Safety and Feasibility of Transcranial Direct Current Stimulation to Enhance Auditory Rehabilitation in Cochlear Implant Recipients
Phase: NA
Conditions: Hearing Loss
Sponsor: Duke University

 
 
 
 
 
 
 
 
 
 
Safety and Feasibility of Transcranial Direct Current Stimulation to Enhance Auditory 
Rehabilitation in Cochlear Implant Recipients 
 
Document Date: 11/09/2022 
 
NCT04908631 
 

 
 
 
 
 
Pro007525; PI: Howard Francis, MD 
Version Date: 11/9/2022  
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Safety and Feasibility of Transcranial Direct Current Stimulation to Enhance 
Auditory Rehabilitation in Cochlear Implant Recipients 
 
 
 
 
 
 
 
Sponsor:  
PI – Department of Head and Neck Surgery & Communication 
Sciences 
Funding Source:  
MEDx 
Protocol Source:  
PI – Department of Head and Neck Surgery & Communication 
Sciences 
Duke IRB#:  
Pro00107525  
IND#:  
 N/A 
 
Principal Investigator 
Howard Francis, MD, MBA, FACS 
Department of Head and Neck Surgery & 
Communication Sciences 
(919)- 681-8069 
howard.francis@duke.edu  
 
Sub Investigator(s) 
Angel V. Peterchev, PhD 
angel.peterchev@duke.edu 
 
 
Sherri Smith, AuD, PhD 
Sherri.smith@duke.edu  
 
Erin Blackburn, AuD, CCC-A 
Erin.blackburn@duke.edu  
 
Noam Bartuv, MD 
noam.bartuv@duke.edu 
 
See IRB submission for a detailed list of study 
personnel. 
 
Study Coordinator 
Victoria Johnson 
HNSCS 
victoria.a.johnson@duke.edu  
 
Amy Walker 
HNSCS 
Amy.walker1@duke.edu  
 
Ellie Wood 
Brain Stimulation and Neurophysiology 
eleanor.wood@duke.edu  
 
Regulatory Coordinator 
Stacy Murray 
stacy.murray@duke.edu  
 
Data Manager 
Erika Juhlin 
Erika.juhlin@duke.edu  
 
Version date: 11/9/2022 
 
 
1) Protocol Title:   Safety and Feasibility of Transcranial Direct Current Stimulation to Enhance Auditory 
Rehabilitation in Cochlear Implant Recipients 

 
 
 
 
 
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2) Purpose of the Study:  
a) To evaluate the safety and feasibility of reliable Transcranial Direct Current Stimulation (tDCS) 
administration at home in combination with home-based auditory training therapy and practice in 
Cochlear Implant (CI) patients 
b) To evaluate changes in speech perception performance after a 4-week intervention consisting of 
tDCS combined with auditory rehabilitation and training. 
 
3) Background & Significance:   
Hearing loss is a prevalent source of disability in the population, particularly with advancing age (Goman 
and Lin 2016). Data from the National Health and Nutrition Examination Survey suggests that 10.5% of 
adults aged 55 to 64 years have hearing loss sufficiently disabling to warrant amplification, increasing to 
25% for those 65 to 74 years and 50% for those 75+ years of age (NIDCD). There is increasing evidence 
of a strong correlation between sensorineural hearing loss in older adults and declines in general health 
including cognitive decline, social isolation, depression, and early mortality (Deal et al. 2017; Genther et 
al. 2015). Hearing restoration using cochlear implant (CI) technology and post-operative rehabilitation for 
moderately severe or greater hearing loss has proven crucial for improving quality of life, and reducing 
isolation and depression, which may serve as precursors for associated cognitive and general health 
declines (Contrera et al. 2017; Rutherford et al. 2018).  
Nevertheless, there is substantial variability in the efficacy of hearing restoration interventions by CIs. 
Almost all CI patients improve dramatically after its activation, but some patients will reach a plateau in 
their performance even with a full auditory rehabilitation program. A recent meta-analysis was only able 
to explain 22% of the variability in speech perception results (Zhao et al. 2020). Some patients might even 
grow reluctant to wear the external part of the implant and become non-users (Távora-Vieira, Acharya, 
and Rajan 2020). Poor speech understanding in noise is a common complaint of patients using CIs and 
remains a major source of disability in these individuals. Therefore, there is an unmet need for approaches 
that can boost patients’ speech perception performance with CIs more than current standard rehabilitation 
programs.  
 
As for individuals using hearing aids (Chisolm et al. 2013; Smith et al. 2016), auditory rehabilitation after 
cochlear implantation has been associated with higher speech perception results (Fu and Galvin 2008; 
Stacey et al. 2010) and better quality of life (Tang et al. 2017). Neurocognitive functioning has become 
increasingly recognized as an important determinant of speech perception performance in older adults 
with CIs (Moberly, Castellanos, and Mattingly 2018). The history of hearing deprivation appears to be a 
prominent determinant of speech perception gain in the first few months after CI activation (Francis, 
Yeagle, and Thompson 2015). The subsequent gains are slower and appear to be more strongly associated 
with general health and a variety of psychosocial factors. This study proposes to evaluate an intervention 
that may facilitate adaptation of auditory brain circuits in response to salient but novel auditory 
stimulation with a CI, while engaged in auditory therapy and practice. 
 
tDCS is a non-invasive brain stimulation technique that delivers low-intensity current via electrodes on 
the scalp to modify neuronal excitability in the underlying cortex (Paulus, Peterchev, and Ridding 2013). 
Over the past two decades, tDCS has been studied extensively in healthy subjects, patient populations, as 

 
 
 
 
 
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well as animal models, 
demonstrating robust safety (Antal et 
al. 2017) and promising efficacy 
(Buch et al. 2017). Previous 
neurostimulation studies have 
demonstrated that tDCS improves 
motor learning, cognition, and 
memory for healthy participants as 
well as in stroke patients (Ciechanski 
et al. 2019; Elsner et al. 2017; Shaker 
et al. 2018). Members of this study 
team have also reported faster 
acquisition of manual laparoscopic 
surgical skills among trainees 
receiving tDCS therapy (Cox et al. 
2020) (see Fig. 1).  
 
