How Does the Length of Pulse Trains and Pulse Intervals Affect Tolerability With Transcutaneous Auricular Vagus Nerve Stimulation?
Phase: NA
Conditions: Healthy
Sponsor: University of Miami

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TITLE PAGE
Full protocol title: How does the length of pulse trains and pulse intervals 
affect tolerability with transcutaneous auricular vagus nerve stimulation?
Abbreviated title: taVNS Dosage Study 1
IRB Number (eProst ID): 20240134
Protocol Version Number: 1
Protocol Version Date: 3/5/2024
PI Name: Marlon Wong
NCT Number: NCT06381102
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1)
Protocol Title
How does the length of pulse trains and pulse intervals affect 
tolerability with transcutaneous auricular vagus nerve stimulation?
Short Title: taVNS Dosage Study 1
2)
IRB Review History*
Not applicable
3)
Objectives*
We will compare the tolerability and intended physiological effects for 2 different 
pulse train length applications of transcutaneous auricular vagus nerve stimulation 
(taVNS).  Specifically, a crossover design will be used to assess if 30 seconds on 
and 30 seconds off (Protocol 1) is equally tolerable and effective to 10 seconds on 
and 10 seconds off (Protocol 2) with a set stimulation intensity (2 mA) for 60 
minutes. This study is part of a larger research agenda designed to inform the 
development of personalized pain relief programs based on using patient 
preferences and a mechanistic understanding of the interventions to integrate 
neurostimulation interventions into multimodal care for persistent pain.  30 healthy 
adults (15 female) will receive  60-minute sessions of 2 different taVNS protocols.  
Both taVNS protocols will have a 50% duty cycle, but Protocol-1 will have a 30s 
on and 30s off cycle, while Protocol-2 will use a 10s on and 10s off cycle.  Each 
participant will receive both protocols in random order and on separate days.
Aim 1: Determine the effects of different taVNS pulse train and interval 
lengths on tolerability and heart rate variability (HRV).   Tolerability will be 
assessed using semi-structured interviews and questionnaires.  HRV will be 
assessed using a chest-strap heart rate monitor (H10, Polar, Finland).
We hypothesize that Protocol-2 will have greater tolerability and it will be 
associated with a greater increase in HRV.  
Aim 2: Determine if the taVNS protocols differ in their effects on pain 
sensitivity and cortical excitability response . A subset of the participants (n=12) 
will be used to assess the how the different protocols affect corticospinal 
excitability and pain sensitivity.  Corticospinal excitability will be assessed using 
transcranial magnetic stimulation (TMS) single and paired pulse paradigms.  Pain 
sensitivity response will be assessed using thermal and mechanical quantitative 
sensory testing.  We hypothesize that there will be no difference between protocols 
on the effect of corticospinal excitability or pain sensitivity. 
4)
Background*
Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive 
technique that involves the application of electrical currents through surface 
electrodes on the outer ear to target the auricular branch of the vagus nerve 
(ABVN). The vagus nerve is part of the autonomic nervous system, which regulates 
various bodily functions such as heart rate, blood pressure, digestion, and 
inflammation.1 taVNS has shown to have various therapeutic effects on different 
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conditions, such as depression, anxiety, inflammation, pain, migraine, and tinnitus.2-
4 The mechanism of action and influence of stimulation parameters on clinical 
outcomes are still under investigation.
taVNS is a relatively safe and well-tolerated technique.5-7 However, there is no 
clear consensus on the optimal parameters for taVNS. Different studies have used 
different types of waveforms, frequencies, intensities, durations, and duty cycles for 
taVNS, making it difficult to compare their results and mechanisms.
One issue that affects comfort with electrical stimulation modalities is the current 
density. taVNS uses small electrodes that fit onto the ear.  Smaller electrode pads 
concentrate the current in a smaller area. This increases the current density and 
potentially decreases tolerability for a given intensity. This is important as higher 
dosages are associated with greater physiological responses.
Duty cycle and current density are limited by safety and tolerability, respectively. 
Thus, identifying the  optimal pulse train and interval length  for comfort, given a 
set duty cycle and current density, may be the best way to optimize monophasic 
taVNS.   Our aim is to determine the effects of different pulse train and interval 
lengths on tolerability and response to taVNS in 30 healthy adults.  Specifically, a 
crossover design will be used to assess if 30 seconds on and 30 seconds off 
(protocol 1) is equally tolerable and effective to 10 seconds on and 10 seconds off 
(protocol 2) with a set stimulation intensity (2 mA) for 60 minutes. 
 
5)
Inclusion and Exclusion Criteria*
We will recruit 30 healthy participants (15 males, 15 females). 
Inclusion Criteria: 1) between the ages of 18-80 years, 2) English speaking (must be 
able to consent and complete the interviews in English)
Exclusion Criteria:  1) chronic pain (average intensity >2/10 on 0-10 scale, for 
longer than 3 months), 2) acute pain of intensity greater than 3/10, 3) chronic 
inflammatory conditions that are poorly controlled (e.g., diabetes, autoimmune 
disease), 4) any unstable medical condition or medical contraindication to moderate 
physical exertion (e.g., unstable angina or cardiac arrythmia), 5) pregnancy, 6) 
currently taking Buprenorphine or recently stopped taking (within 1 month), 7) 
presence of cognitive impairment or language barrier that impairs full autonomy in 
the consent process or in the ability to participate in detailed interviews, 8) implants 
in the head or neck, cochlear implants, or pacemaker, 9) head or neck metastasis or 
recent ear trauma, 10) history of epilepsy, 11) history of autonomic nervous system 
dysfunction (e.g., postural orthostatic tachycardia syndrome).
6)
Number of Subjects*
30
7)
Study-Wide Recruitment Methods*
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Only healthy individuals (no patients) will be recruited for this study.  All 
recruitment will be in accordance with the UM Human Subjects and 
Research Office guidelines. We will only recruit participants via flyers.
Participants will be recruited from the University of Miami Department of 
Physical Therapy, The University of Miami Student Complex, and The 
University of Miami Health and Wellness Centers, and the community.
15 female and 15 male healthy individuals will be recruited. Flyers 
advertising the study will be posted in University of Miami campuses (i.e., 
Plumer Building, Wellness Center) and in community centers (e.g., churches 
and gyms). The flyer will also be distributed to UM Physical Therapy 
faculty, students, and alumni via email listserv. 
Participants will receive $10 ($5 per visit), if participating in the Plumer site 
data collection, or $30 ($15 per visit) if participating in the Christine Lynn 
Center data collection, for their time.
 
8)
Study Design 
Primary Purpose: The primary purpose is to determine the effects of different pulse 
train and interval lengths on tolerability and response to taVNS in healthy adults. 
Study Phase: N/A
Interventional Study Model: Crossover design
Number of Arms: 2
Masking: none
Allocation: Block randomization with stratification by sex 
Enrollment: 30
9)
Study Timelines*
Each participant will complete 2 visits on separate days.  18 of the participants will  
for a total of ~60 minutes.  Thus, participants will be enrolled for one day. 
10) Study Endpoints*
A. Primary Outcome Measure Title: Tolerability
Primary Outcome Measure Description: Tolerability will be 
assessed with semi-structured interviews and a questionnaire with 
scores ranging from 0-10 for comfort.. 
Primary Outcome Measure Timeframe: at visit 1 and 2
B. Secondary Outcome Measure Title: Change in Heart Rate 
Variability (HRV) 
Primary Outcome Measure Description: HRV will be measured 
with an H10 chest strap device (Polar, Finland). Post values will be 
subtracted from pre values; thus, a positive number will indicate an 
increase in HRV post taVNS.
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Secondary Outcome Measure Timeframe: at visit 1 and 2, 15 
minutes at rest pre taVNS application and 15 minutes post taVNS 
C. Exploratory Outcome Measure Title: Effects on pain sensitivity 
(thermal and mechanical)
Exploratory Outcome Measure Description: Quantitative sensory 
testing utilizing pinprick, pressure pain threshold, and hot/cold 
thermodes will be assessed pre and post taVNS application 
Exploratory Outcome Measure Timeframe: at visit 1 and 2, pre and 
post taVNS application 
D. Exploratory Outcome Measure Title: Change in corticospinal 
excitability 
Exploratory Outcome Measure Description: For 12 of the 30 
participants, corticospinal excitability will be assessed using TMS 
single and paired pulse paradigms. 
Exploratory Outcome Measure Timeframe: at visit 1 and 2, pre and 
post taVNS application 
11) Arms and Interventions
All participants will receive both taVNS protocols in random order.  Thus, half of 
the participants will receive Protocol-1 first followed by Protocol-2, and the other 
half will receive Protocol-2 first followed by Protocol-1. 
Protocol-1 will consist of 30 seconds on and 30 seconds off duty cycle, and 
Protocol-2 will consist of a 10 seconds on and 10 seconds off duty cycle.  All other 
parameters will remain the same between protocols (Table 1). 
Table 1. Common Parameters between Protocols 1 and 2
Stimulation intensity
 2 mA
Session Duration
60 minutes
Frequency
25 Hz
Pulse width
500µS
12) Procedures Involved*
Data collection will take place at the Lynn Rehabilitation Center and at the 
Plumer Building on the UM Coral Gables Campus (Table 2).  All 
participants will complete 2 visits, receiving both taVNS protocols in 
random order.  All participants will also receive HRV assessment before 
and after each taVNS trial, and they will complete interviews and 
questionnaires after each trial.  Only the 12 participants who complete data 
collection at the Lynn Center and will receive additional assessments of 
quantitative sensory testing (QST) and transcranial magnetic stimulation 
(TMS).
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Table 2. Study Overview
Location
Pre-trial 
assessment
taVNS Trial
Post-trial 
assessment
Plumer Building 
(n=18)
PTQ, HRV, 
Protocol 1 and 
Protocol 2*  
Semi-structured 
interview, tolerability 
questionnaire, HRV
Lynn Center 
(n=12)
PTQ, HRV, 
QST, TMS 
Protocol 1 and 
Protocol 2*
Semi-structured 
interview, tolerability 
questionnaire, HRV, 
QST, TMS 
taVNS=transcutaneous auricular vagus nerve stimulation; PTQ= Perseverative Thinking 
Questionnaire; HRV= Heart rate variability; QST= quantitative sensory testing; 
TMS=transcranial magnetic stimulation; *= random order
A detailed description of each procedure is provided below:
Perseverative Thinking Questionnaire (PTQ)8: The PTQ is a 15-item, Likert-type 
scale designed to measure the broad idea of repetitive negative thought. It is 
expected to take less than 10 minutes to complete and it will be completed at visit 
1.
Semi-structured interviews: Post-trial semi-structured interviews will be used to 
examine the perceived experience of each taVNS protocol.  See interview 
template. Each interview is expected to take 5 minutes and will be conducted at 
the end of visits 1 and 2.
Tolerability questionnaire: A questionnaire will be used to assess pain ratings 
(with scores ranging from 0 for no pain to 10 for the worst pain), potential side 
effects, and belief in taVNS after each session.  This questionnaire is expected to 
take ~5 minutes to complete and it will be administered at visits 1 and 2.
Heart rate variability (HRV): HRV will be measured with an H10 chest 
strap device (Polar, Finland) and will serve as the primary endpoint for 
response to taVNS in Aim 2.  Participants will wear the chest strap 
continuously throughout the application of taVNS, and for 15 minutes 
prior (baseline) and 15 minutes post taVNS trial at each session.
Quantitative Sensory Testing (QST): Each of the 12 participants who complete 
data collection at the Lynn Center will undergo pressure pain threshold (PPT) 
using the Algomed Digital Algometer (Medoc, Israel), thermal pain testing using 
the TSA2 Air (Medoc, Israel), and temporal summation pain sensitivity (wind-up 
ratio) testing using the PinPrick stimulator (MRC Systems GmbH, Germany). The 
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entire QST protocol will take less than 15 minutes to complete.  The purpose of 
these tests are to determine the threshold for pain; thus, the stimulus will be 
discontinued immediately as soon as the participant indicates that the stimulus has 
become painful.
PPT: PPT is the force at which pressure begins to be perceived as pain. PPT 
assists in quantifying static mechanical hyperalgesia to blunt pressure and has 
been recommended for capturing pain sensitivity. PPT will be measured at the 
mid-belly of the upper trapezius with a probe area of 1 cm2 (probe diameter of 1.1 
cm). The tip of the algometer will be placed perpendicular to the skin and gradual 
pressure will be applied at a rate of 30 kPa/s. Participants will be asked to press a 
button to indicate as soon as a painful sensation is perceived, and then rate the 
intensity of the painful sensation. The PPT will be determined as the average of 
three trials.  
Thermal pain testing: All measurements will be completed using a 30x30mm 
thermode. Cold Pain Threshold (CPT) is the temperate at which cold begins to be 
perceived as pain. CPT assists in quantifying static thermal hyperalgesia to 
contact thermodes. CPT will be measured on the forearm. The thermode will be 
placed perpendicular to the skin and gradual decreasing temperature will be 
applied at a rate of 5℃/𝑠 with a maximum cut-off at 0℃. Participants will be 
asked to press a button to indicate as soon as a painful sensation is perceived, and 
then rate the intensity of the painful sensation on a NRS. The CPT will be 
determined with three series of descending stimulus intensities, as described 
above, at each point over 3 rounds.
HPT is the temperature at which heat begins to be perceived as pain. HPT will be 
measured on the forearm. The thermode will be placed perpendicular to the skin 
and gradual increasing temperature will be applied at a rate of 5℃/𝑠 with a 
maximum cut-off at 50℃. Participants will be asked to press a button to indicate 
as soon as a painful sensation is perceived, and then rate the intensity of the 
painful sensation on a NRS. The HPT will be determined with three series of 
ascending stimulus intensities, as described above, at each point over 3 rounds.
Wind-up ratio: A 256 mN pinprick will be used to assess wind-up ratio over the 
participants’ hand. The perceived intensity of a single pinprick will be compared 
with that of a series of 10 repetitive pinprick stimuli of the same physical intensity 
(1/s applied within an area of 1 cm2). The participant will be asked to give a pain 
rating representing the single stimulus, and the estimated mean over the whole 
series of 10 stimuli using a ‘0–10’ numerical rating scale. The whole procedure 
will be repeated 3 times. Wind-up ratio (WUR) will be calculated as the ratio: 
mean rating of the 3 series divided by the mean rating of the three single stimuli.
Quantitative sensory testing is expected to take <15 minutes to complete and will 
be completed pre and post taVNS at visits 1 and 2 for a subset of the participants 
(n=12). 
