Cochlear Implantation for Treatment of Single-sided Deafness
Phase: NA
Conditions: Total Unilateral Deafness, Unilateral Partial Deafness
Sponsor: Dr. Daniel Lee

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COVER PAGE 
Clinical Protocol Title: Cochlear Implantation for treatment of Single-Sided Deafness 
HSC #: 448090 
IRBNet ID: 448090-7 
NCT: NCT02532972 
Version number and date: Version 7, Aug 17, 2015 
Phase of clinical investigation: 4 
Name of all sites (if applicable): Massachusetts Eye and Ear Infirmary 
IDE number: G130174/A001 
Investigational drug(s) or device(s): 
MED-EL MAESTRO Cochlear Implant with Flex 28 electrode array 

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Regulatory Sponsor:     
Daniel J. Lee MD FACS 
Department of Otolaryngology 
Mass. Eye and Ear, 243 Charles Street 
Boston, MA 02114 
Funding Sponsor: 
Study Monitor 
Medical Director:  N/A 
Investigator(s): 
Principal Investigator: 
Dr. Daniel J. Lee, MD FACS 
Division of Otology, Neurotology, and Skull Base Surgery 
Department of Otolaryngology 
Massachusetts Eye and Ear Infirmary 
243 Charles Street 
Boston, MA 02114 
617-573-3130 
Daniel_Lee@meei.harvard.edu 
 
Co-Investigator: 
Dr. Ruth Litovsky, PhD 
Department of Communication Disorders 
University of Wisconsin - Madison 
1500 Highland Avenue 
Madison, WI 53705 
608-262-5045 
Litovsky@waisman.wisc.edu 
 

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Clinical Laboratories, Technical Departments, and Institutions Providing Clinical 
Study Services: 
Massachusetts Eye and Ear Infirmary Department of Otology and Neurotology 
Massachusetts Eye and Ear Infirmary Department of Audiology 
University of Wisconsin Department of Communication Disorders 
 

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STUDY DESIGN SCHEMATIC 
 

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1. CLINICAL PROTOCOL 
 
1.1 
Background 
Our study aims to determine the efficacy of the MAESTRO Cochlear Implant in patients 
with postlingual, single-sided deafness.  Single-sided deafness can arise from base of 
skull/temporal bone fractures leading to hearing loss, infection such as meningitis or 
labyrinthitis, vascular disease affecting the inner ear, Ménière’s disease, or sudden 
sensorineural hearing loss, each of which prevents the faithful transmission of auditory 
information from the cochlea to the brainstem.  Patients with single-sided deafness may also 
suffer from tinnitus in the affected ear, which can be debilitating. Unlike current treatments 
for single sided deafness, cochlear implantation has the potential to improve hearing abilities 
and suppress tinnitus in these patients.  
Many patients with single-sided deafness experience difficulty hearing in the setting of 
background noise, impaired sound localization and tinnitus. These symptoms can affect 
communication in social settings, causing psychosocial stress and resulting in a decreased 
quality of life. Treatment options for single sided deafness in the United States include the 
contralateral routing of signals (CROS) hearing aid and the implantable bone conduction 
hearing aid. These devices take sound from the affected ear and transmit it to the unaffected 
ear. Although these options can improve sound and speech awareness on the deaf side, 
studies have shown that use of these devices does not significantly improve sound 
localization and does not address the issue of tinnitus in the deaf ear. Recently, several 
European studies have shown that cochlear implantation can improve both perceived hearing 
ability and measured speech comprehension and localization in adult and pediatric patients 
with unilateral hearing loss. Furthermore, many patients experience tinnitus suppression 
following cochlear implantation. These clinical data suggest that cochlear implantation 
provides clinical benefits not seen with the CROS or bone-conduction devices. 
 
 

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1.2 
Rationale 
Single-sided deafness (SSD) afflicts approximately 60,000 new patients per year in the 
United States (Popelka et al., 2010).  The most common causes of these single-sided losses are 
sudden sensorineural hearing loss, Ménière’s disease, trauma, infections, and vascular insults.  
Patients with SSD face significant difficulty with sound localization and communicating in the 
presence of background noise (Bishop and Eby, 2010; Kamal et al., 2012).  Tinnitus is another 
significant problem for some SSD patients; this can be incapacitating and no available 
effective therapies exist outside of cochlear implantation (Arts et al., 2012).  Difficulty 
hearing in background noise and increased tinnitus can lead to significant frustration in 
social situations and contribute to increased isolation and a decreased quality of life.   
In the United States, options to treat SSD have included contralateral routing of signals to 
the hearing ear via (CROS) hearing aids and the bone-anchored hearing aid (BAHA) system, an 
osseointegrated device that provides direct transcranial stimulation of the contralateral side.  
For SSD, the BAHA appears to outperform other types of CROS aids (Niparko et al., 2003).  
Indeed, the BAHA provides some benefit to SSD patients, as measured both by subjective 
patient reports and an improvement on hearing-in-noise tests.  However, these aids are 
unable to provide information regarding sound localization, even after long-term use (Nicolas 
et al., 2012; Snapp et al., 2012; Linstrom et al., 2009; Niparko et al., 2003).  SSD patients using 
the BAHA do, moreover, continue to suffer significant deficits on hearing-in-noise testing 
relative to normal hearing adults (Linstrom et al., 2009).  Taken as a whole, data supporting 
the use of the BAHA in SSD suggest that while SSD patients derive some benefit from the 
device, this benefit is limited.   
Tinnitus is another problem experienced by a significant fraction of SSD patients.  While 
the precise neural substrates of tinnitus remain to be elucidated, hearing loss is highly 
correlated with the development of ipsilateral tinnitus.  Current treatment strategies for 
tinnitus involve cognitive behavioral therapy in conjunction with optimization of aural inputs 
(Arts et al., 2012) and, in some cases, antidepressant therapy.  As SSD patients have by 
definition lost useful hearing on one side, optimizing input on that side is not useful.  The 
treatment of tinnitus in SSD patients has therefore been limited to helping these patients deal 
with the symptom rather than addressing the root cause of the problem.  

