A double-blinded, randomized controlled clinical trial of hydrogen inhalation therapy for idiopathic sudden sensorineural hearing loss

Masahiro Okada; Hideo Ogawa; Taro Takagi; Eriko Nishihara; Tadashi Yoshida; Jun Hyodo; Yusuke Shinomori; Nobumitsu Honda; Takashi Fujiwara; Masato Teraoka; Hiroyuki Yamada; Shin-Ichi Hirano; Naohito Hato

doi:10.3389/fnins.2022.1024634

A double-blinded, randomized controlled clinical trial of hydrogen inhalation therapy for idiopathic sudden sensorineural hearing loss

Front Neurosci. 2022 Nov 24:16:1024634. doi: 10.3389/fnins.2022.1024634. eCollection 2022.

Authors

Masahiro Okada¹, Hideo Ogawa², Taro Takagi^{1

3}, Eriko Nishihara^{1

3}, Tadashi Yoshida⁴, Jun Hyodo⁵, Yusuke Shinomori⁶, Nobumitsu Honda², Takashi Fujiwara⁷, Masato Teraoka¹, Hiroyuki Yamada¹, Shin-Ichi Hirano⁸, Naohito Hato¹

Affiliations

¹ Department of Otolaryngology, Head and Neck Surgery, Ehime University Graduate School of Medicine, Toon, Japan.
² Department of Otolaryngology, Head and Neck Surgery, Ehime Prefectural Central Hospital, Matsuyama, Japan.
³ Department of Otolaryngology, Ehime Prefectural Niihama Hospital, Niihama, Japan.
⁴ Department of Otolaryngology, Head and Neck Surgery, Uwajima City Hospital, Uwajima, Japan.
⁵ Department of Otolaryngology, Takanoko Hospital, Matsuyama, Japan.
⁶ Department of Otolaryngology, Matsuyama Red Cross Hospital, Matsuyama, Japan.
⁷ Department of Public Health Research, Kurashiki Clinical Research Institute, Kurashiki, Japan.
⁸ Department of Research and Development, MiZ Company Limited, Kamakura, Japan.

Abstract

Background: Hydrogen (H₂) has been reported to be effective in reducing hearing loss due to several causes in animal studies. However, no study has examined the effectiveness of H₂ in treating hearing loss in humans. Thus, we investigated whether H₂ is effective for the treatment of idiopathic sudden sensorineural hearing loss (ISSNHL).

Materials and methods: We conducted a double-blind randomized controlled trial at six hospitals between June 2019 and March 2022. The study protocol and trial registration have been published in the Japan Registry of Clinical Trials (jRCT, No. jRCTs06119004). We randomly assigned patients with ISSNHL to receive either H₂ (H₂ group) or air as a placebo (control group) through inhalation combined with the administration of systemic glucocorticoids and prostaglandin E1. The primary outcome was the hearing threshold and changes in hearing threshold 3 months after therapy. In contrast, the secondary outcomes included the proportion of patients with a good prognosis (complete recovery or marked improvement).

Results: Sixty-five patients with ISSNHL (31 and 34 in the H₂ and control groups, respectively) were included in this study. The hearing threshold 3 months after treatment was not significantly different between the groups; 39.0 decibels (dB) (95% confidence interval [CI]: 28.7-49.3) and 49.5 dB (95% CI: 40.3-58.7) in the H₂ and control groups, respectively. In contrast, the changes in hearing threshold 3 months after treatment was 32.7 dB (95% CI: 24.2-41.3) and 24.2 dB (95% CI: 18.1-30.3) in the H₂ and control groups, respectively. Consequently, the changes in hearing threshold were significantly better in the H₂ group than in the control group (P = 0.048). However, no adverse effects due to the inhalation of H₂ gas have been reported.

Conclusion: This is the first study to investigate the efficacy of H₂ for the treatment of ISSNHL in humans. The results suggest that H₂ therapy may be effective for ISSNHL treatment.

Clinical trial registration: [https://jrct.niph.go.jp/re/reports/detail/10442], identifier [jRCTs06119004].

Keywords: free radical; hearing loss; hydrogen; inner ear; sudden deafness.