Prevention of Noise-induced Hearing Loss

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ClinicalTrials.gov Identifier: NCT02049073

Recruitment Status : Withdrawn (new data makes this trial unethical)

First Posted : January 29, 2014

Last Update Posted : November 6, 2017

Sponsor:

Information provided by (Responsible Party):

Judith Lieu, Washington University School of Medicine

Study Description

Brief Summary:

Noise-induced hearing loss affects an estimated 5% of the worldwide population, with 30-40 million Americans exposed to hazardous sound or noise levels regularly. Sources of noise may be occupational, blast noise, or recreational. Trauma to the inner ear can occur through transient hearing loss or permanent hearing loss. Although hearing recovers after temporary transient hearing loss, growing evidence suggests that repeated temporary transient hearing loss may lead to a permanent hearing loss. Currently, there are no treatments and there are no known medications that can be used clinically to prevent noise-induced hearing loss in humans.

The long-term goal of this research is to find medications that can prevent noise-induced hearing loss. The purpose of the present pilot study is to evaluate zonisamide and methylprednisolone as medications to prevent temporary transient hearing loss in humans.

Condition or disease	Intervention/treatment	Phase
Noise-induced Hearing Loss	Drug: Zonisamide Drug: Methylprednisolone	Phase 1 Phase 2

Detailed Description:

Noise-induced hearing loss (NIHL) affects an estimated 5% of the worldwide population, with 30-40 million Americans exposed to hazardous sound or noise levels regularly. Sources of noise may be occupational (e.g., manufacturing, construction), blast noise (e.g., firearms or explosions), or recreational (e.g., loud music, power tools). Trauma to the inner ear can occur through transient hearing loss (temporary threshold shifts, TTS) or permanent hearing loss (permanent threshold shift, PTS). Although hearing recovers after a TTS in about 24-48 hours, growing evidence suggests that repeated TTS may lead to PTS. Both TTS and PTS lead to a decrease in hearing thresholds at 3000 to 6000 Hz.

Currently, there are no treatments for human NIHL although this is an area of active investigation. Protection against NIHL consists of limiting noise exposure through Occupational Safety and Health Administration (OSHA) limits to occupational noise and the wearing of hearing-protection devices (e.g., ear muffs or earplugs). There are no known medications that can be used clinically to prevent NIHL in humans.

LePrell and colleagues have successfully established a protocol for inducing TTS using digitally-modified pop or rock music. This model of experimentally-induced TTS was intended to provide an ethical way of testing medications that might prevent NIHL.

In a mouse model, Bao and colleagues were able to use zonisamide, an anti-epileptic medication approved for the treatment of partial seizures, and methylprednisolone, a glucocorticoid medication, to protect against noise-induced PTS. The long-term goal of this research is to find medications that can prevent NIHL. The goal of the present pilot study is to evaluate zonisamide and methylprednisolone as medications to prevent TTS in humans.

Specific Aim 1: Examine zonisamide as a possible prophylactic medication to prevent noise-induced hearing loss, using an escalating dose protocol. Healthy volunteers would be given 100 or 200 mg of zonisamide as one-time doses or as a daily medication for two week (to establish a steady-state). They would be exposed to digitally-modified pop or rock music for 4 hours and undergo serial testing of hearing and monitoring for side effects after their sound exposure for 3-4 hours. They would be monitored at one day and one week post-exposure for hearing and other side effects.

Hypothesis: Zonisamide is able to protect against noise-induced hearing loss in humans.

Specific Aim 2: Examine methylprednisolone as a possible prophylactic medication to prevent noise-induced hearing loss, using an escalating dose protocol. Healthy volunteers would be given 32 or 64 mg of methylprednisolone as one-time doses. They would undergo the same music exposure and post-sound exposure monitoring as described above.

Hypothesis: Methylprednisolone is able to protect against noise-induced hearing loss in humans

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	0 participants
Allocation:	Non-Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Prevention
Official Title:	Zonisamide and Methylprednisolone to Prevent Noise-induced Temporary Hearing Loss
Actual Study Start Date :	October 31, 2017
Actual Primary Completion Date :	November 1, 2017
Actual Study Completion Date :	November 1, 2017

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Nonsyndromic hearing loss

MedlinePlus related topics: Hearing Disorders and Deafness Noise

Drug Information available for: Prednisolone Prednisolone acetate Methylprednisolone acetate Methylprednisolone Prednisolone sodium phosphate Prednisolone phosphate Prednisolone sodium succinate Methylprednisolone sodium succinate Zonisamide

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Zonisamide Zonisamide 100 mg or 200 mg pill administered orally every day for 2 weeks	Drug: Zonisamide Zonisamide 100 mg or 200 mg pill administered orally every day for 2 weeks Other Name: Zonegran
Experimental: Methylprednisolone Methylprednisolone 32 mg or 64 mg pill administered orally once	Drug: Methylprednisolone Methylprednisolone 32 mg or 64 mg pill administered orally once Other Names: Medrol Solu-Medrol Depo-Medrol Hybrisil A-Methapred
No Intervention: Control no medication

Outcome Measures

Primary Outcome Measures :

Pure Tone Thresholds [ Time Frame: 15 minutes post-music exposure ]
The primary outcome will be pure tone hearing thresholds (particularly 2000, 3000, 4000, and 6000 Hz) as measured by audiogram in a soundproof booth.

Secondary Outcome Measures :

DPOAE [ Time Frame: visit 2, pre-music exposure; visit 3-one week after music exposure ]
Distortion-product otoacoustic emissions (DPOAE) will be used as a secondary auditory outcome. A tinnitus questionnaire (Tinnitus Handicap Inventory) will be used to measure the secondary outcome of tinnitus, which frequently accompanies TTS.
Pure tone thresholds [ Time Frame: 1 hr 15 min, 2 hr 15 min, and 3 hr 15 min post exposure. ]
This outcome measures recovery of hearing after loud music exposure

Other Outcome Measures:

Pure tone thresholds [ Time Frame: One week after music exposure. ]
Recovery of hearing after noise exposure

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 30 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

adults 18 to 30 years old
normal hearing
good to excellent health

Exclusion Criteria:

hearing loss
history of seizures
history of allergy or hypersensitivity to sulfonamide or oral steroid medications

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02049073

Locations

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United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110

Sponsors and Collaborators

Washington University School of Medicine

Investigators

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Principal Investigator:	Judith Lieu, MD	Washington University School of Medicine

More Information

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Responsible Party:	Judith Lieu, Associate Professor of Otolaryngology, Washington University School of Medicine
ClinicalTrials.gov Identifier:	NCT02049073 History of Changes
Other Study ID Numbers:	NIHL2014
First Posted:	January 29, 2014 Key Record Dates
Last Update Posted:	November 6, 2017
Last Verified:	November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided
Plan Description:	undecided

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Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No
Product Manufactured in and Exported from the U.S.:	Yes

Keywords provided by Judith Lieu, Washington University School of Medicine:


hearing loss noise induced hearing loss zonisamide

Additional relevant MeSH terms:

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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 Methylprednisolone Methylprednisolone Acetate Methylprednisolone Hemisuccinate Prednisolone	Prednisolone acetate Zonisamide Prednisolone hemisuccinate Prednisolone phosphate Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Neuroprotective Agents Protective Agents

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