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

Primary Purpose

Sensorineural Hearing Loss

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Blood sampling
Perilymph sampling
Sponsored by
University Hospital, Montpellier
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Sensorineural Hearing Loss focused on measuring Perilymph, Proteomics, Metabolomics, Sensorineural hearing loss, Residual hearing, Cochlear implantation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria for the "Cochlear implantation" group : 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 Inclusion Criteria for the "Control" group: 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 Exclusion Criteria for the "Cochlear implantation" group: 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 Exclusion Criteria for the Control group: 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 Active viral or bacterial infection on the day of inclusion visit or surgery 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 Participation in another pharmacological therapeutic interventional clinical research

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Other

    Arm Label

    "Cochlear Implantation" group

    Control group

    Arm Description

    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.

    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.

    Outcomes

    Primary Outcome Measures

    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
    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

    Secondary Outcome Measures

    PBMC cell counting
    Counting of activated blood immune cells, using FACS technique after the PBMC cells culture is performed
    PBMC cell counting
    Counting of activated blood immune cells, using FACS technique after the PBMC cells culture is performed
    PBMC cell counting
    Counting of activated blood immune cells, using FACS technique after the PBMC cells culture is performed
    PBMC cell counting
    Counting of activated blood immune cells, using FACS technique after the PBMC cells culture is performed
    PBMC cell counting
    Counting of activated blood immune cells, using FACS technique after the PBMC cells culture is performed
    Expression levels of identified molecules in the 2 groups of implanted patients after the surgery
    Expression levels of identified molecules for each group over time
    Expression levels of identified molecules in the 2 groups of implanted patients after the surgery
    Expression levels of identified molecules for each group over time
    Expression levels of identified molecules in the 2 groups of implanted patients after the surgery
    Expression levels of identified molecules for each group over time
    Expression levels of identified molecules in the 2 groups of implanted patients after the surgery
    Expression levels of identified molecules for each group over time

    Full Information

    First Posted
    December 12, 2022
    Last Updated
    January 2, 2023
    Sponsor
    University Hospital, Montpellier
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05670158
    Brief Title
    Immunity After Cochlear Implantation and Perilymph Molecular Profiles in Sensorineural Hearing Loss
    Acronym
    PERILOTO
    Official Title
    Study on the Inner Ear Immunisation Post-cohlear Implantation and Perilymph Molecular Profiling in Sensorineural Hearing Loss
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    January 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    January 2023 (Anticipated)
    Primary Completion Date
    July 2025 (Anticipated)
    Study Completion Date
    July 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    University Hospital, Montpellier

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    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.
    Detailed 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

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Sensorineural Hearing Loss
    Keywords
    Perilymph, Proteomics, Metabolomics, Sensorineural hearing loss, Residual hearing, Cochlear implantation

    7. Study Design

    Primary Purpose
    Other
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Model Description
    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.
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    80 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    "Cochlear Implantation" group
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    Control group
    Arm Type
    Other
    Arm Description
    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.
    Intervention Type
    Biological
    Intervention Name(s)
    Blood sampling
    Intervention Description
    Blood will be collected into 2 dry tubes and 1 EDTA tube (4ml of blood in each). The 2 dry tubes 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. The EDTA tube will be sent to the Bacteriology-Virology Department for the active PBMC counting.
    Intervention Type
    Procedure
    Intervention Name(s)
    Perilymph sampling
    Intervention Description
    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.
    Primary Outcome Measure Information:
    Title
    Expression levels of proteins and metabolites in the perilymph before surgery in the 2 groups of implanted patients
    Description
    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
    Time Frame
    Before cochlear implantation surgery (V1)
    Title
    Expression levels of proteins and metabolites in the blood before surgery in the 2 groups of implanted patients
    Description
    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
    Time Frame
    Before cochlear implantation surgery (V1)
    Secondary Outcome Measure Information:
    Title
    PBMC cell counting
    Description
    Counting of activated blood immune cells, using FACS technique after the PBMC cells culture is performed
    Time Frame
    Before cochlear implantation surgery (V1)
    Title
    PBMC cell counting
    Description
    Counting of activated blood immune cells, using FACS technique after the PBMC cells culture is performed
    Time Frame
    At 1 month post-implantation (V2)
    Title
    PBMC cell counting
    Description
    Counting of activated blood immune cells, using FACS technique after the PBMC cells culture is performed
    Time Frame
    At 3 months post-implantation (V3)
    Title
    PBMC cell counting
    Description
    Counting of activated blood immune cells, using FACS technique after the PBMC cells culture is performed
    Time Frame
    At 6 months post-implantation (V4)
    Title
    PBMC cell counting
    Description
    Counting of activated blood immune cells, using FACS technique after the PBMC cells culture is performed
    Time Frame
    At 12 months post-implantation (V5)
    Title
    Expression levels of identified molecules in the 2 groups of implanted patients after the surgery
    Description
    Expression levels of identified molecules for each group over time
    Time Frame
    At 1 month post-implantation (V2)
    Title
    Expression levels of identified molecules in the 2 groups of implanted patients after the surgery
    Description
    Expression levels of identified molecules for each group over time
    Time Frame
    At 3 months post-implantation (V3)
    Title
    Expression levels of identified molecules in the 2 groups of implanted patients after the surgery
    Description
    Expression levels of identified molecules for each group over time
    Time Frame
    At 6 months post-implantation (V4)
    Title
    Expression levels of identified molecules in the 2 groups of implanted patients after the surgery
    Description
    Expression levels of identified molecules for each group over time
    Time Frame
    At 12 months post-implantation (V5)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria for the "Cochlear implantation" group : 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 Inclusion Criteria for the "Control" group: 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 Exclusion Criteria for the "Cochlear implantation" group: 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 Exclusion Criteria for the Control group: 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 Active viral or bacterial infection on the day of inclusion visit or surgery 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 Participation in another pharmacological therapeutic interventional clinical research
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Akil Kaderbay, MD
    Phone
    +33467336890
    Email
    a-kaderbay@chu-montpellier.fr
    First Name & Middle Initial & Last Name or Official Title & Degree
    Frédéric Venail, PhD, MD
    Phone
    +33467336890
    Email
    f-venail@chu-montpellier.fr

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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

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