Clinical trial NCT02049073: Prevention of Noise-induced Hearing Loss
Official title: Zonisamide and Methylprednisolone to Prevent Noise-induced Temporary Hearing Loss
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Noise-induced Hearing Loss
Keywords: hearing loss
noise induced hearing loss
zonisamide
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2014-01-29
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Noise-induced hearing loss affects an estimated 5% of the worldwide population, with 30-40 million Americans exposed to hazardous sound or noise levels regularly. Sources of noise may be occupational, blast noise, or recreational. Trauma to the inner ear can occur through transient hearing loss or permanent hearing loss. Although hearing recovers after temporary transient hearing loss, growing evidence suggests that repeated temporary transient hearing loss may lead to a permanent hearing loss. Currently, there are no treatments and there are no known medications that can be used clinically to prevent noise-induced hearing loss in humans.

The long-term goal of this research is to find medications that can prevent noise-induced hearing loss. The purpose of the present pilot study is to evaluate zonisamide and methylprednisolone as medications to prevent temporary transient hearing loss in humans.

Detailed description: Noise-induced hearing loss (NIHL) affects an estimated 5% of the worldwide population, with 30-40 million Americans exposed to hazardous sound or noise levels regularly. Sources of noise may be occupational (e.g., manufacturing, construction), blast noise (e.g., firearms or explosions), or recreational (e.g., loud music, power tools). Trauma to the inner ear can occur through transient hearing loss (temporary threshold shifts, TTS) or permanent hearing loss (permanent threshold shift, PTS). Although hearing recovers after a TTS in about 24-48 hours, growing evidence suggests that repeated TTS may lead to PTS. Both TTS and PTS lead to a decrease in hearing thresholds at 3000 to 6000 Hz.

Currently, there are no treatments for human NIHL although this is an area of active investigation. Protection against NIHL consists of limiting noise exposure through Occupational Safety and Health Administration (OSHA) limits to occupational noise and the wearing of hearing-protection devices (e.g., ear muffs or earplugs). There are no known medications that can be used clinically to prevent NIHL in humans.

LePrell and colleagues have successfully established a protocol for inducing TTS using digitally-modified pop or rock music. This model of experimentally-induced TTS was intended to provide an ethical way of testing medications that might prevent NIHL.

In a mouse model, Bao and colleagues were able to use zonisamide, an anti-epileptic medication approved for the treatment of partial seizures, and methylprednisolone, a glucocorticoid medication, to protect against noise-induced PTS. The long-term goal of this research is to find medications that can prevent NIHL. The goal of the present pilot study is to evaluate zonisamide and methylprednisolone as medications to prevent TTS in humans.

Specific Aim 1: Examine zonisamide as a possible prophylactic medication to prevent noise-induced hearing loss, using an escalating dose protocol. Healthy volunteers would be given 100 or 200 mg of zonisamide as one-time doses or as a daily medication for two week (to establish a steady-state). They would be exposed to digitally-modified pop or rock music for 4 hours and undergo serial testing of hearing and monitoring for side effects after their sound exposure for 3-4 hours. They would be monitored at one day and one week post-exposure for hearing and other side effects.

Hypothesis: Zonisamide is able to protect against noise-induced hearing loss in humans.

Specific Aim 2: Examine methylprednisolone as a possible prophylactic medication to prevent noise-induced hearing loss, using an escalating dose protocol. Healthy volunteers would be given 32 or 64 mg of methylprednisolone as one-time doses. They would undergo the same music exposure and post-sound exposure monitoring as described above.

Hypothesis: Methylprednisolone is able to protect against noise-induced hearing loss in humans

Eligibility criteria: Inclusion Criteria:

* adults 18 to 30 years old
* normal hearing
* good to excellent health

Exclusion Criteria:

* hearing loss
* history of seizures
* history of allergy or hypersensitivity to sulfonamide or oral steroid medications

Primary outcomes:
measure: Pure Tone Thresholds
timeFrame: 15 minutes post-music exposure
Secondary outcomes:
measure: DPOAE
timeFrame: visit 2, pre-music exposure; visit 3-one week after music exposure
measure: Pure tone thresholds
timeFrame: 1 hr 15 min, 2 hr 15 min, and 3 hr 15 min post exposure.
Other outcomes:
measure: Pure tone thresholds
timeFrame: One week after music exposure.
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Judith Lieu, MD
role: PRINCIPAL_INVESTIGATOR
References: