International journal of audiology | 2021
Oral D-methionine protects against cisplatin-induced hearing loss in humans: phase 2 randomized clinical trial in India.
Abstract
Objective: This exploratory Phase 2 clinical trial is the first determining safety and efficacy of oral D-methionine (D-met) in reducing cisplatin-induced ototoxicity.Design: Randomised parallel double-blind placebo-controlled exploratory Phase 2 study.Study samples: Fifty adult cancer patients received oral D-met or placebo before each cisplatin dose. Physical examination, blood collection and audiometry occurred at baseline and subsequent visits plus post-treatment audiometry. After attrition, final analysis included 27 patients.Results: Significant treatment group by ear and time (baseline vs. post-treatment) interactions occurred at 10\u2009kHz and 11.2\u2009kHz. Placebo and D-met groups differed in threshold shift for left ear at 11.2\u2009kHz (mean difference = 22.97\u2009dB [9.59, 36.35]). Averaging across ears, placebo group showed significant threshold shifts from baseline to post-treatment at 10\u2009kHz (mean shift=\u2009-13.65\u2009dB [-21.32,-5.98]), 11.2\u2009kHz (-16.15\u2009dB [-25.19,-7.12]), and 12.5\u2009kHz (-11.46\u2009dB [-19.18,-3.74]) but not 8\u2009kHz (-8.65\u2009dB [-17.86, 0.55]). The D-met group showed no significant threshold shifts (8\u2009kHz: -1.25\u2009dB [-7.75, 5.25]; 10\u2009kHz:-3.93\u2009dB [-8.89, 1.03]; 11.2\u2009kHz:-4.82\u2009dB [-11.21, 1.57]; 12.5\u2009kHz:-3.68\u2009dB [-11.57, 4.21]). Side effects did not significantly differ between groups.Conclusion: Oral D-met reduces cisplatin-induced ototoxicity in humans.