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To directly address the tinnitus experienced by SSD patients by increasing signal through 
the cochlear nerve, several groups have carried out cochlear implantation (Arts et al., 2012).  
These results have been promising, with 80-95% of patients in the largest series finding 
improvement in their tinnitus or even, in a fraction of cases, complete tinnitus suppression.  
In nearly all cases, this effect is dependent on signal from the cochlear implant, supporting 
the idea that decreased input from the cochlear nerve contributes to the development of 
tinnitus (Van de Heyning et al., 2008; Arndt et al., 2010; Ramos et al., Kleine Punte et al., 
2011).   
Cochlear implantation in SSD patients has also resulted in significantly improved sound 
localization and ability to hear in noise (Kamal et al., 2013).  One important study examined 
SSD patients who were treated with cochlear implantation; the untreated side was either 
normal or treated with a hearing aid.  The data demonstrated that, although there was a 
significant benefit in speech understanding and subjective quality of sound, sound 
localization only improved in patients with normal hearing on the opposite side (Vermeire 
and Van de Heyning, 2009).  These findings are consistent with a more recent pilot study, in 
which three patients with short-term SSD and normal hearing in the other ear received a 
cochlear implant on the deafened side.  These patients all achieved open-set speech 
recognition, improved sound localization, and improved word recognition in noise (Firszt et 
al., 2012).  Another critical study evaluated SSD patients who had undergone cochlear 
implantation, comparing use of the cochlear implant to a CROS or BAHA.  This study found 
that cochlear implantation resulted in significant gains with respect to objective sound 
localization and hearing-in-noise testing relative to the CROS or BAHA device in the same 
patients.  Subjective and quality of life measures were also significantly improved with use of 
the implant (Arndt et al., 2010).  Taken together, early data indicate that cochlear 
implantation in SSD can result in significant tinnitus suppression, improved sound 
localization and hearing-in-noise, and better quality of life overall.   
2 Our hypotheses are that adult patients with postlingual, single-sided deafness who 
undergo cochlear implantation will 1) wear the implant full-time, 2) report that the 
cochlear implant provides benefit, 3) show improvement in speech comprehension in 
quiet and in background noise, 4) demonstrate an improvement in sound localization, and 
5) report a reduction in the frequency and intensity of tinnitus compared to before 

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surgery.  To test these hypotheses, we will formally and systematically test patients both 
before and after surgery as detailed below. 
 
 
 
 
 
 
 
 
 
 

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2. STUDY OBJECTIVES 
 
2.1 Primary Objective 
The primary objective of this study is to better assess the efficacy of cochlear implants 
in enhancing hearing abilities in patients with single sided deafness.  The parameters being 
assessed include hearing in background noise, sound localization, tinnitus suppression, and 
overall quality of life. Our study will address several specific aims including: 
Aim 1: Determine the audiologic outcomes following CI surgery for single sided deafness.   
We will implant ten adult patients with postlingual single sided deafness with the MED-
EL MAESTRO CI with Flex 28 electrode array using a round window insertion approach. 
Intraoperative imaging with a reverse Stenver xray will be performed to confirm proper 
electrode placement.  We will assess sound-field thresholds for the cochlear implant alone 
and word recognition ability in the monoaural and binaural condition. .  We will also have 
patients complete the following questionnaires: 1) Hearing Handicap Inventory for adults,  2) 
Abbreviated Profile of Hearing Aid Benefit and 3) Speech, Spatial, and Qualities of Hearing 
Scale (SSQ)(Noble and Gatehouse, 2006) prior to and after implantation to assess subjective 
benefit outcomes.  Finally, we will document the reported frequency of implant use and the 
use settings of the implant.  
Aim 2: Determine the spatial hearing benefits following CI surgery for single sided 
deafness. 
The bilateral benefits of understanding speech-in-noise will be evaluated in 
collaboration with Dr. Ruth Litovsky at the University of Wisconsin. Briefly, subjects will be 
flown to Madison and undergo spatial hearing testing in Dr. Litovsky’s lab pre- and post-
operatively. Funding from Dr. Litovsky’s lab will cover all costs for travel, accommodations 
and meals for the subject and one travel companion. Subjects will be their own control and 
testing will take place at time points before and after surgery.  They will be tested with the 
acoustic ear alone before the CI surgery.  Following CI surgery, testing will be done with the 
bilateral condition and with the acoustic ear alone.  On one task, subjects will identify a single 

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word randomly chosen from a set of fifty possible alternatives and presented from a 
loudspeaker directly in front of the subject.  Speech intelligibility will be tested by masking 
sentences co-presented at different spatial configurations (-90° or +90°).  The presentation 
level of the target speech will be varied in order to generate different signal-to-noise-ratios at 
each condition.  We will evaluate implanted SSD patients with the device turned on and off to 
directly evaluate the contribution of the cochlear implant to understanding speech-in-noise.  
On a second task, we will evaluate sound localization in a 19-loudspeaker array. Stimuli are 
brief speech sounds; the overall level is roved and the spectrum is roved within a critical 
band to eliminate monaural level and spectral cues. Listeners identify the location of the 
loudspeaker emitting the sound, and testing is done in quiet, and with background noise at 
SNRs that vary from negative to positive values. Data are analyzed to yield root mean square 
error for localization, patterns of localization within a hemifield and across a hemifield, as is 
standard in the Litovsky lab (Litovsky et al., 2006; 2009).   
2.2 Secondary Objective(s) 
 
SSD patients with significant tinnitus will be identified using the Tinnitus Handicap 
Inventory (THI) questionnaire, which is a validated measure of the degree to which 
tinnitus can adversely affect patients.  The THI administered preoperatively and at 3, 6 
and 12 month intervals following CI surgery will provide a primary measure of tinnitus 
relief. A secondary measure, obtained at the same time points, will be tinnitus 
loudness (1) rated by the patient on a 0 – 10 scale and (2) measured as the level of 
sound stimulation of the hearing ear needed to match the loudness of the sound to 
that of the tinnitus.  Auditory brainstem responses (ABR) to monaural sound 
stimulation of the hearing ear (specifically wave V amplitude) will be measured pre- 
and 6 months post-operatively to test whether CI use reverses previously-documented 
brainstem hyperactivity related to tinnitus (Gu et al., 2012; Schaette and McAlpine, 
2011).  

