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

• ClinicalTrials.gov Identifier: NCT04774250
• Recruitment Status: Enrolling by invitation
• First Posted: March 1, 2021
• Last Update Posted: December 14, 2021
• Sponsor: Washington University School of Medicine
• Collaborators: United States Department of Defense; University of Texas; Gateway Biotechnology, Inc.
• Information provided by (Responsible Party): Washington University School of Medicine

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Hearing Loss, Noise-Induced	Drug: Zonisamide 100Mg Cap; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 126 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized, double-blind, and placebo-controlled
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Masking Description: 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.
• Primary Purpose: Prevention
• Official Title: Pharmaceutical Interventions for Noise-Induced Hearing Loss-Acute Exposure Treatment
• Actual Study Start Date: November 10, 2021
• Estimated Primary Completion Date: December 2024
• Estimated Study Completion Date: December 2025

Arms and Interventions

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 Name: microcrystalline cellulose

Outcome Measures

Primary Outcome Measures :

1. The primary outcome measure is the proportion of officers with permanent threshold shift (PTS) [ Time Frame: 30 days (+/- 3 days) after training ]
   The proportion of officers with PTS is defined as the ratio of officer with ≥10 dB shift at 30 days (+/- 3 days) after training to the total number of officers enrolled in the study group.

Secondary Outcome Measures :

1. Distortion product otoacoustic emissions (DPOAE) [ Time Frame: baseline (before shooting), within 5-10 minutes after shooting and 30 days (+/-3 days) after training ]
   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).
2. Ultra-high frequency audiometry [ Time Frame: baseline (before shooting), within 5-10 minutes after shooting and 30 days (+/-3 days) after training ]
   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.
3. Electrocochleography (ECochG) [ Time Frame: baseline (before shooting) and 30 days (+/-3 days) after training ]
   To measure for changes in ECochG AP amplitude, latency and width.
4. Words In Noise Test (WIN) [ Time Frame: baseline (before shooting) and 30 days (+/-3 days) after training ]
   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 babble is set at 80 dB SPL, and the target word levels decrease from 104 dB SPL to 80 dB SPL. The SNR at 24 dB HL is the easiest, with words presented at 24 dB above the noise background, whereas the SNR of 0 dB is the most difficult with target words being presented at the same level as the background noise (Wilson and Burks, 2005; Wilson and Watts, 2012). The WIN 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.
5. Determine a link between noise induced hearing loss (NIHL) and zonisamide (ZNS) treatment effect as assessed by pharmacogenetic testing [ Time Frame: Baseline prior to training ]
   Exploratory DNA analysis and phenotypic correlations with ZNS treatment

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Ohio

University of Akron

Akron, Ohio, United States, 44325-3001

Sponsors and Collaborators

Washington University School of Medicine

United States Department of Defense

University of Texas

Gateway Biotechnology, Inc.

Investigators

• Principal Investigator: Craig A Buchman, MD, FACS; Washington University School of Medicine

More Information

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT04774250
• Other Study ID Numbers: PINIHL-AET_UA
• First Posted: March 1, 2021
• Last Update Posted: December 14, 2021
• Last Verified: November 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Hearing Loss; Deafness; Hearing Loss, Noise-Induced; Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Hearing Loss, Sensorineural; Zonisamide; Anticonvulsants; Calcium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs