Hearing Loss in Older Adults: A Randomized Controlled Trial of Immediate Versus Delayed Cochlear Implantation.
Phase: NA
Conditions: Hearing Loss, Sensorineural, Hearing Loss, Bilateral
Sponsor: Cochlear

Immediate vs delayed CI
on hearing handicap
CLTD5693 
D1168460 
Version: 11 
State: Approved (T+B) 
Approver:
Date : 23 Aug 2019 
Document Control Note: Hardcopies of this document 
are non-controlled unless the relevant Transmittal Advice 
Notification (TAN) information is stamped in the box below. 
Number of pages (include Coversheet): 34

 
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Document Type: Clinical Investigation Plan 
 
 
 
 
 
Clinical Investigation Plan 
 
Randomized controlled trial of immediate versus delayed 
cochlear implantation  
Hearing Loss in Older Adults Study 
 
 
Investigation Number: CLTD5693 
 
Version Number: Version 11.0 
 
Date: August 16, 2019 
 
 
 
 

 
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Document Type: Clinical Investigation Plan 
Sponsor 
Cochlear Limited 
1 University Avenue 
Macquarie University 
NSW 2109 
Phone 
 
 
Local Sponsor Representatives; 
Cochlear Americas 
13059 East Peakview Avenue 
Centennial, CO 80111 USA 
Phone 
 
 
 
A complete list of participating Principal Investigators names, titles, and addresses, and the names 
and addresses of participating institutions (sites) will be maintained by the Sponsor and will be 
distributed as a separate Principal Investigator List. 

 
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Document Type: Clinical Investigation Plan 
1 SPONSOR AND COORDINATING INVESTIGATOR SIGNED 
AGREEMENT 
 
Investigation Title 
Randomized controlled trial of immediate versus delayed cochlear 
implantation. 
Short Study Title 
Hearing Loss in Older Adults Study. 
Investigation Number 
CLTD5693 
 
Signature on behalf of Sponsor 
I agree with the content in this clinical investigation plan, including all appendices. 
Name 
Title 
 
 
Signature 
Date 
(dd-mmm-yyyy) 
 
 
 
Signature of Principal Investigator 
I agree to the content of this clinical investigation plan, including all appendices. 
Name 
Title 
 
 
Site 
 
Signature 
Date 
(dd-mmm-yyyy) 
 
 
 
 

 
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Document Type: Clinical Investigation Plan 
2 TABLE OF CONTENTS 
1 
Sponsor and Coordinating Investigator Signed Agreement ............................................................ 3 
2 
Table of Contents ............................................................................................................................ 4 
3 
Synopsis .......................................................................................................................................... 7 
4 
Investigation Design ........................................................................................................................ 9 
5 
Investigation Procedures ............................................................................................................... 10 
6 
Background and Rationale ............................................................................................................ 12 
6.1 
Hearing interventions to reduce cognitive decline .............................................................. 12 
7 
Justification for the design of the clinical investigation .................................................................. 13 
7.1 
Anticipated Clinical Benefits ................................................................................................ 13 
7.2 
Anticipated Adverse Device Effects .................................................................................... 13 
7.3 
Residual risks related to the use of the investigational device ........................................... 14 
7.4 
Risks associated with participation in the clinical investigation .......................................... 14 
7.5 
Possible interactions with concomitant medical treatments ................................................ 14 
7.6 
Risk mitigations ................................................................................................................... 14 
7.7 
Risk to benefit rationale ....................................................................................................... 14 
8 
Objectives and Hypotheses ........................................................................................................... 14 
8.1 
Primary Objective ................................................................................................................ 14 
8.2 
Secondary Objectives ......................................................................................................... 14 
8.3 
Primary Hypotheses ............................................................................................................ 14 
9 
Design of the clinical investigation ................................................................................................ 15 
9.1 
General ................................................................................................................................ 15 
9.1.1 
Primary Endpoint ................................................................................................... 15 
9.1.2 
Secondary Endpoints ............................................................................................ 15 
9.2 
Assessments ....................................................................................................................... 15 
9.2.1 
Neuropsychological Test Battery .......................................................................... 15 
9.2.2 
Verification of Hearing Aid Fitting .......................................................................... 16 
9.2.3 
Audiologic Measures ............................................................................................. 16 
9.2.4 
Psychosocial Measures ........................................................................................ 17 
9.2.5 
Physical Functioning Measures ............................................................................ 17 
9.2.6 
Quality of Life Measure ......................................................................................... 18 
9.2.7 
Medical and Hearing History ................................................................................. 18 
9.3 
Methods ............................................................................................................................... 18 
9.3.1 
Screening and Informed Consent ......................................................................... 18 
9.3.2 
Randomization ...................................................................................................... 19 
9.3.3 
Hearing Aids and Glasses ..................................................................................... 19 
9.3.4 
Preoperative Visit 1 (POV1) - Screening............................................................... 19 

 
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9.3.5 
Preoperative Visit 2 (POV2) - Baseline ................................................................. 19 
9.3.6 
Surgery – Arm A .................................................................................................... 20 
9.3.7 
Imaging .................................................................................................................. 20 
9.3.8 
Clinical Review Visits (CRV) ................................................................................. 20 
9.3.9 
Follow-up Visit 1 (FUV1) ....................................................................................... 21 
9.3.10 
Surgery – Arm B .................................................................................................... 21 
9.3.11 
Imaging ................................................................................................................. 21 
9.3.12 
CI review – Arm B ................................................................................................. 21 
9.3.13 
Follow-up Visit 2 (FUV2) ....................................................................................... 22 
9.3.14 
Follow-up Visit 3 (FUV3) ....................................................................................... 22 
9.4 
Subjects ............................................................................................................................... 22 
9.4.1 
Inclusion Criteria .................................................................................................... 22 
9.4.2 
Exclusion Criteria .................................................................................................. 23 
9.5 
Statistical Considerations .................................................................................................... 23 
9.6 
Data Management ............................................................................................................... 23 
9.7 
Data Monitoring ................................................................................................................... 24 
9.8 
Amendments to the Protocol ............................................................................................... 24 
9.9 
Deviations from the Protocol ............................................................................................... 24 
9.10 Device accountability .......................................................................................................... 24 
10 Statements of compliance ............................................................................................................. 24 
10.1 Declaration of Helsinki and compliance with standards ...................................................... 24 
10.2 Institutional Review Board Approval ................................................................................... 24 
11 Informed consent process ............................................................................................................. 25 
11.1 Obtaining informed consent ................................................................................................ 25 
11.2 Data Privacy ........................................................................................................................ 25 
12 Safety Reporting ............................................................................................................................ 26 
12.1 Definitions ............................................................................................................................ 26 
12.2 Reporting Process ............................................................................................................... 26 
12.3 Data Monitoring Committee ................................................................................................ 26 
13 Vulnerable population .................................................................................................................... 26 
14 Suspension or premature termination ........................................................................................... 26 
15 Presentation and Publication Policy .............................................................................................. 27 
16 References .................................................................................................................................... 27 
16.1 Internal References ............................................................................................................. 27 
16.2 External References ............................................................................................................ 27 
16.3 Referenced Literature ......................................................................................................... 28 
17 Change History .............................................................................................................................. 30 

 
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18 Definitions ...................................................................................................................................... 32 
 
 

 
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Document Type: Clinical Investigation Plan 
3 SYNOPSIS 
Investigation title 
Randomized controlled trial of immediate versus delayed cochlear 
implantation. 
Short Study Title 
Hearing Loss in Older Adults Study1 
Investigation number 
CLTD5693 
Total expected duration of 
the clinical investigation 
30 months 
Expected duration per 
subject 
15-21 months 
Investigational design 
Prospective, 1:1 randomized controlled trial of immediate versus 
delayed cochlear implantation (CI) on hearing handicap, 
communicative function, loneliness, mental wellbeing, and cognitive 
functioning. Subjects are randomized 1:1 to an immediate cochlear 
implant intervention arm versus a hearing aid control intervention.  
Number of subjects 
Up to 60 subjects in a 1:1 allocation  
Inclusion criteria 
1. Aged 65 to 85 years, inclusive 
2. Community-dwelling 
3. Proficient in English 
4. Oral communicator 
5. PTA (500, 1000 & 2000 Hz) ≥ 70 dB HL hearing loss duration 
≥1 and no more than 30 years. 
6. Active hearing aid users: daily use of hearing aids.  
7. Hearing Handicap Inventory for the Elderly - Screening                
(HHIE-S): Score ≥ 24 indicating a significant hearing handicap.  
8. Hearing Impaired Montreal Cognitive Assessment (HI-MoCA): 
Score ≥ 20 indicating mild cognitive impairment to normal 
cognitive function. 
9. Cochlear implant candidacy: Participants must have 
postlinguistic onset sensorineural hearing loss and meet 
applicable FDA and/or Medicare candidacy criteria for cochlear 
implantation.  
10. Willingness to consent for the study, to be randomized to either 
the immediate or delayed cochlear implantation arm, to utilize 
bimodal hearing for the duration of the trial (if clinically 
appropriate) and follow the study protocol for the duration of 
the trial. 
Exclusion criteria 
1. Prelingual or perilingual severe-to-profound hearing loss.  
2. Previous cochlear implantation in either ear. 
3. Hearing loss of neural or central origin. 
4. Permanent conductive hearing impairment (e.g. otosclerosis). 
5. Medical, audiological or psychological conditions, as judged by 
the investigator that might contraindicate participation in the 
clinical investigation. 
6. Self-reported disability in ≥ 2 activities of daily living. 
7. Unwilling to wear a device or comply with the surgical and 
rehabilitation requirements of the study. 
8. Vision impairment: worse than 20/40 (corrected) on a Near 
Vision Card. 
                                                            