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3. STUDY DESIGN 
 
3.1 Study Design Description 
The study of the MAESTRO Cochlear Implant system in patients with single sided deafness 
will be conducted as a prospective study with ten patients undergoing cochlear implantation 
(ten patients total).  Pre-operative baseline measures will be obtained as outlined below.  Post-
operative evaluations will be conducted at initial device activation, and three, six, and twelve 
months post-activation.  Because the presence or absence of a cochlear implant is easily 
recognized from visual inspection, blinding and masking procedures will not be utilized as 
part of the study design.  The safety of the implant will be determined by monitoring major 
and minor complications in the cohort of study participants. 
 
Candidates that are suitable for surgery will undergo placement of a cochlear implant.  The 
cochlear implant wires will then be placed in the cochlea and tested intra-operatively.  After 
confirmation of optimal electrode array placement, the receiver will be implanted within the 
temporal bone posterior to the pinna.  The overlying subcutaneous tissue and skin will then 
be closed and covered with dressings using standard surgical techniques. Intra-operative 
imaging with a reverse Stenver X-ray will be performed to confirm proper electrode 
placement.  
 
Following surgical implantation of the MAESTRO Cochlear Implant and two to three weeks of 
healing, the device will be activated and auditory performance will be assessed at the time of 
activation and at three, six, and twelve months post-activation.  Subjects will be evaluated 
with the prior approved cochlear implant speech processor programmed with an approved 
sound-processing algorithm.  Post-operative auditory function will be tested with a battery of 
pure tone threshold audiometry, word recognition testing, and spatial hearing testing. The 
degree of tinnitus present will be assessed using the Tinnitus Handicap Inventory. 
 
The detailed list of assessments includes: 

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Prior to Surgery 
Important baseline and control tests will be performed pre-operatively to obtain data for 
comparison.  These will include: 
•  Modified Hearing Handicap Inventory and Quality of Life (SF-36) questionnaires will be 
administered (see attached) 
•  Tinnitus Handicap Index and Auditory Brainstem Response (ABR) testing 
•  Psychophysical measures 
•  Spatial hearing testing at the Binaural Hearing and Speech Lab at the University of 
Wisconsin – Madison (Dr. Ruth Litovsky’s lab) 
 
Initial Activation 
Approximately four weeks post-operatively, subjects will be fitted with an approved MED-EL 
Sound Processor and initial stimulation will take place.  The following procedures will occur 
at this visit: 
•  Modified Hearing Handicap Inventory and Quality of Life (SF-36) questionnaires will be 
administered (see attached) 
•  Detection measures 
•  Psychophysical measures 
•  Safety measures 
 
Three, Six, and Twelve Months Post-activation Visits (to MEEI): 
The following procedures will occur at all these visits unless otherwise specified:  
•  Modified Hearing Handicap Inventory and Quality of Life (SF-36) questionnaires will be 
administered (see attached) 
•  Pure tone threshold audiometry at each post-activation interval 
•  Word recognition testing at each post-activation interval 
•  Tinnitus assessment at each post-activation interval, along with ABR testing at the six 
month mark  
•  Psychophysical measures at each post-activation interval 
•  Safety measures at each post-activation interval 
 

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Visit to University of Wisconsin – Madison after Twelve Months Post-activation: 
Once time has been established to acclimate to the cochlear implant, subjects will undergo 
study-related spatial hearing testing in addition to clinical follow up visits.  Depending on 
subject availability in schedule, the following procedure will take place unless otherwise 
specified: 
•  Spatial hearing testing at the Binaural Hearing and Speech Lab at UW – Madison (Dr. Ruth 
Litovsky’s lab) 
 
3.2 Allocation to Treatment 
Because our study is a repeated-measure, single subject experimental design with up to ten 
replications, there is no proposed plan or procedure for allocating study participants to 
various cohorts of arms of the proposed clinical investigation. 
3.2.1 Randomization Procedures: N/A 
3.2.2 Masking Procedures: N/A 
 3.2.3 Breaking the Mask: N/A 

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4. SUBJECT SELECTION 
 
4.1 Subject Inclusion Criteria 
 
18 years of age or older with the ability to provide informed consent 
 
English as the primary language 
 
Medically and psychologically suitable 
 
Willing to receive/have received meningitis vaccinations 
 
Unsuccessful trial of non-invasive hearing amplification devices or tinnitus treatment 
as defined by standard of care of six months 
 
Able to pay for all care received through the study, either through the subject’s 
insurance company or through self-pay 
 
Able to comply with study requirements, including travel to the investigational sites 
 
Severe to profound sensorineural hearing loss (≥70 dB thresholds between 500 and 
4000 Hz) in the worse ear with ≤ 20% CNC word scores 
 
Duration of single-sided deafness ≥ one year 
 
Tinnitus localized to the affected ear, both ears or in the head localized to the affected 
ear, both ears, or in the head 
o Expected subjects include those with: 
 
Unilateral hearing loss secondary to viral or bacterial infection, such as 
meningitis or labyrinthitis 
 
Ménière’s disease 
 
Sudden sensorineural hearing loss 
 
Vascular disease affecting the inner ear 
 
A combination of any number of the above conditions 
 
4.2 Subject Exclusion Criteria 
 
Duration of single-sided deafness ≥ ten years  
 
Pure tone thresholds ≥ 35dB at 500, 1000, 2000, and 4000 Hz in the better ear 
 
CNC word scores ≤ 70% in the better ear 

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 
Chronic otitis media in either ear 
 
Inner ear malformation in either ear 
 
Autoimmune inner ear disease (fluctuation sensorineural hearing loss in either ear) 
 
Evidence of retrocochlear pathology, including vestibular schwannoma 
 
 
Unilateral tinnitus in the unaffected ear  
 
Cochlear ossification 
 
Demonstrated cognitive and/or developmental challenges 
 
Major depression or anxiety; post-traumatic stress disorder; substance abuse 
 
Medical or psychological conditions that serve as contraindication to surgery  
 
Additional handicaps that would prevent or limit participation in evaluations 
 
Unrealistic patient or family expectations regarding the benefits, risks, and limitations 
inherent to the procedure and the prosthetic device 
 
Pregnant women: We will specifically ask all women of childbearing age if there is a 
possibility they are pregnant or trying to become pregnant at the initial clinic visit; any 
women who are pregnant or actively trying to become pregnant will be excluded. In 
cases that are questionable on the day of planned surgery, a pregnancy test will be 
performed as per current MEEI anesthesia pre-operative protocols. 

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5. STUDY DRUG(S)/DEVICE(S)  
 
5.1 Study Drug/Device Information 
The MAESTRO Cochlear Implant system consists of a receiver/stimulator, a pocket sized 
speech processor worn on the body, and a microphone/headset. The system consists of an 
internal receiver/stimulator and an external audio processor. During surgery, a 
receiver/stimulator is implanted behind the ear.  A wire leads from the receiver/stimulator to 
the nerve fibers of the cochlea.  The audio processor picks up sound and transduces it into 
electrical impulses that are sent to the implanted receiver/stimulator.  The impulse travels 
down the wire to the electrodes, which electrically stimulates the cochlea. This signal is 
transmitted through the auditory nerve to the brain. 
The MAESTRO Cochlear Implant system is marketed under the brand name of MAESTRO 
Cochlear Implant and manufactured by MED-EL Corporation, USA (Durham, NC).  The FDA has 
approved use of this cochlear implant device in patients with bilateral deafness. 
5.2 Study Drug/Device Compliance/Adherence  
Because the cochlear implant system is an implanted device, there are few concerns regarding 
compliance and adherence compared to most drug-based clinical trials.  Our study is 
designed as a prospective, repeated-measure single subject trial.  Participants in the 
experimental group will serve as their own controls. Throughout the study, we will confirm 
that subjects have been using the device through routine clinical follow-up and 
questionnaires at each appointment.  Both qualitative and quantitative measures will be 
obtained to determine if subjects are benefiting from the cochlear implant system, and the 
individual activation parameters at each visit will be compared to the prior visit to ensure 
that settings on the device have not been altered or changed between visits.   
Although we anticipate that the vast majority of subjects will derive a safe and substantial 
clinical benefit from use of the cochlear implant system, if a given subject is non-compliant 
or non-adherent with use of the cochlear implant system or external sound processor, then 
we will collect a final set of qualitative and quantitative measures and simply follow their 
outcomes through routine clinical exams.  This approach will allow for monitoring of any 

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adverse safety or health concerns that may arise.  Thus, no subjects in our study will be 
formally withdrawn for non-compliance or non-adherence and all study participants will be 
followed for one year after cochlear implant surgery.  Any patient choosing to withdraw from 
the study will be replaced by a new study participant recruited from the clinic. The reasons 
for withdrawal or termination will of course be reported and documented at the time of 
occurrence. 
If a subject withdraws or is terminated after implantation, a new subject will replace him or 
her. In principle, then, more than 10 subjects may end up with an implant based on their 
participation in the study.  
5.3 Study Drug Supplies 
The MAESTRO Cochlear Implant system is already FDA-approved for use in patients with 
bilateral deafness.  As with other cochlear implants, the MAESTRO Cochlear Implant device is 
ordered prior to surgery.  As the MAESTRO Cochlear Implant System is already being used in 
patients with bilateral deafness, standard storage, dispensation, handling, and disposal 
protocols are already in place.  Similar protocols will be used in our study.  In particular, 
upon receipt the device will be kept in storage with other electrical implant devices at MEEI, 
and at the time of surgery, dispensed/opened and subsequently handled with appropriate 
sterile technique.   
5.4 Study Drug/Device Storage and Accountability 
The cochlear implant system is stored at room temperature upon receipt and kept securely 
until it is used during surgery.  Cochlear implants utilized for this study will be kept separate 
from devices for clinical use within device locked storage.  Given its electronic components, 
prolonged exposure to extreme temperatures should be avoided.  In our study, the cochlear 
implant system will be kept in storage with other electrical implant devices at MEEI, and at 
the time of surgery, dispensed/opened and subsequently handled with appropriate sterile 
technique.  Nearly all aspects of the device are implanted in the patient (with the exception of 
the speech processor and microphone/headset, which are worn externally).  The device 
contains a few disposable components, which are primarily used to accurately place the 
device intra-operatively.  These components will be disposed of in biological waste containers 
during the surgery.  Because the MAESTRO cochlear implant system is an implanted device, 

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protocols for the proper destruction or disposition of study devices upon completion or 
termination of the clinical research are not necessary. 
5.5 Other Medications 
Our study does not include the planned use of other medications concomitantly with 
the MAESTRO Cochlear Implant.  If patients experience complications or medical 
concerns related to the cochlear implant device, these will be handled appropriately 
through routine medical management in the Otology clinic or appropriate referral to 
other providers.  There are no specific medications that are not allowed in participants 
of our clinical research study.  In addition, rescue medication or therapies will not be 
used in this study. 

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6. BIOSPECIMEN COLLECTION (IF APPLICABLE) 
 
 
Biospecimens will not be collected as part of our study. Thus, specimen preparation, handling 
and storage are not applicable.  
6.1 Specimen preparation, handling, and shipping: N/A 
 
6.2 Instruction for specimen preparation, handling and storage: N/A 
 
6.3 Specimen shipment: N/A 
 
6.4 Future use of stored specimens: N/A 

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7. STUDY PROCEDURES 
 
7.1 Screening Procedures 
After confirming that potential study participants meet basic demographic inclusion criteria, 
patients will be evaluated by a trained Otologist at MEEI.  A detailed history will be obtained 
and a physical exam will be completed.  Subjects will also be evaluated for baseline 
qualitative measures using questionnaires and quantitative measures using audiologic 
testing.  
In accordance with 21 CFR 812.25 (c), we will attempt to match the proportions of women 
and minorities included in past trials for the indication of CI surgery in patients with SSD. We 
will also attempt to include an even distribution of patients with regards to age, sex, race and 
ethnicity as there is no particular population of patients affected by the conditions addressed 
by our study. However, given the small sample size of our study, it will be difficult to capture 
all patient demographics.  
7.2 Enrollment/Baseline Procedures 
All baseline procedures will be completed at the time of screening.  This includes qualitative 
measurement using the Modified Hearing Handicap Inventory, Abbreviated Profile of Hearing 
Aid Benefit (APHAB), the Speech Spatial and Qualities of Hearing Scale (SSQ) and Quality of 
Life (SF-36) questionnaires as well as audiologic tests such as Early Speech Perception Testing 
and Consonant-Nucleus-Consonant testing. The degree to which tinnitus in the non-hearing 
ear affects the participant’s well-being will be assessed using the Tinnitus Handicap 
Inventory.  Auditory Brainstem Response (ABR) will be measured in patients with tinnitus as 
an additional clinical correlation, conducted for research purposes.  Finally, patients will 
travel to the Binaural Hearing and Speech Lab at the University of Wisconsin – Madison for 
hearing-in-noise and spatial hearing testing pre- and post-operatively (see below). All costs for 
airfare, accommodations, meals and a daily stipend will be covered by funding from Dr. 
Litovsky’s laboratory.  
 

