A randomized controlled clinical trial of topical insulin-like growth factor-1 therapy for sudden deafness refractory to systemic corticosteroid treatment.

Takayuki Nakagawa,Atsushi Yonezawa,Harue Tada,Keiji Tabuchi,Kozo Kumakawa,Norio Yamamoto,Mariko Takahashi,Takafumi Ikeda,Akira Sasaki,Harukazu Hiraumi,Akira Shimizu,Tatsunori Sakamoto,Juichi Ito,Michio Yamamoto,Shizuo Komune,Naohito Hato,Yasuhiko Tabata,Shiro Tanaka,Kenshu Fujiwara ,Toshiko Ito‐Ihara ,Shin Ichi Usami

doi:10.1186/s12916-014-0219-x

Abstract

BackgroundTo date, no therapeutic option has been established for sudden deafness refractory to systemic corticosteroids. This study aimed to examine the efficacy and safety of topical insulin-like growth factor-1 (IGF-1) therapy in comparison to intratympanic corticosteroid therapy.MethodsWe randomly assigned patients with sudden deafness refractory to systemic corticosteroids to receive either gelatin hydrogels impregnated with IGF-1 in the middle ear (62 patients) or four intratympanic injections with dexamethasone (Dex; 58 patients). The primary outcome was the proportion of patients showing hearing improvement (10 decibels or greater in pure-tone average hearing thresholds) 8 weeks after treatment. The secondary outcomes included the change in pure-tone average hearing thresholds over time and the incidence of adverse events.ResultsIn the IGF-1 group, 66.7% (95% confidence interval [CI], 52.9–78.6%) of the patients showed hearing improvement compared to 53.6% (95% CI, 39.7–67.0%) of the patients in the Dex group (P = 0.109). The difference in changes in pure-tone average hearing thresholds over time between the two treatments was statistically significant (P = 0.003). No serious adverse events were observed in either treatment group. Tympanic membrane perforation did not persist in any patient in the IGF-1 group, but did persist in 15.5% (95% CI, 7.3–27.4%) of the patients in the Dex group (P = 0.001).ConclusionsThe positive effect of topical IGF-1 application on hearing levels and its favorable safety profile suggest utility for topical IGF-1 therapy in patients with sudden deafness.Trial registrationUMIN Clinical Trials Registry Number UMIN000004366, October 30th, 2010.

Highlights

To date, no therapeutic option has been established for sudden deafness refractory to systemic corticosteroids
Eligible participants were all adults, 20 years or older, who had SSHL defined as a unilateral sensorineural hearing loss of at least 30 decibels sound pressure level (SPL) over at least three test frequencies that developed within 3 days
They met the following eligibility criteria: they had been diagnosed as having SSHL within 25 days of onset; they presented with an abnormality in the distortion product of otoacoustic emissions; and they showed less than 30 dB hearing improvement in the mean hearing level, based on pure-tone audiometry (PTA) at five tested frequencies (0.25 kHz, 0.5 kHz, 1.0 kHz, 2.0 kHz, and 4.0 kHz) after more than 7 days of systemic corticosteroid treatment

Summary

Introduction

No therapeutic option has been established for sudden deafness refractory to systemic corticosteroids. 35,000 patients with SSHL consult a doctor each year in Japan [2]. Systemic corticosteroid treatment often causes adverse events [6] that can occasionally be life-threatening [7]. As an alternative for systemic corticosteroids, intratympanic corticosteroid treatment by direct injection into the middle ear has recently gained wide popularity because of the low risk for systemic adverse events and because of the potential delivery of high concentrations of a corticosteroid into the inner ear [8]. Intratympanic corticosteroid therapy is commonly used for the treatment of SSHL, after the failure of systemic corticosteroid treatment [9,10,11,12,13,14,15]. The supporting evidence for its use is weak because of the limitation in the study design and power [16]

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