Applying Proton Pump Inhibitor to Prevent and Treat Acute Fluctuating Hearing Loss in Patients With SLC26A4 Mutation

November 10, 2008 updated by: National Taiwan University Hospital

Disequilibrium between acid and base in the inner ear was suggested to be an important factor leading to hearing impairment associated with SLC26A4 mutations. For acid-base homeostasis in the inner ear, gastric-type proton pumps might demonstrate antagonistic effects to pendrin, the protein encoded by SLC26A4. To investigate whether proton pump inhibitors might prevent or treat acute fluctuating hearing loss related to SLC26A4 mutations, we launch the current double-blind randomized clinical trial.

Study Overview

Status

Unknown

Conditions

Hearing Loss

Intervention / Treatment

Drug: Proton pump inhibitor

Detailed Description

Hereditary hearing loss is the most common inherited sensory defect, affecting about 1 per 1000 children. With the advances in molecular genetics, the nature of hereditary hearing loss has started to be unraveled. A plethora of deafness genes were discovered in the past years, and among them certain genetic mutations were noted to be extraordinarily popular in the hearing-impaired population. For example, mutations in the SLC26A4 gene have been documented with high prevalence in a variety of ethnic backgrounds, including Caucasians, Japanese and Han Chinese.

The two specific clinical features of patients with SLC26A4 mutations are inner ear malformations and fluctuating hearing loss. For decades, the latter has constituted a treatment difficulty for pediatric otologists, because traditional regimens, such as steroid or intracranial-pressure-lowering-medication, usually could not achieve satisfactory and predictable outcomes. Nevertheless, as basic researches in recent years began to shed light on the pathogenesis of hearing loss from SLC26A4 mutations, novel strategies could be developed based on some of these crucial findings. For instance, disequilibrium between acid and base in the inner ear was reported to be an important factor leading to deafness in SLC26A4 knock-out mice. And for acid-base homeostasis in the inner ear, proton pumps were found to demonstrate antagonistic effects to pendrin, the protein encoded by SLC26A4. Consequently, regimens which can modulate the function of proton pumps, like proton pump inhibitors, might be a good choice to prevent or treat acute or chronic hearing loss related to SLC26A4 mutations or degenerative dysfunction.

Corresponding to this postulation, clinically we experienced significant recovery of hearing loss in several patients with SLC26A4 mutations who suffered from acute fluctuating hearing loss which was refractory to traditional treatment. In some cases, acute hearing loss recurred after the medication was discontinued. Therefore, we launch the current clinical trial to investigate the efficacy of proton pump inhibitor in preventing and treating acute hearing loss in patients with SLC26A4 mutations.

Study Type

Interventional

Enrollment (Anticipated)

120

Phase

Phase 2
Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Taiwan
- - Taipei, Taiwan, 100
    - Recruiting
    - National Taiwan University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

ADULT
OLDER_ADULT
CHILD

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

Inclusion Criteria:

Patients with homozygous or heterozygous SLC26A4 mutations
Patients with acute hearing loss

Exclusion Criteria:

Patients who do not fulfill both of the above criteria

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: PREVENTION
Allocation: RANDOMIZED
Interventional Model: PARALLEL
Masking: TRIPLE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Decrease in attack frequency or improvement of hearing loss Time Frame: 3 years	3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Taiwan University Hospital

Investigators

Study Director: Chuan-Jen Hsu, MD, Department of Otolaryngology, National Taiwan University Hospital
Principal Investigator: Chen-Chi Wu, MD, Department of Otolaryngology, National Taiwan University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2006

Primary Completion (ANTICIPATED)

March 1, 2008

Study Completion (ANTICIPATED)

July 1, 2009

Study Registration Dates

First Submitted

July 8, 2007

First Submitted That Met QC Criteria

November 10, 2008

First Posted (ESTIMATE)

November 11, 2008

Study Record Updates

Last Update Posted (ESTIMATE)