Antioxidation Medication for Noise-induced Hearing Loss

This study will examine whether oral intake of 1200mg N-Acetylcysteine/day will prevent temporary threshold shift in hearing among workers exposed to noise

Study Overview

• Status: Completed
• Conditions: Hearing Loss
• Intervention / Treatment: Drug: N-acetylcysteine (NAC); Drug: glucose

Detailed Description

Both genetic and environmental factors contribute to noise-induced hearing loss (NIHL). The cellular antioxidant system appears to protect cochlear hair cells from oxidative stress due to noise. Previous animal studies showed protective effects of anti-oxidant medicines against NIHL.The objective of this study is to test the hypothesis that preventive medication of antioxidation is related to susceptibility to NIHL.

The 53 noise-exposed workers from steel industries in Taiwan will be recruited, and divided into N-Acetylcysteine (NAC)(Acetine, 1200mg/day) group and placebo one. The duration of medication is 2 weeks initially. After washout for 2 weeks, the kinds of medications in these 2 groups will be crossover and used for 2 weeks. Firstly, questionnaires interview about noise exposure, smoking, alcohol drinking, drug habit history and calculation of Body Mass Index (BMI) will be done. The following methods would be performed individually after medication. With detailed local examination with otoscope, these subjects receive hearing tests by pure-tone audiometry (PTA) and distortion product otoacoustic emissions (DPOAE) before and after their daily works. The possible confounding factors including background noise, solvent, heavy metals, carbon monoxide and temperature in the workplaces will be assessed. The amount of noise exposure is evaluated by personal dosimeter. Early morning, Blood samples will be collected. Deletion polymorphisms in the Glutathione S-transferase (GST)T1 and GSTM1 genes will be determined. Statistical analysis will be performed to evaluate the relation between intake of anti-oxidant medicine and noise-induced temporal threshold shift (TTS).

The expected results of this study are to determine whether anti-oxidant supplements protect workers from noise-induced TTS.

We anticipate that these human studies might help elucidate the relative importance of anti-oxidant enzymes as risk factors for NIHL.

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 2

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • Environmental and Occupational Medicine, National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• workers in steel industry
• known exposure to noise at work

Exclusion Criteria:

• ever diagnosed as having diabetes mellitus
• fasting glucose of 120 or greater

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acetin	Drug: N-acetylcysteine (NAC); 600mg twice daily for 2 weeks; Other Names: acetin (600mg)
Placebo Comparator: Glucose	Drug: glucose; 1 gm glucose capsule; Other Names: Sugar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Temporary Threshold Shift Measurement by Pure Tone Audiometry (A Total of Four Hearing Assessments Were Completed for Each Formulation Period on the 1st Day Pre- and Post-shift, and the 14th Day Pre- and Post-shift)	The hearing threshold level (HL) at high frequency (HF) by pure-tone audiometry (PTA) was defined as the average of HLs at 3k,4k,6kHz for each ear examined. A total of four hearing assessments by PTA were completed for each formulation period on the 1st day pre- and post-shift, and the 14th day pre- and post-shift. The amount of temporary threshold change was calculated by subtracting the pre-shift hearing threshold from the post-shift hearing threshold at each frequency.	A total of four hearing assessments were completed for each formulation period on the 1st day pre- and post-shift, and the 14th day pre- and post-shift

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Temporary Threshold Changes Measurement by Distortion Product Otoacoustic Emissions (DPOAE) (A Total of Four Hearing Assessments Were Completed for Each Formulation Period on the 1st Day Pre- and Post-shift, and the 14th Day Pre- and Post-shift)	Distortion product otoacoustic emissions (DPOAE) is an objective measure to assess the cochlear changes. DPOAE response threshold at high frequency (HF) was defined as the average of response levels (dB SPL) at 3k,4k,6kHz for each ear examined. A total of four hearing assessments by DPOAE were completed for each formulation period on the 1st day pre- and post-shift, and the 14th day pre- and post-shift. The amount of DPOAE temporary threshold change was calculated by subtracting the pre-shift DPOAE response threshold from the post-shift DPOAE response threshold at each frequency.	A total of four hearing assessments were completed for each formulation period on the 1st day pre- and post-shift, and the 14th day pre- and post-shift

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Collaborators: Institute of Occupational Safety and Health, Taiwan; Municipal Hospital of Tainan, Taiwan
• Investigators: Principal Investigator: Yue-Liang L Guo, MD, MPH, PHD, National Taiwan University Hospital; Study Director: Tung-Sheng Shih, PHD, Institute of Occupational Safety and Health, Taiwan

Publications and helpful links

General Publications

• Coleman JK, Kopke RD, Liu J, Ge X, Harper EA, Jones GE, Cater TL, Jackson RL. Pharmacological rescue of noise induced hearing loss using N-acetylcysteine and acetyl-L-carnitine. Hear Res. 2007 Apr;226(1-2):104-13. doi: 10.1016/j.heares.2006.08.008. Epub 2006 Oct 4.
• Kopke R, Bielefeld E, Liu J, Zheng J, Jackson R, Henderson D, Coleman JK. Prevention of impulse noise-induced hearing loss with antioxidants. Acta Otolaryngol. 2005 Mar;125(3):235-43. doi: 10.1080/00016480410023038.
• Duan M, Qiu J, Laurell G, Olofsson A, Counter SA, Borg E. Dose and time-dependent protection of the antioxidant N-L-acetylcysteine against impulse noise trauma. Hear Res. 2004 Jun;192(1-2):1-9. doi: 10.1016/j.heares.2004.02.005.
• Kopke RD, Jackson RL, Coleman JK, Liu J, Bielefeld EC, Balough BJ. NAC for noise: from the bench top to the clinic. Hear Res. 2007 Apr;226(1-2):114-25. doi: 10.1016/j.heares.2006.10.008. Epub 2006 Dec 20.
• Lin CY, Wu JL, Shih TS, Tsai PJ, Sun YM, Ma MC, Guo YL. N-Acetyl-cysteine against noise-induced temporary threshold shift in male workers. Hear Res. 2010 Oct 1;269(1-2):42-7. doi: 10.1016/j.heares.2010.07.005. Epub 2010 Jul 16.

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): January 1, 2008
• Study Completion (Actual): March 1, 2008

Study Registration Dates

• First Submitted: November 1, 2007
• First Submitted That Met QC Criteria: November 1, 2007
• First Posted (Estimate): November 2, 2007

Study Record Updates

• Last Update Posted (Estimate): July 27, 2010
• Last Update Submitted That Met QC Criteria: July 1, 2010
• Last Verified: November 1, 2009

More Information

Terms related to this study

• Keywords: hearing loss; noise; temporary threshold shift
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Otorhinolaryngologic Diseases; Ear Diseases; Sensation Disorders; Hearing Disorders; Hearing Loss, Sensorineural; Hearing Loss; Deafness; Hearing Loss, Noise-Induced; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Protective Agents; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: 200704018M