1 As registered on ClinicalTrials.gov 

 
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Document Type: Clinical Investigation Plan 
Primary objective 
To determine the effect of treating hearing loss with cochlear 
implantation (CI) versus continued use of hearing aids (HA) on hearing 
satisfaction using the Speech, Spatial and Qualities of Hearing 
(SSQ12) in older adults. 
Primary endpoint 
Assessment of the impact of cochlear implantation versus continued 
hearing aid use on hearing satisfaction as measured using the Speech, 
Spatial and Qualities of Hearing (SSQ12) at Follow-up Visit 1 (FUV1). 
Secondary objective 
To assess cognition in older adults with hearing loss with a Cogstate® 
battery of neuropsychological tests.      
Secondary endpoint 
Assessment of the impact of cochlear implantation versus continued 
hearing aid use on cognition with a Cogstate® battery of 
neuropsychological tests at Follow-up Visit 1 (FUV1). 
Ancillary analyses 
Ancillary analyses include: 
 
Investigating treatment effect on neuropsychological measures 
using the Hearing Impaired Montreal Cognitive Assessment 
(HI-MoCA) at Follow-Up Visit 1 (FUV1). 
 
Investigate the treatment effect of immediate cochlear 
implantation vs continued use of HAs on psychosocial 
measures such as loneliness and depression using the UCLA 
Loneliness Scale and the Geriatric Depression Scale (GDS) at 
Follow-up Visit 1 (FUV1). 
 
Investigate the treatment effect of immediate cochlear 
implantation vs continued use of HAs on physical functioning 
measures such as daily activity and lifestyle using the Lifestyle 
Activity Questionnaire (LAQ) at Follow-up Visit 1 (FUV1).  
 
To determine the effect of treating hearing loss with CI versus 
continued use of HAs on quality of life in each arm (immediate 
CI vs continued HA use) using the Health Utilities Index Mark 
III (HUI-III) at Follow-up Visit 1 (FUV1).  
 
To quantify pre- to post-implantation outcomes associated with 
cochlear implantation.  
o 
Self-reported hearing ability using the Hearing 
Handicap Inventory for the Elderly – Screening (HHIE-
S).   
o 
Outcomes for both the treated ear and everyday 
listening condition (bimodal): speech perception in 
quiet using CNC Words presented 60 dBA and speech 
perception in speech-weighted noise using AzBio 
sentences presented at 65 dBA using a +10 dB Signal 
to Noise Ratio (SNR).  
 
Investigate maintenance of treatment effect on 
neuropsychological, psychosocial, physical, quality of life and 
audiometric measures obtained at: 
o 
FUV2 compared to FUV1 (Arm A). 
o 
FUV3 compared to FUV2 (Arm B). 
 

 
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Document Type: Clinical Investigation Plan 
4 INVESTIGATION DESIGN 
          
4       
to      
6       
wks  
        
6       
mth  
6 
mth  
6 
mth  

 
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5 INVESTIGATION PROCEDURES  
Procedure 
Screening 
POV1        
Arm A&B 
Baseline 
POV2       
Arm A&B 
Surgery 
Arm A        
Clinical 
Review 
Visits        
Arm A&B     
FUV1         
Arm A&B     
Surgery 
Arm B        
FUV2         
Arm A&B     
FUV3         
Arm B        
Timeline 
 
4-6 weeks 
from POV1 
(+/- 2 weeks) 
1 week from 
POV2        
(+/- 1 week) 
1-5 months 
from POV2    
(+/- 2 weeks) 
6 months 
from POV2    
(+/- 2 weeks) 
1 week from 
FUV1         
(+/- 1 week) 
12 months 
from POV2    
(+/- 4 weeks) 
18 months 
from POV2    
(+/- 4 weeks) 
Consent 
X 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Concomitant Medications 
 
X 
X 
X 
X 
X 
X 
X 
Adverse Events 
 
X 
X 
X 
X 
X 
X 
X 
Medical History 
 
X 
 
 
 
 
 
 
Hearing History 
X 
 
 
 
 
 
 
 
Randomization 
X 
 
 
 
 
 
 
 
HI-MoCA 
X 
 
 
 
X 
 
 
 
Near Vision Screening 
X 
 
 
 
 
 
 
 
Activities of daily living 
X 
 
 
 
X 
 
X 
X 
HHIE-S 
X 
 
 
 
X 
 
X 
X 
Cogstate computerized test battery 
X 
X 
 
 
X 
 
X 
X 
Imaging 
 
 
X-ray         
(Arm A) 
CT scan2  
(Arm A) 
 
X-ray         
(Arm B) 
CT scan3 
(Arm B) 
 
                                                            
2 CT scan will occur post-surgery and prior to FUV1 (Arm A) 
3 CT scan will occur post-surgery and prior to FUV2 (Arm B) 

 
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Document Type: Clinical Investigation Plan 
Procedure 
Screening 
POV1        
Arm A&B 
Baseline 
POV2        
Arm A&B 
Surgery 
Arm A        
Clinical 
Review    
Visits        
Arm A&B     
FUV1         
Arm A&B     
Surgery 
Arm B        
FUV2         
Arm A&B     
FUV3         
Arm B        
Timeline 
 
4-6 weeks 
from POV1 
(+/- 2 weeks) 
1 week from 
POV2        
(+/- 1 week) 
1-5 months 
from POV2    
(+/- 2 weeks) 
6 months 
from POV2    
(+/- 2 weeks) 
1 week from 
FUV1         
(+/- 1 week) 
12 months 
from POV2    
(+/- 4 weeks) 
18 months 
from POV2    
(+/- 4 weeks) 
SSQ12 
 
X 
 
 
X 
 
X 
X 
UCLA Loneliness Scale 
 
X 
 
 
X 
 
X 
X 
GDS-short form 
 
X 
 
 
X 
 
X 
X 
LAQ 
 
X 
 
 
X 
 
X 
X 
HUI-III 
 
X 
 
 
X 
 
X 
X 
Rehabilitation 
 
 
 
X (4-6 visits) 
 
 
 
 
Unaided air conduction testing 
X 
 
 
 
X 
 
X 
X 
Aided soundfield testing 
 
X 
 
X (3 mths) 
 
 
 
 
Tympanometry 
X 
 
 
 
X 
 
X 
X 
Aided AzBio Sentences in Noise 
Ear to be implanted/implant ear 
Everyday Listening 
 
 
X 
X 
 
 
 
X 
X 
 
 
X 
X 
 
X 
X 
Aided CNC Words in Quiet 
Ear to be implanted/implant ear 
Everyday Listening 
 
 
X 
X 
 
X (3 mths) 
 
X 
X 
 
 
X 
X 
 
X 
X 
Datalogs 
 
X 
 
X 
X 
 
X 
X 
 

 
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6 BACKGROUND AND RATIONALE 
Prospective studies have demonstrated reduced hearing handicap following cochlear implantation in 
adults (1, 2). However this has not been assessed in a randomized clinical trial. Epidemiologic data 
strongly suggest that age-related peripheral hearing loss is independently associated with accelerated 
rates of cognitive decline and incident dementia (2, 3). A conceptual model (Figure 1) developed by 
Lin and Albert (3) depicts the causal mechanisms that may mediate the effects of hearing impairment 
on impaired cognitive functioning and dementia. Common factors that could underlie a simple 
correlation between hearing and cognition include age, shared pathologic etiologies (e.g., diabetes, 
hypertension, neurodegenerative processes), and demographic factors (e.g., education). In contrast, 
mechanistic pathways through which hearing loss could contribute to poorer cognitive functioning 
include effects on cognitive load, brain structure/function, and decreased social engagement. The 
effects of poor audition and distorted peripheral encoding of sound on cognitive load could reduce 
capacity for other functions, such as cognition. Changes in brain structure could lead to downstream 
changes in brain function which may affect cognitive processing (4-10). Alternatively reduced social 
engagement could be a mediating factor. 
 
Figure 1. Conceptual model of the association of hearing impairment with cognitive 
functioning and dementia. 
6.1 Hearing interventions to reduce cognitive decline  
Whether existing interventions for hearing loss can mitigate declines in cognitive function is unknown. 
Previous studies provide proof-of-principle that interventions that provide enhanced auditory stimuli 
can engage and modify the hypothesized mechanistic pathways linking hearing and cognition through 
reducing cognitive load (11-14), altering functional pathways and brain structure (4-10), and improving 
social engagement. A planned trial, the Aging, Cognition, and Hearing Evaluation Trial (ACHIEVE), 
will investigate the impact of best practice hearing health care, including the provision of hearing aids, 
on cognitive functioning in older adults with mild-to-moderate hearing loss.  
The trial described in this protocol will be the first randomized controlled trial to investigate the impact 
of cochlear implantation versus continued use of hearing aids on cognitive function in individuals with 
severe-to-profound hearing loss. To date, only one published study has examined the effects of 
cochlear implantation on cognition in older adults (15). This longitudinal, multi-center study examined 
94 adults aged 65-85 years who met candidacy requirements for a cochlear implant. 
Neuropsychological tests, speech perception tests and quality of life and depression questionnaires 
were administered before cochlear implantation (baseline) and at 6 and 12 months post cochlear 
implant activation.  