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7.3 Study Drug or Device Procedures 
Subjects will undergo pre-operative evaluation for cochlear implant surgery.  Those subjects 
that are appropriate for surgery will undergo a procedure for implantation of the MAESTRO 
Cochlear Implant system.  As per manufacturer protocol, the parameters of the cochlear 
implant system including adjustment of electrode sensitivities and activation of specific 
electrodes will be completed at each follow-up visit post-operatively.  This process involves 
adjustment of device parameters by a trained audiologist who subsequently administers 
audiologic tests to confirm optimal activation of the cochlear implant device. 
7.4 Standard of Care Procedures 
All audiologic testing and assessments represent the standard of care.  Aspects of our study 
that go beyond routine standard of care are outlined above and in the informed consent.  
7.5 Follow-up Procedures 
Study participants will have audiologic testing and device activation and adjustment 
completed at follow-up appointments.  These post-operative follow-up appointments will 
occur at 4 weeks, and at three, six, and twelve months.  Timing of these appointments may 
vary by as much as four weeks prior to or after the planned follow-up date (e.g. between 2-4 
months for the 3 month follow-up). 
7.6 Unscheduled Visits 
Unscheduled visits will be taken in the Otology clinic as needed to address any concerns 
study participants may have regarding the use of their cochlear implant device. 
7.7 Early Termination 
Subjects whose participation in the study is terminated early will be replaced through the 
recruitment of additional subjects through Otology clinic.  All subjects may voluntarily 
withdraw from the study at any time. 
7.8 Schedule of Activities (Study Table) 
Please see attached. 
  

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8. SAFETY AND EFFECTIVENESS ASSESSMENTS 
 
8.1 Safety Assessments 
Safety assessments will include questionnaires to assess for complications and frequent post-
operative follow-up visits.  Inquiries about both major and minor complications will be made 
and any complications will be recorded.  A research assistant will regularly review safety 
measures every month for all study participants and discuss any safety concerns/adverse 
outcomes with the investigator.   
Any reported safety issues will be carefully recorded and following completion of the study, 
safety outcomes will be analyzed.  Any unanticipated adverse events will be reported to the 
HSC, FDA, and MED-EL Corporation (see Section 9). 
8.2 Effectiveness Assessments 
Effectiveness assessments will be completed based on audiologic testing and subjective 
questionnaires at each follow-up appointment.  These will be compared to the subjects’ pre-
operative baseline measures.  In particular, primary dependent measures will include: 
 
Pure Tone Threshold Audiometry 
 
Sound Localization Testing (University of Wisconsin – Madison) 
 
Speech Perception Measures - Consonant-Nucleus-Consonant (CNC) Testing 
 
Psychophysical Measures  
 
Tinnitus Assessment - Tinnitus Handicap Inventory (THI) 
 
Subjective Questionnaires - Hearing Handicap Inventory, Abbreviated Profile of Hearing 
Aid Benefit (APHAB) questionnaire, Speech Spatial and Qualities of Hearing Scale (SSQ), 
and Quality of Life (SF-36) questionnaire 
 
Each CI subject’s speech perception ability will be ranked on a continuum of performance by 
using standardized speech perception tests that document the range of perception abilities. 
We will use the Consonant-Nucleus-Consonant (CNC) test (House Ear Institute). The CNC open 
set single-syllable test will be administered and scored both for whole-word and phonemic 
items. All speech tests will use recorded materials at a level of 65dB HL and will be presented 
in the soundfield through a speaker to the subject at 0 degree azimuth and calibrated at a set 

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distance, typically 1 meter.   We will test SSD patients in the bilateral condition, using the 
good ear only and use contralateral masking to eliminate contributions from the good ear to 
evaluate the implanted ear.   
 
Each subject’s spatial hearing ability will be assessed in collaboration with Dr. Ruth Litovsky 
at the University of Wisconsin. Subjects will identify a single word randomly chosen from a 
set of fifty possibly alternatives and presented from a loudspeaker directly in front of the 
subjects. Speech intelligibility will be tested by masking sentences co-presented at different 
spatial configurations. The presentation level of the target speech will be varied in order to 
generate different signal-to-noise ratios at each condition. We will evaluate implanted SSD 
patients with the device turned on and off to directly evaluate contribution of the cochlear 
implant to understanding speech-in-noise.  
 
Recorded test materials, test keys and patient response forms will be collected and 
documented as part of the study. Number of test items and percentage scores on each test 
will be documented and included in the data analysis.  
 
 
All subjective questionnaires will serve as an additional qualitative assessment of 
hearing and will not be used to directly guide quantitative audiologic testing. Measures 
from subjective questionnaires will be carefully documented for each subject and 
included in data analysis. These questionnaires will be completed before the activation 
appointment and prior to each of the follow-up appointments. 

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9. ADVERSE EVENT RECORDING AND REPORTING 
9.1 Recording Requirements 
Research subjects will be routinely questioned about adverse events at study follow-up visits.  
 RECORDING REQUIREMENT 
All observed or volunteered adverse events (serious or non-serious) and abnormal test 
findings, regardless of suspected causal relationship to the study device will be 
recorded in the subjects’ case histories (source data, case report form).  For all adverse 
events, sufficient information will be obtained to permit 1) an adequate determination 
of the outcome of the event (i.e., whether the event should be classified as a serious 
adverse event) and; 2) an assessment of the casual relationship between the adverse 
event and the cochlear implant system.    
 
