Immunity After Cochlear Implantation and Perilymph Molecular Profiles in Sensorineural Hearing Loss — PERILOTO  

Sensorineural Hearing Loss Clinical Trial

Official title: Study on the Inner Ear Immunisation Post-cohlear Implantation and Perilymph Molecular Profiling in Sensorineural Hearing Loss

Status Recruiting

Clinical Trial Summary

Many patients receiving cochlear implant (CI) have some residual hearing prior to implantation surgery. However, approximately one third of them will lose it in next 6 months after cochlear implantation. Although the mechanisms involved in the residual audition loss remain unknown, animal experiments suggest the role of inflammatory or immune reaction in the cochlea. The goal of this project is to search in the perilymph (a fluid which fills the scala vestibuli and scala tympani of the cochlea) some predictive biomarkers of the residual hearing loss using modern proteomics and immunological techniques. A parallel search for blood biomarkers of post-implantation residual hearing loss and for molecular and cellular evidences of immune response to cochlear implantation will be performed.

The study will recruit 50 subjects-candidates for cochlear implantation surgery; 30 normally hearing individuals eligible for other types of otological interventions will form a control group. For all the participants blood samples will be collected and preserved. In addition, the perilymph sampling will be performed during cochlear implantation surgery.

This project relies on the calculation that from 50 patients post-cochlear implantation, 15 patients will form a group with maintained residual hearing and 15 will display delayed hearing loss. For these 30 subjects together with the control group the blood biomarkers search will be performed.

For the group of implanted patients, the follow-up will last for 12 months with 6 visits in total :

• the inclusion visit V0 during which the study will be presented and the consent form will be signed

• the surgery visit V1 with blood sample and perilymph collection

• the activation visit V2, 1 month ± 1 week after V1, visit V3 3 months ± 7 days after V1, V4 6 months ± 7 days after V1, V5 12 months ± 1 month after V1. During each of this visit blood sampling will be performed.

For the control group, the follow up will be 6 months long with 4 visits in total arranged during the routine follow-up appointments:

• the inclusion visit V0 during which the study will be presented and the consent form will be signed

• the surgery visit V1, the 1 month visit V2 and the 6 months visit V3 during which the blood sampling will be performed.

Clinical Trial Description

With the progress of technologies and surgical methods, cochlear implantation, initially proposed only to patients with completely non-functional inner ear, can be now performed on individuals with still some measurable hearing left in some frequencies. Such patients can additionally benefit from a special treatment by electric-acoustic stimulation (EAS). Combining the electric stimulation with cochlear implant (CI) and acoustic amplification of residual hearing using a conventional hearing aid (HA) can drastically improve one's quality of life and ameliorate the performance in noisy environment as well as music perception.

Since the main condition for EAS is the residual hearing preservation, it is important to understand the reasons of its loss post-cochlear implantation. This loss can occur in 2 periods:

• Early after surgery (˂ 1 month): mainly due to the trauma from electrode insertion. This risk decreases with the development of surgical techniques. Another possible reason is early inflammation processes in the cochleae.

• Later after surgery (˃ 1 month): occurs mainly about 3 months post-implantation in 30-40 % of patients. This loss is the main reason for dropping out the EAS leaving the patient to rely on CI only.

Animal studies suggest that the delayed residual hearing loss might happen as consequence of cochlear fibrosis development, supposedly due to the inflammation and foreign body response to the CI materials within the cochlea. In its natural state, the cochlea does not contain any immune cells and is well protected from immune stimulation by infectious agents. Cochlear implantation, however, provides a single clinical cause for infectious or autoimmune fibrosis. Such immune response might be provoked by autoantigens against cochlear proteins like Cochline or TectB. This study aims to search blood markers of immunisation against inner ear proteins after cochlear implantation. Another goal is to seek potential biomarkers of delayed residual hearing loss directly in perilymph. Proteomic analysis will be performed using Liquid Chromatography - High Resolution Mass Spectroscopy (HRMS) technique.

The main objective of this study is

• to identify, in the perilymph of implanted patients, biomarkers predictive of the delayed residual hearing loss

• to identify blood biomarkers predictive of delayed residual hearing loss in implanted patients

The secondary objectives are

• to describe qualitatively and quantitatively the time evolution for blood biomarkers of interest after cochlear implantation

• to correlate quantitative values of identified biomarkers with clinical data of implanted patients

• to identify perilymph and blood biomarkers of early residual hearing loss post-cochlear implantation

• depending on molecular profiles identified, to study metabolic pathways and mechanisms involved in delayed residual hearing loss post-cochlear implantation

• to seek for blood indicators in favour of anti-cochlear immunisation through screening for peripheral blood mononuclear cells (PBMC)

• to create a bio collection of human perilymph and blood serum biobank of cochlear implants users for future proteomics/molecular studies ;

Related Conditions & MeSH terms

• Deafness
• Hearing Loss
• Hearing Loss, Sensorineural
• Sensorineural Hearing Loss

• NCT number: NCT05670158
• Study type: Interventional
• Source: University Hospital, Montpellier
• Contact: Akil Kaderbay, MD
• Phone: +33467336890
• Email: a-kaderbay@chu-montpellier.fr
• Status: Recruiting
• Phase: N/A
• Start date: December 7, 2023
• Completion date: March 2027