Deep Phenotyping of Hearing Instability Disorders: Cohort Establishment, Biomarker Identification, Development of Novel Phenotyping Measures, and Discovery of Therapeutic Targets

Meniere's Disease Clinical Trial

Official title: Deep Phenotyping of Hearing Instability Disorders: Cohort Establishment, Biomarker Identification, Development of Novel Phenotyping Measures, and Discovery of Therapeutic Targets

Status Recruiting

Clinical Trial Summary

Background:

Disorders of hearing instability (HI) are poorly characterized and ineffectively treated. HI can cause fluctuations in hearing thresholds and speech understanding. Researchers want to use a specialized form of magnetic resonance imaging (MRI) and blood tests to learn more about HI.

Objective:

To characterize a cohort of people with HI and to correlate HI with other data, including hearing evaluations, as well as radiologic and immunologic biomarkers of inflammation over time.

Eligibility:

Adults ages 18-80 who have symptoms consistent with possible HI.

Design:

Participants will be screened with a medical and hearing history and medical record review.

Participants will have physical exams. Their head and neck will be examined. They will have blood drawn.

Participants will have hearing tests. They will wear headphones or foam earplugs. They will listen to different tones. They may describe what they hear.

Participants will have balance tests. They will wear goggles as they watch moving lights or while cold or warm air is blown into their ears. They will sit in a spinning chair in a quiet, dark booth. From a reclining position, they will raise their head while clicking sounds are played into their ears.

Participants will have MRIs of the inner ear and brain. The MRI scanner is a metal cylinder surrounded by a strong magnetic field. During the MRIs, participants will lie on a table that slides in and out of the scanner. Soft padding or a coil will be placed around their head. They will get a contrast agent through an intravenous catheter.

Participation will last up to 15 months.

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Clinical Trial Description

Title:

Deep Phenotyping of Hearing Instability Disorders: Cohort Establishment, Biomarker Identification, Development of Novel Phenotyping Measures and Discovery of Therapeutic Targets

Study Description:

Disorders of hearing instability remain poorly characterized, phenotyped and ineffectively treated, and may result in sudden changes in hearing. These disorders include, but are not limited to, sudden sensorineural hearing loss (SSNHL) as well as hearing fluctuation, including, but not limited to, autoimmune inner ear disease (AIED), Meniere s disease (MD) and enlarged vestibular aqueduct syndrome (EVAS). While this group of disorders is likely to be clinically and etiologically heterogeneous, a common feature is fluctuation of hearing thresholds and speech understanding as measured by word recognition scores (WRS). This protocol seeks to ascertain a cohort of patients with hearing fluctuation to correlate these main phenotypic features with other phenomic data including audiometric indicators of endolymphatic hydrops as well as radiologic and immunologic biomarkers of inflammation over time. The overall hypothesis is that phenomic data will enable stratification of the phenotype of patients with hearing instability disorders. Healthy volunteers will be recruited to establish the normative range of endolymph and perilymph on contrast-enhanced delayed FLAIR MRI to allow for quantitative computational analysis of contrastenhanced delayed FLAIR MRI images.

Objectives:

Primary objective: To develop a cohort of patients with hearing instability (HI).

Secondary objectives:

1. To correlate evidence of HI with changes in phase-shift distortion product otoacoustic emissions (DPOAEs).

2. To compare phase-shift DPOAEs to existing measures of auditory function including word recognition score (WRS), standard DPOAEs, and electrocochleography (ECochG) over time.

3. To compare phase-shift DPOAEs to vestibular measures including cervical and ocular vestibular evoked myogenic potentials (VEMPs) over time.

4. To correlate auditory and vestibular indicators of hearing instability and endolymphatic hydrops (EH) on MRI with quantitative differences in immunologic markers of inflammation over time.

5. Establish the normative range of endolymph and perilymph volume on contrast-enhanced delayed FLAIR MRI to allow for quantitative computational analysis of contrast-enhanced delayed FLAIR MRI images.

Exploratory objective:

1. To stratify patients with hearing instability (HI) by differences in cytokine levels, which will inform the identification of clinical subtypes of HI and potentially identify therapeutic targets for future treatment with targeted agents.

2. To perform transcriptional and immunoprofiling of PBMCs at time points associated with hearing fluctuation from phenotyped patient cohorts.

Endpoints:

Primary Endpoint: Identification of phenomic features associated with HI.

Secondary Endpoint:

(1) Identification of a variety of phenomic features of patients with HI that allow assignment to clinical subdivisions.

Exploratory Endpoints

1. Identification of potential targets for therapeutics based on longitudinal immune/transcriptional profiling of patients with hearing instability.

2. Identification of subtype-specific immune cell distributions

3. Identification of immune profiles as well as immune cell transcriptional profiles related to hearing fluctuation ;

Related Conditions & MeSH terms

• Autoimmune Inner Ear Disease
• Ear Diseases
• Enlarged Vestibular Aqueduct Syndrome
• Labyrinth Diseases
• Labyrinthitis
• Meniere Disease
• Meniere's Disease

• NCT number: NCT04806282
• Study type: Observational
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Anna E Clements Centeno
• Phone: (301) 451-1215
• Email: anna.clements@nih.gov
• Status: Recruiting
• Start date: August 17, 2021
• Completion date: December 31, 2030