Micronutrients to Prevent Noise-induced Hearing Loss

• ClinicalTrials.gov Identifier: NCT00808470
• Recruitment Status: Completed
• First Posted: December 15, 2008
• Results First Posted: May 19, 2017
• Last Update Posted: May 19, 2017
• Sponsor: University of Michigan
• Collaborators: National Institute on Deafness and Other Communication Disorders (NIDCD); University of Florida; Southern Illinois University; Hearing Health Science, Inc.
• Information provided by (Responsible Party): Glenn Green, University of Michigan

Study Description

Brief Summary:

Noise-induced hearing loss (NIHL) is a significant clinical, social, and economic issue. Studies in animals have allowed us to identify mechanisms contributing to NIHL, including direct mechanical trauma, free radicals formed in association with metabolic stress, and reduced blood flow. A combination of antioxidant vitamins (beta-carotene, and vitamins C and E) and the mineral magnesium (which acts in part as a vasodilator but also as an antioxidant) is highly effective in preventing NIHL in animals. These studies evaluate efficacy of this intervention in humans.

Hypothesis: Treatment with these micronutrients provides safe, effective attenuation of acute hearing changes induced by exposure to real-world sounds producing temporary (non-permanent) or permanent hearing changes induced by exposure to real-world sounds.

Experiment 1: "Digital Audio Player" studies (University of Florida, Gainesville). Prevention of *temporary* elevations in hearing thresholds, induced by exposure to moderately loud music, will be measured. Subjects will be 70 young adults with equal numbers of male and female participants.

Condition or disease	Intervention/treatment	Phase
Noise-Induced Hearing Loss	Drug: beta-carotene, vitamins C and E, magnesium; Other: Placebo	Phase 2

Detailed Description:

This study assessed the potential for prevention of the temporary changes in hearing that can occur after use of a music player device for 4 hours. All participants listened to one of two playlists (pop or rock) set at the same volumes to provide equivalent and consistent exposures across participants. Participants received either a dietary supplement or a placebo once/daily for three days prior to the day of music exposure, and also on the day of music exposure. The fourth and final dose was consumed immediately prior to music listening and consumption was observed by a member of the study team. Changes in hearing were assessed 15-min post-music, and then 1, 2, and 3 hours later, as well as the following day and 1 week later.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 72 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Micronutrient Intervention to Reduce Noise-Induced Hearing Loss: Prevention of Temporary Threshold Changes Induced by Use of a Digital Music Player
• Study Start Date: October 2008
• Actual Primary Completion Date: December 2013
• Actual Study Completion Date: December 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: Nutrients; Subjects in University of Florida music player study who are assigned to nutrient condition(beta-carotene, vitamins C and E, magnesium). Nutrient tablets are consumed for 4 days.	Drug: beta-carotene, vitamins C and E, magnesium; 6 mint-flavored tablets per day, taken once daily total daily dose label claim: micronutrient combination of 500 mg vitamin C (magnesium ascorbate), 315 mg magnesium (magnesium citrate, magnesium ascorbate, magnesium stearate), 267 mg vitamin E (d-α-tocopherol acetate), and 18 mg beta carotene.; Other Name: Soundbites®
Placebo Comparator: Placebo for nutrients; Subjects in University of Florida music player study who are assigned to control (placebo) condition. Placebo tablets are consumed for 4 days.	Other: Placebo; 6 mint-flavored tablets per day, containing inactive substances including mannitol, peppermint flavor, sucralose, color prep, iron oxide yellow synthetic, stearic acid (vegetable grade), and silicon dioxide colloidal.

Outcome Measures

Primary Outcome Measures :

1. Average Threshold Shift at 4 kHz in Both Ears [ Time Frame: 15 min, 1 hr intervals for 3 hours to measure temporary changes; additional tests at 1 day and 1 week post-exposure. ]
   The study measures the quietest decibel level the participants can hear before the 4 hour music exposure The first post-music test to measure shift is 15 minutes after the music exposure is completed and again at 1 hour intervals. The shift represents the mean change in quietest decibel volume detected between baseline (pre-music) and post music.