 
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To avoid potential confounding effects of audibility and diminished speech perception understanding, 
all instructions for the neuropsychological tests were provided in written form in the Mosnier et al. 
study. The number of individuals with scores classified as abnormal decreased after implantation: At 
baseline, 25% of subjects had normal scores on six cognitive tasks, 31% had one abnormal score, 
24% had two abnormal scores, and 20% had three abnormal scores. At 12 months, 40% had normal 
scores on six cognitive tasks, 33% had one abnormal score, 22% had two abnormal scores and only 
5% had three abnormal scores. While informative, the Mosnier et al. study did not have a control arm, 
so it is possible that some of the improvement could be attributed to learning effects. The CI-Cognition 
trial described in this protocol incorporates a watchful waiting control arm and overcomes this 
limitation.  
An additional study, the Studying Multiple Outcomes after Aural Rehabilitative Treatment (SMART) 
study prospectively assessed cognitive functioning in 145 adults aged 50 years or older before 
receiving hearing aids or cochlear implants and at 6 and 12 months after treatment (16). Data from Li 
et al showed improved cognitive performance at 6 and 12 months, albeit with a smaller effect size 
than that found in the study previously reviewed by Mosnier et al (15). Li et al. also reported that CI 
subjects had significantly greater loneliness, social isolation and poorer hearing and communicative 
function compared to HA subjects. 
7 JUSTIFICATION FOR THE DESIGN OF THE CLINICAL 
INVESTIGATION 
We propose a randomized controlled trial design whereby up to sixty (60) participants with severe-to-
profound hearing loss are randomized 1:1 to an immediate cochlear implant (CI) intervention (Arm A) 
versus a hearing aid (HA) control intervention (Arm B). The immediate CI treatment arm will be 
implanted with either the Cochlear Nucleus® Profile™ Slim Modiolar (532) cochlear implant or the 
Cochlear Nucleus® Profile™ Plus CI632 cochlear implant with Slim Modiolar electrode. The HA 
control intervention provides a comparison arm representing standard clinical care for conventional 
amplification (HAs).  Randomization seeks balance between the two arms. The control arm will also 
receive the CI intervention (Nucleus CI532 or CI632 implant) after a watchful waiting delay period of 6 
months post baseline. Both arms will receive the neuropsychological battery twice before the 
intervention (once at screening and again at baseline) to minimize the impact of learning effects on 
analyses of post-intervention cognitive change. 
7.1 Anticipated Clinical Benefits 
The information obtained from participation in the study will potentially be useful to the participating 
subjects, the Sponsor as well as future candidates and health care providers in better understanding 
the potential benefits of cochlear implantation on hearing handicap, communicative function, 
loneliness, mental wellbeing, and cognitive functioning.    
7.2 Anticipated Adverse Device Effects  
Known anticipated adverse device effects are currently detailed in the Cochlear Nucleus® Profile™ 
Slim Modiolar (532) cochlear implant or the Cochlear Nucleus® Profile™ Plus CI632 cochlear implant 
with Slim Modiolar electrode Physician’s Guide (17). There are no additional anticipated adverse 
device effects related to participation in this clinical study.  The surgeon will conduct the surgical 
procedure as per standard clinical practice and individuals will be exposed only to the normal risks 
associated with routine cochlear implantation.   

 
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7.3 Residual risks related to the use of the investigational device 
The study does not involve use of an investigational device.  
7.4 Risks associated with participation in the clinical investigation 
Participation in this study does not include any additional risks to those known for individuals 
undergoing neurocognitive evaluations, cochlear implantation or hearing aid use clinically. The risks 
associated with each procedure will be outlined in the Informed Consent (IC) document. All risks 
should be thoroughly reviewed with the potential subject prior to participation in the study.        
7.5 Possible interactions with concomitant medical treatments 
There is potential that concomitant medical treatments may influence the outcomes of this study.  All 
concomitant medical treatments will be collected as part of this study.  
7.6 Risk mitigations 
The investigators or qualified delegates will be required to review the terms of the Informed Consent 
with each potential subject. Information such as the subject’s ongoing audiologic and medical history 
will be captured for the duration of the trial.  
7.7 Risk to benefit rationale 
Since the participants recruited for this study are already considering cochlear implantation as a 
hearing health option, the risk benefit rationale is such that participation in this study may provide 
subjects with additional useful health information pertaining to their cognitive status that they would 
not otherwise have.  
8 OBJECTIVES AND HYPOTHESES 
8.1 Primary Objective 
To determine the effect of treating hearing loss with cochlear implantation (CI) versus continued use 
of hearing aids (HA) on hearing satisfaction using the Speech, Spatial and Qualities of Hearing 
(SSQ12) in older adults. 
8.2 Secondary Objectives 
To assess cognition in older adults with hearing loss with a Cogstate® battery of neuropsychological 
tests.      
8.3 Primary Hypotheses 
Cochlear implantation is associated with greater reduction on hearing satisfaction as measured using 
the Speech, Spatial and Qualities of Hearing (SSQ12) compared to continued hearing aid use at 
Follow-up Visit 1 (FUV1). 

 
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9 DESIGN OF THE CLINICAL INVESTIGATION 
9.1 General 
9.1.1 Primary Endpoint 
Assessment of the impact of cochlear implantation versus continued hearing aid use on hearing 
satisfaction as measured using the Speech, Spatial and Qualities of Hearing (SSQ12) at Follow-up 
Visit 1 (FUV1). 
9.1.2 Secondary Endpoints 
Assessment of the impact of cochlear implantation versus continued hearing aid use on cognition with 
a Cogstate® battery of neuropsychological tests on at Follow-up Visit 1 (FUV1). 
9.2 Assessments 
9.2.1 Neuropsychological Test Battery 
9.2.1.1 Hearing Impaired Montreal Cognitive Assessment (HI-MoCA) 
The Montreal Cognitive Assessment (MoCA) is an interviewer administered screening tool used to 
detect mild cognitive impairment (18). It has been demonstrated to have high sensitivity and 
specificity for detecting mild cognitive impairment (18-20). The MoCA has been used in clinical 
evaluations to assess cognitive function and treatment effect in older patients undergoing cochlear 
implantation (21, 22). The MoCA has been converted into a timed PowerPoint (Microsoft Corp., 
Redmond, WA) presentation, and verbal instructions converted into visual instructions to assist in the 
assessment of severely hearing impaired adults - the Hearing Impaired Montreal Cognitive 
Assessment (HI-MoCA) (23). The HI-MoCA has been validated as a screening for cognitive 
impairment in the severely hearing impaired older populations. No conversion factor from HI-MoCA to 
MoCA scores were required in the cohort of cognitively intact subjects. The HI-MoCA will be used in 
the clinical investigation to assess cognitive function of older adults undergoing cochlear implantation.  
9.2.1.2 Cogstate computerised test battery 
The Cogstate® computerised test battery is a self-administered, iPad-based neuropsychological 
measure of processing speed, attention, visual learning, working memory and executive function. The 
Cogstate computerised test battery for the current clinical investigation consists of the Cogstate Brief 
Battery™ and the Groton Maze Learning Test. 
The Cogstate Brief Battery (CBB) provides a measure of four core cognitive domains: processing 
speed, attention, visual learning and working memory. The CBB consists of the Detection Test, 
Identification Test, One Card Learning Test and One Back Test. The Detection test measures 
processing speed using a simple reaction time paradigm. The Identification test measures attention 
using a choice reaction time paradigm. The One Card Learning test measures visual memory using a 
pattern separation paradigm. The One Back test measures working memory using an n-back 
paradigm. For all tests in the CBB, a playing card is presented on the screen and the participant is 
encouraged to work as quickly as they can and be as accurate as possible. 
The Cogstate Groton Maze Learning Test measures executive function using a maze learning 
paradigm. A 28-step pathway is hidden among these tiles. The participant must move one step at a 
time from the start toward the end by touching a tile next to their current location. If the correct move 
is made a green checkmark appears and if the move is incorrect a red cross is revealed. Once 
completed, they are returned to the start location to repeat the test and must try to remember the 

