Evaluation of the CochSyn Test Prototype to Measure Cochlear Synaptopathy

Study Overview
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Brief Summary
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This study investigates a newly developed test, The CochSyn test that can quantify cochlear synaptopathy (CS) (a new type of sensorineural hearing loss (SNHL)) earlier than the current golden standard pure-tone audiogram.This newly developed test is based on auditory evoked brain potentials. A hardware prototype (the Cochsyn test prototype) was developed to use the Cochsyn test in clinical practice. Additionally a CS-based sound-processing algorithm (CoNNear) that is designed to improve speech intelligibility in subjects that are identified to have CS, will be investigated in this study.

Detailed Description
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Cochlear synaptopathy is a new type of sensorineural hearing loss (SNHL) and is related to ageing, noise exposure and ototoxicity. There is currently no diagnostic test of CS on the market, whereas CS is an important form of SNHL. CS occurs before the golden standard clinical hearing test (pure- tone audiogram in which participants raise their hand when hearing tones of different frequencies and the threshold of hearing is determined), shows any signs of hearing damage. The investigators have developed a test, the CochSyn test that may quantify SNHL earlier than the audiogram. The newly developed test is based on auditory evoked potentials. This is a method in which an auditory stimulus is presented, and encephalogram (EEG) electrodes capture the sound-evoked brain potentials. The most popular auditory evoked potential metric to diagnose sensorineural hearing loss (SNHL) is the auditory brainstem response (ABR). The first animal research studies on CS confirmed that the ABR wave-I amplitude is a sensitive marker of CS when the inflicted hearing damage is well-controlled and specific. Even though it can be assumed that the ABR wave-I amplitude will also be sensitive to CS in humans, it may not be a differential marker for it, and hence other candidate auditory evoked potential markers for CS have been investigated in recent studies. In particular, the envelope-following-response (EFR), has also been shown to be specific to CS in animal research studies. EFRs are recorded using the standard ABR electrode montage but use another type of stimulus. Based on model simulations and a recent study in which the investigators compared candidate EFR markers for use in human studies , the investigators have developed a new stimulus for EFRs that uses both a different type of modulator waveform and a different analysis method than was adopted earlier. In this trial, the investigators wish to test the performance of the new method (the CochSyn test) in listeners with or without self-reported hearing difficulties using a newly developed hardware prototype (the CochSyn test prototype), dedicated for the CochSyn-test in clinical practice. The assessment also includes the testing of a CS-based sound-processing algorithm (CoNNear) that is designed to improve speech intelligibility in subjects that are identified to have CS, based on our CochSyn test. To this end, the investigators will first assess whether our CochSyn test prototype is equally good at capturing the standard ABR waveform as a comparator device available on the market (the Intelligent Hearing Systems Universal Smart Box). The investigators will also test which stimulation characteristics and electrode configurations for the CochSyn test are best able to quantify individual differences in standard objective hearing tests (audiogram, otoacoustic emission, speech reception thresholds) and subjective hearing complaints (validated HHIE-s questionnaire).

Official Title
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Evaluation of the CochSyn Test Prototype to Measure Cochlear Synaptopathy

Conditions
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Hearing Loss, Sensorineural, Cochlear Synaptopathy, Cochlear Hearing Loss

Intervention / Treatment
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* Device: CochSyn test prototype
* Device: Universal Smart Box (USB)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Session 1 Test group 18 - 87 years old Flemish/Dutch as native language Ability to fill out a questionnaire and to perform a speech intelligibility test Self-reported hearing difficulties according to HHIE-s questionnaire (score of >4) Normal audiogram (for age group 18-77): audiometric thresholds up to 4 kHz ≤ 20 dB HL and for 6 kHz ≤ 30 dB HL in at least 1 ear OR impaired audiogram (for age group 18-87): audiometric thresholds between 20 and 64.9 dB HL pure tone average at 0.5, 1, 2, and 4 kHz in at least 1 ear (=Mild to moderately severe hearing loss according to the recommendation by the Global Burden of Disease Expert Group on Hearing Loss) Control group 18 - 77 years old Flemish/Dutch as native language Ability to fill out a questionnaire and to perform a speech intelligibility test No self-reported hearing difficulties according to HHIE-s questionnaire (score of ≤4) Normal audiogram: audiometric thresholds up to 4 kHz ≤ 20 dB HL and for 6 kHz ≤ 30 dB HL in at least 1 ear Session 2 Participation in session 1 in the test group 18 - 77 years old EFR magnitude at 4 kHz with Snap electrode in session 1 reduced by 30-100% compared to average EFR magnitude of age group 18-27 of control group (session 1) Exclusion Criteria: Applicable for both sessions: Pregnant woman Breastfeeding woman Applicable for both sessions and the ear which fulfils the inclusion criteria: Chronic (longer than 6 months) permanent tinnitus Hearing loss due to a genetic condition, a middle ear condition, or surgery Blocked ear canal

