Hearing Loss, Noise-Induced
Conditions
Brief summary
The purpose of this study is to assess the safety and efficacy of zonisamide for the treatment of noise-induced hearing loss in adults.
Detailed description
This study is a randomized, double-blinded placebo-control trial with three parallel groups, to make use of a common control group. 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. Participants who meet the eligibility requirements will be randomized in a balanced fashion into one of 3 arms: Group 1) Zonisamide 100 milligrams (mg) pre-op + Placebo post-op; Group 2) Placebo pre- + placebo post-op; and Group 3) Zonisamide 100 mg post-op + placebo post-op
Interventions
ZONEGRAN® is commercially available for oral administration as capsules containing 100 mg of Zonisamide.
DRUGPlacebo
The placebo will contain microcrystalline cellulose which is the predominant filler in the generic capsule.
Sponsors
University of Texas
Gateway Biotechnology, Inc.
United States Department of Defense
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Masking description
Subjects will be randomized in a balanced fashion into one of 3 arms: Zonisamide 100 mg pre-op, Placebo, or Zonisamide 100 mg post-op. To ensure double-blinding of the trial, each subject will be assigned a previously prepared envelope with one package labeled 1 and designated to be taken 4 hours prior to surgery and another package labeled 2 designated to be taken within 4-12 hours after surgery or when the patient is released clinically to oral medication.
Intervention model description
This study is a randomized, double-blinded placebo-control trial with three parallel groups, to make use of a common control group.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Patients who are scheduled to undergo a skull-based surgery that requires at least 45 minutes of surgical-drilling * At least 18 years of age * Air conduction thresholds in the non-operated ears are to be no worse than 25 decibel (dB) hearing loss (HL) for pure tone average 0.5, 1, and 2 kilohertz (kHz) with no individual threshold greater than 30 dB HL, and no worse than 45dB HL at 4 kHz at screening. * Observed air-bone gap \< 10 dB HL at 0.5, 1, 2, and 4 kHz, with normal tympanometry. * Ability to understand and willingness to sign an Institutional Review Board (IRB) approved written informed consent document.
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 ear disorder and/or central auditory dysfunction in the non-operated ear * History of ototoxic drug use * Current use of strong/moderate 3A4 inhibitor/inducer and grapefruit juice
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Ratio of PTS-positive Subjects | 30 days | The primary efficacy endpoint will be 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-surgery as compared to baseline audiogram. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Rate of Distortion Product Otoacoustic Emissions (DPOAE) Shift | 30 days | The secondary efficacy outcome measures will be the rate of temporary cochlear change as measured by a DPOAE amplitude shift at any frequency that is significantly greater than the stability of each measurement (i.e., 95% confidence interval of each measurement do not overlap). The rate of DPOAE shift is the ratio of DPOAE shift-positive subjects to total subjects within each arm. |
Countries
United States
Participant flow
Pre-assignment details
24 participants were consented for the study and enrolled. However, after consent but before any study activities could occur (including randomization), one participant chose to no longer participate. This excluded participant did not complete any study activities after consent. Thus, only 23 participants were consented and completed study activities including randomization.
Participants by arm
| Arm | Count |
|---|---|
| Zonisamide Pre-op + Placebo Post-op For subjects randomized to zonisamide pre-op, the pre-op package will contain one zonisamide capsule (100 mg PO) and the post-op package will contain one placebo capsule that looks, smells, and tastes the same as zonisamide capsules.
Zonisamide 100Mg Cap: ZONEGRAN® is commercially available for oral administration as capsules containing 100 mg of Zonisamide.
Placebo: The placebo will contain microcrystalline cellulose which is the predominant filler in the generic capsule. | 8 |
| Placebo Pre-op + Placebo Post-op For the subjects randomized to placebo, both pre- and post-op packages will contain placebo capsules that looks, smells, and taste the same as zonisamide capsules.
