Noise-induced hearing loss (NIHL) is highly prevalent among occupationally at-risk
service groups like the military and firefighters, with disabilities that result in
significant healthcare burden, negatively impacting performance on duty and quality of
life. Exposure to noise can cause permanent threshold shifts (PTS) with accompanying hair
cell loss, or temporary threshold shifts (TTS), with no evident hair cell loss. Noise
exposure can also result in rapid and permanent loss of synaptic elements and cochlear
nerve terminals with irreversible hearing impairment and long-term degeneration of spiral
ganglion (SG) cell bodies.
Currently no FDA-approved treatments are available to prevent or treat NIHL. Delivering
pharmaceutical compounds over time, identification of safe dosages, and a critical
timeframe relative to noise-exposure remain clinically challenging. RestorEar Devices LLC
has developed a non-pharmaceutical application of mild therapeutic hypothermia (MTH) to
protect residual sensory structures and function of the cochlea. MTH is a proven and
well-established therapy for neuroprotection. This approach for MTH application is based
on significant prior and on-going research that highlights its utility for residual
hearing preservation against cochlear implant surgical trauma, ototoxicity, and noise
exposure. With SBIR Phase I support, the investigators have successfully demonstrated
that effective non-invasive, non-pharmaceutical therapeutic hypothermia can be delivered
to the inner ear sensory structures. The investigators have built, calibrated, and tested
ReBoundTM, a headband with cooling gel packs placed in contact with the surface of the
mastoid. ReBoundTM delivers MTH safely and repeatedly for up to 30 minutes. In this
study, the investigators aim to extend this application to human subjects and test safety
and efficacy against NIHL in noise-exposed firefighters and matched controls with the
collaboration of researchers at the University of Miami.
Aim 1: Evaluate safety of MTH with ReBoundTM devices. With the first in-human studies,
the investigators aim to show that MTH can be safely delivered to the inner ear using
ReBound. In a randomized study, non-firefighter control subjects will receive
MTH-treatment and normothermia-sham (non-cooled gel pack) through the device alternated
over 8 sessions. Subjective assessments and audiologic testing (pure tone audiometry,
auditory brainstem responses, distortion product otoacoustic emissions and
electrocochleography) pre- and post-treatments will be compared between MTH-treatment and
sham in each subject. Results of Aim 1 will support the hypothesis that this approach
will deliver therapeutic hypothermia to the cochleae and that repeated application will
not negatively affect hearing function in healthy subjects.
Aim 2: Validate efficacy of the ReBoundTM MTH devices for mitigating NIHL in an
occupationally at-risk group. Based on strong preliminary results, the investigators
hypothesize that acute application of MTH in noise-exposed firefighters will reduce
temporary changes in auditory function. Firefighters will be divided equally into two
treatment groups, MTH-treatment and normothermia-sham. These treatments will be delivered
with ReBound, with and without cooled gel packs, applied post-duty. MTH-treatment will
also be applied in an age- and sex-matched control group over the same duration. Baseline
hearing function will be measured prior to initiation of the treatment. Treatments and
the functional assessments will be repeated quarterly over one year. Temporary and
permanent threshold changes in this chronically the noise exposed group of firefighters
receiving MTH-treatment will be compared with firefighters receiving sham-treatment and
with controls receiving MTH-treatment. MTH-groups will also be sent home with a ReBound
band and instructed to use it after noise exposure. Subjective assessments will be sent
weekly to these groups to evaluate the use pattern of the device. Results of these
studies will firmly establish MTH for mitigating NIHL.
This research will be highly impactful given the significant adverse effects of NIHL, an
unmet clinical need, and the high translational potential of MTH for mitigating NIHL.