Importantly, anodal tDCS can modulate linguistic abilities in healthy individuals and improve language 
performance in patients with post-stroke aphasia, via modulation of effective connectivity in the brain 
(Fiori et al. 2018). Indeed, anodal tDCS affects structural plasticity in the auditory cortex of normal-
hearing and noise-exposed rats (Paciello et al. 2018). These effects are thought to result from enhanced 
neuroplasticity that can occur as relevant groups of neurons are stimulated to fire together, thereby 
strengthening neural pathways and improving signal processing. Studies of tDCS and transcranial 
magnetic stimulation of auditory cortex are limited to normal hearing subjects and have demonstrated 
several perceptual effects including modulation of the mismatch negativity evoked response potential 
component, increased temporal resolution, phonetic categorization, and pitch discrimination (see review 
by (Heimrath et al. 2016)) as well as modulation of the right ear advantage in dichotic listening (Heimrath 
et al. 2020). However, tDCS has not been studied for enhanced rehabilitation of speech perception in 
patients with hearing loss.  
 
4) Design & Procedures:  
This prospective study involves the completion of a 4 week computer-based auditory training program 
while administering tDCS. Patients with a unilateral Cochlear Implant will be asked to complete 30-
minute sessions of self-directed auditory training while administering tDCS, at least five times per week 
for 4 weeks. Subjects will be asked to complete daily electronic logs for adverse event reporting and 
documentation of auditory training compliance. Subjects will be provided with a customized learning and 
practice plan during the initial baseline visit and given instructions on use of the tDCS device.  Subjects 
will be selected whose sentence recognition scores (AzBio) have plateaued below 65%, which provides 
an opportunity to detect a measurable improvement in response to the proposed intervention.  
 
The following assessments/procedures will be performed at the MOSCH lab located in the Hock Building 
on Erwin Road: 
 
Auditory training methods: Subjects will be provided customized auditory training program using 
materials from two existing computer-based auditory training programs that can be completed in the home. 
Specifically, we will use consonant and vowel discrimination and recognition modules from Speech 
Banana to focus on bottom-up processing tasks. This will allow for practice in discriminating between 
letters/words (e.g., bat/pat/mat or hid/hood/had). Additionally, modules from the Sound Success program 
Fig. 1. Beneficial effects of tDCS during training on the acquisition of manual 
skills. A) tDCS electrode montages and associated electric field distribution in 
cortex. B) Results showing significantly greater improvement for the bM1 
montage (green) over sham (black) (Cox et al, 2020). 

 
 
 
 
 
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will be used, which focuses on understanding sentences/conversations in quiet and in noise using different 
talkers. The latter program also allows the patient to practice listening in familiar contexts (e.g., topics on 
weather, shopping, and family life). Both programs use an adaptive approach such that the difficulty of 
training stimuli is adjusted based on performance. Participants will be asked to bring their personal laptop 
or tablet to the baseline visit (if applicable) so they can download the auditory training software and conduct 
a practice session before leaving the clinic.  
 
Transcranial Direct Current Stimulation (tDCS): We will use a device that was designed and validated 
to allow safe and reliable tDCS delivery at home (1x1 tES mini-CT, Soterix Medical, USA). This tDCS 
system incorporates a customizable headgear for individualized electrode placement and disposable, snap-
in electrodes that are easy for the patient to apply at home without assistance. The device also allows the 
clinical team to control and monitor the home use by the patient. Based on the reports of listening related 
functional brain imaging (Price 2012), and transcranial stimulation studies (Heimrath et al. 2016), we will 
deliver anodal stimulation (positive electrode over target) of the primary auditory cortex contralateral to 
the CI implant.   
 
Patient Reported Outcome Measures will be collected: Speech, Spatial, Qualities of Hearing (SSQ-12), 
and Cochlear Implant Quality of Life Questionnaire (CIQOL) will be collected at baseline, and the 1 month 
and 6 month follow-up visits.   
 
An adverse event questionnaire will be collected continuously during the 4 week auditory training sessions 
and reviewed during each of the weekly tele-visits with a member of the study team. 
 
Hearing and Speech Evaluation:  Hearing thresholds and speech perception performance will be 
measured during the baseline visit, and 1 month and 6 month follow up visits using standard, validated 
and standard word and sentence lists presented in quiet and in noise (AzBio Quiet, AzBio +5/+10dB; 
CNC 50-item list) while the patient is wearing an appropriately programmed CI alone and/or with 
appropriately fitted contralateral hearing aid (if this is typically worn by the patient).   
 
5) Study Schedule: 
Visit 1/Baseline:   
Subjects will undergo a screening visit to determine eligibility.  The screening visit may be combined with 
a standard of care visit for patients already being seen for cochlear implant evaluation. Each participant 
will sign an informed consent before committing to any study-related tests or procedures and will include 
the following assessments: 
 
• Obtain and document consent from potential participant on informed consent form (ICF). 
• Conduct baseline hearing threshold and speech perception testing using standard audiological 
procedures (e.g., AzBio Quiet, AzBio +5/+10dB; CNC 50-item list) for screening for eligibility 
and baseline assessment 
• Obtain patient reported outcome questionnaires (SSQ-12 and CIQOL) 
• Auditory training and assignment of home-based personalized, computer-based 
rehabilitation/practice plan  
• Orientation to tDCS equipment, determination of appropriate stimulation levels and electrode 
placement 

 
 
 
 
 
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• Conduct integrity evaluation of device using telemetry during initial tDCS trial.  
• Repeat subset of speech perception assessment before, during and after the initial tDCS 
application.  
• Instructions for completion of electronic daily diary to record adverse events and compliance of 
auditory training  
  
The tDCS current will be programmed to 2.5mA prior to the start of integrity testing.  If 2.5mA is 
intolerable, then the current will be reduced to 2.0mA.  If a participant is still not able to tolerate 2.0mA, 
then this will be considered a screen fail and the subject will be removed from study.   
 
Study participants meeting the screening criteria upon completion of the baseline visit will continue on 
study. Enrolled participants will be given a tDCS device to take home to complete study procedures with 
instructions to return it at the 1 month post-treatment visit to be completed in person.  
Weeks 2-5 (Visits 2 – 5) 
During the 30-day treatment period, subjects will be expected to complete the following:  
• Complete daily web-based auditory training with tDCS stimulation for 30-minute sessions, at 
least five times per week for 4 weeks.  
• 
Completion of a daily diary to record compliance of auditory training with tDCS, as well as to 
document adverse events that may occur during or after the sessions.    
• 
Video visits will be conducted at least weekly by a member of the research team, starting more 
frequently in the first week, to provide technical assistance as needed, review reported adverse 
events, and give reminders regarding completion of the daily diary.   
 
 
One-Month post-treatment (Visit 6) 
  
Participants will be asked to return at the end of the 30-day treatment period for an in-person visit and 
undergo the following assessments: 
 
• Hearing threshold and speech perception testing using standard audiological procedures (AzBio 
Quiet, AzBio +5/+10dB; CNC 50-item list) 
• 
Obtain patient reported outcome questionnaires (SSQ-12 and CIQOL) 
• Conduct integrity evaluation of device using telemetry 
• Review of adverse events 
• Return tDCS device 
 
Six-Month post-treatment (Visit 7) 
 
Participants will be asked to return for an in-person visit and undergo the following assessments: 
• 
Hearing threshold and speech perception using standard audiological procedures (AzBio Quiet, AzBio 
+5/+10dB; CNC 50-item list) 

 
 
 
 
 
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• Obtain patient reported outcome questionnaires (SSQ-12 and CIQOL) 
• 
Conduct integrity evaluation of device using telemetry 
• Review of adverse events since the last visit 
 
 
 
Schedule of Events Table 
 
Baseline 
Week 2 
(televisit) 
 
Week 3 
(televisit) 
 
Week 4 
(televisit) 
 
Week 5 
(televisit) 
 
 1 month 
post-
assessment 
(in-office 
visit) 
 
6 month post - 
assessment  
(in-office visit) 
 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Consent 
X 
 
 
 
 
 
 
Hearing and Speech 
Reception Thresholds 
X 
 
 
 
 
X 
X 
Patient Reported 
Outcome Measures 
(SSQ12 and CIQOL) 
X 
 
 
 
 
X 
X 
Auditory Training in 
office – establish 
therapy plan 
X 
X 
 
 
 
 
 
In-office tDCS – 
establish protocol, 
patient training 
X 
 
 
 
 
 
 
Home Auditory 
training and tDCS 
(daily)  
 
 
 
Weekly video visit to 
review use & 
compliance of 
training 
 
X 
X 
X 
X 
 
 
Review of symptoms 
and adverse events 
 
X 
X 
X 
X 
X 
X 
Subject 
Compensation 
X 
 
 
  
 
X 
X 

 
 
 
 
 
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6) Selection of Subjects: 
 
Inclusion Criteria 
1. Age > 18 years of age 
2. Patients with a unilateral Cochlear Implant device in use for a minimum of 1 year  
3. Sentence recognition scores (AzBio) are below 65% in quiet and/or word recognition scores (CNC) 
are below 75% in the implanted ear for > one year following cochlear implant activation. 
4. Ability to access internet to conduct computer-based auditory trainings and weekly video visits with 
study team weeks 2–5 
 
Exclusion Criteria 
1. Non-English speaking 
2. Diagnosis (documented or self-reported) of a psychiatric or neurologic condition, or any other 
comorbidities that may interfere with the study or increase the level of risk (such as dementia, 
seizures, legal blindness, brain tumor) 
3.  Implants, other than CI, above collar bone level that may interact with delivery of tDCS 
4. Inability to or unwillingness to use electronic devices/computers, participate in video visits, or make 
required visits 
 
7) Subject Recruitment and Compensation:  
10 patients from the Duke Head and Neck and Communication Science clinics and/or the Duke Raleigh 
HNSCS Clinic will be recruited. Patients who meet the inclusion and exclusion criteria listed above will 
be approached for possible study participation after a member of the clinical care team asks the patient’s 
permission to be contacted by the study team. The study coordinator (or member of the research team) 
will then review the records, and upon determination that the patient is deemed eligible for this protocol, 
the clinical research coordinator (CRC) will contact the patient. This may occur in clinic or via phone 
using an IRB approved phone script. If the patient indicates interest in study participation, the study 
coordinator will thoroughly explain the required elements of informed consent and all aspects of the 
study to the subject including inclusion/exclusion criteria, risks, benefits, and alternative to study 
participation.  Up to 14 patients will be enrolled, allowing for 4 drop-outs.  
 
