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

NCT05670158 | Recruiting

• 1 other identifier: RECHMPL21_0380
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Sensorineural Hearing Loss

Keywords

Perilymph; Proteomics; Metabolomics; Sensorineural hearing loss; Residual hearing; Cochlear implantation

Outcome Measures

Primary Outcomes (2)

• Expression levels of proteins and metabolites in the perilymph before surgery in the 2 groups of implanted patients

  Expression levels of proteins and metabolites identified by high-resolution mass spectrometry (Lc-HRMS) in the perilymph of group 1, "delayed residual hearing loss" and group 2, "maintained residual hearing" patients, collected before cochlear implantation surgery

  Before cochlear implantation surgery (V1)

• Expression levels of proteins and metabolites in the blood before surgery in the 2 groups of implanted patients

  Expression levels of proteins and metabolites identified by high-resolution mass spectrometry (Lc-HRMS) in the blood of group 1 "delayed residual hearing loss" and group 2 "maintained residual hearing" patients, collected before cochlear implantation surgery

  Before cochlear implantation surgery (V1)

Secondary Outcomes (9)

• PBMC cell counting

  Before cochlear implantation surgery (V1)

• PBMC cell counting

  At 1 month post-implantation (V2)

• PBMC cell counting

  At 3 months post-implantation (V3)

• PBMC cell counting

  At 6 months post-implantation (V4)

• PBMC cell counting

  At 12 months post-implantation (V5)

Study Arms (2)

"Cochlear Implantation" group

EXPERIMENTAL

50 patients with sensorineural hearing loss eligible for cochlear implantation surgery. The blood and perilymph sampling will be performed during surgery (visit V1). The blood sampling will be additionally done during the visits V2, V3 and V4. After the visit V4, this arm will be subdivided into 2 groups: group 1, 15 patients with the delayed residual hearing loss, and group 2,15 patients with preserved residual hearing. For these 30 patients, blood sampling will be also performed during the visit V5.

Biological: Blood sampling; Procedure: Perilymph sampling

Control group

OTHER

30 normally hearing patients who will undergo through an otological surgery other than cochlear implantation. A blood sampling will be performed during surgery (visit V1) as well as during the visits V2 and V3.

Biological: Blood sampling

Interventions

Blood sampling BIOLOGICAL

Blood will be collected into 2 EDTA and 1 heparin tube. The 2 EDTA tubes (4ml of blood in each) will be transported on ice to the proteomics platform in the next three hours, centrifuged and stored on -80 degrees Celcius in low-binding tubes for further molecular analysis. 1 heparin tube (5mL) will be sent to the Bacteriology-Virology Department for the active PBMC counting.

"Cochlear Implantation" group; Control group

Perilymph sampling PROCEDURE

The perilymph collection will be performed during the cochlear implantation surgery at the same time as the round window opening. 5 to 15 microliters will be aspirated using an atraumatic spinal needle mounted onto 1 ml insulin syringe.

"Cochlear Implantation" group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged 18 years or more
• Indication for the cochlear implantation surgery according to the criteria of French National Authority for Health (Severe to profound sensorineural deafness with indication for cochlear implant surgery: Intelligibility less than or equal to 50% when performing vocal audiometry tests with Fournier's list in free field with recent devices.)
• Presence of "useful" residual hearing ≤ 80 dB on at least 2 consecutive frequencies (in air conduction) from the range 125, 250, 500, 1000 kHz on pure-tone audiometry
• Patients given their free and informed written consent
• Patients affiliated to a French social security system
• Patients aged 18 years or more
• Indication for otological surgery of the middle ear (excluding active infectious or inflammatory pathology e.g. myringoplasty, ossiculoplasty, cure for otosclerosis)
• Normal hearing (non affected inner ear): average hearing loss (mean threshold for the frequencies 500, 1000, 2000, 4000 Hz) ≤ 35 dB in bone conduction
• Patients given their free and informed written consent
• Patients affiliated to a French social security system

You may not qualify if:

• Contraindication to surgery detected during the preoperative assessment
• Pre-implantation cochlear assessment unfavorable to the implantation surgery
• Absence of residual hearing shown by preoperative audiometry
• History of bacterial labyrinthitis or bacterial meningitis
• Cochlear ossification shown on preoperative imaging
• Homozygous pathogenic mutations identified by molecular diagnosis of the SCL26A5 (prestin), TECTB (Beta-Tectorin) genes, and heterozygous of the COCH gene (Cochlin) prior to implantation (if available)
• Vulnerable subject: minors, protected adults as defined by the Public Health Code, pregnant or breastfeeding women, subject under guardianship or subject deprived of liberty
• Participation in another pharmacological therapeutic interventional clinical research
• Contraindication to surgery detected during the preoperative assessment
• Fluctuating hearing = fluctuating hearing thresholds on at least one ear (shown by past bone conduction pure-tone audiometries)
• History of bacterial labyrinthitis or bacterial meningitis
• Middle ear infection or inflammation on the day of the surgery
• Chronical immune or inflammatory disease
• Fever on the day of the first blood sample
• Vulnerable subject: minors, protected adults as defined by the Public Health Code, pregnant or breastfeeding women, subject under guardianship or subject deprived of liberty

Sponsors & Collaborators

• University Hospital, Montpellier: lead

Study Sites (1)

UH Montpellier

Montpellier, 34295, France

RECRUITING

MeSH Terms

Conditions

Hearing Loss, Sensorineural

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Hearing Loss; Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Central Study Contacts

Akil Kaderbay, MD

CONTACT

+33467336890; a-kaderbay@chu-montpellier.fr

Frédéric Venail, PhD, MD

CONTACT

+33467336890; f-venail@chu-montpellier.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study will recruit individuals eligible for cochlear implantation surgery. In parallel, the control group will be formed from normal hearing patients - candidates for other otological interventions. The two groups will be matched by age and gender of participants.

Study Record Dates

• First Submitted: December 12, 2022
• First Posted: January 4, 2023
• Study Start: December 7, 2023
• Primary Completion: March 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: January 18, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)