Safety Study to Evaluate the Effect of Lowering Body Temperature During Cochlear Implantation

Hypothermia has been shown to have a protective effect following trauma to the central
nervous system and the peripheral auditory system. We have previously demonstrated a
protective effect of mild hypothermia on auditory function caused by cochlear implant
electrodes in animal models. Preservation of residual hearing of patients undergoing
cochlear implantation is highly desirable and based on these animal studies, it may be
possible to achieve in human subjects using mild degrees of hypothermia. We propose to
investigate the hypothesized protective effect of intra-operative hypothermia on adult
subjects undergoing cochlear implantation.

Inclusion Criteria: Adults greater than or equal to 18 years of age with some measurable
auditory function who are undergoing cochlear implantation as routine management of severe
to profound hearing loss.

Exclusion Criteria: Pure tone average hearing (mean of .5, 1 and 2 KHz) worse than 100dB;
Age > 70 years; History of arrhythmia or ischemic heart disease; sickle cell trait or
disease; immune incompetence; coagulation disorders; revision cochlear implant; body-mass
index > 35; cold related disorders.

Phase I: Up to 40 healthy adult subjects who have qualified for CI will undergo implantation
with core body temperature lowered to 34 degree Centigrade for approximately one hour before
electrode insertion and 30 minutes after insertion. Otherwise, the surgical technique will
be unchanged from our standard procedure.

The heating/cooling blanket is an FDA approved device. similar temperature controlling
blankets are used in virtually all operations done under general anesthesia. Each subject's
temperature will be gradually lowered only after they are put to sleep. Warming will being
at least 30 minutes before the subject is awakened. We will measure and record the subject's
temperature every 5 to 15 minutes while they are in the operating room and also while they
are in the recovery room.

Each subject will undergo a battery of audiometric tests (CNC words, HINT sentences, pure
tone thresholds, and immittance) within one month prior to implantation, at one month post
operatively, at 6 months post operatively and 1 year postoperatively. Outcomes will be
analyzed by PI after 10 subjects have completed the 1 month test interval. If outcomes
indicate proof of principle (measurable pure tone responses in greater than or equal to 60%
of subjects), phase two of the study will be initiated. If not, outcomes will be analyzed
after 20, 30, and 40 subjects until evidence of hearing conservation or lack of it is
established, leading to the following study or precluding it.

Phase II: Up to 80 healthy adults who have qualified for CI will be randomized into control
group (CI surgery using standard procedure at core body temperature of 37 degree C) or
active group (identical core body temperature of 34 degrees C). Subjects will be randomized
using a random table of numbers. The patient, surgeon and audiologist will be blinded to the
group assignment. Only the study coordinator will have the sequestered and locked list of
randomization and blinding. Only the anesthesiologist will know the patients' assignment at
the time of surgery. The audiologist will not be present in the O.R. or in the outpatient
clinic, but will only test the patient post surgery. Each subject will undergo a battery of
audiometric tests (CNC words, HINT sentences, pure tone thresholds, and immittance) just
prior to implantation, at 1 month post operatively, at 6 months post operatively and at 1
year postoperatively.

Inclusion Criteria:

- Adults undergoing measurable auditory function who are undergoing cochlear
implantation as routine management of severe to profound hearing loss.

Exclusion Criteria:

- Pure tone average hearing ( mean of .5, 1 adn 2 KHz) worse than 100dB

- Age> 70 years

- History of arrhythmia or ischemic heart disease

- Sickle cell trait or disease

- Immune incompetence; coagulation disorders

- Revision cochlear implant; body-mass index >35

- Cold related disorders