Expanded Indications in the MED-EL Pediatric Cochlear Implant Population

Hearing Loss, Cochlear Clinical Trial

Official title:

Expanded Indications in the MED-EL Pediatric Cochlear Implant Population

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04130113
• Other study ID #: G180269
• Status: Recruiting
• Phase: N/A
• Start date: September 18, 2019
• Est. completion date: November 30, 2022

Study information

• Verified date: October 2019
• Source: Ann & Robert H Lurie Children's Hospital of Chicago
• Contact: Nancy Young, MD
• Phone: 312-227-6239
• Email: nyoung[@]luriechildrens.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Sixty (60) subjects between the ages of 7 months and 5 years, 11 months will be implanted with the MED-EL SYNCHRONY/SYNCHRONY 2 Cochlear Implant System. All subjects will demonstrate a severe to profound sensorineural hearing loss (SNHL) in the high frequencies (2000 Hz and above) and insufficient functional access to sound with appropriately fit amplification and aural habilitation. Additionally, subjects implanted under 12 months of age will demonstrate a severe to profound sensorineural hearing loss, defined by a 3-frequency Pure Tone Average (PTA) of ≥ 70 dB HL at 500, 1000 and 2000 Hz, while subjects 12 months to 5 years, 11 months of age will demonstrate a mild to profound sensorineural hearing loss in the low frequencies, defined by a 3-frequency PTA of ≥ 25 dB HL at 500, 1000 and 2000 Hz. For the purposes of this study, insufficient functional access to sound for children who lack the requisite language to complete open-set word recognition testing will be based on the LittlEARS Auditory Questionnaire (LEAQ) and defined as a Total Score below the expected value for normal hearing (NH) children of the same chronological age1. For children with the requisite language to complete MLNT/LNT testing, insufficient functional access to sound will be defined by word recognition scores of ≤ 60% on the MLNT/LNT. Subjects will be followed for twelve (12) months following initial activation of the audio processor, with post-operative evaluations occurring at device.

Description:

First enacted in 2000, the federal Early Hearing Detection and Intervention (EHDI) Act aims to identify hearing loss and provide early intervention at an early age for children in all 50 states. According to the CDC, untreated hearing loss not only delays a child's speech and language development, but also his or her thinking, learning and social skills. The first three goals of the EHDI program are often referred to as the 1-3-6 plan, meaning that all newborns will be screened for hearing loss before one month of age and, if needed, undergo a diagnostic audiological evaluation before 3 months of age and receive appropriate early intervention services before six months of age.

With the current FDA-approved indications for cochlear implantation limited to children 12 months of age and older, this creates a significant gap between identification and appropriate intervention for children with hearing loss that cannot be optimally fit with conventional amplification. This has created a large population of children who are fit with hearing aids by 6 months of age and must wait an additional 6 months without sufficient access to spoken language before receiving a cochlear implant. For children with congenital hearing loss, this results in greater developmental delays and additional hardships in closing that gap. The current study aims to evaluate the safety and effectiveness of implantation in children below the age of 12 months and, thus, reduce the gap between identification of hearing loss and appropriate intervention.

A number of studies have published data on the safety and effectiveness of cochlear implantation in children below 12 months of age. Several studies have demonstrated that cochlear implantation can be performed safely in children 6-12 months of age, with no greater surgical or anesthetic complications than those expected in older children and adults.

Furthermore, a number of studies report substantial benefit in children implanted between 6 and 12 months of age, compared to those implanted after 12 months of age. In 2000, Waltzman and Roland concluded that "it is possible that severely to profoundly deaf children can avoid the gaps in auditory perception that require learning at a faster-than-normal rate to enable them to reach the age-appropriate levels." In 2004, Lesinski-Schiedat et al. reported that children implanted before the age of 1 year show a superior rate of progress and greatly superior speech understanding at 2.5 years of age, compared to children implanted between the ages of 1 and 2 years. A 2005 publication by Colletti et al. found that children implanted prior to 12 months of age show a more rapid increase in Categories of Auditory Performance test (CAP) scores than those implanted after 12 months. In some cases, early implantation led to speech and language development similar to that of normal hearing children. Schauwers et al. reported that "children implanted in their first year of life showed a normal CAP development as early as 3 months after implantation."

While early studies indicate that the sensitive period for word identification extends to approximately three years of age, more recent studies demonstrate that speech production and language development have much earlier sensitive periods. Leigh and colleagues suggest "that the critical period for speech perception extends beyond the first year of life, whereas the critical period for language development is within the first year of life." This, in part, may explain contradictory findings within and across studies showing a limited or modest advantage for speech perception and auditory skill development,versus more significant benefits for speech production, language development, and developmental trajectories, in children implanted by 12 months of age, compared to those implanted after 12 months of age. In general, however, many studies agree that language delay is positively correlated with age at implantation.