Subjects will be compensated $75 upon completion of the baseline visit (visit 1), $100 upon completion 
of the one-month f/u visit (visit 6) and $75 upon completion of the six-month follow up visit (visit 7) for 
total of $250.   
 
8) Consent Process: 
The principal investigator, cochlear implant audiologist/coordinator, study coordinator, or authorized key 
personnel will explain all aspects of the study in lay language and answer all questions regarding the 
study. The consent process will occur in a private room or via phone and eConsent.  eConsent is 
available via REDCap.  This functionality provides the ability to consent remote participants or 
participants in clinic via tablets or touchscreen device.   
 
Participants will have the capability to sign electronically with a stylus, mouse, or finger. Once the 
consent form is submitted, participants will receive an email that includes a PDF attachment with a copy 

 
 
 
 
 
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of the signed consent form. The PDF will be emailed to Health Information Management from REDCap 
for incorporation into Epic. 
 
The subject will be asked for permission to proceed if other people are in the room. The potential subject 
will have as much time as they need to decide if they would like to participate or not. The potential 
subject will be encouraged to review the consent and discuss it with any family members if they wish. 
The subject and will be given the contact information of the study coordinator and PI to call with any 
questions before or after consent is signed. The investigator will discuss all treatment options with 
potential subjects and they will be informed that participation in this study is voluntary and will not affect 
access to their health care at Duke, and that they may stop participating at any time. 
 
If the participant decides to participate in the study, he/she will be asked to sign and date the Informed 
Consent document. No study procedures will be conducted without prior written informed consent. 
Subjects who refuse to participate or who withdraw from the study will be treated without prejudice.  
 
9) Subject’s Capacity to Give Legally Effective Consent: It is not anticipated that we will enroll subjects 
who do not have the capacity to give legally effective consent. Non-English speaking subjects will not be 
approached for the study. 
 
10) Study Interventions:   
 
Refer to the Design and Procedure section. 
 
11) Risk/Benefit Assessment: 
 
Safety of Stand-Alone tDCS 
 
tDCS uses low voltage (typically < 20 V) and direct currents (typically < 2 mA) applied through scalp 
surface electrodes. Thus, it is comparable to connecting a conventional 9 V battery to the electrodes. The 
low voltages and currents contribute to an excellent safety profile of tDCS. According to a recent review 
paper (Bikson et al 2016) there are no known long-term health risks from the use of tDCS, per se, when 
operated within consensus safety guidelines. However, minimal, acute side effects of tDCS may include 
discomfort, skin irritation, lightheadedness, and headache. 
• Potential risk of skin irritation. The most commonly reported side effect is skin irritation at the 
sites of the tDCS electrodes. This may include reddening of the skin underneath the electrodes or 
itching at the site of stimulation. Skin lesions, such as burn-like lesions or contact dermatitis, have 
also been observed. 
• Potential risk of lightheadedness. While rare, feelings of pre-syncope, or lightheadedness, with 
stimulation can occur. This condition can sometimes occur during the “ramp-up” or “ramp-down” 
phase at the beginning and end of the protocol as the current is changing.  
• Potential risk of headache. A potential side effect of tDCS is a headache that could develop during 
or immediately after the stimulation and may last for minutes to hours following the end of the 
stimulation. It is typically limited to the day of stimulation, and usually responds promptly to single 
doses of over-the-counter analgesics. 
• Potential risk of impairments in cognitive function. There has been no evidence of neuronal damage 
or cognitive impairment induced by tDCS as demonstrated in Nitsche and Paulus (2001) and 
Nitsche et al. (2003).  
 

 
 
 
 
 
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As noted above, the primary side effects of tDCS are mostly related to interactions between the electrodes 
and the scalp skin.  These side effects however are mitigated by the proper selection and application of the 
electrodes. To minimize chemical reactions at the electrode–skin interface, non-metallic, conductive rubber 
electrodes, covered completely with saline-saturated sponges will be used in this study, as recommended 
by Nitsche and Paulus, 2000. The electrodes will be single-use and packaged for convenient and safe use 
at home by the patients.  
 
The team has experience with the application of tDCS in healthy volunteers and patients at Duke. For 
example, as part of IRB Protocol #00078782 “Laparoscopic Skills Training”, Dr. Appelbaum and 
colleagues ran over 69 healthy subjects in 191 sessions with no adverse events. As well, Dr. Peterchev 
consulted on tDCS device application in a multi-center trial, including Duke, of tDCS in patients with 
depression (Loo et al, 2018). That study included 130 participants (27 at Duke). The most common side 
effects were tingling, redness, burning sensation, itching, and light-headedness/dizziness.  
 
