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

NCT04806282 | Suspended

• 2 other identifiers: 10000141000141-DC
• Study Type: observational
• Target: 58
• Locations: 1 country
• Sites: 1

Brief 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. ...

Conditions

Meniere's Disease; Enlarged Vestibular Aqueduct Syndrome; Autoimmune Inner Ear Disease

Keywords

Biomarkers; immunoprofiling; Auditory

Outcome Measures

Primary Outcomes (1)

• Phenomic features

  To identify phenotype features associated with hearing fluctuation

  Day 90, 180, 270, 360, and 450, respectively +/- 14 days

Secondary Outcomes (1)

• Subdivisions of phenomic features

  Day 90, 180, 270, 360, and 450, respectively +/- 14 days

Study Arms (1)

1/All Patients

Documented hearing instability

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

This study will enroll up to a total of 150 patients with HI. The enrollment target is between 10-30 patients per clinical subtype for at least 2 clinical subtypes of HI (i.e., without or with EH, without or with significant immune cell, cytokine or FLAIR positivity). 20 cytokines/chemokines in patients with Meniere s disease that revealed statistically higher levels of IL-1Beta compared to healthy controls (Flook et al., 2019), a sample size of 40-50 patients would be required for 80% power to detect an immune subtype associated with IL-1Beta.

You may not qualify if:

• Affected and unaffected individuals who meet any of the following criteria will be excluded from participation in this study:
• Presence of non-MRI compatible devices (cardiac pacemaker, meta\<specific devices (e.g., cardiac pacemaker)
• Pregnancy or lactation
• Known allergic reactions to gadolinium
• Febrile illness within 2 weeks that could affect immune profiling\*
• Evidence of active outer or middle ear disease or anomaly (e.g. otitis media, stenotic ear canal, otorrhea)
• History of chronic, as defined by fluid in the middle ear for more than 4 months, or recurrent otitis media, as defined by more than 4 episodes of acute otitis media in one year.
• Current PE tubes
• Bilateral profound (Pure tone average (PTA) \> 90 dB HL) sensorineural hearing loss
• History or diagnosis of a central nervous system disorder, including but not limited to:
• Intracranial tumors
• Cerebrovascular disease
• Degenerative CNS disorder
• CNS trauma
• Encephalitis

Sponsors & Collaborators

• National Institute on Deafness and Other Communication Disorders (NIDCD): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Telischi J, Strepay D, Li B, Chisholm J, Cheng H, Brewer C, Hsu LY, Butman J, Hoa M. MRI-based measurement of inner ear fluids reveals increased endolymph volume variability in patients with endolymphatic hydrops and hearing instability. Sci Rep. 2025 Jul 2;15(1):22560. doi: 10.1038/s41598-025-06083-w.

  PMID: 40596438 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Meniere Disease

Condition Hierarchy (Ancestors)

Endolymphatic Hydrops; Labyrinth Diseases; Ear Diseases; Otorhinolaryngologic Diseases

Study Officials

• Ronna P Hertzano, M.D.

  National Institute on Deafness and Other Communication Disorders (NIDCD)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2021
• First Posted: March 19, 2021
• Study Start: August 17, 2021
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2030
• Last Updated: December 8, 2025

Record last verified: 2025-12-04

Locations

US (1)