 
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pathway they have just completed. The outcome measure is the total number of errors made in 
attempting to learn the same hidden pathway on five consecutive trials during a single session. 
9.2.2 Verification of Hearing Aid Fitting 
Real ear insertion gain measurements (REIG) will be used to verify hearing aid fitting. The frequency 
response of the hearing aid should not deviate from the National Acoustic Laboratories’ non-linear 
procedure (NAL-NL2) target by greater than +/- 5 dB for a modulated speech stimulus (International 
Speech Test Signal (ISTS)), except in circumstances where adjustments have been made for patient 
comfort/preference or feedback management. 
9.2.3 Audiologic Measures 
9.2.3.1 Audiometric Thresholds and Tympanometry 
9.2.3.1.1 
Unaided audiometric thresholds 
Unaided audiometric thresholds will be obtained for each ear, with insert earphones, using the 
standard audiometric technique for pure-tone air-conduction testing. All preimplantation testing will be 
completed using an audiometer calibrated to American National Standards Institute (ANSI) standards 
with maximum output for frequencies of 0.5 to 4 kHz of no less than 110 dB HL.  Pure tone threshold 
exploration will be completed using the adaptive Hughson & Westlake procedure (24). 
Testing in each ear will include the following: 
Air conduction thresholds:  250, 500, 1000, 2000, 4000, 6000, 8000 Hz with appropriate masking as 
required; 
Tympanometry in each ear. 
An audiogram completed up to 90 days prior to POV1 will be considered for determination of eligibility 
and data collection as part of POV1. 
9.2.3.1.2 
Aided audiometric thresholds 
Aided audiometric thresholds will be obtained for the everyday listening condition (aided bilaterally or 
bimodally post-CI) during a clinical review visit three months post POV2 (+/- 2 weeks), in a calibrated 
sound field, using the standard audiometric technique for sound field testing. All post-implantation 
testing will be completed using warble tones in a sound field calibrated to American National 
Standards Institute (ANSI) standards with maximum output for frequencies of 0.5 to 4 kHz of no less 
than 80 dB SPL.   
Testing in the everyday listening condition (both ears) will include the following: 
Aided sound field thresholds:  500, 1000, 2000, 4000 Hz  
9.2.3.2 Speech perception in quiet 
The CNC Word Test (25) is a validated test used clinically and in research to assess the performance 
of adults with hearing aids or cochlear implants on open-set word recognition.  The test consists of 10 
recorded lists of 50 monosyllabic words in CD format.  For this study, two lists will be administered in 
quiet at a level equal to 60 dBA in the sound field and scored as total number of words and phonemes 
correct, which will be expressed as a percentage correct for this study.  Subjects will be tested using a 
configuration of speech at 0º azimuth in quiet (S0). 
9.2.3.3 Speech perception in noise 
The AzBio Sentence Test (26) is a validated test used clinically and in research to assess the open-
set sentence recognition in speech-weighted noise of adults with hearing aids or cochlear implants. It 

 
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consists of 15 lists of 20 sentences each.  AzBio sentences are spoken by different talkers in a 
conversational style with limited contextual cues that the listener can use to predict or ‘fill in’ 
unintelligible words. The sentences will be presented at a fixed level of 65 dBA at a fixed +10 dB 
signal-to-noise ratio (SNR).  Each list includes 5 sentences from 4 different male and female 
speakers.  The average level of intelligibility of each list is 85% +/- 1%.  Each word in the sentence 
counts towards the overall score.  Subjects will be tested using a configuration of speech and noise at 
0º azimuth (S0N0). 
9.2.3.4 Hearing Handicap Inventory for the Elderly 
The Hearing Handicap Inventory for the Elderly - screening (27) is an interviewer-administered 
questionnaire that measures the perception of the impact of hearing loss. This questionnaire 
assesses the social and emotional components of perceived hearing impairment such as 
embarrassment, and limits on personal and social life. 
9.2.3.5 Speech, Spatial, and Qualities of Hearing Scale (SSQ12) 
The SSQ is a validated 12-question self-assessment metric commonly used in hearing research, 
designed to measure auditory disability across a wide variety of everyday world domains. The SSQ-
12 (28) has twelve questions and is derived from the original 49 item SSQ (29). In addition to a 
reduced administration time, the SSQ-12 has been shown to have similar results to the original 49 
item scale (28). 
9.2.4 Psychosocial Measures 
9.2.4.1 UCLA Loneliness Scale 
The UCLA Loneliness Scale version 3 (30) is an interviewer-administered questionnaire. The 20-item 
scale designed to measure one’s subjective feelings of loneliness as well as feelings of social 
isolation. Subjects rate each item on a scale from 1 (Never) to 4 (Often). This measure is a revised 
version of both the original UCLA Loneliness Scale and the Revised UCLA Loneliness Scale. The first 
revision was done to make 10 of the 20 original items reverse scored. The second revision was done 
to simplify the scale so less educated populations could comprehend it. 
9.2.4.2 Geriatric Depression Scale (GDS) 
The GDS Short Form is an interviewer-administered 15-item questionnaire in which subjects are 
asked to respond by answering yes or no in reference to how they felt over the past week. Questions 
from the Long Form GDS which had the highest correlation with depressive symptoms in validation 
studies were selected for the short version (31). Of the 15 items, 10 indicated the presence of 
depression when answered positively, while the rest (question numbers 1, 5, 7, 11, 13) indicated 
depression when answered negatively. Scores of 0-4 are considered normal, depending on age, 
education, and complaints; 5-8 indicate mild depression; 9-11 indicate moderate depression; and 12-
15 indicate severe depression. The GDS Short form has been tested and used with the older 
population receiving cochlear implants (15, 32-34). 
9.2.5 Physical Functioning Measures 
9.2.5.1 Lifestyle Activity Questionnaire 
The Lifestyle Activity Questionnaire (LAQ) (35) is a self-administered questionnaire which assesses 
the frequency of self-reported activities over the past year. The questionnaire includes intellectual 
(e.g. discussing local or national issues, reading), social (e.g. caretaking, clubs), physical (e.g. 
shopping, gardening), creative (e.g. drawing or painting), and passive (e.g. listening to music, 
watching TV) activities. The LAQ has been shown to be sensitive to assessing relationships between 

 
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cognitively and socially stimulating activities and cognitive aging in both observational studies (35) 
and in trials (36, 37). 
9.2.5.2 Near Vision Screening 
The Near Vision Screening chart is an eye chart to measure visual acuity in the near field (within 16”). 
The first line consists of two very large letters and a number. Subsequent rows have increasing 
numbers of letters and numbers that decrease in size. A person (with corrected vision) taking the test 
with holds the card at a distance of 16” under standard room illumination, and reads aloud the letters 
and numbers of each row, beginning at the top. The smallest row that can be read accurately 
indicates the visual acuity.  
9.2.6 Quality of Life Measure 
9.2.6.1 Health-Utilities Index 3 
The Health Utilities Index Mark 3 (HUI3) (38, 39) is a widely used self-administered generic instrument 
measuring health-related quality of life. This instrument covers eight domains (vision, hearing, 
speech, ambulation, dexterity, emotion, cognition, and pain), each having five or six levels of difficulty. 
There are 970,000 possible combinations of levels, of which a subset has been evaluated by 
members of the Canadian general public (39). The HUI3 focuses on physical and emotional wellbeing 
and includes questions specific to hearing and the ability to be understood whilst speaking. As a result 
it is sensitive to improvements in quality of life due to better hearing (40-42). This questionnaire 
follows the principles of economic evaluation in that a utility score is derived where 1 indicates perfect 
health and zero corresponds to being dead, therefore it can be used in cost-effectiveness analyses.  
9.2.7 Medical and Hearing History  
9.2.7.1 Medical History via the Adult Comorbity Evaluation-27 (ACE-27) 
Medical history will be collected at Pre-operative Visit 2. The ACE-27 is an index which includes 27 
conditions or comorbid ailments across various bodily organ systems. Each of the comorbid ailments 
are graded on severity (none, mild, moderate, or severe) with the end result of an overall index score. 
Early research in patients with hearing loss indicated untreated hearing loss resulted in a higher 
incidence of morbidity compared to individuals with no hearing loss. This index allows for consistent 
collection of medical history data across subjects and clinical sites. It will be used as a minimum 
medical history reporting standard for this clinical investigation. Additional medical history may be 
added at the Investigator’s discretion for relevant study conduct.   
9.2.7.2 Hearing History 
Hearing history will be collected at Pre-operative Visit 1 as outlined on the CRF. Information collected 
will include duration, type and etiology of hearing loss in addition to hearing aid details (e.g., 
consistent vs intermittent hearing aid use).   
9.3 Methods 
9.3.1 Screening and Informed Consent 
Subjects who have been deemed appropriate candidates for cochlear implantation according to 
standard clinical practice will be considered potential research subjects for this study. Informed 
consent must occur prior to study related activities with the exception of an audiogram performed 
within 90 days of POV1.  Individuals will be appropriately counseled on the risks and benefits of study 
participation prior to participating in any study related activity.  If needed, the potential participant may 
take the informed consent form home with them for review prior to completion. If the participant 

 
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agrees to participate, a copy of the executed informed consent will be provided to the participant. To 
maintain confidentiality, subject names will not be recorded on any study document other than the 
informed consent form. All individuals who provide informed consent are considered enrolled into the 
study and will be assigned a unique identifier. A unique alphanumeric code will identify each subject 
throughout the course of the study. For example, US01-HOA-xxxx where: 
 
US = United States 
 
01 = a sequential numeral corresponding to the order in which a subject is enrolled into the 
study for a given study site.  In this case this would correspond to the first subject recruited 
into the study for a particular site 
 
HOA = an abbreviation for the study, Hearing Loss in Older Adults 
 
xxxx = a unique numeric study site identification 
9.3.2 Randomization 
The design of the clinical investigation is a prospective, 1:1 randomized clinical trial.  The intervention 
arm to which a participant is assigned is determined by an allocation schedule developed by 
 
