Trial Outcomes & Findings for Noise-Induced Hearing Loss-Acute Exposure Treatment (UA) (NCT NCT04774250)

Last Updated: 2026-02-13

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

3 participants

Primary outcome timeframe

30 days (+/- 3 days) after training

Results posted on

2026-02-13

Participant Flow

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	1	2
Overall Study COMPLETED	1	2
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: 30 days (+/- 3 days) after training

Population: 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.

Outcome measures

Outcome measures
Measure	Zonisamide n=1 Participants 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.	Placebo n=2 Participants 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.
Proportion of Officers With Permanent Threshold Shift (PTS) PTS-positive participants	0 Participants	1 Participants
Proportion of Officers With Permanent Threshold Shift (PTS) PTS-negative participants	1 Participants	1 Participants

SECONDARY outcome

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

Population: Each participant's left and right ears were analyzed for threshold shifts at 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).

Outcome measures

Outcome measures
Measure	Zonisamide n=2 ears 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.	Placebo n=4 ears 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.
Distortion Product Otoacoustic Emissions (DPOAE) No Shift	1 ears	0 ears
Distortion Product Otoacoustic Emissions (DPOAE) Shift	1 ears	3 ears
Distortion Product Otoacoustic Emissions (DPOAE) Excluded	0 ears	1 ears

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Zonisamide n=1 Participants 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.	Placebo n=2 Participants 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.
Ultra-high Frequency Audiometry Experienced a change in ultra-high frequencies greater than 5 dB	1 Participants	2 Participants
Ultra-high Frequency Audiometry Did not experience a change in ultra-high frequencies greater than 5 dB	0 Participants	0 Participants

SECONDARY outcome

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

To measure for changes in ECochG AP amplitude between baseline (before training) visit and 30-days after training visits.

Outcome measures

Outcome measures
Measure	Zonisamide n=1 Participants 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.	Placebo n=2 Participants 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.
Electrocochleography (ECochG) AP Amplitude	0.035 millivolts (mV) Standard Deviation 0	0.1025 millivolts (mV) Standard Deviation 0.159

SECONDARY outcome

Timeframe: 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 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.

Outcome measures

Outcome measures
Measure	Zonisamide n=1 Participants 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.	Placebo n=2 Participants 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.
Change in Words In Noise (WIN) Test Signal-to-Noise Ratio Threshold	-0.267 dB SNR Standard Deviation 0	1.933 dB SNR Standard Deviation 0.660

SECONDARY outcome

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

To measure for changes in ECochG latency between baseline (before training) visit and 30-days after training visits.

Outcome measures

Outcome measures
Measure	Zonisamide n=1 Participants 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.	Placebo n=2 Participants 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.
Electrocochleography (ECochG) Latency	0.105 milliseconds (ms) Standard Deviation 0	-0.053 milliseconds (ms) Standard Deviation 0.046

SECONDARY outcome

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

To measure for changes in ECochG width between baseline (before training) visit and 30-days after training visits.

Outcome measures

Outcome measures
Measure	Zonisamide n=1 Participants 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.	Placebo n=2 Participants 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.
Electrocochleography (ECochG) Width	0.295 milliseconds (ms) Standard Deviation 0	0.030 milliseconds (ms) Standard Deviation 0.028

SECONDARY outcome

Timeframe: Baseline prior to training

Population: 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.

Exploratory analysis to determine a pharmacogenetic link between noise induced hearing loss (NIHL) and zonisamide (ZNS) treatment effect.

Outcome measures

Outcome measures
Measure	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.	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.
Determine PGx Link Between Noise Induced Hearing Loss (NIHL) and Zonisamide (ZNS) Differential miRNA expression	NA participants	NA participants
Determine PGx Link Between Noise Induced Hearing Loss (NIHL) and Zonisamide (ZNS) Pathway enrichment	NA participants	NA participants

Adverse Events

Zonisamide

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Craig Buchman, Lindburg Professor & Chair, Department of Otolaryngology-Head & Neck Surgery

Washington University in St. Louis

Phone: 314-362-2914

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Zonisamide n=1 Participants 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.	Placebo n=2 Participants 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.	Total n=3 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=12 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=6 Participants	2 Participants n=6 Participants	3 Participants n=12 Participants
Age, Categorical >=65 years	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=12 Participants
Age, Continuous	44 years STANDARD_DEVIATION 0 • n=6 Participants	37 years STANDARD_DEVIATION 6 • n=6 Participants	39 years STANDARD_DEVIATION 5.9 • n=12 Participants
Sex: Female, Male Female	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=12 Participants
Sex: Female, Male Male	1 Participants n=6 Participants	2 Participants n=6 Participants	3 Participants n=12 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=12 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants n=6 Participants	2 Participants n=6 Participants	3 Participants n=12 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=12 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=12 Participants
Race (NIH/OMB) Asian	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=12 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=12 Participants
Race (NIH/OMB) Black or African American	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=12 Participants
Race (NIH/OMB) White	1 Participants n=6 Participants	2 Participants n=6 Participants	3 Participants n=12 Participants
Race (NIH/OMB) More than one race	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=12 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=12 Participants
Region of Enrollment United States	1 participants n=6 Participants	2 participants n=6 Participants	3 participants n=12 Participants