Natural History in Children up to 10 Years With Moderate to Profound Hearing Loss Due to Mutations in GJB2 / OTOF Genes (Otoconex)

Longitudinal Study of the Natural History of Two Autosomal Recessive Non Syndromic Deafness (DFNB1A and DFNB9) in Children up to 10 Years of Age

The purpose of this study is to follow the natural history of non-syndromic hearing loss caused by mutations in two genes (GJB2 or OTOF) in children up to 10 years of age.

Study Overview

• Status: Recruiting
• Conditions: Sensorineural Hearing Loss, Bilateral; Congenital Deafness; AUNB1; DFNB1A; DFNB9; OTOF Gene Mutation; GJB2 Gene Mutation
• Intervention / Treatment: Other: Pure Tone Audiometry Assessment; Other: Quality of Life Questionnaires

Detailed Description

The study aims to:

• better describe the prevalence of cases of DFNB1A and DFNB9, including the type of mutations, and to assess the clinical course of the disease in children up to 10 years of age who have a moderate to profound deafness.
• better understand the audiological and genetic characteristics of the participants with congenital versus evolutive DFNB1A and DFNB9 deafness.

• Study Type: Observational
• Enrollment (Estimated): 180

Contacts and Locations

• Study Contact: Name: Géraldine HONNET, MD; Email: geraldine.honnet@sensorion-pharma.com
• Study Contact Backup: Name: Judith LAREDO, PhD; Phone Number: +33(0)663737108; Email: judith.laredo@sensorion-pharma.com

Study Locations

• France
  • Paris, France
    • Recruiting
    • Necker Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 8 years (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Male and female participants aged ≤ 10 years at selection, with a diagnosis of bilateral, moderate to profound, sensorineural, non-syndromic hearing loss, with genotyping results showing mutation(s) in GJB2 or OTOF genes, with and without cochlear implant (CI).

Description

Main Inclusion Criteria:

Participants meeting all the following main inclusion criteria will be eligible to participate in the study:

• Aged ≤ 10 years on the date of signed informed consent;
• With a diagnosis of non-syndromic, bilateral, moderate to profound, sensorineural hearing loss (according to the American Speech Language-Hearing Association);
• With documented genotyping results showing mutation(s) in GJB2 or OTOF genes;
• Written informed consent as required by local regulations.
• Either without Cochlear Implant, or with unilateral or bilateral Cochlear Implant(s)

Exclusion Criteria:

Participants presenting with any of the following main exclusion criteria will not be included in the study

• Other type of deafness, such as unilateral deafness, persistent conductive deafness, malformation syndrome, syndromic deafness, known familial deafness linked to mutations in other genes than OTOF or GJB2;
• Documented genotyping results showing pathogenic mutation(s) in other gene(s) than GJB2 or OTOF genes in the tested panel;
• Unable and/or unwilling to comply with all the protocol requirements and/or study procedures.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort 1a; Patients without Cochlear Implant, with or without Hearing Aid(s) at study entry	Other: Pure Tone Audiometry Assessment; Collection of Pure Tone Audiometry data performed in routine practice during study period; Other: Quality of Life Questionnaires; Collection of Quality of Life questionnaire's answers during study period
Cohort 1b; Patients receiving unilateral or bilateral Cochlear Implant(s) during the study period, after study entry	Other: Pure Tone Audiometry Assessment; Collection of Pure Tone Audiometry data performed in routine practice during study period; Other: Quality of Life Questionnaires; Collection of Quality of Life questionnaire's answers during study period
Cohort 2; Patients with Cochlear Implant(s) (unilateral or bilateral) at study entry	Other: Pure Tone Audiometry Assessment; Collection of Pure Tone Audiometry data performed in routine practice during study period; Other: Quality of Life Questionnaires; Collection of Quality of Life questionnaire's answers during study period

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Audiological characteristics	Pure Tone Audiometry, thresholds on 500, 1000, 2000, 4000 Hz Speech audiometry	Up to 2 years
Electrophysiological characteristics: ABR	Auditory Brainstem Response, thresholds	Up to 2 years
Electrophysiological characteristics: OAE	Otoacoustic Emissions thresholds	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genotypic and phenotypic characterisation	Genotypic and phenotypic characterisation of the population will be assessed in Cohort 1a. Frequency of autosomal recessive 1 and 9 deafness (GJB2 and OTOF genes) and type of mutations will be evaluated among the screened population of male and female children aged ≤ 10 years, with a diagnosis of bilateral moderate to profound, sensorineural, non-syndromic hearing loss.	1 Day
Hearing-related Quality of Life questionnaire	The Hearing Environments And Reflection on Quality of Life (HEAR-QL) measurement questionnaires will be used to assess the quality of life of children. Depending on child's age, the HEAR-QL questionnaires will be completed either by parents/caregivers (child aged 2 to 6 years) either by the child (child aged 7 to 12 years). The items of the questionnaires are focused on situations affecting interactions with family and friends, participation in social and school activities, and impact of Hearing Loss on the child's emotional well being. Children/parents will be asked to rate how frequently each item was a problem for them/child in the past month using the following response choices: "never" (1), "almost never" (2), "sometimes" (3), "often" (4), or "Almost always" (5). Scores are transformed with 1=100, 2=75, 3=50, 4=25, and 5=0 points. Higher scores indicate higher perceived Quality Of Life.	Up to 2 years

Collaborators and Investigators

• Sponsor: Sensorion
• Investigators: Principal Investigator: Natalie LOUNDON, MD, Necker Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2022
• Primary Completion (Estimated): November 18, 2026
• Study Completion (Estimated): November 18, 2026

Study Registration Dates

• First Submitted: May 16, 2022
• First Submitted That Met QC Criteria: May 30, 2022
• First Posted (Actual): June 2, 2022

Study Record Updates

• Last Update Posted (Actual): September 6, 2023
• Last Update Submitted That Met QC Criteria: September 1, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Otorhinolaryngologic Diseases; Ear Diseases; Sensation Disorders; Hearing Disorders; Hearing Loss; Deafness; Hearing Loss, Sensorineural; Hearing Loss, Bilateral
• Other Study ID Numbers: SENS-NH01

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: No