  
To ensure balance between the treatment arms, participants will be randomized as described in the 
Statistical Analysis Plan (D1309522).  Block size will not be revealed to field center staff as this would 
allow them to determine the final treatment assignment of a block before ascertaining eligibility and 
obtaining consent. The randomization will be maintained by the sponsor within a data management 
system. Randomization will be performed at POV1. 
9.3.3 Hearing Aids and Glasses 
For the purposes of this study, subjects have the option to use their own hearing aids if they are 
appropriately fit.  If a subject does not have appropriately fit hearing aids they will be provided prior to 
any study related assessments.  Impressions will be taken and earmolds provided if needed.  The 
decision to replace hearing aids will be based on the clinical judgement of the investigator with 
verification of such recorded on a study Case Report Form.   
Subjects are required to have a minimum corrected near vision acuity of 20/40 as measured on a 
Near Vision Screening test. If a subject does not meet this criteria and does not have appropriately fit 
glasses, they will be withdrawn from the study. 
9.3.4 Preoperative Visit 1 (POV1) - Screening 
Participants are consented into the study.  Eligibility for the study will be confirmed. During this 
preoperative screening visit, each participant will be randomized in a 1:1 ratio to either the immediate 
CI (Arm A) or hearing aid (delayed CI Arm B). During POV1, both Arm A and Arm B subjects will 
complete the neuropsychological assessments as described in Section 9.2.1 with appropriately fitted 
hearing aids and glasses (if required).  
9.3.5 Preoperative Visit 2 (POV2) - Baseline 
Preoperative visit 2 (POV2) baseline will occur 4-6 weeks post POV1 (+/- 2 weeks) to enable 
scheduling of surgery for Arm A subjects. Both Arm A and Arm B subjects will complete POV2 with 
appropriately fit hearing aids and glasses (if required).  The full neuropsychological battery in addition 
to the audiologic, psychosocial, physical, and quality of life metrics will be completed as described in 
Section 9.2. Speech recognition will be assessed in the everyday listening condition (aided bilaterally) 
and the ear to be implanted listening conditions with the contralateral ear plugged. Datalogs will be 
retrieved for the hearing aid. 

 
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Medical history will be completed minimally via the ACE 27 index. The Investigator or appropriately 
delegated staff may add additional otologic history (hearing history) which they deem relevant to the 
study.  
9.3.6  Surgery – Arm A 
Arm A subjects will be implanted with the Cochlear Nucleus® Profile™ Slim Modiolar (532) cochlear 
implant or the Cochlear Nucleus CI632 cochlear implant 1 week (+/- 1 week) post POV2. 
An intraoperative X-ray will be obtained (preferably a lateral or modified Stenver’s view) following the 
placement of the electrode and prior to closing.  
9.3.7 Imaging 
Following surgery, subjects will undergo a Computed Tomography (CT) scan according to the 
specifications provided by the study sponsor. Retrospective analysis of the CT scan will be done via 
reconstruction to determine electrode position and distance to the modiolus by an independent 
centralized imaging review center and a de-identified report will be sent to the sponsor in line with 
HIPAA Standards.  
9.3.8 Clinical Review Visits (CRV) 
9.3.8.1 CI review – Arm A 
CI activation will occur in the standard clinical manner at each field site at approximately two weeks 
post-surgery (+/- 3 weeks). Four to six clinical review visits will be scheduled at each field site 
between activation and FUV1, six (6) months from POV2.  These visits can contain device 
adjustments as well as counselling on hearing and listening strategies, and discussion of hearing 
assistive technology. 
We propose the following topics are discussed during the six months of cochlear implant use: 
 
Hearing assistive technology 
 
Communication strategies 
 
Listening in noise 
 
Understanding hearing loss 
Needs for various hearing assistive technologies (HATs) will be assessed and, if the audiologist 
deems that it is appropriate, recommendations will be made. 
Following each CI mapping appointment an anonymized .cdx file labelled with the Subject ID will be 
provided to the study sponsor in order to evaluate program settings and usage data. 
9.3.8.1.1 
Audibility Review – three months post POV2. 
As part of a clinical review visit, at three (3) months (+/- 4 weeks) post POV2, audibility will be 
assessed: 
 
Implanted ear only: Aided speech recognition with CNC words at 60 dBA (2 lists) 
 
Everyday listening condition (bimodal): Sound field thresholds at 500, 1000, 2000, 4000 Hz 
9.3.8.2 Hearing aid review – Arm B 
Over the course of the hearing aid intervention, the subjects will be followed for hearing aid checks 
including verification of fitting, be counselled on hearing and listening strategies, and discuss hearing 

 
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assistive technology. Four to six clinical review visits will be scheduled at each field site between 
FUV1 and six (6) months from POV2. 
We propose the following topics are discussed during the six months of the hearing aid intervention: 
 
Hearing assistive technology 
 
Communication strategies 
 
Listening in noise 
 
Understanding hearing loss 
Needs for various hearing assistive technologies (HATs) will be assessed and, if the audiologist 
deems that it is appropriate, recommendations will be made.  
Following each hearing aid fitting and follow up session an anonymized program settings file will be 
provided to the study sponsor in order to evaluate program settings and usage data.   
9.3.8.2.1 
Audibility Review – three months post POV2. 
As part of the clinical review visits, at three (3) months (+/- 4 weeks) post POV2, audibility will be 
assessed. 
 
Implanted ear only: Aided speech recognition with CNC words at 60 dBA (2 lists) 
 
Everyday listening condition (bilateral hearing aids): Sound field thresholds at 500, 1000, 
2000, 4000 Hz 
9.3.9 Follow-up Visit 1 (FUV1) 
Both Arm A and Arm B subjects will complete FUV1 in the aided condition six (6) months post POV2 
(+/- 2 weeks).  The full neuropsychological battery in addition to the audiologic, psychosocial, 
physical, and quality of life metrics will be completed as described in Section 9.2. Speech recognition 
will be assessed in the everyday listening condition (aided bilaterally) and implanted ear (Arm A) or 
ear to be implanted (Arm B) only listening conditions. Datalogs will be retrieved for the sound 
processor (Arm A) and hearing aid (Arm B). 
9.3.10 
Surgery – Arm B 
Arm B subjects will be implanted with the Cochlear Nucleus® Profile™ Slim Modiolar (532) cochlear 
implant or the Cochlear Nucleus CI632 cochlear implant 1 week (+/- 1 week) post FUV1.  
An intraoperative X-ray will be obtained (preferably a lateral or modified Stenver’s view) following the 
placement of the electrode and prior to closing.  
9.3.11 
Imaging 
Following surgery, subjects will undergo a Computed Tomography (CT) scan according to the 
specifications provided by the study sponsor. Postoperative analysis of the CT scan will be done via 
reconstruction to determine electrode position and distance to the modiolus. Retrospective analysis of 
the CT scan will be done via reconstruction to determine electrode position and distance to the 
modiolus by an independent centralized imaging review center and a de-identified report will be sent 
to the sponsor in line with HIPAA Standards.  
9.3.12 
CI review – Arm B 
CI activation will occur in the standard clinical manner for each field site at approximately two weeks 
post-surgery (+/- 3 weeks). Four to six clinical review visits will be scheduled at each field site 
between activation and FUV2, twelve (12) months from POV2.  These visits can contain device 

 
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adjustments as well as counselling on hearing and listening strategies, and discussion of hearing 
assistive technology. 
We propose the following topics are discussed during the six months of cochlear implant use: 
 
Hearing assistive technology 
 
Communication strategies 
 
Listening in noise 
 
Understanding hearing loss 
Needs for various hearing assistive technologies (HATs) will be assessed and, if the audiologist 
deems that it is appropriate, recommendations will be made. 
Following each CI mapping appointment an anonymized .cdx file labelled with the Subject ID will be 
provided to the study sponsor in order to evaluate program settings and usage data. 
9.3.13 
Follow-up Visit 2 (FUV2) 
Both Arm A and Arm B subjects will complete FUV2 in the aided condition twelve (12) months post 
POV2 (+/- 4 weeks). The full neuropsychological battery in addition to the audiologic, psychosocial, 
physical, and quality of life metrics will be completed as described in Section 9.2. Speech recognition 
will be assessed in the everyday listening condition (aided bilaterally) and implanted ear only listening 
condition. Datalogs will be retrieved for the sound processor. 
9.3.14 
Follow-up Visit 3 (FUV3) 
Arm B subjects will complete FUV3 in the aided condition eighteen (18) months post POV2 (+/- 4 
weeks). The full neuropsychological battery in addition to the audiologic, psychosocial, physical, and 
quality of life metrics will be completed as described in Section 9.2. Speech recognition will be 
assessed in the everyday listening condition (aided bilaterally) and implanted ear only listening 
condition. Datalogs will be retrieved for the sound processor. 
9.4 Subjects  
9.4.1 Inclusion Criteria 
1. Aged 65 to 85 years, inclusive 
2. Community-dwelling 
3. Proficient in English 
4. Oral communicator 
5. PTA (500, 1000 & 2000 Hz) ≥ 70 dB HL hearing loss duration ≥1 year and no more than 30 
years. 
6. Active hearing aid users: daily use of hearing aids.  
7. Hearing Handicap Inventory for the Elderly - Screening (HHIE-S): Score ≥ 24 indicating a 
significant hearing handicap  
8. Hearing Impaired Montreal Cognitive Assessment (HI-MoCA): Score ≥ 20 indicating mild 
cognitive decline to normal cognitive function. 
9. Cochlear implant candidacy: Participants must have postlinguistic onset sensorineural 
hearing loss and meet applicable FDA and/or Medicare candidacy criteria for cochlear 
implantation 