Secondary Outcome Measures :

1. Threshold Shift at Individual Frequencies, Including 0.25, 0.5, 1, 2, 3, 6, and 8 kHz, 15 Min Post-music [ Time Frame: 15 min ]
   The study measures the quietest decibel level the participants can hear before the 4 hour music exposure The first post-music test to measure shift is 15 minutes after the music exposure is completed and again at 1 hour intervals. The shift represents the mean change in quietest decibel volume detected between baseline (pre-music) and post music.
2. Tinnitus [ Time Frame: immediate, repeated measures at 1 hr intervals for 3 hours to measure temporary changes; additional tests at 1 day and 1 week post-exposure. ]
   Presence of tinnitus was assessed using yes/no question. If tinnitus was reported, perception was assessed using survey.

Other Outcome Measures:

1. Distortion Product Otoacoustic Emission (DPOAE) Amplitude - f1+3328 HZ, F2+ 3984 Hz; 30 Minutes [ Time Frame: 15 min ]
   DPOAE amplitude was measured following the audiometric testing completion at approximately 30 minutes post music. Test time was approximate as DPOAE tests began as soon as threshold testing was completed. F1 and F2 frequency pairs included 3328 and 3984 Hz, F1 sound levels started at 65 dB SPL at each frequency, and decreased in 5 dB steps to a level of 25 dB SPL. F2 levels were 10 dB lower than F1 levels. Threshold tests began precisely at 15 min, 1 hr 15 min, 2 hr 15 min, 3 hr 15 min. Threshold tests take approximately 15 min, but the exact duration of testing varies from subject to subject. The OAE testing began as soon as threshold testing completed. Thus, OAE tests began approx. 30 min, 1 hr 30 min, 2 hr 30 min, and 3 hr 30 min post music, but for some it may have been a little bit earlier or a little bit later (i.e., the test may have begun as early as 25 min or as late as 35 min post music, depending on how quickly the subject completed threshold testing).
2. Threshold Shift at Individual Frequencies, Including 0.25, 0.5, 1, 2, 3, 6, 8, kHz [ Time Frame: repeated measures at 1 hr intervals for 3 hours to measure temporary changes; additional tests at 1 day and 1 week post-exposure. ]
3. Distortion Product Otoacoustic Emission (DPOAE) Amplitude - Additional Time Measures [ Time Frame: repeated measures at 1 hr intervals for 3 hours to measure temporary changes; additional tests at 1 day and 1 week post-exposure. ]
   DPOAE amplitude was measured following the audiometric testing completion at each of the post-music test times. F1 and F2 frequency pairs included 6656 and 8015 Hz, 5016 and 6000 Hz, 3328 and 3984 Hz, 2484 and 3000 Hz, and 1687 and 2015 Hz. F1 sound levels started at 65 dB SPL at each frequency, and decreased in 5 dB steps to a level of 25 dB SPL. F2 levels were 10 dB lower than F1 levels.
4. Distortion Product Otoacoustic Emission (DPOAE) Amplitude - Additional Pairs [ Time Frame: 15 minutes ]
   Distortion Product Otoacoustic Emission (DPOAE) Amplitude was measured following the audiometric testing completion at approximately 30 minutes post music. F1 and F2 frequency pairs included 6656 and 8015 Hz, 5016 and 6000 Hz, 2484 and 3000 Hz, and 1687 and 2015 Hz. F1 sound levels started at 65 dB SPL at each frequency, and decreased in 5 dB steps to a level of 25 dB SPL. F2 levels were 10dB lower than F1 Levels. Threshold tests began precisely at 15 min, 1 hr 15 min, 2 hr 15 min, 3 hr 15 min. The OAE testing began as soon as threshold testing completed. Threshold tests take approximately 15 min, but the exact duration of testing varies among subjects. Thus, OAE tests began approx. 30 min, 1 hr 30 min, 2 hr 30 min, and 3 hr 30 min post music, but for some it may have been a little bit earlier than for others (i.e., the test may have begun as early as 25 min or as late as 35 min post music, depending on how quickly the subject completed threshold testing).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 35 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