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TMS single pulse, short-interval intracortical inhibition (SICI), and 
intracortical facilitation (ICF): Paired-pulse transcranial magnetic 
stimulation (i.e., SICI and ICF) has become an increasingly popular 
method of using TMS techniques to probe intra and inter cortical 
connections. For paired-pulse transcranial magnetic stimulation, a 
subthreshold conditioning stimulus is followed by the suprathreshold 
individual test stimulus (TS) with varying interstimulus intervals. ICF can 
be elicited with ISI of 6–25 ms while SICI is elicited at 1–6 ms. Both, 
SICI and ICF prove intracortical excitability but through different 
mechanisms. 
 SICI and ICF will be assessed using TMS paired-pulse paradigms with 
the Magpro X100 (MagVenture, Alpharetta, GA).  These TMS paired-
pulse measures will serve as secondary endpoints for response to taVNS in 
Aim 2. 
Participants will be comfortably seated in an armchair with 
the head on a foam headrest. TMS will be delivered 
through a focal figure-of-eight shaped magnetic coil.  The 
coil will be placed flat on the head over the left motor 
cortex (Figure 1), at an approximate angle of 45° to the 
sagittal plane, inducing a current in the brain roughly 
perpendicular to the central sulcus, flowing from posterior to 
anterior, as this has been reported to be the most effective 
way to activate the corticospinal system transsynaptically.  
Motor evoked potentials (MEP) will be recorded using 
surface EMG Ag/AgCl electrodes placed over the right abductor digiti 
minimi muscle in a belly-tendon montage. The optimal coil placement will 
be determined by recording MEPs while varying the coil position. The coil 
position leading to the highest peak-to-peak amplitude of the MEP (‘hot 
spot’) will be marked using the TMS navigation system (Localite, 
Germany) to ensure accurate coil positioning throughout the testing.  A 
fixed sequence of TMS measurements will be followed: First, TS and 
resting motor threshold (RMT) will be defined as the lowest stimulator 
output intensity that induced MEP peak-to-peak amplitude greater than 50 
μV in five out of 10 consecutive trials.
 Then the single pulse and paired-pulse parameters, SICI and ICF, will be 
obtained in a pseudo-random order. EMG response to single pulse stimuli 
of 130% of RMT will be recorded.  For paired pulse, the conditioning 
stimulus will be set to an intensity of 70% of the RMT as this does not 
produce MEPs, and the intensity of the following suprathreshold test 
stimulus will be set to 130% of RMT. We will use multiple interstimulus 
intervals (ISIs), including 1, 2, 3, and 5 milliseconds for SICI and 7, 10, or 
15 milliseconds for ICF, with 10 pulses at each interval, to produce a 
response curve. The average of the 10 trials will be used to define the 
amplitude of the peak-to-peak MEP for each condition. 
Figure 1. TMS coil 
placement
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taVNS: A portable taVNS Stimulator (Soterix Medical, Woodbridge, NJ) or the 
DS8R Biphasic Constant Current Stimulator (Digitimer, United Kingdom) will 
be used with flexible hydrogel electrodes to administer taVNS at the cymba 
concha (Figure 1), using the parameters described in Table 1.  Both devices 
are approved for research purposes, and these parameters have been shown 
to safe in healthy people and across a variety of patient populations.  
Participants will be quiet sitting in a comfortable chair during the 
application of taVNS.
Please see the Risks to Subjects section for procedures performed to lessen the 
probability or magnitude of risks.
13) Data and Specimen Banking*
NA 
14) Data Management*
The principal investigator (Marlon Wong) will be responsible for all data 
management and analyses.  A research assistant will assist with data entry 
and qualitative data coding. All quantitative data will be entered and stored 
in the University of Miami REDCap system. NVivo software (QSR 
International, United States) will be used for qualitative data management 
and analyses, and SPSS version 28 (IBM, United States) will be used for 
quantitative analyses.  
Qualitative Analysis:  The Interviews will be recorded and transcribed 
verbatim. Transcripts will be checked for accuracy against recordings. We 
will apply rapid qualitative analysis to the interview transcripts to create 
structured templates and matrix displays. Analysis will be performed 
independently by two coders to minimize bias and ensure credibility and 
dependability of findings. First, qualitative team members will use the 
interview guide, while reviewing the transcripts, to create summaries 
(structured templates) of the interviews. The structured templates will be 
aggregated to create matrices that enable systematic comparison between 
participants.  After rapid qualitative analyses are completed, the transcripts 
will be uploaded into NVivo for coding.
Quantitative Analysis: Descriptive statistics will be assessed, including 
sample mean, standard deviation, median, interquartile range for each 
continuous variable, and frequencies and percentages for categorical 
variables. We will test distributional assumptions of all variables by using 
normality tests and visual inspection.  Paired T tests will be used to assess 
differences in post-trial values between protocols.    
Convergence of Qualitative and Quantitative Data: An exploratory 
sequential mixed methods approach will be used to integrate qualitative and 
quantitative data, when appropriate, for determining tolerability.
Figure 1.