There is also a growing body of evidence that cochlear implants can provide significant improvements for children with residual hearing, compared to traditional hearing aids. Recent studies have shown that pediatric cochlear implant candidates with pre-operative thresholds and speech perception scores outside of the current FDA-approved criteria continue to struggle with conventional amplification. Authors suggest that traditional hearing aids provide inadequate high-frequency amplification, particularly for patients with steeply sloping hearing losses (the amount of loss changes dramatically from the low to high-frequency area), resulting in poorer speech understanding in noise and at presentation levels below 70 dB SPL. Wilson and colleagues also suggest that "the use of frequency transposition aids will show good detection, but the more important discrimination resolution will be compromised." Furthermore, the amount of gain required with conventional amplification for severe losses can result in distortions of the speech signal.

A number of studies in both children and adults with severe hearing loss or a ski-slope configuration demonstrate significant benefit with cochlear implants and combined electric-acoustic stimulation, compared to acoustic amplification. In 2016, Wilson et al. reported that "all children in the investigator's group have preserved hearing and perform better with their CI than with their hearing aids, regardless of the level of preservation." Gratacap and colleagues also demonstrated post-operative improvement in word scores for children with varying degrees and configurations of residual hearing, stratified into five groups. Group 1, for example, included five children with low-frequency residual hearing and average open-set word scores of 79 percent, pre-operatively, and 86 percent post-operatively. Overall, pre-operative open-set word scores were greater than 50 percent in 22 of 53 children, with a group mean for all subjects of 48 percent. The group mean, open-set word scores improved to 74 percent at 12 months and 81 percent at 24 months post-operatively. All five groups showed statistically significant improvement on the open-set word list (OSW) at 24 months post-operatively, and the authors concluded that "CIs provide better results compared with hearing aids in children with residual hearing".

Preliminary studies on the use of electric-acoustic stimulation (EAS) in children demonstrate hearing preservation, improved speech perception in quiet and noise, subjective benefit, and improved classroom listening skills. Kuthubutheen et al. demonstrated significant improvement in both monosyllabic word scores and sentence scores in children with normal or aidable residual hearing in the low frequencies. Pre-operative word scores on the NU-CHIP were between 50 and 72 percent, for an average of 57 percent. Subjects showed improved speech perception scores on monosyllabic word and sentences in quiet and in noise at three, six, twelve, and 18 months post-activation, compared to pre-operative performance with hearing aids. Monosyllabic word scores on the NU-CHIP (test for young children includes pictures) at 18 months post-activation ranged from 72 to 98 percent, for an average of 86 percent and a group mean improvement of 29 percentage points.

Multi-center clinical trials in adults with the MED-EL Electric-Acoustic Stimulation (EAS) System and Nucleus Hybrid show significant improvement with combined electric and acoustic stimulation for patients with normal or aidable residual hearing in the low frequencies. FDA-approved indications for this population include adults with pre-operative monosyllabic word scores of up to 60% in the ear to be implanted. Clinical trials with the MED-EL EAS System showed significant improvement post-operatively in both the EAS and CI-alone conditions, compared to pre-operative performance with hearing aids. This demonstrates that patients with residual hearing and pre-operative performance of 60% can benefit from cochlear implantation, even without acoustic amplification.

Recent publications argue that candidacy criteria in the pediatric cochlear implant population should be at least equal to that in the adult population. Gifford contends that "given the critical importance of hearing for various aspects of a child's neurodevelopmental abilities, having such stringent criteria for pediatric implant candidacy holds considerable potential to negatively impact a child's neural development, academic success, psychosocial skills, and overall quality of life." Similarly, Carlson et al. state that "ironically, audiometric criteria for cochlear implantation are significantly more restrictive for pediatric patients compared to adults, yet it is the early formative years of life that are most critical to speech and language development." Thus, many authors advocate for a large-scale reassessment of pediatric cochlear implant candidacy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: November 30, 2022
• Est. primary completion date: September 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 7 Months to 6 Years

Eligibility

Inclusion Criteria:

• Children 7 months to 5 years, 11 months of age at the time of implantation Page 15 of 55

• Bilateral, severe to profound sensorineural hearing loss (SNHL) in the high frequencies (> 70 dB HL at 2000 Hz and above) and:

• For subjects implanted under 12 months of age: bilateral, severe to profound SNHL, defined by a 3-frequency Pure Tone Average (PTA) of = 70 dB HL at 500, 1000 and 2000 Hz

• For subjects implanted at 12 months to 5 years, 11 months of age: bilateral, mild to profound sensorineural hearing loss in the low frequencies, defined by a 3-frequency PTA of = 25 dB HL at 500, 1000 and 2000 Hz.

• For bilateral implantation, unaided audiometric thresholds of = 70 dB HL at each required frequency between 250 and 8000 Hz.

• Insufficient functional access to sound with appropriately fit amplification and aural habilitation (based on clinic standard of care), defined as:

• For children who lack the requisite language to complete open-set word recognition testing: LEAQ Total Score below the expected value for normal hearing (NH) children of the same chronological age1 in the everyday listening condition, or

• For children with the requisite language to complete open-set word recognition testing: Monosyllabic word score < 60% on the MLNT/LNT at 60 dB SPL, in the ear(s) to be implanted.

