Applying Proton Pump Inhibitor to Prevent and Treat Acute Fluctuating Hearing Loss in Patients With SLC26A4 Mutation
Summary
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.
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 Design
Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention
Conditions
Hearing Loss
Intervention
Proton pump inhibitor
Location
National Taiwan University Hospital
Taipei
Taiwan
100
Status
Recruiting
Source
National Taiwan University Hospital
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00789061
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Hearing Loss, Noise-induced
Hearing loss due to exposure to explosive loud noise or chronic exposure to sound level greater than 85 dB. The hearing loss is often in the frequency range 4000-6000 hertz.
Hearing Loss, Central
Hearing loss due to disease of the AUDITORY PATHWAYS (in the CENTRAL NERVOUS SYSTEM) which originate in the COCHLEAR NUCLEI of the PONS and then ascend bilaterally to the MIDBRAIN, the THALAMUS, and then the AUDITORY CORTEX in the TEMPORAL LOBE. Bilateral lesions of the auditory pathways are usually required to cause central hearing loss. Cortical deafness refers to loss of hearing due to bilateral auditory cortex lesions. Unilateral BRAIN STEM lesions involving the cochlear nuclei may result in unilateral hearing loss.
Omeprazole
A highly effective inhibitor of gastric acid secretion used in the therapy of STOMACH ULCERS and ZOLLINGER-ELLISON SYNDROME. The drug inhibits the H(+)-K(+)-ATPase (H(+)-K(+)-EXCHANGING ATPASE) in the proton pump of GASTRIC PARIETAL CELLS.
Proton Pumps
Integral membrane proteins that transport protons across a membrane. This transport can be linked to the hydrolysis of ADENOSINE TRIPHOSPHATE. What is referred to as proton pump inhibitors frequently is about POTASSIUM HYDROGEN ATPASE.
Hearing Loss, Mixed Conductive-sensorineural
Hearing loss due to damage or impairment of both the conductive elements (HEARING LOSS, CONDUCTIVE) and the sensorineural elements (HEARING LOSS, SENSORINEURAL) of the ear.
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