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15) Provisions to Monitor the Data to Ensure the Safety of Subjects*
16) Withdrawal of Subjects*
To address the challenge of early identification of an increased risk of a 
known adverse event, all adverse event data will be tracked and evaluated 
by the study team on a regular basis. A participant may be taken out of the 
study if any of the following criteria are met: (i) the participant chooses to 
withdraw from the study; (ii) the participant’s physician determines that 
the participant should not continue for physical or mental health reasons; 
(iii) a physical injury that would prohibit continuation of the study is 
sustained by the participant; (iv) continuing involvement in the study 
would result in a degradation of participant health; (v) personal, family, or 
other obligations prohibit further involvement in the study. 
No special precautions are needed for the participants before, during, or 
after the study, including medication or dietary restrictions. No special 
care is required for or by the participants.
Participants may be withdrawn from the research without their consent if 
it is deemed that they are unsafe to participate (e.g., abnormal vital signs, 
signs of distress such as unexplained diaphoresis, change in cognitive 
status, and/or signs of intoxication) or if there has been a change in their 
medical status (e.g., recent surgery or ongoing illness).
If a participant is withdrawn without their consent (fully or partially), the 
reason will be explained to them and will be notated in REDCap.
17) Risks to Subjects*
The risks associated with participation in the study are deemed to be extremely low. 
Nevertheless, this study involves the administration of assessment instruments that 
may cause minor discomfort, the application of an experimental intervention, and 
the risk of loss of confidentiality. All participants will be informed that all aspects 
of this study are voluntary.  It is also important to note that we have used very 
similar procedures in a previous study involving cancer survivors with 
chemotherapy induced peripheral neuropathy (IRB#20230154) with no adverse 
effects.
Transcutaneous Vagus Nerve Stimulation is reported in numerous systematic 
reviews to be effective in treatment of insomnia and relief of acute and chronic 
pain. Given the non-invasive nature of taVNS, its use is growing for clinical 
purposes as well as in healthy populations for basic research in cognitive 
neuroscience and related fields.  
Risks/discomforts associated with taVNS: A systematic literature review on the 
safety and tolerability of tVNS has evaluated 51 studies, independent of the area of 
application. The authors report that the most prevalent side effect was local skin 
irritation from electrode placement, occurring in about 18% of included subjects 
following long-term stimulation. Headache (3.6%) and nasopharyngitis (1.7%) were 
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more rare side effects, and only 2.6% of participants dropped out of studies due to 
side effects. taVNS will be administered in a laboratory by an investigator and 
participants will be monitored for any adverse responses. Adverse responses will be 
tracked and reported to the SCCC Data & Safety Monitoring Committee.
Risks/discomforts associated with TMS: 
Seizure or syncope: Induction of seizures is the most severe acute adverse effect of 
TMS; however, the risk is very low. A published search of the literature only 
identified 41 reports of seizures. The estimated standardized risk for paired-pulse 
TMS stimulation is 2/100,000 sessions. Such a seizure has never been reported to 
result in any permanent damage, and the risk only occurs during the stimulation: 
there is no heightened risk of seizure after the stimulation. A licensed physical 
therapist, and certified basic life support (CPR and AED) provider, will be present 
at all times. In the case of a seizure, TMS will be terminated immediately, and the 
provider will follow guidelines for seizure managment4 and activate emergency 
response if needed. The subject will be assisted in controlled reclining without 
impact. Airway breathing and circulation will be assessed. Unless tonic-clonic 
seizure activity occurs, the subject will be turned on one side to help clear the 
airway and avoid aspiration and maintained in that position until recovery of 
awareness. Delayed recovery of normal consciousness beyond 30 s following a 
seizure will mandate further medical evaluation.
Hearing: There is a very small risk of hearing damage. After exposure to the TMS 
stimulus, a few adult subjects have experienced transient increases in auditory 
thresholds, and there was a single report of permanent small threshold shift in a 
person whose ear plug slipped out during stimulation. To minimize the risk of 
hearing damage, participants will be fitted with ear plugs. 
Local pain, headache, or discomfort: TMS is generally well tolerated and 
experienced as painless by most participants; however, there is a small risk of pain 
or discomfort with paired-pulse TMS.  Less than 2% of patients in TMS trials 
discontinued treatment due to pain.
Risks/discomforts associated with completion of questionnaires: Some questions 
may be emotionally distressful to some participants or make them uncomfortable. 
Participants will be instructed that they can skip any questions which they do not 
wish to answer.
Risks/discomforts associated with measurement of sensory function (QST): Pain 
thresholds will be measured for pressure as well as for pinprick. This will result in 
slight discomfort for the participant. As soon as the participant indicates that the 
stimulus has become painful, the stimulus will be discontinued immediately. The 
equipment used for sensory testing has been used in our laboratory for the last few 
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years, without any adverse events. This equipment is also used in many other 
laboratories and has an excellent track record.
Risks/discomforts associated with heart rate variability monitoring:  Heart rate 
variability data will be gathered through two standard ECG pads on the chest that 
will be worn continuously.  There are no significant risks associated with heart rate 
variability monitoring.  Some people have minor discomfort or skin irritation where 
the sensors (electrodes) are placed, and we will inspect the skin after assessment. 