Adverse events or abnormal test findings felt to be associated with the cochlear 
implant system will be followed until the event (or its sequel) or the abnormal test 
finding resolves or stabilizes at a level acceptable to the Sponsor-Investigator. 
 ABNORMAL TEST FINDINGS 
An abnormal test finding will be classified as an adverse event if one or more of the 
following criteria are met: 
o The test finding is accompanied by clinical symptoms 
o The test finding necessitates additional diagnostic evaluation(s) or 
medical/surgical intervention, including significant additional concomitant drug 
treatment or other therapy  
o The test finding leads to discontinuation of subject participation in the clinical 
research study 
o The test finding is considered an adverse event by the Sponsor-Investigator of 
the IND or IDE application 
 
 CASUALTY AND SEVERITY ASSESMENT 

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The Sponsor-Investigator of the IND or IDE application will promptly review 
documented adverse events and abnormal test findings to determine 1) if the 
abnormal test finding should be classified as an adverse event; 2) if there is a 
reasonable possibility that the adverse event was caused by the MAESTRO cochlear 
implant system; and 3) if the adverse event meets the criteria for a serious adverse 
event. 
 
If the Sponsor-Investigator’s final determination of causality is “unknown and of 
questionable relationship to the study device”, the adverse event will be classified as 
associated with the use of the cochlear implant system for reporting purposes.  If the 
Sponsor-Investigator’s final determination of causality is “unknown but not related to 
the study device,” this determination and the rationale for the determination will be 
documented in the respective subject’s case history (case report form).  
9.2 REPORTING PROCEDURES 
 REPORTING OF ADVERSE EVENTS TO FDA 
o Written IDE Safety Reports  
o Telephoned IDE Safety Reports – Fatal or life-threatening suspected adverse 
reactions 
  Reporting Adverse Events to Other External Entities 
o Adverse event reports will also be submitted to the MED-EL Corporation, which 
has provided a Right of Reference Letter for the MAESTRO Cochlear Implant 
system in accordance with their respective reporting guidelines.  
 Reporting Adverse Events to the Human Studies Committee  
o The Principal Investigator will reports to the HSC any serious adverse events 
that are unexpected and related/possibly related to research within 7 calendar 
days from the time the PI became aware of the event.  
o Any unexpected and study-related death will be reported to the HSC within 24 
hours of PI’s knowledge of the event by email or telephone.  
o The PI will report to the HSC all non-serious adverse events that are unexpected 
and related or possibly related to the research within 30 calendar days from the 
time the PI became aware of the event. 

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o The PI will promptly report to the HSC Unanticipated Problems (UAPs) involving 
risks to the subjects or others. 
 
9.3 Withdrawal of Subjects due to Adverse Events 
1. 
Reporting of Unexpected and Related/Possibly Related Events 
Serious Adverse Event (SAE) 
Any serious adverse event will be reported to the HSC.  These SAE include those 
that both (i) are unexpected and related/possibly related to research; and (ii) 
occur while the subject is enrolled in the study or that occur within 30 days of 
the conclusion of the subject’s participation in the study, of which the PI or 
study staff become aware.  In order to determine whether a specific adverse 
event is unexpected, the PI will consider whether the event is consistent with the 
risks described in the protocol-related documents (e.g. protocol, consent form, 
Investigator’s Brochure).  In order to determine whether a specific adverse event 
is related or possibly related to subject’s participation in the research, the PI will 
consider the temporal relationship between the event and the investigational 
product being studied or study procedure. If an adverse event is at least 
partially caused by the procedures and /or investigational products, it will be 
considered related/possibly related to research. 
 
Any adverse events that are serious, unexpected and related or possibly related 
to the study will be reported to the HSC within 7 calendar days from the time 
the PI becomes aware of the event.  Any unexpected and study-related death will 
be reported to HSC within 24 hours of the PI’s knowledge of the event by e-mail 
or telephone.  A completed AE report form will be submitted to HSC within 7 
calendar days of initial HSC notification. If the PI becomes aware more than 30 
days after the conclusion of a subject’s participation of a serious adverse event 
that is both related to the research and unexpected, the PI will report the event 
to HSC at the time he/she becomes aware of it. 
 
Non-Serious Adverse Event 

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All non-serious adverse events that are unexpected and related or possibly 
related to the research will be reported to the HSC within 30 calendar days from 
the time the PI becomes aware of the event. 
 
2. 
Reporting of Expected and Related/Possibly Related Events 
The PI will submit a summary report to the HSC for all serious and non-serious 
events that are expected and related/possibly related to the study at the time of 
continuing review. 
 
3.  
Reporting of Unanticipated Problems 
The PI will promptly report to the HSC Unanticipated Problems (UAPs) involving 
risks to subjects or others.  In order to determine whether a specific problem 
constitutes a UAP, the PI will consider the following: 
- 
The vast majority of adverse events occurring in human subjects do not 
represent UAP because most AEs are expected in the context of known 
toxicities or side effects of the research procedures and/or are due to the 
natural history of subjects’ underlying diseases and conditions; 
- 
a small proportion of AEs do represent UAPs; and 
- 
UAPs may include events that are not adverse events. 
 
All UAPs involving risks to subjects or others will be reported in writing to 
the HSC within 7 calendar days from the time the PI becomes aware of the 
event. If a UAP or an unexpected SAE results in a subject’s death or was 
potentially life-threatening, the PI will notify HSC through e-mail or phone 
within 24 hours from the time the event is identified. A follow-up report will be 
submitted at a later date when more information is available. The PI will notify 
HSC through e-mail or phone within 24 hours from the time the event is 
identified for UAPs that take the form of a data loss. 
9.3 Withdrawal of Subjects due to Adverse Events 
 
Subjects experiencing major adverse events will be referred for appropriate care as 
needed.  The severity of adverse events will be determined by the investigator in 

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consultation with the HSC.  Briefly, events that lead to irreversible or permanent 
disability of the patient will be considered serious and the subject will be reminded 
that participation in the study is voluntary and that withdrawal is possible at any time.  
If the subject remains interested in continuing to participate in the study, then after 
receiving the appropriate care, data will continue to be collected from the subject at 
follow-up visits as described in the study design.  Medical attention and follow-up for 
any adverse events will continue until the adverse health concern has resolved or if 
not, then continued indefinitely.  If a subject withdraws from the study due to an 
adverse event, he/she will be replaced by recruiting a new study participant from 
clinic.  The reasons for withdrawal or termination will of course be reported and 
documented at the time of the occurrence.  In principle, then, more than 10 subjects 
may end up with an implant based on their participation in the study.  

