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

BMC Medicine

Juichi Ito⁶  Yasuhiko Tabata⁸  Akira Shimizu^1,13  Takafumi Ikeda^1,13  Toshiko Ito-Ihara^1,10  Atsushi Yonezawa³  Michio Yamamoto⁷  Harue Tada⁷  Shiro Tanaka⁷  Norio Yamamoto⁶  Harukazu Hiraumi⁶  Tatsunori Sakamoto⁶  Shizuo Komune⁴  Akira Sasaki⁵  Keizo Fujiwara¹  Mariko Takahashi^1,12  Keiji Tabuchi^1,14  Naohito Hato⁹  Shin-ichi Usami^1,11  Kozo Kumakawa²  Takayuki Nakagawa⁶ 

[1] Department of Otolaryngology, Kobe City Medical Center General Hospital, Kobe 650-0047, Japan;Department of Otolaryngology, Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo 105-8470, Japan;Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Kyoto 606-8507, Japan;Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan;Department of Otorhinolaryngology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan;Department of Otolaryngology, Head and Neck Surgery, Graduate school of Medicine, Kyoto University, Kyoto 606-8507, Japan;Department of Data Science, Institute for Advancement of Clinical and Translational Science, Kyoto University, Kyoto 606-8507, Japan;Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8397, Japan;Department of Otolaryngology, Ehime University Graduate School of Medicine, Ehime 791-0295, Japan;Department of Clinical Innovative Medicine, Institute for Advancement of Clinical and Translational Science, Kyoto University, Kyoto 606-8507, Japan;Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan;Department of Otolaryngology, Head and Neck Surgery, Nagoya City University Graduate School of Medical Sciences and Medical School, Nagoya 467-8601, Japan;Department of Experimental Therapeutics, Institute for Advancement of Clinical and Translational Science, Kyoto University, Kyoto 606-8507, Japan;Department of Otolaryngology, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, 305-8575, Japan

关键词: Sudden sensorineural hearing loss;    Local application;    IGF-1;    Drug delivery system;    Dexamethasone;   

Others  :  1118184
DOI  :  10.1186/s12916-014-0219-x

 received in 2014-08-21, accepted in 2014-10-24,  发布年份 2014

【 摘 要 】

Background

To 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.

Methods

We 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.

Results

In 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).

Conclusions

The 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 registration

UMIN Clinical Trials Registry Number UMIN000004366 webcite, October 30^th, 2010.

【 授权许可】

   
2014 Nakagawa et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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