Risks/discomforts associated with completion of questionnaires: Some questions may 
be emotionally distressful to some participants or make them uncomfortable. Participants 
will be instructed that they can skip any questions which they do not wish to answer.
18)  Potential Benefits to Subjects*
There are no direct benefits to participants.
19) Vulnerable Populations*

NA
20) Multi-Site Research*

NA
21) Sharing of Results with Subjects*
NA
22) Setting
The research procedures will be conducted at the Lynn Rehabilitation 
Center and at the Plumer Building on the UM Coral Gables Campus. The 
Christine E. Lynn Rehabilitation Center was designed from scratch to be 
one of the country’s elite facilities for patients recovering from traumatic 
brain injury, spinal cord injury, cancer treatment, and other complex 
conditions. The stunning 250,000-square-foot, nine-story structure opened 
in 2020, and it houses 80 inpatient beds and features world-class amenities 
and next-generation rehabilitative technology.  Every aspect of the facility 
underscores a focus on comprehensive care. The building’s layout ensures 
that clinical care and research share space, so that patients and families see 
the scientists who are developing treatments, and researchers interact with 
real people who need the results of their work—a constant reminder of the 
way Lynn Rehabilitation Center integrates academic study with the day-
to-day treatment of patients.
Dr. Wong’s APReCIAT Pain Research Lab is located in the Lynn 
Rehabilitation Center.  His dedicated lab space is equipped with a PC, 
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laptop, secured internet access, filing cabinets, office and medical 
supplies, and research equipment and supplies.
The Plumer Building is the hub of the UM Physical Therapy Department 
educational activities.  It includes multiple floors of educational and 
research laboratory facilities and Dr. Wong’s primary office is located in 
the Plumer Building. His office is equipped with a PC, laptop, secured 
internet access, filing cabinets, office and medical supplies, and research 
equipment and supplies. Research activities at the Plumer building will 
take place in a laboratory space that is equipped with a PC, laptop, secured 
internet access, filing cabinets, office and medical supplies, and research 
equipment and supplies.
23) Resources Available
Research Team:
Marlon Wong, PT, DPT, PhD
Principal Investigator
Dr. Marlon Wong is an Associate Professor of Clinical at the University of Miami Miller School 
of Medicine within the Department of Physical Therapy. Dr. Wong has extensive research and 
clinical experience in the assessment and management of pain in a variety of patient populations.  
As the PI, he will provide expertise and oversee the execution of the aims outlined in this research 
project. He will develop and conduct the methodology, data collection, data analysis, and 
manuscript preparation. 
Gabriel Gonzalez, PT, DPT
Research Coordinator, PhD Student
Dr. Gabriel Gonzalez, PT, DPT has two years of clinical experience working with 
chronic pain patients.  In addition, he is currently a PhD student in the University of 
Miami, Physical Therapy Department, under Dr. Wong.  Dr. Gonzalez will coordinate the 
study activities including participant recruitment, scheduling, data collection, and data 
management.
Juan Gonzalez, DPT
Research Assistant, PhD Student
Dr. Juan P. Gonzalez PT, DPT, has four years of clinical experience specializing in the 
assessment and management of patients with chronic pain. In addition, he is currently a 
PhD student in the University of Miami, Physical Therapy Department, under Dr. Wong. 
Dr. Gonzalez has developed expertise with quantitative sensory testing and data 
management and will assist with those aspects of the project.  
Lisa McTeague, PhD
Mentor/Collaborator
Dr. McTeague is a clinical psychologist and an Associate Professor in the Brain Stimulation 
Laboratory of the Department of Psychiatry and Behavioral Sciences at the Medical University of 
South Carolina.  Dr. McTeague is an expert in neurostimulation techniques, specifically in taVNS 
and TMS, and she serves as faculty in the National Center of Neuromodulation for Rehabilitation 
at the Medical University of South Carolina (MUSC).   She has over ten years of experience 
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working with these modalities to develop innovative assessment and treatment methods to 
renormalize neural networks and restore behavior related to anxiety and mood disorders and 
trauma exposure. Her current work is purposefully transdiagnostic and significantly applicable to 
pain research.  She will provide expertise and mentorship on neurostimulation research and heart 
rate variability.  Dr. Wong will spend a week at Dr. McTeague’s lab in MUSC to complete 
intensive training in paired-pulse TMS procedures prior to initiating research activities. Dr. 
McTeague will only have access to de-identified information.
Eva Widerstrom-Noga, PhD, DDS
Mentor/Collaborator
 Dr. Widerstrom-Noga is a Professor of Neurological Surgery and Rehabilitation Medicine at 
UM, and she is the Principal Investigator of the Clinical Pain Research Laboratory of The Miami 
Project to Cure Paralysis. She is an expert in pain assessment and pain classification, and cross-
disciplinary clinical pain research (pain physiology and pain psychology), with three decades of 
experience in the field.  Her research involves both qualitative and quantitative pain 
methodologies in persons with chronic pain after neurotrauma. She will provide expertise and 
mentorship on pain and mixed methods research. Dr Widerstrom-Noga will only have access to 
de-identified information.
