
to profound hearing loss. However, it may lend us foundational knowledge to assess whether
the Iowa/Nucleus 10/ 10 mm and Nucleus Freedom implants can provide useful bilateral hearing
while at the same time preserving the scala media, organ of Corti and supporting cells of the
ear implanted with the Iowa/Nucleus 1Oil0 mm array for future advances in molecular and/or
genetic treatments of the inner ear.
