Noise-induced hearing disorders: Clinical and investigational tools.

A series of articles discussing advanced diagnostics that can be used to assess noise injury and associated noise-induced hearing disorders (NIHD) was developed under the umbrella of the United States Department of Defense Hearing Center of Excellence Pharmaceutical Interventions for Hearing Loss working group. The overarching goals of the current series were to provide insight into (1) well-established and more recently developed metrics that are sensitive for detection of cochlear pathology or diagnosis of NIHD, and (2) the tools that are available for characterizing individual noise hazard as personal exposure will vary based on distance to the sound source and placement of hearing protection devices. In addition to discussing the utility of advanced diagnostics in patient care settings, the current articles discuss the selection of outcomes and end points that can be considered for use in clinical trials investigating hearing loss prevention and hearing rehabilitation.

Verification of Attenuation for Premolded Hearing Protection Devices Designed for Music.

High-fidelity premolded earplugs (HiFi HPDs) are designed to provide relatively uniform attenuation across frequencies. The primary goal of this study was to verify the amount and flatness of individual user attenuation. HiFi HPD attenuation was measured using real-ear attenuation at threshold (REAT) measurements under circumaural earphones. Participants were 16 adults tested using commercial HiFi HPDs marketed for use at recreational music events and/or for use by musicians. There was significant individual variation in attenuation both within and across HiFi HPD brands. In addition to significant differences in achieved attenuation, there were significant differences in the uniformity of the attenuation. These data suggest verification of attenuation is important in musicians who are at risk for music-induced hearing disorders even when using "over-the-counter" uniform-fit HPDs.

Preclinical prospects of investigational agents for hearing loss treatment.

INTRODUCTION: : Hearing loss has a high prevalence, with aging, noise exposure, ototoxic drug therapies, and genetic mutations being some of the leading causes of hearing loss. Health conditions such as cardiovascular disease and diabetes are associated with hearing loss, perhaps due to shared vascular pathology in the ear and in other tissues. AREAS COVERED: : Issues in the design of preclinical research preclude the ability to make comparisons regarding the relative efficacy of different drugs of interest for possible hearing loss prevention or hearing restoration. This has not slowed the advancement of candidate therapeutics into human clinical testing. There is a robust pipeline with drugs that have different mechanisms of action providing diverse candidate therapies and opportunities for combination therapies to be considered. EXPERT OPINION: : Much of the preclinical research literature lacks standard study design elements such as dose response testing, and lack of standardization of test protocols significantly limits conclusions regarding relative efficacy. Nonetheless, the many positive results to date have supported translation of preclinical efforts into clinical trials assessing potential human benefits. Approval of the first hearing loss prevention therapeutic is a major success, providing a pathway for other drugs to follow.

Prevention of Noise-Induced Hearing Loss Using Investigational Medicines for the Inner Ear: Previous Trial Outcomes Should Inform Future Trial Design.

Significance: Noise-induced hearing loss (NIHL) is an important public health issue resulting in decreased quality of life for affected individuals, and significant costs to employers and governmental agencies. Recent Advances: Advances in the mechanistic understanding of NIHL have prompted a growing number of proposed, in-progress, and completed clinical trials for possible protections against NIHL via antioxidants and other drug agents. Thirty-one clinical trials evaluating prevention of either temporary or permanent NIHL were identified and are reviewed. Critical Issues: This review revealed little consistency in the noise-exposed populations in which drugs are evaluated or the primary outcomes used to measure NIHL prevention. Changes in pure-tone thresholds were the most common primary outcomes; specific threshold metrics included both average hearing loss and incidence of significant hearing loss. Changes in otoacoustic emission (OAE) amplitude were relatively common secondary outcomes. Extended high-frequency (EHF) hearing and speech-in-noise perception are commonly adversely affected by noise exposure but are not consistently included in clinical trials assessing prevention of NIHL. Future Directions: Multiple criteria are available for monitoring NIHL, but the specific criterion to be used to define clinically significant otoprotection remains a topic of discussion. Audiogram-based primary outcome measures can be combined with secondary outcomes, including OAE amplitude, EHF hearing, speech-in-noise testing, tinnitus surveys, and patient-reported outcomes. Standardization of test protocols for the above primary and secondary outcomes, and associated reporting criterion for each, would facilitate clinical trial design and comparison of results across investigational drug agents. Antioxid. Redox Signal. 36, 1171-1202.

Investigational Medicinal Products for the Inner Ear: Review of Clinical Trial Characteristics in ClinicalTrials.gov.

BACKGROUND: The previous 30 years have provided information on the mechanisms of cell death in the inner ear after noise exposure, ototoxic drug injury, and during aging, and clinical trials have emerged for all of these acquired forms of hearing loss. Sudden hearing loss is less well understood, but restoration of hearing after sudden hearing loss is also a long-standing drug target, typically using steroids as an intervention but with other agents of interest as well. PURPOSE: The purpose of this review was to describe the state of the science regarding clinical testing of investigational medicinal products for the inner ear with respect to treatment or prevention of acquired hearing loss. DATA COLLECTION AND ANALYSIS: Comprehensive search and summary of clinical trials listed in the National Library of Medicine (www. CLINICALTRIALS: gov) database identified 61 clinical trials. RESULTS: Study phase, status, intervention, and primary, secondary, and other outcomes are summarized for studies assessing prevention of noise-induced hearing loss, prevention of drug-induced hearing loss, treatment of stable sensorineural hearing loss, and treatment of sudden sensorineural hearing loss. CONCLUSION: This review provides a comprehensive summary of the state of the science with respect to investigational medicinal products for the inner ear evaluated in human clinical trials, and the current challenges for the field.