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Low accrual
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| Name | Class |
|---|---|
| United States Department of Defense | FED |
| University of Texas | OTHER |
| Gateway Biotechnology, Inc. | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Zonisamide | Experimental | For subjects randomized to zonisamide, the package will contain one zonisamide capsule (100 mg PO). |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Zonisamide 100Mg Cap | Drug | ZONEGRAN® is commercially available for oral administration as capsules containing 100 mg of Zonisamide. |
|
| 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 |
| 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 |
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Screening Inclusion Criteria:
Enrollment Inclusion Criteria:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Craig A Buchman, MD, FACS | Washington University School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Akron | Akron | Ohio | 44325-3001 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Zonisamide | For subjects randomized to zonisamide, the package will contain one zonisamide capsule (100 mg PO). Zonisamide 100Mg Cap: ZONEGRAN® is commercially available for oral administration as capsules containing 100 mg of Zonisamide. |
| FG001 | Placebo | For the subjects randomized to placebo, the package will contain one placebo capsule that looks, smells, and taste the same as zonisamide capsule. Placebo: The placebo will contain microcrystalline cellulose which is the predominant filler in the generic capsule. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Zonisamide | For subjects randomized to zonisamide, the package will contain one zonisamide capsule (100 mg PO). Zonisamide 100Mg Cap: ZONEGRAN® is commercially available for oral administration as capsules containing 100 mg of Zonisamide. |
| BG001 | Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The study was prematurely terminated. Due to the very low number of subjects in each study group there was no statistical analysis performed; no statistical test, p-value, or parameter estimation can be reported. | Posted | Count of Participants | Participants | 30 days (+/- 3 days) after training |
|
6 months
Documentation of adverse events at all follow-up visits (5-30 minutes post, within 24 hours, and at 30 day visit; follow-up visit 3, 4, and 5).
Adverse events were tracked post dose within 30 minutes, 24 hours, and at 30 days. All adverse events were recorded on an Adverse Events tracking case report form (CRF). Adverse events related to study medication only were tracked.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Zonisamide | For subjects randomized to zonisamide, the package will contain one zonisamide capsule (100 mg PO). Zonisamide 100Mg Cap: ZONEGRAN® is commercially available for oral administration as capsules containing 100 mg of Zonisamide. |
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The study was prematurely terminated due to the low number of eligible subjects (3 subjects); therefore, statistical analyses were not performed.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Craig Buchman, Lindburg Professor & Chair, Department of Otolaryngology-Head & Neck Surgery | Washington University in St. Louis | 314-362-2914 | buchmanc@wustl.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 23, 2022 | Nov 28, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 18, 2022 | Nov 28, 2023 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D006317 | Hearing Loss, Noise-Induced |
| ID | Term |
|---|---|
| D006319 | Hearing Loss, Sensorineural |
| D034381 | Hearing Loss |
| D006311 | Hearing Disorders |
| D004427 | Ear Diseases |
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| ID | Term |
|---|---|
| D000078305 | Zonisamide |
| D002214 | Capsules |
| C109691 | microcrystalline cellulose |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D013450 | Sulfones |
| D013457 |
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Randomized, double-blind, and placebo-controlled
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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.
| Placebo | Drug | The placebo will contain microcrystalline cellulose which is the predominant filler in the generic capsule. |
|
|
| 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 |
For the subjects randomized to placebo, the package will contain one placebo capsule that looks, smells, and taste the same as zonisamide capsule. Placebo: The placebo will contain microcrystalline cellulose which is the predominant filler in the generic capsule. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Placebo | For the subjects randomized to placebo, the package will contain one placebo capsule that looks, smells, and taste the same as zonisamide capsule. Placebo: The placebo will contain microcrystalline cellulose which is the predominant filler in the generic capsule. |
|
|
| Secondary | 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). | Each participant's left and right ears were analyzed for threshold shifts at 30 days (+/- 3 days) after training. | Posted | Count of Units | ears | baseline (before shooting), 30 days (+/-3 days) after training | ears | ears |
|
|
|
| Secondary | 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. | The study was prematurely terminated. Due to the very low number of subjects in each study group there was no statistical analysis performed; no statistical test, p-value, or parameter estimation can be reported. | Posted | Count of Participants | Participants | baseline (before shooting), within 5-10 minutes after shooting and 30 days (+/-3 days) after training |
|
|
|
| Secondary | Electrocochleography (ECochG) AP Amplitude | To measure for changes in ECochG AP amplitude between baseline (before training) visit and 30-days after training visits. | The study was prematurely terminated. Due to the very low number of subjects in each study group there was no statistical analysis performed; no statistical test, p-value, or parameter estimation can be reported. | Posted | Mean | Standard Deviation | millivolts (mV) | baseline (before shooting) and 30 days (+/-3 days) after training |
|
|
|
| Secondary | 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. | The study was prematurely terminated. Due to the very low number of subjects in each study group there was no statistical analysis performed; no statistical test, p-value, or parameter estimation can be reported. | Posted | Mean | Standard Deviation | dB SNR | baseline (before shooting) and 30 days (+/-3 days) after training |
|
|
|
| Secondary | Electrocochleography (ECochG) Latency | To measure for changes in ECochG latency between baseline (before training) visit and 30-days after training visits. | The study was prematurely terminated. Due to the very low number of subjects in each study group there was no statistical analysis performed; no statistical test, p-value, or parameter estimation can be reported. | Posted | Mean | Standard Deviation | milliseconds (ms) | baseline (before shooting) and 30 days (+/-3 days) after training |
|
|
|
| Secondary | Electrocochleography (ECochG) Width | To measure for changes in ECochG width between baseline (before training) visit and 30-days after training visits. | The study was prematurely terminated. Due to the very low number of subjects in each study group there was no statistical analysis performed; no statistical test, p-value, or parameter estimation can be reported. | Posted | Mean | Standard Deviation | milliseconds (ms) | baseline (before shooting) and 30 days (+/-3 days) after training |
|
|
|
| Secondary | 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. | While samples were collected, the miRNA assay was not completed and will never be completed, as miRNA assays require a minimum of 3 samples from each group to be completed and produce results. As only 1 sample was obtained from the zonisamide group and 2 samples from the placebo group, the threshold was never reached. This threshold was not explicitly stated in the protocol, but it is a widely accepted standard among statisticians for ensuring interpretable results. | Posted | Number | participants | Baseline prior to training |
|
|
|
| 0 |
| 1 |
| 0 |
| 1 |
| 0 |
| 1 |
| EG001 | Placebo | For the subjects randomized to placebo, the package will contain one placebo capsule that looks, smells, and taste the same as zonisamide capsule. Placebo: The placebo will contain microcrystalline cellulose which is the predominant filler in the generic capsule. | 0 | 2 | 0 | 2 | 0 | 2 |
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| D010038 |
| Otorhinolaryngologic Diseases |
| D012678 | Sensation Disorders |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Sulfur Compounds |
| D007555 | Isoxazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |
| Excluded |
|