Placebo: The placebo will contain microcrystalline cellulose which is the predominant filler in the generic capsule. | 7 |
| Placebo Pre-op + Zonisamide Post-op For subjects randomized to zonisamide post-op, the pre-op package will contain one placebo capsule and the post-op 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: The placebo will contain microcrystalline cellulose which is the predominant filler in the generic capsule. | 8 |
| Total | 23 |
Baseline characteristics
| Characteristic | Zonisamide Pre-op + Placebo Post-op | Total | Placebo Pre-op + Zonisamide Post-op | Placebo Pre-op + Placebo Post-op |
|---|---|---|---|---|
| Age, Continuous | 49.4 years STANDARD_DEVIATION 15.2 | 51.0 years STANDARD_DEVIATION 12.23 | 53.6 years STANDARD_DEVIATION 9.75 | 49.7 years STANDARD_DEVIATION 12.37 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 23 Participants | 8 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 22 Participants | 8 Participants | 7 Participants |
| Region of Enrollment United States | 8 participants | 23 participants | 8 participants | 7 participants |
| Sex: Female, Male Female | 7 Participants | 17 Participants | 6 Participants | 4 Participants |
| Sex: Female, Male Male | 1 Participants | 6 Participants | 2 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 7 | 0 / 8 |
| other Total, other adverse events | 8 / 8 | 7 / 7 | 8 / 8 |
| serious Total, serious adverse events | 2 / 8 | 1 / 7 | 1 / 8 |
Outcome results
Primary
The Ratio of PTS-positive Subjects
The primary efficacy endpoint will be 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-surgery as compared to baseline audiogram.
Time frame: 30 days
Population: ITT Sample Set
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Zonisamide Pre-op + Placebo Post-op | The Ratio of PTS-positive Subjects | PTS-positive Subjects at Post-op 30 Days Visit | 3 Participants |
| Zonisamide Pre-op + Placebo Post-op | The Ratio of PTS-positive Subjects | PTS-negative Subjects at Post-op 30 Days Visit | 5 Participants |
| Placebo Pre-op + Placebo Post-op | The Ratio of PTS-positive Subjects | PTS-positive Subjects at Post-op 30 Days Visit | 1 Participants |
| Placebo Pre-op + Placebo Post-op | The Ratio of PTS-positive Subjects | PTS-negative Subjects at Post-op 30 Days Visit | 6 Participants |
| Placebo Pre-op + Zonisamide Post-op | The Ratio of PTS-positive Subjects | PTS-positive Subjects at Post-op 30 Days Visit | 1 Participants |
| Placebo Pre-op + Zonisamide Post-op | The Ratio of PTS-positive Subjects | PTS-negative Subjects at Post-op 30 Days Visit | 7 Participants |
Secondary
The Rate of Distortion Product Otoacoustic Emissions (DPOAE) Shift
The secondary efficacy outcome measures will be the rate of temporary cochlear change as measured by a DPOAE amplitude shift at any frequency that is significantly greater than the stability of each measurement (i.e., 95% confidence interval of each measurement do not overlap). The rate of DPOAE shift is the ratio of DPOAE shift-positive subjects to total subjects within each arm.
Time frame: 30 days
Population: ITT Sample
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Zonisamide Pre-op + Placebo Post-op | The Rate of Distortion Product Otoacoustic Emissions (DPOAE) Shift | Shift | 4 Participants |
| Zonisamide Pre-op + Placebo Post-op | The Rate of Distortion Product Otoacoustic Emissions (DPOAE) Shift | No shift | 2 Participants |
| Zonisamide Pre-op + Placebo Post-op | The Rate of Distortion Product Otoacoustic Emissions (DPOAE) Shift | Excluded | 2 Participants |
| Placebo Pre-op + Placebo Post-op | The Rate of Distortion Product Otoacoustic Emissions (DPOAE) Shift | Shift | 4 Participants |
| Placebo Pre-op + Placebo Post-op | The Rate of Distortion Product Otoacoustic Emissions (DPOAE) Shift | No shift | 2 Participants |
| Placebo Pre-op + Placebo Post-op | The Rate of Distortion Product Otoacoustic Emissions (DPOAE) Shift | Excluded | 1 Participants |
| Placebo Pre-op + Zonisamide Post-op | The Rate of Distortion Product Otoacoustic Emissions (DPOAE) Shift | No shift | 1 Participants |
| Placebo Pre-op + Zonisamide Post-op | The Rate of Distortion Product Otoacoustic Emissions (DPOAE) Shift | Excluded | 6 Participants |
| Placebo Pre-op + Zonisamide Post-op | The Rate of Distortion Product Otoacoustic Emissions (DPOAE) Shift | Shift | 1 Participants |