 
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10. Willingness to consent for the study, to be randomized to either the immediate or delayed 
cochlear implantation arm, to utilize bimodal hearing for the duration of the trial (if clinically 
appropriate) and follow the study protocol for the duration of the trial. 
9.4.2 Exclusion Criteria 
1. Prelingual or perilingual severe-to-profound hearing loss. 
2. Previous cochlear implantation in either ear 
3. Hearing loss of neural or central origin 
4. Permanent conductive hearing impairment (e.g. Otosclerosis).  
5. Medical, audiological or psychological conditions, as judged by the investigator that might 
contraindicate participation in the clinical investigation. 
6. Self-reported disability in ≥ 2 activities of daily living. 
7. Unwilling to wear a device or comply with the surgical and rehabilitation requirements of the 
study. 
8. Vision impairment: Worse than 20/40 (corrected) on a Near Vision Card.  
9.5 Statistical Considerations 
Statistical considerations for the clinical investigation are fully described within the Randomized 
controlled trial of immediate versus delayed cochlear implantation Statistical Analysis Plan 
(D1309522). 
9.6 Data Management 
The Case Report Forms (CRFs) will capture subject status according to the following criteria: 
 
Consented: Signed consent and eligibility evaluations underway 
 
Screen Fail: Subject determined not to be eligible to proceed for participation 
 
Enrolled: Following confirmation of eligibility and randomization 
 
Withdrawn: Enrolled subjects who withdraw or are withdrawn by the Investigator or Sponsor 
before the expected End of Study visit.  
 
Complete: Enrolled subjects who complete the planned follow up schedule.  
Source data collection will be performed through Medidata Rave, a web-based system for electronic 
data capturing (EDC). Site personnel will be trained to use this system. Data validity has to be 
confirmed by the investigator through an electronic signature. An audit trail is kept by this system and 
data clarifications may be generated by the system and sponsor personnel after review of data. 
The web-based system has been verified and validated by the vendor. Investigation-specific 
implementations are validated and consist of verification that all required items are included, validity of 
edit checks and appropriate functionality of conditional fields. The investigation-specific data in in the 
EDC can only be accessed by those that have been allocated their individual account, which are 
personnel of the investigational sites, Clinical Project Managers, Investigation Monitors and Data 
Management. 

 
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9.7 Data Monitoring 
The study will be monitored for data quality as referenced in the associated monitoring plan as well as 
in compliance with Cochlear Americas Standard Operating Procedures (SOPs). Monitoring 
considerations for the clinical investigation are described within the Randomized controlled trial of 
immediate versus delayed cochlear implantation Monitoring Plan (D1309523). 
9.8 Amendments to the Protocol 
No changes in the protocol or investigation procedures shall be effected without agreement by the 
sponsor. Changes related to the scientific intent of the study shall be documented in the protocol and 
requires signatures from the sponsor and the principal investigator. Such changes will require 
notification to the Institution Review Board (IRB) by the principal investigators.  
9.9 Deviations from the Protocol 
The investigator is not allowed to deviate from the protocol except under emergency circumstances to 
protect the rights, safety and well-being of the subjects. Such deviation shall be documented and 
reported to the sponsor and the IRB as soon as possible.  
The procedure for recording and reporting protocol deviations shall be via a Protocol Deviation CRF in 
the EDC system.  Analysis of protocol deviations shall be undertaken by the sponsor and Data 
Management.   
In the event of a protocol deviation, the investigator shall notify the sponsor and respective IRB 
according to local reporting guidelines.   
9.10 Device accountability 
Investigational devices (iPads) will be shipped to the investigational site indicating the study number. 
Sites should preserve the packaging to enable them to return the iPads to Cogstate at the end of the 
clinical investigation. 
Commercially released products shall be registered following the standard product registration 
process at each field site.  
10 STATEMENTS OF COMPLIANCE 
10.1  Declaration of Helsinki and compliance with standards 
The clinical investigation shall be conducted in accordance with the ethical principles that have their 
origin in the Declaration of Helsinki (2013), The U.S. Food & Drug Administration’s Code of Federal 
Regulations, ISO 14155: 2011, and any regional or national regulations, as appropriate. 
10.2  Institutional Review Board Approval 
A participating site shall not commence subject enrollment prior to the written approval from the local 
IRB is obtained. 
The final version of the protocol, the informed consent and all supporting documents to the IRB.  A 
copy of the IRB approval shall be provided to the sponsor.  
The investigator shall forward any amendment made to the approved informed consent to the sponsor 
for review prior to submission to the IRB.  

 
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The sponsor and principal investigator shall continue the communication with the IRB as required by 
national regulations and the clinical investigational plan.  
Documentation if any extension, amendment or renewal of the IRB approval is required. In particular, 
substantial amendments to the protocol, the informed consent, or other written information provided to 
subjects shall be approved in writing by the IRB.  
Additionally, the investigator will report to the IRB any new information that may affect the safety of 
the subjects or the conduct of the clinical investigation. The investigator shall send written status 
summaries of the investigation to the IRB as required.  
Upon completion of the clinical investigation, the investigator shall provide the IRB with a brief report 
of the outcome of the clinical investigation as per local requirements. 
The clinical investigation is covered by a clinical trial insurance as per local requirements. 
11 INFORMED CONSENT PROCESS 
11.1  Obtaining informed consent 
The investigator shall obtain written informed consent using an approved Informed Consent Form 
from the subject prior to any clinical investigation related activity. NOTE: If the subject was seen as 
part of routine clinical care prior to study consent, information relevant to the study may be included 
such as but not limited to: hearing history, medical history (via completion of the ACE 27), prior 
hearing aid use, audiometric status, etc. as long as performed within 90 days from POV1.   
The informed consent shall include the following but is not limited to: rationale for and details of the 
study, aims and objectives, the risks and benefits and alternative treatments, and the extent of the 
subject’s involvement. Ample time shall be provided for the subject to inquire about details of the 
clinical investigation and to decide whether to participate. All questions about the clinical investigation 
shall be answered to the satisfaction of the subject or the subject’s legally acceptable representative 
prior to signing the Informed Consent. Subjects shall not be coerced or unduly influenced to 
participate or to continue to participate in a clinical investigation. 
Each subject and the person who conducted the informed consent discussion shall sign the informed 
consent. Where required, a witness shall sign and personally date the informed consent. The subject 
shall be provided a copy of the signed informed consent and the original signed version of the 
informed consent shall be filed in the respective subjects file at the clinical site.  
11.2  Data Privacy 
Subjects will be identified on CRFs or similar documents (for example, questionnaires) by a unique 
subject identification code. Completed CRFs or similar documents are confidential documents and will 
only be available to the sponsor and their representatives, the investigator, the investigational 
statistician, and if requested, to the local IRB. The Patient ID log CRF is explicitly excluded from this 
requirement. Analysis of post-operative CT scans will be undertaken by an independent centralized 
imaging review center and a de-identified report will be sent to the sponsor in line with HIPAA 
Standards. 
A description of this clinical investigation will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law.  

 
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12 SAFETY REPORTING  
12.1 Definitions 
All definitions are according to 21 CFR Part 812, 50, 54, 56 & 11 as well as EN ISO 14155:2011 
standard and described in Section 17. 
12.2  Reporting Process 
The investigator shall report all serious adverse events without delay to the sponsor through the 
eCRF. The Sponsor will appoint a medical monitor to review any adverse events requiring 
adjudication.  
The investigator must report all AEs, SAEs, SADEs and USADEs to their IRB using the applicable 
report form as per local requirement.  
Subjects shall be carefully monitored during the clinical investigation for potential adverse events and 
shall be routinely questioned about adverse events at investigation visits. For all adverse events, 
information obtained by the investigator shall be recorded in the Adverse Event CRF. The investigator 
shall attempt to assess the relationship between the procedure and the adverse event with final 
review by the sponsor.   
12.3  Data Monitoring Committee 
Given that routine surgical procedures will be applied a DMC will not be established. 
13 VULNERABLE POPULATION 
The target study population is the older adult population, specifically individuals aged 65 to 85 years 
of age. The inclusion criteria screens for significant impaired mental capacity using the Hearing 
Impaired Montreal Cognitive Assessment (HI-MoCA). Specifically, adults who score ≥ 20 on the HI-
MoCA.  Additionally, individuals with self-reported disability and visual impairments are excluded. 
Potential study subjects will not be of child bearing age nor will the investigation include children.  This 
study does not pose additional physical risks for older adults than for the general population and 
subjects will be under the medical supervision and care of the investigational site for the duration of 
the trial. 
14 SUSPENSION OR PREMATURE TERMINATION 
The sponsor reserves the right to discontinue the study for any safety, ethical, or administrative 
reason at any time.  Subjects already implanted will continue to be supported by their hearing health 
care provider, independent of any decision made about study continuation.   
The sponsor will withdraw from sponsorship of the clinical investigation if: 
 
major non-adherence to the protocol is occurring 
 
it is anticipated that subject recruitment will not be adequate to meet the objectives of the 
clinical investigation 
Should the sponsor withdraw from sponsorship of the clinical investigation, the sponsor will continue 
sponsorship for the subjects already recruited into the investigation to primary endpoint. 
An ongoing clinical investigation can be discontinued in case of: 
 
