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

NCT04774250 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: PINIHL-AET_UA
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hearing Loss, Noise-Induced

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Distortion Product Otoacoustic Emissions (DPOAE)

  baseline (before shooting), 30 days (+/-3 days) after training

• Ultra-high Frequency Audiometry

  baseline (before shooting), within 5-10 minutes after shooting and 30 days (+/-3 days) after training

• Electrocochleography (ECochG) AP Amplitude

  baseline (before shooting) and 30 days (+/-3 days) after training

• Change in Words In Noise (WIN) Test Signal-to-Noise Ratio Threshold

  baseline (before shooting) and 30 days (+/-3 days) after training

• Electrocochleography (ECochG) Latency

  baseline (before shooting) and 30 days (+/-3 days) after training

Study Arms (2)

Zonisamide

EXPERIMENTAL

For subjects randomized to zonisamide, the package will contain one zonisamide capsule (100 mg PO).

Drug: Zonisamide 100Mg Cap

Placebo

PLACEBO COMPARATOR

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

Interventions

Zonisamide 100Mg Cap DRUG

ZONEGRAN® is commercially available for oral administration as capsules containing 100 mg of Zonisamide.

Also known as: Zonegran, ZNS

Zonisamide

Placebo DRUG

The placebo will contain microcrystalline cellulose which is the predominant filler in the generic capsule.

Also known as: microcrystalline cellulose

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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.
• ECochG: Participants will be excluded if the ECochG/ABR wave I response is absent.
• WIN test: Participants with WIN scores greater than moderate difficulty or 14.9 dB SNR will be excluded.

Sponsors & Collaborators

• University of Texas: collaborator
• Gateway Biotechnology, Inc.: collaborator
• Washington University School of Medicine: lead
• United States Department of Defense: collaborator

Study Sites (1)

University of Akron

Akron, Ohio, 44325-3001, United States

Location

MeSH Terms

Conditions

Hearing Loss, Noise-Induced

Interventions

Zonisamide; Capsules; microcrystalline cellulose

Condition Hierarchy (Ancestors)

Hearing Loss, Sensorineural; Hearing Loss; Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dosage Forms; Pharmaceutical Preparations

Limitations and Caveats

The study was prematurely terminated due to the low number of eligible subjects (3 subjects); therefore, statistical analyses were not performed.

Results Point of Contact

• Title: Dr. Craig Buchman, Lindburg Professor & Chair, Department of Otolaryngology-Head & Neck Surgery
• Organization: Washington University in St. Louis

buchmanc@wustl.edu

314-362-2914

Study Officials

• Craig A Buchman, MD, FACS

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study will be "masked" or "blinded" in the sense that all the study participants and the study team members will be blinded to the assignment in the study groups. Only the pharmacist who will prepare the drug packets and will seal the envelopes, and the programmer not involved with the study who will produce the random treatment assignments and print the labels will know the order of treatments for any subject. An independent medical professional who is not part of the study team will complete the de-identification of the study drug, and a procedure and documentation log will be in place for quality assurance purposes. The ZNS and placebo capsules will look, taste, and smell the same.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, double-blind, and placebo-controlled

Study Record Dates

• First Submitted: February 23, 2021
• First Posted: March 1, 2021
• Study Start: November 10, 2021
• Primary Completion: December 23, 2022
• Study Completion: December 23, 2022
• Last Updated: February 13, 2026
• Results First Posted: September 12, 2025

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)