title: Efficacy and safety of N-acetylcysteine in prevention of noise induced hearing loss: a randomized clinical trial.
abstract: Despite a robust hearing conservation program, military personnel continue to be at high risk for noise induced hearing loss (NIHL). For more than a decade, a number of laboratories have investigated the use of antioxidants as a safe and effective adjunct to hearing conservation programs. Of the antioxidants that have been investigated, N-acetylcysteine (NAC) has consistently reduced permanent NIHL in the laboratory, but its clinical efficacy is still controversial. This study provides a prospective, randomized, double-blinded, placebo-controlled clinical trial investigating the safety profile and the efficacy of NAC to prevent hearing loss in a military population after weapons training. Of the 566 total study subjects, 277 received NAC while 289 were given placebo. The null hypothesis for the rate of STS was not rejected based on the measured results. While no significant differences were found for the primary outcome, rate of threshold shifts, the right ear threshold shift rate difference did approach significance (p = 0.0562). No significant difference was found in the second primary outcome, percentage of subjects experiencing an adverse event between placebo and NAC groups (26.7% and 27.4%, respectively, p = 0.4465). Results for the secondary outcome, STS rate in the trigger hand ear, did show a significant difference (34.98% for placebo-treated, 27.14% for NAC-treated, p-value = 0.0288). Additionally, post-hoc analysis showed significant differences in threshold shift rates when handedness was taken into account. While the secondary outcomes and post-hoc analysis suggest that NAC treatment is superior to the placebo, the present study design failed to confirm this. The lack of significant differences in overall hearing loss between the treatment and placebo groups may be due to a number of factors, including suboptimal dosing, premature post-exposure audiograms, or differences in risk between ears or subjects. Based on secondary outcomes and post hoc analyses however, further studies seem warranted and are needed to clarify dose response and the factors that may have played a role in the observed results.
authors.affiliation: Hough Ear Institute, University of Oklahoma, USA. Electronic address: rkopke@houghear.org.
authors.forename: Richard
authors.initials: R
authors.lastname: Kopke
authors.affiliation: Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Martin D
authors.initials: MD
authors.lastname: Slade
authors.affiliation: Spatial Orientation Center, Department of Otolaryngology, Naval Medical Center, San Diego, CA, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Jackson
authors.affiliation: TLC Research Solutions, LLC, New Braunfels, TX, USA.
authors.forename: Tanisha
authors.initials: T
authors.lastname: Hammill
authors.affiliation: VA Medical Center, R & D-NCRAR, Portland, OR, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Fausti
authors.affiliation: Department of Otolaryngology, University of Colorado Health Sciences Center, Denver, CO, USA.
authors.forename: Brenda
authors.initials: B
authors.lastname: Lonsbury-Martin
authors.affiliation: Spatial Orientation Center, Department of Otolaryngology, Naval Medical Center, San Diego, CA, USA.
authors.forename: Alicia
authors.initials: A
authors.lastname: Sanderson
authors.affiliation: Auditory Physiology and Psychoacoustics Laboratory, San Diego State University, San Diego, CA, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Dreisbach
authors.affiliation: Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Rabinowitz
authors.affiliation: Auditory Physiology and Psychoacoustics Laboratory, San Diego State University, San Diego, CA, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Torre
authors.affiliation: Spatial Orientation Center, Department of Otolaryngology, Naval Medical Center, San Diego, CA, USA.
authors.forename: Ben
authors.initials: B
authors.lastname: Balough
mesh_terms: D000111:Acetylcysteine / Q000009:adverse effects / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D001301:Audiometry, Pure-Tone; D001309:Auditory Threshold; D019610:Cytoprotection; D004311:Double-Blind Method; D006309:Hearing; D006317:Hearing Loss, Noise-Induced / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control* / Q000523:psychology; D006801:Humans; D008297:Male; D008889:Military Personnel; D009622:Noise / Q000009:adverse effects*; D009784:Occupational Diseases / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control* / Q000523:psychology; D016273:Occupational Exposure / Q000009:adverse effects*; D011446:Prospective Studies; D020011:Protective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D054041:Weapons; D055815:Young Adult
chemical_list: D020011:Protective Agents; D000111:Acetylcysteine