device failure 

 
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 
serious or intolerable adverse device effect, leading to the explant or discontinued use of the 
device 
 
subject’s death 
 
investigator’s decision 
 
sponsor’s decision 
15 PRESENTATION AND PUBLICATION POLICY 
Cochlear is committed to the responsible publishing of data from its clinical research program. 
Cochlear will manage the timely publication of results in a suitable journal(s). The authors of any 
publication will be involved in this process. Cochlear will assess authorship eligibility according to the 
guidelines issued by the International Committee of Medical Journal Editors (43). 
In accordance with these recommendations, authorship credit will be based on: 1) Substantial 
contributions to conception and design, or acquisition of data, or analysis and interpretation of data; 2) 
Drafting the article or revising it critically for important intellectual content; and 3) Final approval of the 
version to be published. All three above points should be met to qualify for authorship. 
The lead author for any publication must be a study investigator or a major contributor to the study, 
and must have participated sufficiently in the work to take public responsibility for appropriate portions 
of the content. 
16 REFERENCES 
16.1  Internal References 
ID 
Document Title 
Number 
1 
Randomized controlled trial of immediate versus delayed cochlear 
implantation on hearing handicap Clinical Investigation Project Plan 
D1309524 
2 
Randomized controlled trial of immediate versus delayed cochlear 
implantation on hearing handicap Statistical Analysis Plan 
D1309522 
3 
Randomized controlled trial of immediate versus delayed cochlear 
implantation on hearing handicap Monitoring Plan 
D1309523 
 
16.2  External References 
 
ID 
Document Title 
Number 
1 
Clinical investigation of medical devices for human subjects – Good 
clinical practice 
ISO 14155:2011 
2 
World Medical Association Declaration of Helsinki – Ethical Principles 
for Medical Research Involving Human Subjects (2013) 
N/A 
3 
Code of Federal Regulations for Medical Devices Title 21 
Part 11, 50, 54, 
56 and 812 
 

 
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16.3  Referenced Literature 
 
1. 
Lin FR, Yaffe K, Xia J, Xue QL, Harris TB, Purchase-Helzner E, et al. Hearing loss and 
cognitive decline in older adults. JAMA Intern Med. 2013;173(4):293-9. 
2. 
Lin FR, Metter EJ, O'Brien RJ, Resnick SM, Zonderman AB, Ferrucci L. Hearing loss and 
incident dementia. Arch Neurol. 2011;68(2):214-20. 
3. 
Lin FR, Albert M. Hearing loss and dementia - who is listening? Aging Ment Health. 
2014;18(6):671-3. 
4. 
Li W, Li J, Xian J, Lv B, Li M, Wang C, et al. Alterations of grey matter asymmetries in 
adolescents with prelingual deafness: a combined VBM and cortical thickness analysis. Restorative 
neurology and neuroscience. 2013;31(1):1-17. 
5. 
Sharma A, Glick H. Cross-Modal Re-Organization in Clinical Populations with Hearing Loss. 
Brain Sci. 2016;6(1). 
6. 
Shiell MM, Champoux F, Zatorre RJ. Reorganization of auditory cortex in early-deaf people: 
functional connectivity and relationship to hearing aid use. Journal of cognitive neuroscience. 
2015;27(1):150-63. 
7. 
Philibert B, Collet L, Vesson JF, Veuillet E. Intensity-related performances are modified by 
long-term hearing aid use: a functional plasticity? Hear Res. 2002;165(1-2):142-51. 
8. 
Hribar M, Suput D, Carvalho AA, Battelino S, Vovk A. Structural alterations of brain grey and 
white matter in early deaf adults. Hear Res. 2014;318:1-10. 
9. 
Munro KJ. Reorganization of the adult auditory system: perceptual and physiological evidence 
from monaural fitting of hearing aids. Trends Amplif. 2008;12(3):254-71. 
10. 
Hwang JH, Wu CW, Chen JH, Liu TC. Changes in activation of the auditory cortex following 
long-term amplification: an fMRI study. Acta Otolaryngol. 2006;126(12):1275-80. 
11. 
Sarampalis A, Kalluri S, Edwards B, Hafter E. Objective measures of listening effort: effects of 
background noise and noise reduction. J Speech Lang Hear Res. 2009;52(5):1230-40. 
12. 
Hornsby BW. The effects of hearing aid use on listening effort and mental fatigue associated 
with sustained speech processing demands. Ear and hearing. 2013;34(5):523-34. 
13. 
Picou EM, Ricketts TA, Hornsby BW. How hearing aids, background noise, and visual cues 
influence objective listening effort. Ear and hearing. 2013;34(5):e52-64. 
14. 
Desjardins JL. The Effects of Hearing Aid Directional Microphone and Noise Reduction 
Processing on Listening Effort in Older Adults with Hearing Loss. J Am Acad Audiol. 2016;27(1):29-
41. 
15. 
Mosnier I, Bebear JP, Marx M, Fraysse B, Truy E, Lina-Granade G, et al. Improvement of 
Cognitive Function After Cochlear Implantation in Elderly Patients. JAMA Otolaryngol Head Neck 
Surg. 2015. 
16. 
Li L, Blake C, Sung Y, Shpritz B, Chen D, Genther DJ, et al. The Studying Multiple Outcomes 
After Aural Rehabilitative Treatment Study: Study Design and Baseline Results. Gerontol Geriatr Med. 
2017;3:1-10. 
17. 
Cochlear. CochlearTM Nucleus CI632 cochlear implant with Slim Modiolar electrode 
Physician's Guide. Cochlear Limited; 2018. 
18. 
Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, et al. The 
Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. Journal 
of the American Geriatrics Society. 2005;53(4):695-9. 
19. 
Pinto TCC, Machado L, Bulgacov TM, Rodrigues-Junior AL, Costa MLG, Ximenes RCC, et al. 
Is the Montreal Cognitive Assessment (MoCA) screening superior to the Mini-Mental State 
Examination (MMSE) in the detection of mild cognitive impairment (MCI) and Alzheimer's Disease 
(AD) in the elderly? Int Psychogeriatr. 2018:1-14. 
20. 
Lim MYL, Loo JHY. Screening an elderly hearing impaired population for mild cognitive 
impairment using Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment 
(MoCA). Int J Geriatr Psychiatry. 2018;33(7):972-9. 
21. 
Ambert-Dahan E, Routier S, Marot L, Bouccara D, Sterkers O, Ferrary E, et al. Cognitive 
Evaluation of Cochlear Implanted Adults Using CODEX and MoCA Screening Tests. Otol Neurotol. 
2017;38(8):e282-e4. 
22. 
Claes AJ, de Backer S, Van de Heyning P, Gilles A, Van Rompaey V, Mertens G. 
Postoperative cognitive dysfunction after cochlear implantation. European archives of oto-rhino-
laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies. 
2018;275(6):1419-27. 

 
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                                         Hearing Loss in Older Adults Study (CLTD5693) 
CIP Version: 10.0 
 
