Micronutrients to Prevent Noise-induced Hearing Loss

Noise-Induced Hearing Loss Clinical Trial

Official title:

Micronutrient Intervention to Reduce Noise-Induced Hearing Loss: Prevention of Temporary Threshold Changes Induced by Use of a Digital Music Player

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00808470
• Other study ID #: U01DC008423
• Secondary ID: U01DC008423-02S1
• Status: Completed
• Phase: Phase 2
• First received: December 11, 2008
• Last updated: January 23, 2014
• Start date: October 2008
• Est. completion date: December 2013

Study information

• Verified date: January 2014
• Source: University of Michigan
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government (National Institutes of Health: National Institute on Deafness and Other Communication Disorders)United States: Food and Drug AdministrationUnited States: Institutional Review Board (University of Florida IRB-01 Approval #560-2009)Sweden: Regional Ethical Review Board
• Study type: Interventional

Clinical Trial 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.

Experiment 2: "Urban warfare" military studies (Karolinska Institutet, Sweden). Prevention of *temporary* elevations in hearing thresholds, induced by automatic gunfire sound inside a concrete bunker, will be measured. Subjects will be 31 adult male or female officers in the Swedish army required to participate in urban combat training regardless of study participation. All subjects are required to wear standard hearing protection during combat exercises.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 101
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 35 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Deafness
• Hearing Loss
• Hearing Loss, Noise-Induced
• Noise-Induced Hearing Loss

Intervention

Dietary Supplement:
• Micronutrient Supplement, capsule form
18 mg beta-carotene 500 mg vitamin C (delivered as 500 mg ascorbic acid) 270 mg vitamin E (delivered as 305 mg alpha-tocopherol acetate) 315 mg magnesium (delivered as 1949 mg magnesium citrate) All substances will be given to subjects orally in capsule form. The total daily dose will be divided into two equal half-doses, and the half doses will be consumed for two consecutive days (cross-over studies).

Other:
• Placebo, capsule form
Inert Inert placebo control will be given to subjects orally in capsule form; capsules appear identical to active agent capsules with respect to both shape and color. Capsules will be consumed as two equal "half-doses," on a time-schedule that is identical to active agent treatments. Half doses will be consumed for two consecutive days (cross-over studies).

Drug:
• Dietary supplement consisting of 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-a-tocopherol acetate), and 18 mg beta carotene.

Other:
• Placebo Control
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.

Locations

Country	Name	City	State
Sweden	Karolinksa Institutet	Stockholm
United States	University of Florida	Gainesville	Florida

Sponsors (7)

Lead Sponsor	Collaborator
University of Michigan	Hearing Health Science Inc (clinical supply funding: mint tablets), Karolinska Institutet, National Institute on Deafness and Other Communication Disorders (NIDCD), OtoMedicine Inc (clinical supply funding: capsules), Southern Illinois University, University of Florida

Countries where clinical trial is conducted

United States,  Sweden, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Average threshold shift at 4 kHz in both ears		15 min, repeated measures at 1-1.5 hr intervals for 3-3.5 hours to measure temporary changes; additional tests at 1 day and 1 week post-exposure.	No
Secondary	Threshold shift at individual frequencies, including 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12.5, 14 and 16 kHz		15 min, repeated measures at 1-1.5 hr intervals for 3-3.5 hours to measure temporary changes; additional tests at 1 day and 1 week post-exposure.	No
Secondary	Distortion Product Otoacoustic Emission (DPOAE) amplitude		15 min, repeated measures at 1-1.5 hr intervals for 3-3.5 hours to measure temporary changes; additional tests at 1 day and 1 week post-exposure.	No
Secondary	Tinnitus		15 min, repeated measures at 1-1.5 hr intervals for 3-3.5 hours to measure temporary changes; additional tests at 1 day and 1 week post-exposure.	No