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

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.

Towards Clinical Application of Neurotrophic Factors to the Auditory Nerve; Assessment of Safety and Efficacy by a Systematic Review of Neurotrophic Treatments in Humans

“…Patient demographics and outcome data on treatment modalities extracted from the 20 RCTs [27,28,31,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51] included in the present review are reported in Table 3 and summarized in Table 4. A total of 2445 patients were treated with a NF, while the remaining 1529 patients were assigned to the placebo group.…”

“…The remaining six articles [36,38,48,49,50,51] concluded the NF therapy to be effective (Table 3), which will be discussed in the next subsection.…”

“…The placebo group’s weight remained the same, while those receiving CNTF showed weight loss of up to 4.1 kg. Three of the four trials that administered NFs locally, considered NF therapies to be effective; these three trials treated non-neurodegenerative diseases (ulcer [36], macular degeneration [50], and sudden deafness [51]).…”

“…CNTF treatment resulted in improved visual acuity stabilization in the high-dose group (96%) compared with low-dose (83%) and sham (75%) group. The final study that considered NF therapy to be effective applied gelfoam infiltrated with IGF to alleviate sudden deafness [51]. Sixty-six percent of IGF-treated patients showed hearing improvement compared to 53% of the patients treated with conventional steroid dexamethasone.…”

Recent advances in local drug delivery to the inner ear

“…A prospective clinical study using hyaluronic acid with dexamethasone for the 514 treatment of sudden sensorineural hearing loss or Menière's disease, compared to systemic 515 steroid and vasoactive therapy, have shown significant improvement of auditory function 516 without systemic or local side effects.517 Nakagawa et al, (2014)examined the efficacy and safety of gelatin hydrogel containing IGFlocal inner ear therapy based on hydrogel formulations(Table 6). Otonomy 523 is developing OTO-104 (poloxamer 407 hydrogel containing dexamethasone)(Lambert et al, 524 2012).…”