Facilities and Equipment:
Dr. Wong’s Clinical Pain Research Lab is located in the Lynn Rehabilitation Center, 
room 3.412.  His dedicated lab space is equipped with a PC, laptop, secured internet 
access, filing cabinets, office and medical supplies, and research equipment and supplies 
(detailed below). All of the devices are approved for research and will be used according 
to their approved indications.
Item
Description
1. ALGOMED 
digital algometer with real-time visual & auditory 
feedback to control & monitor applied pressure rates 
to measure pressure pain threshold.
2. PinPrick stimulator set
7 pinprick punctate probes (8 – 512 mN) for sharp 
QST
3. taVNS Stimulator by 
Soterix Medical
the first transcutaneous auricular vagus nerve 
stimulator (taVNS) specially developed for clinical 
brain stimulation research. The system has adjustable 
parameter settings (frequency, train duration, inter-
train interval, session duration) and the option to 
unlock device in three different ways (code-based , 
time-based, ElectraRx web-based)
4. DS8R Biphasic 
Constant Current 
Stimulator
A constant current stimulator for human research 
studies involving nerve and muscle stimulation via 
surface electrodes.
5. MagVenture Magpro 
X100
high performance magnetic stimulator designed 
primarily for transcranial magnetic stimulation (TMS) 
research. It can provide both biphasic and 
monophasic pulse waveforms, electronically reverse 
current direction, complex pulse firing patterns, and 
high frequency stimulation up to 100 Hz.
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6. Localite TMS 
Neuronavigation 
system
navigation system for TMS.  Allows for planning 
stimulation areas and monitoring and recording the 
correct positioning of patient and coil
7. ADInstruments 
PowerLab
an EMG system that enables collection of TMS 
neuroplasticity responses
24) Prior Approvals
NA
25) Local Number of Subjects
30
26) Confidentiality
Confidentiality will be maintained by assigning participant identification numbers 
at the beginning of the study. All data will be identified using these ID numbers. 
The personal information included as data will consist of the gender, age, race, 
ethnicity, and cancer type and treatment. This information will be kept in a locked 
file cabinet and stored in a password-protected digital file on the encrypted 
database at the University of Miami Physical Therapy Department located at 5915 
Ponce De Leon Blvd, Plumer Building 1st Floor, Miami, FL 33146. Signed 
consent forms will be kept in a master file in a locked file cabinet. Only the 
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principal investigator and research assistant will have access to participant’s 
personal information and data. 
Choose the statements below that are applicable to this research: 
26(a).  Will the research collect protected health information or personally identifiable 
information from the EMR or from subjects at UHealth and/or JHS?
☐  Yes (If checked go to 26(b))
☒  No (If checked, go to  Section 27)
26(b).  Check the box next to the correct statement below 
☐   Research Subjects will sign a HIPAA Authorization before the research will collect 
this data. 
☐   Research Subjects will not sign a HIPAA Authorization for this data collection and 
the research is requesting a waiver of HIPAA authorization from the IRB for recruitment 
purposes only. 
26(c).  How will the research store the data? 
☐  On a University of Miami electronic device (e.g. encrypted, password-protected 
computer)
☒  On a cloud-based storage system that is approved by the University of Miami 
(REDCap)
☐  On the secured JHS SharePoint environment 
☐  Other, specify:  Click here to enter text.
26(d)  Select one of the following: 
☐  The Principal Investigator (and/or Study Team members) will record (e.g. write 
down, abstract) data acquired in a manner that does not include any indirect or direct 
identifiers (listed in the instructions for Section 26 of this protocol), and the recorded data 
will not be linked to the individual’s’ identity.  
   OR
☒  The Principal investigator (and/or Study Team members) will record (e.g. write 
down, abstract) the data collected in a manner that does not include any direct identifiers 
(see list in the instructions for Section 26 of this protocol) of any subject. Instead, the 
Principal Investigator and/or Study Team members shall will assign a code (that is not 
derived in whole or in part from any direct or indirect identifiers of the individual) to 
each study subject and link the code to the study subject’s identity. The link to each 
subject’s identity and/ or other identifiable information will be maintained on a document 
separate from the research data. 
26(e)  Additional requirement for Jackson Health System Data:
NA
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  Not-applicable, no data will be acquired from JHS under a waiver of authorization. 
  JHS data, including Protected Health Information (PHI) and/or Personally Identifiable 
Information (PII), acquired from JHS for this research under a waiver of authorization shall 
only be stored on the secured JHS SharePoint environment made available by JHS. I and 
the Study Team members shall not copy or store the JHS sourced personally identifiable 
information (PII), including protected health information (PHI) data to any other system, 
including any systems maintained or provided by the University of Miami. I and the Study 
Team shall only copy or transfer JHS-sourced data that has been properly de-identified in 
accordance with all requirements contained in the HIPAA Rules by removing all of the 
identifiers listed in the instructions for Section 26 of this protocol.
27. Biospecimens
  Not applicable.  No biospecimens will be collected
  Bio-Specimens obtained for this research will be stored without any   
direct or indirect identifiers.  