Safety of Combining tDCS and CI 
 
Dr. Peterchev has evaluated the safety of interactions between various transcranial and implanted 
stimulation devices, including tDCS and CIs (Peterchev, Dhamne, et al. 2012; Deng et al. 2010; Deng, 
Lisanby, and Peterchev 2010; Rossi et al. 2009). The tDCS device does not emit a significant 
electromagnetic field and the CI implant is electrically insulated from the patient except for the cochlear 
electrode contacts and reference electrode. Therefore, the primary safety question for the novel 
combination of tDCS and a CI in this study is whether the electric field generated by tDCS in the patient’s 
head injects significant currents in the CI electrodes. Dr. Peterchev and post-doc Dr. Dannhauer conducted 
computer simulations of the maximum electric fields for the proposed tDCS device (for illustration of 
tDCS electric field simulations, see Fig 1A). The simulations indicated that the upper bound of the voltages 
between the CI electrodes (1.75 V at 2.5 mA tDCS current, the maximum output of the tDCS device) is 
below the intrinsic voltages applied by the CI (6.5 V). Further, the capacitive coupling of the CI electrodes 
blocks the direct current applied by tDCS. Safety testing conducted as part of the original FDA approval 
by one of the CI manufacturers (MED-EL Corporation) showed that the implant can tolerate external 
voltages of at least 20 V. Finally, there are reports of patients with CI that developed Parkinson’s disease 
and were implanted with a deep brain stimulation device, which did not interfere with the CI (Buell et al. 
2015). These technical assessments and empirical evidence support the safety of combining tDCS with CI. 
Therefore, the combination of tDCS and CI is not expected to increase the low risk of tDCS alone.  
 
It's possible that tDCS pads may cause damage to hearing aid microphones if they get wet.  Therefore, 
participants who wear a contralateral hearing aid will be instructed to remove it prior to and during the use 
of tDCS.   
 
Participants will record daily symptoms via a link to a REDCap survey. REDCap will be programmed to 
alert the PI and/or SC of symptoms with an intensity level reported at 8 or above on the AE/symptom 
survey, regardless of the duration indicated (refer to table below). The PI, SC, or delegate will contact the 
patient to obtain additional information and determine if tDCS should be discontinued, and if a referral 
for medical evaluation is needed. 
 
In conclusion, given the low risk of tDCS and its combination with CI, the risk/benefit is favorable since 
improvement in the patients’ speech perception due to the administration of tDCS could improve their 
quality of life.   

 
 
 
 
 
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12)  Costs to the Subject:   
The study does not involve any costs to subjects. Costs for the audiological assessments will be covered 
by the study. tDCS devices for in-home use will be provided to study participants at no charge and 
returned at the end of the 1-month follow-up visit.  
13) Data Analysis & Statistical Considerations:   
The primary outcome measures of feasibility are: 1) proportion of eligible CI patients who expressed 
interest in the study; 2) proportion of selected participants who completed tDCS training and 
demonstrated competence in the office and subsequently at home during remote visits; 3) proportion of 
participants who completed most or all of the proposed intervention protocol; 4) proportion who 
completed relevant appointments, and reasons for any missing data; 5) acceptability of patient incentive; 
6) patient report of ease/difficulty carrying out the protocol via a patient survey at Visit 2; 7) proportion 
of people with any adverse events, and 8) other feasibility and acceptability metrics consistent with the 
latest guidelines on pilot studies (Eldridge et al. 2016). After each in-office tDCS application and at the 
immediate one month post-intervention Visit 6, the site of tDCS stimulation and the CI site will be 
visually examined for any skin irritation or tenderness and the internal and external CI devices will be 
examined for signs of abnormal function. Adverse effects of tDCS will be measured by the intensity and 
duration of symptoms recorded on the daily diary.  
 
The primary outcome measures of efficacy will be speech perception performance in the best listening 
condition compared to baseline, progress within the computer-based rehabilitation program and patient 
report of improved daily communication function.  Speech perception performance will be measured 
using validated and standard word and sentence lists presented in quiet and in noise (AzBio Quiet, AzBio 
+5/+10dB; CNC 50-item list).  
 
For the primary outcome we are reporting straightforward proportions and will not be conducting any 
group comparisons. The prevalence with which adverse effects are reported will be determined for the 
study as a whole and for different time windows during the study.  To address efficacy we would 
compare baseline speech perception and survey results with 1 and 6 month data.   
 
Descriptive analysis will including mean and standard deviations, and may also include evaluate for 
improvement using paired t-test. Need for statistical consultation is likely to be minimal but will be 
sought if appropriate.   
 
14) Data & Safety Monitoring:  
The PI will ensure proper data and safety monitoring. Any serious adverse events will be reported by the 
PI to the IRB within 5 business days. Events that are considered both serious and unanticipated will be 
reported to the IRB within 24 hours of the PI’s knowledge of the event. The PI will reconsider study 
design and procedures in discussion with the IRB should adjustments be warranted.  
 
Adverse events will be monitored from the start of auditory training with tDCS at week 2 until the six-
month follow-up visit at visit.  The PI and study team will meet frequently to review patient reported 
adverse events.  
 

 
 
 
 
 
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The investigator’s clinical judgment is used to determine whether a subject is to be removed from 
treatment due to an adverse event. In the event a subject requests to withdraw from protocol-required 
therapies or the study due to an adverse event. 
 
Definition of unanticipated and serious adverse events requiring prompt reporting to the IRB are 
described below: 
Unanticipated Problems  
The Office for Human Research Protections (OHRP) considers unanticipated problems involving risks to 
subjects or others to include, in general, any incident, experience, or outcome that meets all of the 
following criteria: 
• unexpected in terms of nature, severity, or frequency given (a) the research procedures that are 
described in the protocol-related documents, such as the IRB-approved research protocol and 
informed consent document; and (b) the characteristics of the subject population being studied; 
• 
related or possibly related to participation in the research (possibly related means there is a reasonable 
possibility that the incident, experience, or outcome may have been caused by the procedures involved in the 
research); and suggests that the research places subjects or others at a greater risk of harm (including physical, 
psychological, economic, or social harm) than was previously known or recognized. 
Serious Adverse Events  
A serious adverse event (SAE) is one that meets one or more of the following criteria: 
• Results in death 
• Is life-threatening (places the subject at immediate risk of death from the event as it occurred) 
• Results in inpatient hospitalization or prolongation of existing hospitalization 
• Results in a persistent or significant disability or incapacity 
• Results in a congenital anomaly or birth defect 
 
An important medical event that may not result in death, be life threatening, or require hospitalization 
may be considered an SAE when, based upon appropriate medical judgment, the event may jeopardize 
the subject and may require medical or surgical intervention to prevent one of the outcomes listed in this 
definition. 
15) Participant Discontinuation or Withdrawal from the study: 
 Participants will be removed in the event of a serious adverse reaction to tDCS. 
 