 
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Document Type: Clinical Investigation Plan 
23. 
Lin VY, Chung J, Callahan BL, Smith L, Gritters N, Chen JM, et al. Development of cognitive 
screening test for the severely hearing impaired: Hearing-impaired MoCA. Laryngoscope. 2017;127 
Suppl 1:S4-S11. 
24. 
Hughson W, Westlake HD. Manual for program outline for rehabilitation of aural casualties 
both military and civilian. Trans Am Acad Ophthal Oto-lar. 1944(Suppl.):3-15. 
25. 
Peterson GE, Lehiste I. Revised CNC lists for auditory tests. The Journal of speech and 
hearing disorders. 1962;27:62-70. 
26. 
Spahr AJ, Dorman MF, Litvak LM, Van Wie S, Gifford RH, Loizou PC, et al. Development and 
validation of the AzBio sentence lists. Ear and hearing. 2012;33(1):112-7. 
27. 
Ventry IM, Weinstein BE. The hearing handicap inventory for the elderly: a new tool. Ear and 
hearing. 1982;3(3):128-34. 
28. 
Noble W, Jensen NS, Naylor G, Bhullar N, Akeroyd MA. A short form of the Speech, Spatial 
and Qualities of Hearing scale suitable for clinical use: the SSQ12. Int J Audiol. 2013;52(6):409-12. 
29. 
Gatehouse S, Noble W. The Speech, Spatial and Qualities of Hearing Scale (SSQ). Int J 
Audiol. 2004;43(2):85-99. 
30. 
Russell DW. UCLA Loneliness Scale (Version 3): reliability, validity, and factor structure. J 
Pers Assess. 1996;66(1):20-40. 
31. 
Burke WJ, Roccaforte WH, Wengel SP. The Short Form of the Geriatric Depression Scale: A 
Comparison With the 30-Item Form. Topics in geriatrics. 1991;4(3):173-8. 
32. 
Castiglione A, Benatti A, Velardita C, Favaro D, Padoan E, Severi D, et al. Aging, Cognitive 
Decline and Hearing Loss: Effects of Auditory Rehabilitation and Training with Hearing Aids and 
Cochlear Implants on Cognitive Function and Depression among Older Adults. Audiol Neurootol. 
2016;21 Suppl 1:21-8. 
33. 
Poissant SF, Beaudoin F, Huang J, Brodsky J, Lee DJ. Impact of cochlear implantation on 
speech understanding, depression, and loneliness in the elderly. Journal of otolaryngology - head & 
neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale. 2008;37(4):488-94. 
34. 
Sonnet MH, Montaut-Verient B, Niemier JY, Hoen M, Ribeyre L, Parietti-Winkler C. Cognitive 
Abilities and Quality of Life After Cochlear Implantation in the Elderly. Otol Neurotol. 2017;38(8):e296-
e301. 
35. 
Carlson MC, Parisi JM, Xia J, Xue QL, Rebok GW, Bandeen-Roche K, et al. Lifestyle 
activities and memory: variety may be the spice of life. The women's health and aging study II. 
Journal of the International Neuropsychological Society : JINS. 2012;18(2):286-94. 
36. 
Fried LP, Carlson MC, Freedman M, Frick KD, Glass TA, Hill J, et al. A social model for 
health promotion for an aging population: initial evidence on the Experience Corps model. J Urban 
Health. 2004;81(1):64-78. 
37. 
Parisi JM, Kuo J, Rebok GW, Xue QL, Fried LP, Gruenewald TL, et al. Increases in lifestyle 
activities as a result of experience Corps(R) participation. J Urban Health. 2015;92(1):55-66. 
38. 
Feeny D, Furlong W, Torrance GW, Goldsmith CH, Zhu Z, DePauw S, et al. Multiattribute and 
single-attribute utility functions for the health utilities index mark 3 system. Med Care. 2002;40(2):113-
28. 
39. 
Boyle MH, Furlong W, Feeny D, Torrance GW, Hatcher J. Reliability of the Health Utilities 
Index--Mark III used in the 1991 cycle 6 Canadian General Social Survey Health Questionnaire. 
Quality of life research : an international journal of quality of life aspects of treatment, care and 
rehabilitation. 1995;4(3):249-57. 
40. 
Barton GR, Bankart J, Davis AC, Summerfield QA. Comparing utility scores before and after 
hearing-aid provision : results according to the EQ-5D, HUI3 and SF-6D. Applied health economics 
and health policy. 2004;3(2):103-5. 
41. 
Grutters JP, Joore MA, van der Horst F, Verschuure H, Dreschler WA, Anteunis LJ. Choosing 
between measures: comparison of EQ-5D, HUI2 and HUI3 in persons with hearing complaints. 
Quality of life research : an international journal of quality of life aspects of treatment, care and 
rehabilitation. 2007;16(8):1439-49. 
42. 
Group UCIS. Criteria of candidacy for unilateral cochlear implantation in postlingually 
deafened adults II: cost-effectiveness analysis. Ear and hearing. 2004;25(4):336-60. 
43. 
Uniform requirements for manuscripts submitted to biomedical journals: Writing and editing 
for biomedical publication. Journal of pharmacology & pharmacotherapeutics. 2010;1(1):42-58. 
 
 
 

 
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17 CHANGE HISTORY 
 
Version 
Change 
Author 
Date 
1.0 
Introduction of document 
 
December 21, 2016 
2.0 
Addition of Windchill number and study title to 
footer of document. 
Update to Investigation Schedule to include 
CM/AE/MH. 
Update to Medical Monitor details. 
Rewording of primary and secondary endpoints. 
Addition of 12 month follow up visit (FUV2). 
Removal of CANTAB as electronic cognitive test 
battery and replacement with NIH Toolbox 
Removal of SF-12, Cohen Social Network Index, 
and York Hearing Related Quality of Life 
measures.  
Addition of Lubben Social Network Scale and EQ-
D5 
Change from CES-D to Geriatric Depression 
Scale (GDS). 
 
 
August 31, 2017 
3.0 
Removal of NIH Toolbox and replacement with 
Cogstate test battery. 
Updated secondary objectives, endpoints and 
hypothesis. 
Updated reference to Statistical Analysis Plan 
 
 
October 6, 2017 
4.0 
Amendment to Data Privacy Section 
 
 
January 29, 2018 
5.0 
Update to short study title to ‘Immediate vs 
Delayed Cochlear Implantation on Hearing 
Handicap Study’ 
Numbering of inclusion and exclusion criteria. 
Typo correction for exclusion criteria #7 in 
synopsis. 
Clarification of noise type – speech-weighted 
noise. 
 
 
March 9, 2018 

 
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Version 
Change 
Author 
Date 
6.0 
Assessment of phonemes correct added. 
Changed primary objective and endpoint to 
assess Speech, Spatial and Qualities of Hearing 
(SSQ12) replacing Hearing Handicap Inventory 
for the Elderly - Screening (HHIE-S). 
Addition of FUV3 for Arm B subjects to assess 
outcomes at 12 months post-activation to align 
with Arm A post-activation follow up. 
Replacement of Mini Mental State Exam (MMSE) 
with Montreal Cognitive Assessment (MoCA). 
Specification of PTA (500, 1000 & 2000 Hz) ≥ 70 
dB HL in inclusion criteria. 
Removal of EQ-5D, Lubben Social Network, 
SPPB, THI questionnaires. 
Specification of CI532 cochlear implant. 
Addition of clinical review visits including audibility 
review at 3 months after POV2. 
Addition of X-ray preoperatively and CT imaging 
post-operatively. 
Removal of pure tone audiometric testing during 
follow up visits, and requirement for bone 
conduction testing during screening and baseline 
visits. 
 
 
December 5, 2018 
7.0 
Corrected visit window for surgery in Investigation 
Procedures table.  
Referred to Statistical Analysis Plan for 
randomization details. 
 
 
December 6, 2018 
8.0 
Updated Montreal Cognitive Assessment Scale 
(MoCA) to utilize the Hearing Impaired version of 
the Montreal Cognitive Assessment Scale (HI-
MoCA) with a supplemental visual presentation of 
instructions. 
Included text describing the imaging requirements 
for the clinical investigation. 
 
 
February 1, 2019 
9.0 
Alignment of tympanometry, demographics and 
hearing history with EDC System. 
 
 
March 1, 2019 
10.0 
Addition of Cochlear Nucleus CI632 cochlear 
implant with Slim Modiolar electrode and 
exclusion of protocol deviation for inability to 
perform tympanometry due to no seal with probe 
tip. 
 
 
June 17, 2019 
11.0 
Addition of subject status language, ACE 27 index 
for medical history and clarification of hearing 
history information to be collected and protocol 
amendment criteria, Consistent addition of 
Cochlear Nucleus CI632 cochlear implant with 
Slim Modiolar electrode. Removal of protocol 
deviation for inability to perform tympanometry 
and removal of specific medical monitor 
information. 
 
August 16, 2019 

 
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18 DEFINITIONS 
Term 
Description 
Adverse event (AE) 
Any untoward medical occurrence, unintended disease or injury, or 
untoward clinical signs (including abnormal laboratory findings) in subjects, 
users or other persons whether or not related to the investigational medical 
device. 
NOTE 1 This definition includes events related to the investigational medical 
device or the comparator 
NOTE 2 This definition includes events related to the procedures involved.   
NOTE 3 For users and other persons, this definition is restricted to events 
related to investigational medical devices. 
Adverse device effect 
(ADE) 
Adverse device effect is an adverse event related to the use of an 
investigational medical device. 
Note to the author:  
NOTE 1 This includes any adverse event resulting from insufficiencies or 
inadequacies in the instructions for use, the deployment, the implantation, 
the installation, the operation, or any malfunction of the investigational 
medical device. 
NOTE 2 This definition includes any event resulting from use error or from 
intentional misuse of the investigational medical device. 
CRF 
Case Report Form. A form to facilitate the collection of clinical data during a 
clinical investigation.  
DMC 
Data Monitoring Committee 
DD 
Device Deficiency. A device deficiency is an inadequacy of a medical device 
with respect to its identity, quality, durability, reliability, safety or 
performance. Device deficiencies include malfunctions, use errors, and 
inadequate labelling. 
FUV 
Follow-Up Visit 
Incident 
Any malfunction or deterioration in the characteristics and/or performance of 
a device, as well as any inadequacy in the labelling or the instructions for 
use which, directly or indirectly, might lead to or might have led to the death 
of a subject, or USER or of other persons or to a serious deterioration in 
their state of health. 
IC 
Informed Consent 
IRB 
Institutional Review Board 
POV 
Preoperative Visit 

 
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Term 
Description 
Serious adverse event 
(SAE) 
A serious adverse event is any adverse event that: 
a) led to a death, 
b) led to a serious deterioration in the health of the subject that either 
resulted in 
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body function, or 
3) in-patient hospitalization or prolonged hospitalization, or 
4) medical or surgical intervention to prevent life-threatening illness or injury 
or permanent impairment to a body structure or a body function, 
c) led to foetal distress, foetal death or a congenital abnormality or birth 
defect 
NOTE Planned hospitalization for a pre-existing condition, or a procedure 
required by the CIP, without serious deterioration in health, is not 
considered a serious adverse event. 
Serious adverse device 
effect (SADE) 
A serious adverse device effect is an adverse device effect that has resulted 
in any of the consequences characteristic of a serious adverse event. 
Unanticipated serious 
adverse device effect 
(USADE) 
An unanticipated serious adverse device effect is a serious adverse device 
effect which by its nature, incidence, severity or outcome has not been 
identified in the risk analysis report (for the investigational device or its 
comparator).