 
 Bio-Specimens obtained for this research will be stored in a de-identified 
coded manner.   
  When required to transport data or bio-specimens for this research, the research 
team will transport the data and bio-specimens in a de-identified (or anonymous) 
manner with a link to the individual subject’s identity maintain separately from the 
data and/or bio-specimen.
27) Provisions to Protect the Privacy Interests of Subjects
Only IRB approved research team members will have access to study records. 
Overall study results will not be shared with study participants, individually. 
Confidentiality will be maintained by assigning subject identification numbers at 
the beginning of the study. All data will be identified using these ID numbers. 
This information will be kept in a locked file cabinet and stored in a password-
protected digital file on the encrypted database in the office of the PI in the 
University of Miami Department of Physical Therapy located at 5915 Ponce de 
Leon Boulevard, 2nd Floor, Coral Gables, FL 33146. Signed consent forms will 
be kept in a master file in a locked file cabinet. Only the principal investigator 
and research assistant will have access to subject’s personal information and data. 
28) Compensation for Research-Related Injury
Compensation will not be provided for research-related injury.  Funds to 
compensate participants for pain, expenses, lost wages, and other damages 
caused by injury are not available.  However, treatment will be available 
in most cases and their insurance may be billed or participants will have to 
pay.
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29) Economic Burden to Subjects
There are no direct costs associated with participating in this study.  
However, transportation and parking may be an economic burden on some 
participants.  The 18 participants who complete data collection at the 
Plumer building will be paid $10 to compensate them for the economic 
and time burden, and those who complete data collection at the Lynn 
Rehabilitation Center  will be paid $30.  All participants will be paid upon 
completion of visit 2. 
30) Consent Process
We will follow SOP: Informed Consent Process for Research (HRP-090).  
The consent process will begin with the phone screening when interested 
people call to inquire about participation.  If they provide verbal consent 
to the phone screening and are deemed eligible for the study, then they 
will be invited to the Plumer Building or Lynn Center.  Potential 
participants will have the opportunity to consult with family members or 
others and will have all questions addressed by the PI or other members of 
the study team. Potential participants will be briefed on their rights as a 
research subject, including their right to withdraw at any time with no 
negative consequences.
 The study procedures will be reviewed with each participant at each phase 
of the study and verbal consent will be re-obtained to ensure ongoing 
consent.  Each time that the verbal consent is obtained, it will be reiterated 
to the patient that they may choose to withdraw from the study at any 
time.
Waiver or Alteration of Consent Process (consent will not be obtained, 
required information will not be disclosed, or the research involves 
deception)

NA
Cognitively Impaired Adults

NA
Adults Unable to Consent

NA
Adults Unable to Consent

NA
31) Process to Document Consent in Writing
Consent will be documented in REDCap via e-Consent prior to initiating 
onsite data collection.  Please see the attached consent form.  A printed 
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copy will be provided to the participants. During the meeting we will 
review and explain the information in the consent document, answer any 
questions the participant has about the study, ask the participant questions 
about the study to confirm their comprehension, and ask the participant if 
they consent to participate. If the participant agrees, then they will be 
asked to sign and date the consent document electronically.  Then we will 
explain to the participant that they will receive a copy of the signed 
documents via email.
32) Authorization for Use and Disclosure of Protected Health 
Information (HIPAA) 
Since we are collecting data on healthy participants, and not patients, this is 
not applicable.
If you are collecting health information from JHS under a waiver of authorization, you 
must read the paragraph below and sign the signature block to indicate your agreement:  
Not applicable.  This research will not collect data from JHS record under a waiver of 
authorization 
Notwithstanding the preceding “I confirm” statements above, I agree that neither I nor 
any member of the study team listed on the IRB submission for this Protocol shall ever 
re-use or re-disclose any of the information acquired from Jackson Health System in any 
format, whether identifiable or de-identified, to any individual or entity without first 
obtaining written permission from Jackson Health System, even if such re-use or re-
disclosure is permissible by law (e.g., HIPAA).
  
 
______________________________________________
PI Signature                                                               Date
33) Drugs or Devices
The Soterix taVNS device is approved for research purposes, and it is 
being used in this study as intended.  The device will be stored and used in 
our labs at the Lynn Rehabilitation Center and Plumer Building, and it will 
only be used on study participants and administered only by authorized 
investigators.  Our lab space is not a shared space and remains locked at 
all times when not in use.  No patient care takes place in the lab space. 
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Badran BW, Mithoefer OJ, Summer CE, et al. Short trains of transcutaneous 
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Courties A, Deprouw C, Maheu E, et al. Effect of Transcutaneous Vagus Nerve 
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Ferreira NR, Junqueira YN, Correa NB, et al. The efficacy of transcranial direct 
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Stilling JM, Monchi O, Amoozegar F, Debert CT. Transcranial Magnetic and 
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Farmer AD, Strzelczyk A, Finisguerra A, et al. International Consensus Based 
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Ehring T, Zetsche U, Weidacker K, Wahl K, Schonfeld S, Ehlers A. The 
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