Hearing inclusion criteria are as follows for all studies:

• subjects must have a normal audiologic assessment at baseline consisting of:

  1. symmetric hearing with air conduction thresholds no worse than 25 dB HL at tested frequencies between .25 - 8 kHz;
  2. no significant threshold asymmetry (i.e., greater than 15 dB) between the ears at any test frequency;
  3. no significant air-bone gaps (i.e., greater than 10 dB); and
  4. Type A tympanograms bilaterally, defined as a range of -140 to +40 daPa based on the 90% range for adults (Margolis & Hunter 2000).

Additional criteria are as follows:

• No history of ear disease, able to provide informed consent, agree to follow study procedures, normal health screening at study entry

Exclusion Criteria:

• Pregnant or trying to become pregnant within study period (females)
• subjects belonging to vulnerable populations
• subjects with any history of chronic disease
• hearing loss that exceeds limits specified above
• inability or failure to provide informed consent
• medical conditions that require treatment with drugs including anticoagulants
• diuretics
• digoxin
• aspirin/salicylate
• barbiturates
• minocycline

Contacts and Locations

Locations

United States, Florida

University of Florida

Gainesville, Florida, United States, 32610

Sponsors and Collaborators

University of Michigan

National Institute on Deafness and Other Communication Disorders (NIDCD)

University of Florida

Southern Illinois University

Hearing Health Science, Inc.

Investigators

• Principal Investigator: Josef M Miller, PhD; University of Michigan
• Principal Investigator: Colleen G Le Prell, PhD; University of Florida

More Information

Publications of Results:

Le Prell CG, Johnson AC, Lindblad AC, Skjönsberg A, Ulfendahl M, Guire K, Green GE, Campbell KC, Miller JM. Increased vitamin plasma levels in Swedish military personnel treated with nutrients prior to automatic weapon training. Noise Health. 2011 Nov-Dec;13(55):432-43.

Other Publications:

Le Prell CG, Fulbright A, Spankovich C, Griffiths SK, Lobarinas E, Campbell KC, Antonelli PJ, Green GE, Guire K, Miller JM. Dietary supplement comprised of β-carotene, vitamin C, vitamin E, and magnesium: failure to prevent music-induced temporary threshold shift. Audiol Neurotol Extra. 2016 May-Aug;6(2):20-39. Epub 2016 Jul 5.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Spankovich C, Le Prell CG. Associations between dietary quality, noise, and hearing: data from the National Health and Nutrition Examination Survey, 1999-2002. Int J Audiol. 2014 Nov;53(11):796-809. doi: 10.3109/14992027.2014.921340. Epub 2014 Jun 30.

Le Prell CG, Yang Q, Harris JG. Modification of digital music files for use in human temporary threshold shift studies. J Acoust Soc Am. 2011 Oct;130(4):EL142-6. doi: 10.1121/1.3630017.

• Responsible Party: Glenn Green, Associate Professor of Otolaryngology, University of Michigan
• ClinicalTrials.gov Identifier: NCT00808470
• Other Study ID Numbers: U01DC008423 ( U.S. NIH Grant/Contract ); U01DC008423-02S1 ( U.S. NIH Grant/Contract ); U01DC008423-03 ( U.S. NIH Grant/Contract ); U01DC008423 ( U.S. NIH Grant/Contract )
• First Posted: December 15, 2008
• Results First Posted: May 19, 2017
• Last Update Posted: May 19, 2017
• Last Verified: April 2017

Keywords provided by Glenn Green, University of Michigan:

Noise; Hearing Loss; Tinnitus; Antioxidant; Vasodilator; Beta-Carotene; Vitamin C; Vitamin E; Magnesium

Additional relevant MeSH terms:

Hearing Loss; Deafness; Hearing Loss, Noise-Induced; Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Hearing Loss, Sensorineural; Ascorbic Acid; Beta Carotene; Carotenoids; Vitamins; Micronutrients; Physiological Effects of Drugs; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Provitamins