• Objective measures consistent with repeatable unaided audiometric thresholds: optional for subjects 12 months of age and older with reliable, ear-specific behavioral thresholds. Specific measure (e.g., ABR, ASSR, DPOAE, TOAE, etc.), protocol used, and clinical interpretation should be based on clinic judgement and standard of care. (Note: Candidates with Auditory Neuropathy Spectrum Disorder (ANSD) may be considered, if all other inclusion and exclusion criteria are met.)

• Radiologic evidence of potential for full insertion with one of the included electrode arrays in the ear(s) to be implanted

• Ability to undergo general anesthesia. Subjects implanted under 12 months of age must meet the criteria for ASA (American Society of Anesthesiologists) Class 1 or Class 2, as determined by a board-certified anesthesiologist and according to the American Society of Anesthesiologists Physical Status Classification System43

• At least one parent/guardian who is fluent in one of the available languages of the LEAQ

• Parental commitment to study parameters, as determined by the implant team

Exclusion Criteria:

• Magnetic Resonance Imaging (MRI) evidence of cochlear nerve aplasia/hypoplasia in the ear(s) to be implanted

• Active middle ear infection

• Permanent conductive hearing loss, defined as a persistent air-bone-gap (ABG) of greater than 10 dB HL at 3 or more frequencies and diagnosed pathology of the outer or middle ear. (Note: Candidates with a pseudo-conductive hearing loss (like that seen in Enlarged Vestibular Aqueducts) and no diagnosed pathology of the outer or middle ear may be considered, if all other inclusion and exclusion criteria are met.)

• Treatable mixed hearing loss

• Current or history of meningitis

• Common cavity in the ear(s) to be implanted

• Skin or scalp condition precluding use of external audio processor

• Suspected cognitive impairment, organic brain dysfunction, or syndromic etiology that may affect performance (based on medical history, early intervention services, clinical judgment and/or developmental milestones)

• ASA (American Society of Anesthesiologists) Class 3 or higher in subjects under 12 months of age, as determined by a board-certified anesthesiologist and according to the American Society of Anesthesiologists Physical Status Classification System43

• History of prior use of a hearing implant

• Unrealistic parental/patient expectations

• Child is not able to complete developmentally-appropriate speech perception testing in English

Related Conditions & MeSH terms

• Cochlear Implant Surgery
• Hearing Loss
• Hearing Loss, Cochlear
• Hearing Loss, Sensorineural

Intervention

Device:
• Cochlear Implant Surgery
Implanting Synchrony or Synchrony 2 from Med EL

Locations

Country	Name	City	State
United States	Lurie Children's Hospital	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Ann & Robert H Lurie Children's Hospital of Chicago	Med-El Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate the effectiveness of MED-EL cochlear implants for newly implanted children	Little Ears Auditory Questionnaire (LEAQ) total Score will be 25 or greater (out of 35 total points) for subjects who lacked the requisite language to complete MLNT/LNT testing pre-operatively.	12 months
Primary	Improvement in percentage in the MLNT/LNT testing	Improvement of 10 percentage points or greater in the Multi-Syllabic Lexical Neighborhood Test/ Lexical Neighborhood Test (MLNT/LNT) testing in the individual implanted ear(s) post-operatively, compared to pre-operative scores with hearing aids.	12 months
Secondary	Compare post-operative outcomes with the MED-EL SYNCHRONY/SYNCHRONY 2 Cochlear Implant System to pre-operative performance with appropriately fit hearing aids	Look at the change from baseline in Total Score on the LittlEARS Auditory Questionnaire (LEAQ) at 12 months post-activation in the everyday listening condition. The LEAQ is a 35-item parent questionnaire available in 40 languages that has been studied extensively and validated in a number of languages, including American English and Spanish. A Total Score of 25 or greater on the LEAQ is a primary effectiveness endpoint for subjects who lack the requisite language to complete open-set word recognition testing pre-operatively. The LEAQ will be administered pre-operatively, at initial activation and at one, three, six, and twelve months post-activation for all subjects until ceiling performance is reached. Ceiling performance is defined as = 33/35 on the LEAQ.	12 months
Secondary	Compare post-operative outcomes with the MED-EL SYNCHRONY/SYNCHRONY 2 Cochlear Implant System to pre-operative performance with appropriately fit hearing aids.	Look at the change from baseline in Total Score on the Auditory Skills Questionnaire (ASC) at 12 months post-activation in the everyday listening condition. The ASC is a 35-item checklist that incorporates both family and clinician observations. It is administered in an interview format by the clinician and showed "excellent validity when compared to the commonly used [Infant-Toddler Meaningful Auditory Integration Scale] IT-MAIS". ASC will be administered pre-operatively, at initial activation and at one, three, six, and twelve months post-activation for all and = 65/70 on the ASC.	12 months
Secondary	Compare post-operative outcomes with the MED-EL SYNCHRONY/SYNCHRONY 2 Cochlear Implant System to pre-operative performance with appropriately fit hearing aids	Percent change from baseline on a hierarchy of developmentally-appropriate measures of word and sentence recognition in the implanted ear(s), including the ESP, MLNT, LNT, CNC, Pediatric AzBio in quiet and noise	12 months