Back to resultsNoise-Induced Hearing Loss-Acute Exposure Treatment (UA) (PINIHL-AET)
Primary Purpose
Hearing Loss, Noise-Induced
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Zonisamide 100Mg Cap
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Hearing Loss, Noise-Induced
Eligibility 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:
- 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.
Sites / Locations
- University of Akron
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Zonisamide
Placebo
Arm Description
For subjects randomized to zonisamide, the package will contain one zonisamide capsule (100 mg PO).
For the subjects randomized to placebo, the package will contain one placebo capsule that looks, smells, and taste the same as zonisamide capsule.
Outcomes
Primary Outcome Measures
The primary outcome measure is the proportion of officers with permanent threshold shift (PTS)
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
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).
Ultra-high frequency audiometry
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.
Electrocochleography (ECochG)
To measure for changes in ECochG AP amplitude, latency and width.
Words In Noise Test (WIN)
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.
Determine a link between noise induced hearing loss (NIHL) and zonisamide (ZNS) treatment effect as assessed by pharmacogenetic testing
Exploratory DNA analysis and phenotypic correlations with ZNS treatment
Full Information
NCT ID
NCT04774250
First Posted
February 23, 2021
Last Updated
May 24, 2023
Sponsor
Washington University School of Medicine
Collaborators
United States Department of Defense, University of Texas, Gateway Biotechnology, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04774250
Brief Title
Noise-Induced Hearing Loss-Acute Exposure Treatment (UA)
Acronym
PINIHL-AET
Official Title
Pharmaceutical Interventions for Noise-Induced Hearing Loss-Acute Exposure Treatment
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Terminated
Why Stopped
Low accrual
Study Start Date
November 10, 2021 (Actual)
Primary Completion Date
December 23, 2022 (Actual)
Study Completion Date
December 23, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine
Collaborators
United States Department of Defense, University of Texas, Gateway Biotechnology, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hearing Loss, Noise-Induced
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Randomized, double-blind, and placebo-controlled
Masking
ParticipantInvestigatorOutcomes 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.
Allocation
Randomized
Enrollment
38 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Zonisamide
Arm Type
Experimental
Arm Description
For subjects randomized to zonisamide, the package will contain one zonisamide capsule (100 mg PO).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
For the subjects randomized to placebo, the package will contain one placebo capsule that looks, smells, and taste the same as zonisamide capsule.
Intervention Type
Drug
Intervention Name(s)
Zonisamide 100Mg Cap
Other Intervention Name(s)
Zonegran, ZNS
Intervention Description
ZONEGRAN® is commercially available for oral administration as capsules containing 100 mg of Zonisamide.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
microcrystalline cellulose
Intervention Description
The placebo will contain microcrystalline cellulose which is the predominant filler in the generic capsule.
Primary Outcome Measure Information:
Title
The primary outcome measure is the proportion of officers with permanent threshold shift (PTS)
Description
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.
Time Frame
30 days (+/- 3 days) after training
Secondary Outcome Measure Information:
Title
Distortion product otoacoustic emissions (DPOAE)
Description
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).
Time Frame
baseline (before shooting), within 5-10 minutes after shooting and 30 days (+/-3 days) after training
Title
Ultra-high frequency audiometry
Description
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.
Time Frame
baseline (before shooting), within 5-10 minutes after shooting and 30 days (+/-3 days) after training
Title
Electrocochleography (ECochG)
Description
To measure for changes in ECochG AP amplitude, latency and width.
Time Frame
baseline (before shooting) and 30 days (+/-3 days) after training
Title
Words In Noise Test (WIN)
Description
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.
Time Frame
baseline (before shooting) and 30 days (+/-3 days) after training
Title
Determine a link between noise induced hearing loss (NIHL) and zonisamide (ZNS) treatment effect as assessed by pharmacogenetic testing
Description
Exploratory DNA analysis and phenotypic correlations with ZNS treatment
Time Frame
Baseline prior to training
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Craig A Buchman, MD, FACS
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Akron
City
Akron
State/Province
Ohio
ZIP/Postal Code
44325-3001
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Noise-Induced Hearing Loss-Acute Exposure Treatment (UA)
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