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 87 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Session 1 - test group<br>130 subjects with self-reported hearing difficulties according to the HHIE-s questionnaire (score of >4) | Device: CochSyn test prototype<br>* The CochSyn test prototype is intended for use in the evaluation of hearing-related disorders in adults using auditory evoked potentials. The CochSyn test prototype records biopotential waveforms that can be used for hearing screening and diagnostic applications.<br>Device: Universal Smart Box (USB)<br>* Commercially available EEG system intended for use in the diagnosis of hearing related disorders, hearing threshold detection, and other conditions that may affect the responses to auditory, tactile, or visual stimuli. The USB Box hardware and accompanying software programs can be used with patients of all ages. It is intended for use by trained personnel in a hospital, nursery, clinic, audiologist's office, or other appropriate setting.<br>|
| Other: Session 1 - control goup<br>60 subjects with no self-reported hearing difficulties according to HHIE-s questionnaire (score of ≤4) | Device: CochSyn test prototype<br>* The CochSyn test prototype is intended for use in the evaluation of hearing-related disorders in adults using auditory evoked potentials. The CochSyn test prototype records biopotential waveforms that can be used for hearing screening and diagnostic applications.<br>Device: Universal Smart Box (USB)<br>* Commercially available EEG system intended for use in the diagnosis of hearing related disorders, hearing threshold detection, and other conditions that may affect the responses to auditory, tactile, or visual stimuli. The USB Box hardware and accompanying software programs can be used with patients of all ages. It is intended for use by trained personnel in a hospital, nursery, clinic, audiologist's office, or other appropriate setting.<br>|
| Other: Session 2<br>60 subjects who participated in session 1 - test group | Device: CochSyn test prototype<br>* The CochSyn test prototype is intended for use in the evaluation of hearing-related disorders in adults using auditory evoked potentials. The CochSyn test prototype records biopotential waveforms that can be used for hearing screening and diagnostic applications.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Cochsyn test prototype | The difference in terms of wave amplitudes of a standard clinical auditory brainstem response (ABR) recorded with the commercially available USB device and with the CochSyn test prototype during session 1. | end of session 1, after 3 hours | 
| Sensitivity CochSyn test prototype | The difference in sensitivity (i.e., standard deviation/range) between the ABR wave-I amplitude and the EFR magnitude as measured on the CochSyn test prototype with Snap electrodes in session 1. | end of session 1, after 3 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Usability CochSyn test prototype | Written feedback in form of a questionnaire of the test administrator on the usability of the test system for the measurements performed with the CochSyn test prototype during session 1. | end of session 1, after 3 hours | 
| Performance CochSyn test prototype | The difference between the EFR magnitudes obtained with the CochSyn test prototype + cEEGrid electrodes and those obtained with the CochSyn test prototype + Snap electrodes measured for different stimulus carriers during session 1. | end of session 1, after 3 hours | 
| Reliability Cochsyn test prototype | The difference between the EFR magnitudes during session 1 and session 2 (test/re-test). This concerns the recordings made with the CochSyn test prototype + cEEGrid and with the CochSyn test prototype + Snap electrodes. | end of session 2, after 2 hours | 
| Sensitivity related to stimulus changes | The difference in magnitude between EFRs recorded for different stimulus carriers and for different stimulus levels on the CochSyn test prototype with Snap electrodes and the cEEGrid electrodes during session 1. | end of session 1, after 3 hours | 
| Gender differences in EFR magnitude | The difference in EFR magnitude between men and woman of the cohort recorded on the CochSyn test prototype with Snap electrodes and the cEEGrid electrodes during session 1. | end of session 1, after 3 hours | 
| Selectivity of EFR measurements | The difference between the EFR magnitudes of the control group and the test group for different stimulus carriers during session 1. Recordings are made on the CochSyn test prototype + Snap electrodes and differences will be assessed across the age-cohort as well as within each age group. | end of session 1, after 3 hours | 
| Age-related decline in EFR magnitude | The correlation strength and regression slope of the EFR magnitudes with age obtained with the CochSyn test prototype + Snap electrodes measured at different carrier frequencies and sound levels during session 1 for the test subjects with or without self-reported hearing difficulties. | end of session 1, after 3 hours | 
| Subjective hearing handicap | The correlation between the HHIE-s questionnaire score and the EFR magnitude at different carrier frequencies obtained with the CochSyn test prototype + Snap electrodes during session 1. | end of session 1, after 3 hours | 
| Classification accuracy scale | Classification accuracy scale of correctly assigning a subject within a specific age group to have a subjective hearing handicap (based on HHIE-s) based on their EFR magnitude. | session 1, after 3 hours | 
| Hearing thresholds | The correlation strength and regression slope of the EFR magnitude with the hearing threshold across the cohorts with and without self-reported hearing difficulties. Hearing thresholds related to standard clinical measures i.e., the pure-tone average from the audiogram with extended frequencies and distortion-product otoacoustic emission thresholds. EFR magnitudes at different carrier frequencies and sound levels during session 1 are considered. | end of session 1, after 3 hours | 
| Speech intelligibility | The correlation strength and regression slope of the EFR magnitude with the speech reception threshold (objective marker of speech intelligibility, Matrix sentence test) across the cohorts with and without self-reported hearing difficulties. EFR magnitudes at different carrier frequencies and sound levels during session 1 are considered. | end of session 1, after 3 hours | 
| Performance of CoNNear soundprocessing algorithm for normal audiograms | The speech reception threshold change (in dB) for subjects with low EFR magnitudes and normal audiograms that have received personalised CoNNear audio-processing to compensate for their low EFR magnitudes. The baseline situation is the speech reception threshold for unprocessed sound from session 2. | end of session 2, after 2 hours | 
| Performance of CoNNear soundprocessing algorithm for impaired audiograms | The speech reception threshold change (in dB) for subjects with low EFR magnitudes and impaired audiograms that have received personalised CoNNear audio-processing to compensate for their low EFR magnitudes. The baseline situation is the speech reception threshold for unprocessed sound from session 2 and a standard sound processing algorithm. | end of session 2, after 2 hours | 
| Sound quality rating of CoNNear soundprocessing algorithm | The difference in sound quality rating for the different CoNNear processing types compared to the unprocessed test material. | session 2, after 2 hours |