Noise-Induced Hearing Loss-Acute Exposure Treatment (UA) (PINIHL-AET)

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

The purpose of this study is to assess the safety and efficacy of zonisamide (ZNS) for the treatment of noise-induced hearing loss in adults.

Study Overview

• Status: Terminated
• Conditions: Hearing Loss, Noise-Induced
• Intervention / Treatment: Drug: Zonisamide 100Mg Cap; Drug: Placebo

Detailed Description

This is a randomized, double-blind, and placebo-controlled study is to test whether zonisamide (ZNS) can treat noise-induced hearing loss in police officers on the range following training and certifications sessions. Participants who meet the eligibility requirements will be randomized to receive either ZNS 100 milligrams (mg) or placebo.

Study participants will be recruited from the Akron Police Department, Summit County Police Department, and other local surrounding police departments. Police officers will be offered participation if they are training for firearm certification as part of their standard occupational requirements. These are officers that would be recommended and/or required to complete these trainings/certifications despite this investigation and this investigation will have no influence on audiologic recommendations.

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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Akron, Ohio, United States, 44325-3001
      • University of Akron

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Screening Inclusion Criteria:

• Police officers who are scheduled for firearm training and/or certification on the range.
• At least 18 years of age.
• Air conduction thresholds are to be no worse than 25 dB HL from 0.5 kHz to 3 kHz, no worse than 30 dB HL at 4 kHz, and no worse than 45 dB HL at 6 and 8 kHz prior to shooting range exposure.
• Ability to understand and willingness to sign an IRB approved written informed consent document.

Enrollment Inclusion Criteria:

• Observed audiometric TTS ≥ 10 dB HL at 2, 3, 4 and/or 6 kHz
• Observed air-bone gap < 10 dB HL at .5, 1, 2 and 4 kHz, with normal tympanometry

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 otologic disorder.
• History of ototoxic drug use.
• Current use of strong/moderate 3A4 inhibitor/inducer and grapefruit juice.

• For secondary outcomes, exclusion criteria is as follows:

  1. DPOAE data will be used as a secondary outcome measure of TTS, and participants will be excluded if their DPOAE is absent at more than 3/7 frequencies. Criteria for a present response is any response that is > 5 dB SPL above the noise floor and replicable within ±5 dB SPL.
  2. ECochG: Participants will be excluded if the ECochG/ABR wave I response is absent.
  3. WIN test: Participants with WIN scores greater than moderate difficulty or 14.9 dB SNR will be excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zonisamide; For subjects randomized to zonisamide, the package will contain one zonisamide capsule (100 mg PO).	Drug: Zonisamide 100Mg Cap; ZONEGRAN® is commercially available for oral administration as capsules containing 100 mg of Zonisamide.; Other Names: Zonegran; ZNS
Placebo Comparator: Placebo; For the subjects randomized to placebo, the package will contain one placebo capsule that looks, smells, and taste the same as zonisamide capsule.	Drug: Placebo; The placebo will contain microcrystalline cellulose which is the predominant filler in the generic capsule.; Other Names: microcrystalline cellulose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Officers With Permanent Threshold Shift (PTS)	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-shooting as compared to baseline audiogram.	30 days (+/- 3 days) after training

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Distortion Product Otoacoustic Emissions (DPOAE)	DPOAE amplitudes are measured to determine threshold shifts. A change is noted in DPOAE amplitude at any frequency that is significantly greater than the stability of each measurement (i.e., 95% confidence interval of each measurement do not overlap).	baseline (before shooting), 30 days (+/-3 days) after training
Ultra-high Frequency Audiometry	Number of participants that experience a change in ultra-high frequencies greater than 5 dB; to measure for both temporary and permanent high frequency audiometric changes. A significant change is defined for any frequency that is greater than 5 dB HL from baseline thresholds.	baseline (before shooting), within 5-10 minutes after shooting and 30 days (+/-3 days) after training
Electrocochleography (ECochG) AP Amplitude	To measure for changes in ECochG AP amplitude between baseline (before training) visit and 30-days after training visits.	baseline (before shooting) and 30 days (+/-3 days) after training
Change in Words In Noise (WIN) Test Signal-to-Noise Ratio Threshold	The WIN test battery consists of 35 words that are presented in a background noise (speech babble) with varying degrees of signal-to-noise ratios (SNR) from 24 dB HL to 0 dB HL. The WIN score will be repeated three times in order to assess test-retest reliability. The total number of words correctly identified will be used to calculate a dB HL S/N threshold by the Spearman-Karber equation at the mean of 50% correct points. Reported information is the change in score between baseline testing and testing 30 days after training. This measure assesses the change in signal-to-noise ratio (SNR) threshold, reported in decibels SNR (dB SNR), at which a participant correctly identifies 50% of the words presented in background noise.	baseline (before shooting) and 30 days (+/-3 days) after training
Electrocochleography (ECochG) Latency	To measure for changes in ECochG latency between baseline (before training) visit and 30-days after training visits.	baseline (before shooting) and 30 days (+/-3 days) after training
Electrocochleography (ECochG) Width	To measure for changes in ECochG width between baseline (before training) visit and 30-days after training visits.	baseline (before shooting) and 30 days (+/-3 days) after training
Determine PGx Link Between Noise Induced Hearing Loss (NIHL) and Zonisamide (ZNS)	Exploratory analysis to determine a pharmacogenetic link between noise induced hearing loss (NIHL) and zonisamide (ZNS) treatment effect.	Baseline prior to training

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: United States Department of Defense; University of Texas; Gateway Biotechnology, Inc.
• Investigators: Principal Investigator: Craig A Buchman, MD, FACS, Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2021
• Primary Completion (Actual): December 23, 2022
• Study Completion (Actual): December 23, 2022

Study Registration Dates

• First Submitted: February 23, 2021
• First Submitted That Met QC Criteria: February 25, 2021
• First Posted (Actual): March 1, 2021

Study Record Updates

• Last Update Posted (Actual): February 13, 2026
• Last Update Submitted That Met QC Criteria: January 28, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Ear Diseases; Hearing Loss; Hearing Disorders; Hearing Loss, Sensorineural; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hearing Loss, Noise-Induced; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pharmaceutical Preparations; Dosage Forms; Azoles; Amides; Sulfonamides; Sulfones; Isoxazoles; Zonisamide; microcrystalline cellulose; Capsules
• Other Study ID Numbers: PINIHL-AET_UA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No