Noise induced hearing loss affects many people at work and in recreational activities. Ebselen, an investigational drug currently undergoing trials, shows promise in its prevention.
Hearing loss due to exposure to loud noise affects many people both at work and in recreational activities. In 2015, the WHO estimated that 1.1 billion teenagers and young adults (aged 12-35 years) are at risk of noise induced hearing loss, as a result of personal music player use at high levels, firearm use without adequate hearing protection and exposure to loud noise in clubs, concerts and bars.
Noise can cause either no change or a temporary or permanent reduction in hearing in one or both ears. Its effects depend on a number of factors including type, level and duration of noise exposure, use of protective devices, rest interval between exposures and pre-existing hearing loss. Loss of hearing sensitivity that resolves following a noise exposure is called a temporary threshold shift (TTS). Hearing loss that does not resolve even after weeks or months is known as a permanent threshold shift (PTS).
The underlying biology of noise induced hearing loss has been extensively investigated, in particular, its effect on the structures within the ear. The substance glutathione peroxidase 1 (GPx1) is found in high levels in several structures in the cochlea (part of the inner ear) and is thought to be important for normal cochlear function. In animal studies, GPx1 is reduced after acute noise exposure.Ebselen is a drug that mimics the action of GPx-1. It has been shown to reduce both temporary and permanent noise induced hearing loss in animal studies.
The safety and efficacy of ebselenin preventing temporary noise induced hearing loss in healthy young adults have been assessed in a preliminary clinical trial. The results were recently reported in The Lancet.
Between January 2013 and Mar 2014, 83 healthy young adult volunteers with normal hearing were randomly assigned to one of 4 groups to receive 200 mg, 400mg or 600 mg of ebselen or placebo, orally twice daily for 4 days.
A sound challenge test was performed on day 3 of treatment. The subjects listened via earphones to a 4-hour playlist of pre-recorded rock or pop music delivered via a specially calibrated iPod at a level known to cause a temporary hearing loss, or TTS, in young adults with normal hearing.
The subjects’ hearing was tested twice before the sound challenge (2-7 days before starting treatment, and at baseline on the day of the challenge), and 6 times after the sound challenge (on the day of the challenge at 15 mins, 1.25 hours, 2.25 hours, 3.25 hours; at 1 day post-challenge; at 1 week post-challenge).
The researchers compared the hearing test results in the four groups – in particular, the mean TTS at 4kHz measured 15 mins after the sound challenge. The researchers considered a 50% reduction in this result in an ebselen group compared to the placebo group to be clinically relevant.
The mean TTS at 4 kHz was 68% lower in the 400mg ebselen group compared to in the placebo group – a significant reduction. A lower threshold translates into less hearing loss. The mean TTS at 4 kHz was also reduced in the 200mg ebselen group (21%), and in the 600mg group (7%), although these reductions were not considered clinically significant. This means that the participants who took Ebselen were less likely to experience temporary hearing loss due to the study conditions than those who did not take the medicine. Ebselen was well tolerated at all doses with few or no side effects.
The researchers concluded that ebselen was safe and effective at a dose of 400mg twice daily in preventing noise-induced temporary hearing loss. There was not a clear dose-response effect with ebselen – that is, its effectiveness was not directly related to dosage level. This had also been observed in animal studies. Further investigation is required, but this preliminary study suggests that ebselen is a promising new drug for the prevention of noise induced hearing loss.
Written by Julie McShane, Medical Writer
Kil J, Labarinas E, Spankovich C, et al. Safety and efficacy of ebselen for the prevention of noise-induced hearing loss: a randomized, double-blind, placebo-controlled, phase 2 trial. The Lancet. Published online July 14, 2017. http://dx.doi.org/10.1016/S0140-6736(17)31791-9.