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10. STATISTICAL METHODS/DATA ANALYSIS 
10.1 Primary endpoint(s) or outcome measure(s) 
The study has a primary endpoint of one year following cochlear implant surgery for ten 
study participants.  Outcomes measures include audiologic measures and subjective 
questionnaires as described in previous sections, as well as safety assessments completed 
throughout the study. 
 
Our previous work has established the importance of these physiological, psychophysical, 
audiologic tests, questionnaires on efficacy, and safety measures as a comprehensive method 
for assessing the outcomes of cochlear implant surgery.  In particular, the use of these 
measures will allow us to obtain both objective and subjective data to assess the safety and 
efficacy of cochlear implant placement in patients with single sided deafness and thereby 
understand how cochlear implant placement has influenced patients’ hearing and quality of 
life.  By comparing our findings and measures to data obtained in other patient populations 
(such as patients with single sided deafness who do not undergo cochlear implantation), we 
will better understand whether cochlear implant placement in this patient population has 
improved safety and efficacy compared to no treatment.   
10.2 Secondary endpoints or outcome measure(s) 
The secondary outcome measure of this study is the effect of cochlear implantation on 
tinnitus suppression in patients with tinnitus in the non-hearing ear. Outcomes will be 
assessed using the Tinnitus Handicap Inventory and auditory brainstem response testing as 
previously indicated. Prior studies have indicated that cochlear stimulation via a cochlear 
implant device can suppress tinnitus. By comparing our findings and measures to data 
obtained from patients with single sided deafness who do not undergo cochlear implantation, 
we will better understand the utility of cochlear implantation for tinnitus suppression in this 
patient population. 
10.3 Sample Size Determination 

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Our study will recruit ten participants for placement of a MAESTRO Cochlear Implant device 
with follow-up measurements and assessments for one year post-operatively.  Although our 
study is limited to a small sample size of ten patients, the single subject research design will 
allow each subject to serve as his or her own control, accommodating heterogeneity of the 
subjects’ backgrounds and providing adequate power to test the major hypotheses. Previous 
studies have used a similar study design and sample size, with statistically significant 
findings regarding efficacy and safety of cochlear implants in patients with single sided 
deafness. Given that single-sided deafness is an experimental indication for cochlear 
implantation, it is appropriate to assess efficacy in a small cohort prior to recruiting more 
subjects. This will allow us to avoid unnecessary surgery in patients who may not benefit 
from this intervention.  
10.4 Analysis Population  
Given the small sample size of ten patients for our study, we will plan to analyze data 
obtained from all participants.  If a subject withdraws from the study, data obtained from 
their participation in the study will still be incorporated into outcomes and safety analyses. 
10.5 Effectiveness Analysis 
As this study is a single-subject research design, cochlear implant effectiveness results will be 
analyzed for each subject individually. The data will be described using conventional 
descriptive statistics.  Data analyses will be conducted using appropriate non-parametric 
statistical tests.  Audiometric and psychoacoustic performance data from the same ear in a 
subject will be evaluated both prior to and following cochlear implant placement.  For all 
statistical analyses, a p ≤ 0.05 level of significance will be used.  Any subsequent deviations 
from the statistical plan will be described and justified in a protocol amendment and/or in 
the final report submitted to this application. 
10.6 Safety Analysis 
Cochlear implant safety results will be analyzed for each subject individually. The data will be 
described using conventional descriptive statistics.  Data analyses will be conducted using 
appropriate non-parametric statistical tests.  Safety outcomes from patients enrolled in the 
current study will be compared to data collected from patients with single sided deafness 
who do not undergo cochlear implantation using standard statistical tests.  For all statistical 

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analyses, a p ≤ 0.05 level of significance will be used.  Any subsequent deviations from the 
statistical plan will be described and justified in a protocol amendment and/or in the final 
report submitted to this application. 
10.7 Interim Analyses 
 
Interim analyses will be completed once three, five, and eight patients are enrolled.  
These analyses will be completed at six months and one year post-operatively for each 
of these cohorts.  Study staff and the Investigator will perform the interim analyses, 
and results will be shared with the HSC through routine study renewal forms.  If 
significant concerns arise regarding safety of the proposed device, these analyses will 
be shared with the HSC within 7 days and appropriate discussion to follow.  Of note, 
the safety concerns described here do not include adverse or unanticipated safety 
events, which will be handled as described in Section 9. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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11. DATA AND SAFETY MONITORING  
 
11.1 Data and Safety Monitoring Plan  
All persons working on the study will be briefed by the Investigator or other leaders of the 
trial regarding their role in the study and appropriate data management and safety 
monitoring procedures.  During these meetings, the cochlear implant device as well as 
individual trial-related duties and functions will be discussed.  The investigator or other 
leaders of the study will provide an opportunity for all persons assisting with the trial to ask 
questions and clarify the protocol and their individual role.  Each individual will be required 
to read the study protocol and acknowledge that they have read and understand the protocol 
along with their trial related duties and functions. Study activity will be reviewed monthly be 
the MEEI implant board and annual reports will be submitted to both the FDA and the HSC to 
ensure compliance with the approved protocol.  
 
The investigator and study staff will monitor the validity and integrity of the data and any 
safety concerns as well as adherence to the IRB-approved protocol through regular biweekly 
or monthly meetings in which collected data is shared, new analyses are discussed, and any 
issues with protocol adherence are reviewed. As there will be data collected at both MEEI and 
the University of Wisconsin, data will be analyzed both on-site at MEEI and in a centralized, 
secure database that allows for sharing of results between the institutions. The staff at the 
University of Wisconsin that will be conducting the auditory testing will have access to the 
approved case reporting forms for the recording of all test results. These results will be 
shared through the secure MEEI storage website. If any urgent issues arise at either site, the 
primary site investigators will be notified immediately by telephone or secure e-mail. The 
teams at both sites will be thoroughly informed of the timeline for reporting adverse events 
or issues to the HSC and FDA. This information will be communicated securely both in paper 
form and via secure e-mail. Any significant non-compliance with this protocol will be 
addressed immediately by the Principal Investigator and the issues will be reported to the 

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HSC. If the Investigator is unable to successfully address the issue, any non-compliant study 
staff will be removed from the study protocol and denied access to the secure patient 
information.  
 
