Micronutrients to Prevent Noise-induced Hearing Loss - Full Text View

Sponsor:	University of Michigan
Collaborators:	National Institute on Deafness and Other Communication Disorders (NIDCD) Karolinska Institutet Southern Illinois University University of Castilla-La Mancha University of Florida
Information provided by:	University of Michigan
ClinicalTrials.gov Identifier:	NCT00808470

Purpose

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 antioxidants (beta-carotene, and vitamins C and E) and the mineral magnesium (which acts in part as a vasodilator) 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 60 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 24 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.

Experiment 3: "NATO airbase" studies (Universidad de Castilla-La Mancha, Spain). Prevention of permanent hearing loss, induced by daily exposure to aircraft engine noise, will be measured over two-years. Subjects will be 120 adult male or female Spanish NATO soldiers. All subjects are required to wear standard hearing protection regardless of study participation.

Experiment 4: "Stamping Factory" studies (Universidad de Castilla-La Mancha, Spain). Prevention of permanent hearing loss, induced by daily exposure to industrial noise, will be will be measured over two-years. Subjects will be 120 adult male or female personnel at a Spanish stamping factory hired within the past 5 years. All subjects are required to wear standard hearing protection regardless of study participation.

Condition	Intervention	Phase
Noise-Induced Hearing Loss	Dietary Supplement: Micronutrient Supplement Other: Placebo	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Prevention
Official Title:	Phase II Study of Efficacy of Antioxidants and Vasodilator to Reduced Noise-induced Hearing Loss

Resource links provided by NLM:

Genetics Home Reference related topics: nonsyndromic deafness Pendred syndrome

MedlinePlus related topics: Antioxidants Dietary Supplements Hearing Disorders and Deafness Noise Tinnitus Vitamin C Vitamin E

Drug Information available for: Carotenoids beta Carotene Magnesium

U.S. FDA Resources

Further study details as provided by University of Michigan:

Primary Outcome Measures:

Maximum threshold shift at 3, 4, or 6 kHz in either ear [ Time Frame: 15 min, repeated measures at 1-1.5 hr intervals for 3-3.5 hours to measure temporary changes. Tests at 1 year and 2 years to measure permanent changes in Spanish studies. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Threshold shift at individual frequencies, including 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12.5, 14 and 16 kHz [ Time Frame: 15 min, repeated measures at 1-1.5 hr intervals for 3-3.5 hours to measure temporary changes. Tests at 1 year and 2 years to measure permanent changes in Spanish studies. ] [ Designated as safety issue: No ]
Distortion Product Otoacoustic Emission (DPOAE) amplitude [ Time Frame: 15 min, repeated measures at 1-1.5 hr intervals for 3-3.5 hours to measure temporary changes. Tests at 1 year and 2 years to measure permanent changes in Spanish studies. ] [ Designated as safety issue: No ]
Tinnitus [ Time Frame: 15 min, repeated measures at 1-1.5 hr intervals for 3-3.5 hours to measure temporary changes. Tests at 1 year and 2 years to measure permanent changes in Spanish studies. ] [ Designated as safety issue: No ]

Estimated Enrollment:	324
Study Start Date:	October 2008
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Experimental Agent, Two-year Subjects in two-year studies in Spain who are assigned to treatment group in either Airbase or Factory populations.	Dietary Supplement: Micronutrient Supplement 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) or daily, for two years. Other Name: Auraquell
Placebo Comparator: Placebo, Two-year Subjects in two-year studies in Spain who are assigned to control condition in either Airbase or Factory populations.	Other: Placebo 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) or daily, for two years.
Experimental: Experimental Agent, Cross-over Subjects in short-term studies in Sweden and the United States; all subjects are treated with active agents in one arm of the study. All subjects also participate in placebo arm, and order of treatments is masked.	Dietary Supplement: Micronutrient Supplement 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) or daily, for two years. Other Name: Auraquell
Placebo Comparator: Placebo, cross-over Subjects in short-term studies in Sweden and the United States; all subjects are treated with placebo agents in one arm of the study. All subjects also participate in treated arm, and order of treatments is masked.	Other: Placebo 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) or daily, for two years.

Eligibility

Ages Eligible for Study:	18 Years to 35 Years
Genders Eligible for Study:	Both
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
To participate in two-year studies, subjects must be non-smoking individuals, and must have normal electrolytes, BUN, creatinine, hematocrit, and liver enzymes

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00808470

Locations

United States, Florida
University of Florida	Not yet recruiting
Gainesville, Florida, United States, 32610
Contact: Colleen G Le Prell, PhD 352-271-6163 colleeng@phhp.ufl.edu
Principal Investigator: Colleen G Le Prell, PhD
Sub-Investigator: James W Hall, PhD
Sub-Investigator: Patrick J Antonelli
Spain
Universidad de Castille-LaMancha	Not yet recruiting
Albacete, LaMancha, Spain, 02006
Contact: Luis Gonzalez, MD 34 0780 5908 lgonzalezf@solimat.com
Contact: Julio Carbayo 967 24 78 43 jacarbayoh@telefonica.net
Principal Investigator: Jose M Juiz, MD-PhD
Sub-Investigator: Julio Carbayo, MD
Sweden
Karolinksa Institutet	Recruiting
Stockholm, Sweden, 171 76
Contact: Ann-Cathrine Lindblad, MS 08-5858 0148 Anncat.Lindblad@ki.se
Principal Investigator: Mats Ulfendahl, PhD
Sub-Investigator: Ulf Rosenhall, MD

Sponsors and Collaborators

University of Michigan

National Institute on Deafness and Other Communication Disorders (NIDCD)

Karolinska Institutet

Southern Illinois University

University of Castilla-La Mancha

University of Florida

Investigators

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

More Information

No publications provided by University of Michigan

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

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.

Responsible Party:	Gordon Hughes/Program Director, Clinical Trials, NIH-NIDCD
ClinicalTrials.gov Identifier:	NCT00808470 History of Changes
Other Study ID Numbers:	UO1DC008423, U01DC008423-02S1, U01DC008423-03, UO1DC008423
Study First Received:	December 11, 2008
Last Updated:	August 20, 2010
Health Authority:	United States: Federal Government; United States: Institutional Review Board; Spain: Comité Ético de Investigación Clínica; Sweden: Regional Ethical Review Board

Keywords provided by 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
Signs and Symptoms
Hearing Loss, Sensorineural
Antioxidants

Micronutrients
Beta Carotene
Trace Elements
Vasodilator Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Growth Substances
Cardiovascular Agents
Therapeutic Uses
Vitamins

ClinicalTrials.gov processed this record on February 09, 2012