Applying Proton Pump Inhibitor to Prevent and Treat Acute Fluctuating Hearing Loss in Patients With SLC26A4 Mutation
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.
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.
Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention
Proton pump inhibitor
National Taiwan University Hospital
National Taiwan University Hospital
Results (where available)
- 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.
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.
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.
The purpose of this study is to determine whether proton pump inhibitor (PPI) induced hypersecretion leads to acid related symptoms after treatment in healthy volunteers.
This study evaluates whether a 2 hour group session, "The Living Well with Hearing Loss Workshop," can successfully teach hard of hearing people how to best use hearing aids and a variety...
Patients with bleeding ulcers identified by endoscopy will be randomly assigned to receive an acid-blocking drug (called a proton pump inhibitor [PPI]) either by mouth every 3 hours for 24...
Hearing impairment is one of the most common disabilities in veterans. The decreased ability to communicate is troubling in itself, but the strong association of hearing loss with functio...
To determine if prasugrel is superior to clopidogrel in providing adequate antiplatelet effect in a high risk population that requires concomitant use of a Proton Pump Inhibitor (PPI).
Proton pump inhibitors and clopidogrel are commonly prescribed medications, both alone and in combination. In January of 2009 the US Food and Drug Administration and the European Medicines Agency issu...
Objective: To discuss the possible etiopathogenetic mechanism of inner ear damage induced by the ingestion of potassium hydroxide (KOH). Clinical Presentation and Intervention: We report the case of a...
Previous studies have demonstrated an association between chronic proton pump inhibitor (PPI) utilization and adverse events such as fractures, infections, hypomagnesemia, and vitamin B12 deficiency....
There are several causes of small bowel contamination. The effects of the long-term proton pump inhibitor treatment on the development of bowel symptoms and/or small intestinal bacterial overgrowth ha...
To date, 135 loci and 50 genes have been identified as causes of nonsyndromic hearing loss. Until recently, four loci (DFN2, DFN3, DFN4, and DFN6) had been implicated in nonsyndromic X-linked hearing...