Subjects will have the option of withdrawing from the study at any time for any reason. Reason and date 
for withdrawal, as well as any adverse events since the last study visit will be documented. 
 
The Principal Investigator may discontinue a subject from study treatment, or withdraw a patient from 
the study.  Reasons for study treatment discontinuation or withdrawal may include but are not limited to 
the following: 

 
 
 
 
 
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•   Adverse event or hypersensitivity reactions thought to be related to the tDCS device   
•   Patient voluntarily decides to withdraw. 
•   Patient non-compliance with the study protocol. 
•   Intercurrent disease, which in the opinion of the patient’s treating physician, would affect the ability of 
    the patient to continue on the clinical study.  
•   Patient lost to follow-up. 
 
 
16) Privacy, Data Storage & Confidentiality:   
 
Study records that identify subjects will be kept confidential as required by law. Federal Privacy 
Regulations provide safeguards for privacy, security, and authorized access. Except when required by 
law, subjects will not be identified by name, social security number, address, telephone number, or any 
other direct personal identifier in study records disclosed outside of Duke University Health System 
(DUHS). 
 
Potential subjects will be approached and the study will be discussed in a private clinic or hospital room 
or via phone to protect their privacy and allow them to ask any questions. Subjects’ privacy will also be 
protected by assigning each subject a unique identification code. This code will be used for the 
completion of all CRFs and study documents. 
  
Prior to dissemination of any information in this database beyond the DUMC’s secure servers or firewall, 
all identifiers will be stripped from the database and data will only be referenced by the study-specific 
identification numbers.  A master log, which links the study-specific identification number to the study 
subject, will be generated. 
  
Any publications or presentations that result from this research will not identify any subjects 
individually, and will present data in aggregate form only. 
 
Confidentiality of subject data will be ensured by de-identification of subject data.  During data 
collection, subject identifiers and relevant data elements will be recorded in the database.  Then, study-
specific identification numbers will be assigned to each subject.  We will not record Zoom or Webex 
sessions and we will not use the chat functions for research purposes, and no PHI will be recorded within 
the chat window. 
 
Prior to dissemination of any information in this database beyond the DUMC’s secure servers or firewall, 
all identifiers will be stripped from the database and data will only be referenced by the study-specific 
identification numbers. A master log, which links the study-specific identification number to the study 
subject, will be generated.   
 
Any data that is stored in paper or non-digital format will be locked in a file cabinet within a key-
accessed office.  The office will be locked when not in use by the study team.  Any data that is stored in 
electronic format will be housed behind the Duke University Medical Center firewall. Subject data will 
be entered into a password-protected and encrypted REDCap database. De-identified data may be stored 
in a secure, study-specific Duke Box folder with access given to only to IRB approved key personnel.  In 
addition, the Surgery Servers plan in which sensitive electronic information (SEI) is stored on a surgery 
network drive will be used. No SEI will be stored on mobile computing or storage devices. 

 
 
 
 
 
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The adequacy of the Research Data Security Plan (RDSP) will be evaluated and approved by the Surgery 
CRU and Surgery IT personnel prior to study conduct. 
 
 
17) References Cited: 
 