A research assistant will be responsible for monitoring the study, including obtaining source 
documents, organizing completed informed consent forms, reviewing the accuracy and 
completeness of case report forms, and managing the protocol timeline to ensure that all 
assessments are appropriately administered and collected from study participants. This 
individual will receive the required online training required for handling protected patient 
information and will have an in-depth understanding of the protocol such that he or she is 
able to identify issues with data or safety in a timely manner.  
 
A monitoring log will be kept securely within MEEI or the office of the research assistant. The 
log will abide by the guidelines set forth by the FDA and HSC, and will consistently be 
updated with the most recent data.  
 
 
We do not feel that a Data and Safety Monitoring Board is required for this study as the 
cochlear implant device has already been approved for use in adults with bilateral 
hearing loss and therefore the risks are well known.  
 

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12. DATA HANDLING, RECORD-KEEPING AND MONITORING 
 
12.1 Data Recording, Record-Keeping, and Monitoring 
A Case Report Form (CRF) will be completed for each subject enrolled into the clinical study.  
The Sponsor-Investigator will review, approve and sign/date each completed CRF; the 
Sponsor-Investigator’s signature serving as attestation of the Sponsor-Investigator’s 
responsibility for ensuring that all clinical and laboratory data entered on the CRF are 
complete, accurate and authentic.   
 
 
Clinical data that may be recorded directly on the CRF include: subjective report of 
symptoms, audiologic measures, lab values, and physical exam findings.  Any missed, 
unused, or spurious data will be reviewed by the Investigator and followed up by study 
personnel.  Subject specific data and Case Report Forms will be coded with a numeric 
random identifier, with information regarding which codes correspond to which 
subjects stored on secure information systems at MEEI.  Electronic systems used are in 
compliance with FDA electronic records and signature regulations.  Data review will be 
the responsibility of the PI and other members of the study staff.  
 

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13. STUDY DISCONTINUATION CRITERIA 
 
13.1 Discontinuation of Individual Research Subjects 
As described, safety measures will include complications questionnaires and frequent post-
operative follow-up visits.  Inquiries about both major and minor complications will be made 
and any complications will be recorded.  A research assistant will regularly review safety 
measures every month for all study participants and discuss any safety concerns/adverse 
outcomes with the investigator.  The investigator will then decide whether the research study 
should be altered or stopped.  If a clear answer is not evident, the investigator will discuss 
the safety concern with the Human Studies Committee and make appropriate adjustments to 
the study as needed.  Other discontinuation criteria are described under Section 5.2 
(Withdrawal of subjects due to non-compliance/adherence) and section 9.3 (Withdrawal of 
subjects due to adverse events) of the clinical protocol.  
If withdrawn subjects agree to measurements of clinical outcomes and assessments of device 
safety, their data will be collected until one year following cochlear implantation surgery.  As 
with other criteria for withdrawal, subjects that are withdrawn will be replaced through 
recruitment of additional study participants in clinic. 
 
13.2 Sponsor-Investigator Discontinuation of the Clinical Research Study 
 
At this time, the sponsor-investigator has no known criteria for discontinuation of the 
clinical research study.  Any protocol modifications will be submitted prospectively to 
the HSC and to the FDA for discontinuation of parts of the clinical study.  If portions 
of the study must be discontinued, the HSC and the FDA will be notified promptly of 
discontinuation, including which portions of the study (if any) remain.  In addition, 
enrolled subjects will be notified at follow-up appointments or by phone of 
discontinuation of any aspects of the study.  If parts of the clinical study are 
discontinued, a revised informed consent will be discussed and obtained from subjects 

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for continued participation in the study.  All study staff and sub-investigators will be 
notified directly by the investigator of discontinuation of parts or all of the clinical 
research study.  Because all audiologic measurements and safety assessments in this 
study are part of normal routine follow-up after cochlear implantation surgery, these 
measures will continue to be obtained following discontinuation of the study through 
normally scheduled follow-up appointments.  However, subjective questionnaires will 
not be administered to subjects following discontinuation of the study.    

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14. APPENDICES 
 
14.1 Schedule of Events  
14.2 Case Report Forms: see multiple attached documents, each labeled “CRF”  
 

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Schedule of Events 
(M = Billable to Medicare/Insurance/Third Party)     
List of Procedures 
Billable 
to: 
                Pre-Operative 
  
 
  Day of    
 Surgery 
                                                
Post-Operative Visits  
  
  
  
  
  
Visit 1 
Visit 2 
Visit 3 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
Visit 9 
  
  
SCREENING 
PRE-OP 
SOUND 
LOCALIZATION 
DAY 0 
DAY 7, 
+/- 7 
DAYS 
WEEK 4, 
+/- 2 
WKS 
3MOS, 
+/- 4 
WKS  
6MOS, 
+/- 4 
WKS 
12MOS, 
+/- 4 
WKS 
Sound 
localization 
SIGN INFORMED 
CONSENT 
N/A 
X 
  
  
  
  
  
  
  
  
 
EXAMINATION 
M 
X 
  
  
  
  
  
  
  
  
 
QUESTIONNAIRES 
N/A 
  
X 
  
  
 
  
X 
X 
X 
 
PRE-OPERATIVE 
VISIT 
M 
  
X 
  
  
  
  
  
  
  
 
AUDIOLOGIC 
TESTING 
M 
        X 
  
  
  
  
  
  
  
  
 
Tinnitus Handicap 
Index 
N/A 
  
X 
  
  
  
 
X 
X 
X 
 
Auditory Brainstem 
Response 
 
 
X 
 
 
 
 
 
X 
 
 
CNC Test 
M 
        X 
 
  
  
 
X 
X 
X 
X 
 
COCHLEAR 
IMPLANTATION 
M 
  
  
  
X 
  
  
  
  
  
 
POST-OP VISIT 
M 
  
  
  
  
X 
X 
  
  
  
 
CI ACTIVATION  
M 
  
  
  
  
  
X 
  
  
  
 
SAFETY MEASURES 
N/A 
  
  
  
  
  
X 
X 
X 
X 
 
*Sound Localization 
Testing 
N/A 
  
  
X 
  
  
  
  
  
X 
X 
*Sound localization testing to be performed at the Binaural Speech and Hearing Laboratory at the University of 
Wisconsin - Madison