Noise-Induced Hearing Loss-Acute Exposure Treatment

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and efficacy of zonisamide for the treatment of noise-induced hearing loss in adults.

Detailed Description
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This study is a randomized, double-blinded placebo-control trial with three parallel groups, to make use of a common control group. After being informed about the study expectations and potential risks, all individuals providing written informed consent will undergo screening to determine eligibility for study entry. Participants who meet the eligibility requirements will be randomized in a balanced fashion into one of 3 arms: Group 1) Zonisamide 100 milligrams (mg) pre-op + Placebo post-op; Group 2) Placebo pre- + placebo post-op; and Group 3) Zonisamide 100 mg post-op + placebo post-op

Official Title
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Pharmaceutical Interventions for Noise-Induced Hearing Loss-Acute Exposure Treatment

Conditions
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Hearing Loss, Noise-Induced

Intervention / Treatment
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* Drug: Zonisamide 100Mg Cap
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who are scheduled to undergo a skull-based surgery that requires at least 45 minutes of surgical-drilling At least 18 years of age Air conduction thresholds in the non-operated ears are to be no worse than 25 decibel (dB) hearing loss (HL) for pure tone average 0.5, 1, and 2 kilohertz (kHz) with no individual threshold greater than 30 dB HL, and no worse than 45dB HL at 4 kHz at screening. Observed air-bone gap < 10 dB HL at 0.5, 1, 2, and 4 kHz, with normal tympanometry. Ability to understand and willingness to sign an Institutional Review Board (IRB) approved written informed consent document. Exclusion Criteria: History of known sulfa allergy or hypersensitivity to carbonic anhydrase inhibitors History of moderate-to-severe kidney or liver disease Acute viral, bacterial, fungal or parasitic infection History of seizures Currently pregnant or breast-feeding Any current or history of ear disorder and/or central auditory dysfunction in the non-operated ear History of ototoxic drug use Current use of strong/moderate 3A4 inhibitor/inducer and grapefruit juice

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This study is a randomized, double-blinded placebo-control trial with three parallel groups, to make use of a common control group.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Zonisamide Pre-op + Placebo Post-op<br>For subjects randomized to zonisamide pre-op, the pre-op package will contain one zonisamide capsule (100 mg PO) and the post-op package will contain one placebo capsule that looks, smells, and tastes the same as zonisamide capsules. | Drug: Zonisamide 100Mg Cap<br>* ZONEGRAN® is commercially available for oral administration as capsules containing 100 mg of Zonisamide.<br>* Other names: ZNS;Drug: Placebo<br>* The placebo will contain microcrystalline cellulose which is the predominant filler in the generic capsule.<br>* Other names: microcrystalline cellulose;|
| Placebo Comparator: Placebo Pre-op + Placebo Post-op<br>For the subjects randomized to placebo, both pre- and post-op packages will contain placebo capsules that looks, smells, and taste the same as zonisamide capsules. | Drug: Placebo<br>* The placebo will contain microcrystalline cellulose which is the predominant filler in the generic capsule.<br>* Other names: microcrystalline cellulose;|
| Active Comparator: Placebo Pre-op + Zonisamide Post-op<br>For subjects randomized to zonisamide post-op, the pre-op package will contain one placebo capsule and the post-op package will contain one zonisamide capsule (100 mg PO). | Drug: Zonisamide 100Mg Cap<br>* ZONEGRAN® is commercially available for oral administration as capsules containing 100 mg of Zonisamide.<br>* Other names: ZNS;Drug: Placebo<br>* The placebo will contain microcrystalline cellulose which is the predominant filler in the generic capsule.<br>* Other names: microcrystalline cellulose;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The ratio of PTS-positive subjects | The primary efficacy endpoint will be the proportion of PTS-positive subjects defined as the ratio of PTS-positive subjects to total number of subjects within each study arm/group. Subjects defined as PTS-positive will demonstrate an increase in threshold that is ≥10 dB HL at any frequency from 2-6 kHz post-surgery as compared to baseline audiogram. | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rate of distortion product otoacoustic emissions (DPOAE) shift | The secondary efficacy outcome measures will be the rate of temporary cochlear change as measured by a DPOAE amplitude shift at any frequency that is significantly greater than the stability of each measurement (i.e., 95% confidence interval of each measurement do not overlap). The rate of DPOAE shift is the ratio of DPOAE shift-positive subjects to total subjects within each arm. | 30 days |