Antal, A., I. Alekseichuk, M. Bikson, J. Brockmöller, A. R. Brunoni, R. Chen, L. G. Cohen, G. Dowthwaite, J. Ellrich, A. 
Flöel, F. Fregni, M. S. George, R. Hamilton, J. Haueisen, C. S. Herrmann, F. C. Hummel, J. P. Lefaucheur, D. 
Liebetanz, C. K. Loo, C. D. McCaig, C. Miniussi, P. C. Miranda, V. Moliadze, M. A. Nitsche, R. Nowak, F. 
Padberg, A. Pascual-Leone, W. Poppendieck, A. Priori, S. Rossi, P. M. Rossini, J. Rothwell, M. A. Rueger, G. 
Ruffini, K. Schellhorn, H. R. Siebner, Y. Ugawa, A. Wexler, U. Ziemann, M. Hallett, and W. Paulus. 2017. 'Low 
intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines', Clin 
Neurophysiol, 128: 1774-809. 
Bikson, M., C. A. Hanlon, A. J. Woods, B. T. Gillick, L. Charvet, C. Lamm, G. Madeo, A. Holczer, J. Almeida, A. Antal, M. 
R. Ay, C. Baeken, D. M. Blumberger, S. Campanella, J. A. Camprodon, chisolL. Christiansen, C. Loo, J. T. 
Crinion, P. Fitzgerald, L. Gallimberti, P. Ghobadi-Azbari, I. Ghodratitoostani, R. H. Grabner, G. Hartwigsen, A. 
Hirata, A. Kirton, H. Knotkova, E. Krupitsky, P. Marangolo, E. M. Nakamura-Palacios, W. Potok, S. K. Praharaj, 
C. C. Ruff, G. Schlaug, H. R. Siebner, C. J. Stagg, A. Thielscher, N. Wenderoth, T. F. Yuan, X. Zhang, and H. 
Ekhtiari. 2020. 'Guidelines for TMS/tES clinical services and research through the COVID-19 pandemic', Brain 
Stimul, 13: 1124-49. 
Buch, E. R., E. Santarnecchi, A. Antal, J. Born, P. A. Celnik, J. Classen, C. Gerloff, M. Hallett, F. C. Hummel, M. A. 
Nitsche, A. Pascual-Leone, W. J. Paulus, J. Reis, E. M. Robertson, J. C. Rothwell, M. Sandrini, H. M. Schambra, 
E. M. Wassermann, U. Ziemann, and L. G. Cohen. 2017. 'Effects of tDCS on motor learning and memory 
formation: A consensus and critical position paper', Clin Neurophysiol, 128: 589-603. 
Buell, Thomas J., Alexander Ksendzovsky, Binit B. Shah, Bradley W. Kesser, and W. Jeffrey Elias. 2015. 'Deep Brain 
Stimulation in the Setting of Cochlear Implants: Case Report and Literature Review', Stereotactic and 
functional neurosurgery, 93: 245-49. 
Chisolm, T. H., G. H. Saunders, M. T. Frederick, R. A. McArdle, S. L. Smith, and R. H. Wilson. 2013. 'Learning to listen 
again: the role of compliance in auditory training for adults with hearing loss', Am J Audiol, 22: 339-42. 
Ciechanski, P., A. Kirton, B. Wilson, C. C. Williams, S. J. Anderson, A. Cheng, S. Lopushinsky, and K. G. Hecker. 2019. 
'Electroencephalography correlates of transcranial direct-current stimulation enhanced surgical skill learning: 
A replication and extension study', Brain Res, 1725: 146445. 
Contrera, K. J., Y. K. Sung, J. Betz, L. Li, and F. R. Lin. 2017. 'Change in loneliness after intervention with cochlear 
implants or hearing aids', Laryngoscope, 127: 1885-89. 
Cox, M. L., Z. D. Deng, H. Palmer, A. Watts, L. Beynel, J. R. Young, S. H. Lisanby, J. Migaly, and L. G. Appelbaum. 2020. 
'Utilizing transcranial direct current stimulation to enhance laparoscopic technical skills training: A 
randomized controlled trial', Brain Stimul, 13: 863-72. 
Dannhauer, M., D. Brooks, D. Tucker, and R. MacLeod. 2012. 'A pipeline for the simulation of transcranial direct 
current stimulation for realistic human head models using SCIRun/BioMesh3D', Conf Proc IEEE Eng Med Biol 
Soc, 2012: 5486-9. 
Deal, J. A., J. Betz, K. Yaffe, T. Harris, E. Purchase-Helzner, S. Satterfield, S. Pratt, N. Govil, E. M. Simonsick, and F. R. 
Lin. 2017. 'Hearing Impairment and Incident Dementia and Cognitive Decline in Older Adults: The Health ABC 
Study', J Gerontol A Biol Sci Med Sci, 72: 703-09. 
Deng, Z. D., D. E. Hardesty, S. H. Lisanby, and A. V. Peterchev. 2010. 'Electroconvulsive therapy in the presence of 
deep brain stimulation implants: electric field effects', Conf Proc IEEE Eng Med Biol Soc, 2010: 2049-52. 
Deng, Z. D., S. H. Lisanby, and A. V. Peterchev. 2010. 'Transcranial magnetic stimulation in the presence of deep brain 
stimulation implants: Induced electrode currents', Conf Proc IEEE Eng Med Biol Soc, 2010: 6821-4. 
Eldridge, S. M., C. L. Chan, M. J. Campbell, C. M. Bond, S. Hopewell, L. Thabane, and G. A. Lancaster. 2016. 'CONSORT 
2010 statement: extension to randomised pilot and feasibility trials', Pilot Feasibility Stud, 2: 64. 

 
 
 
 
 
Pro007525; PI: Howard Francis, MD 
Version Date: 11/9/2022  
Page 15 of 16 
 
Elsner, B., G. Kwakkel, J. Kugler, and J. Mehrholz. 2017. 'Transcranial direct current stimulation (tDCS) for improving 
capacity in activities and arm function after stroke: a network meta-analysis of randomised controlled trials', 
J Neuroeng Rehabil, 14: 95. 
Fiori, V., L. Kunz, P. Kuhnke, P. Marangolo, and G. Hartwigsen. 2018. 'Transcranial direct current stimulation (tDCS) 
facilitates verb learning by altering effective connectivity in the healthy brain', Neuroimage, 181: 550-59. 
Francis, H. W., J. A. Yeagle, and C. B. Thompson. 2015. 'Clinical and psychosocial risk factors of hearing outcome in 
older adults with cochlear implants', Laryngoscope, 125: 695-702. 
Fu, Q. J., and J. J. Galvin, 3rd. 2008. 'Maximizing cochlear implant patients' performance with advanced speech 
training procedures', Hear Res, 242: 198-208. 
Genther, D. J., J. Betz, S. Pratt, S. B. Kritchevsky, K. R. Martin, T. B. Harris, E. Helzner, S. Satterfield, Q. L. Xue, K. Yaffe, 
E. M. Simonsick, and F. R. Lin. 2015. 'Association of hearing impairment and mortality in older adults', J 
Gerontol A Biol Sci Med Sci, 70: 85-90. 
Goman, A. M., and F. R. Lin. 2016. 'Prevalence of Hearing Loss by Severity in the United States', Am J Public Health, 
106: 1820-2. 
Heimrath, K., M. Fiene, K. S. Rufener, and T. Zaehle. 2016. 'Modulating Human Auditory Processing by Transcranial 
Electrical Stimulation', Front Cell Neurosci, 10: 53. 
Heimrath, K., A. Spröggel, S. Repplinger, H. J. Heinze, and T. Zaehle. 2020. 'Transcranial Static Magnetic Field 
Stimulation Over the Temporal Cortex Modulating the Right Ear Advantage in Dichotic Listening', 
Neuromodulation, 23: 335-40. 
Loo CK, Husain MM, McDonald WM, Aaronson S, O'Reardon JP, Alonzo A, Weickert CS, Martin DM, McClintock SM, 
Mohan A, Lisanby SH; International Consortium of Research in tDCS (ICRT). International randomized-
controlled trial of transcranial Direct Current Stimulation in depression. Brain Stimul. 2018 Jan-Feb;11(1):125-
133. doi: 10.1016/j.brs.2017.10.011. Epub 2017 Oct 27. PMID: 29111077 
Moberly, A. C., I. Castellanos, and J. K. Mattingly. 2018. 'Neurocognitive Factors Contributing to Cochlear Implant 
Candidacy', Otol Neurotol, 39: e1010-e18. 
Nitsche, M. A., and Paulus, W. (2000). Excitability changes induced in the human motor cortex by weak transcranial 
direct current stimulation. J. Physiol. 527(Pt 3), 633–639. doi: 10.1111/j.1469-7793.2000.t01-1-00633.x 
Nitsche, M. A. & Paulus, W. Sustained excitability elevations induced by transcranial DC motor cortex stimulation in 
humans. Neurology 57, 1899–1901 (2001). 
Nitsche, M. A. Facilitation of implicit motor learning by weak transcranial direct current stimulation of the primary 
motor cortex in the human. J. Cogn. Neurosci. 15, 619–626 (2003). 
Paciello, F., M. V. Podda, R. Rolesi, S. Cocco, L. Petrosini, D. Troiani, A. R. Fetoni, G. Paludetti, and C. Grassi. 2018. 
'Anodal transcranial direct current stimulation affects auditory cortex plasticity in normal-hearing and noise-
exposed rats', Brain Stimul, 11: 1008-23. 
Paulus, W., A. V. Peterchev, and M. Ridding. 2013. 'Transcranial electric and magnetic stimulation: technique and 
paradigms', Handb Clin Neurol, 116: 329-42. 
Peterchev, A. V., S. C. Dhamne, R. Kothare, and A. Rotenberg. 2012. 'Transcranial magnetic stimulation induces 
current pulses in transcranial direct current stimulation electrodes', Conf Proc IEEE Eng Med Biol Soc, 2012: 
811-4. 
Peterchev, A. V., T. A. Wagner, P. C. Miranda, M. A. Nitsche, W. Paulus, S. H. Lisanby, A. Pascual-Leone, and M. 
Bikson. 2012. 'Fundamentals of transcranial electric and magnetic stimulation dose: definition, selection, and 
reporting practices', Brain Stimul, 5: 435-53. 
Price, C. J. 2012. 'A review and synthesis of the first 20 years of PET and fMRI studies of heard speech, spoken 
language and reading', Neuroimage, 62: 816-47. 
Rossi, S., M. Hallett, P. M. Rossini, and A. Pascual-Leone. 2009. 'Safety, ethical considerations, and application 
guidelines for the use of transcranial magnetic stimulation in clinical practice and research', Clin 
Neurophysiol, 120: 2008-39. 

 
 
 
 
 
Pro007525; PI: Howard Francis, MD 
Version Date: 11/9/2022  
Page 16 of 16 
 
Rutherford, B. R., K. Brewster, J. S. Golub, A. H. Kim, and S. P. Roose. 2018. 'Sensation and Psychiatry: Linking Age-
Related Hearing Loss to Late-Life Depression and Cognitive Decline', Am J Psychiatry, 175: 215-24. 
Shaker, H. A., S. A. E. Sawan, E. M. Fahmy, R. S. Ismail, and Saea Elrahman. 2018. 'Effect of transcranial direct current 
stimulation on cognitive function in stroke patients', Egypt J Neurol Psychiatr Neurosurg, 54: 32. 
Smith, S. L., G. H. Saunders, T. H. Chisolm, M. Frederick, and B. A. Bailey. 2016. 'Examination of Individual Differences 
in Outcomes From a Randomized Controlled Clinical Trial Comparing Formal and Informal Individual Auditory 
Training Programs', J Speech Lang Hear Res, 59: 876-86. 
Stacey, P. C., C. H. Raine, G. M. O'Donoghue, L. Tapper, T. Twomey, and A. Q. Summerfield. 2010. 'Effectiveness of 
computer-based auditory training for adult users of cochlear implants', Int J Audiol, 49: 347-56. 
Tang, L., C. B. Thompson, J. H. Clark, K. M. Ceh, J. D. Yeagle, and H. W. Francis. 2017. 'Rehabilitation and Psychosocial 
Determinants of Cochlear Implant Outcomes in Older Adults', Ear Hear, 38: 663-71. 
Távora-Vieira, D., A. Acharya, and G. P. Rajan. 2020. 'What can we learn from adult cochlear implant recipients with 
single-sided deafness who became elective non-users?', Cochlear Implants Int: 1-8. 
Zhao, E. E., J. R. Dornhoffer, C. Loftus, S. A. Nguyen, T. A. Meyer, J. R. Dubno, and T. R. McRackan. 2020. 'Association 
of Patient-Related Factors With Adult Cochlear Implant Speech Recognition Outcomes: A Meta-analysis', 
JAMA Otolaryngol Head Neck Surg.