Non-invasive Brain Stimulation to Improve Quadriceps Muscle Function After Anterior Cruciate Ligament Reconstruction
Phase: PHASE1
Conditions: Anterior Cruciate Ligament Reconstruction, Quadriceps Muscle Weakness, Transcranial Direct Current Stimulation
Sponsor: Arcadia University

 
Non-invasive Brain Stimulation to Improve Quadriceps Muscle Function After Anterior Cruciate Ligament 
Reconstruction 
NCT #: ID not assigned yet  
5/28/20 
 
 
 
 

                                      Institutional Review Board (IRB)                                                             
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Please fill in all parts of this form that are required. Provide a non-scientific or lay summary of the project that must 
include the items listed below. The Protocol Summary will be reviewed only if all required sections are completed. (The 
spaces provided will expand as you type and will become scroll boxes). NOTE: If the protocol is part of a grant, 
please upload the grant documents (proposal and budget) to the IRBNet package as an appendix. 
 
1. Background and Objectives - Describe the purpose of the study. Describe any past studies that are related 
to this study (short literature review). 
 
Quadriceps muscle dysfunction persists for years after anterior cruciate ligament reconstruction (ACLR).9  Restoring 
quadriceps function after ACLR is critical as quadriceps performance is related to better self-reported function, reduced 
risk of reinjury, and better movement patterns.4,5,10,12–14  Emerging evidence suggests that alterations in corticospinal 
excitability (CSE) persist after ACLR, and these alterations are related to poor quadriceps performance (i.e. less strength 
and slower rate of torque development (RTD)).3,7,18  However, few studies have evaluated quadriceps performance and 
CSE prior to 6 months after ACLR.7,18  Comprehensive evaluation of quadriceps performance and CSE early after ACLR 
is critical to developing new interventions to mitigate persistent quadriceps dysfunction and improve outcomes.   
My previous work indicates that after ACLR patients demonstrate alterations in CSE as early as 2 weeks after 
surgery,18 and these alterations do not change during the course of post-operative rehabilitation (Zarzycki, in review, 
JOR; Zarzycki, in review, JOSPT).  More specifically, patients after ACLR demonstrated reduced thresholds and altered 
excitability, which suggests that the corticospinal tract has a higher recruitment threshold with potentially steep 
activation curves. Reduced thresholds and steeper recruitment curves may limit a more graded activation of the 
quadriceps necessary for functional movement and stability. The fact that the alterations in CSE did not change from 2 
weeks after surgery to a mean of 4.5 months after surgery suggests that current rehabilitation strategies are not 
addressing alterations in CSE. There is a need to investigate new neuromodulatory interventions, such as transcranial 
direct current stimulation, that have the potential to modify CSE and muscle performance in patients after ACLR.     
Transcranial direct current stimulation (tDCS) increases short-term CSE and isometric strength in healthy 
participants and stroke surviviors.6,16,17 In the proposed pilot study, tDCS will be used as an intervention to determine its 
effects on CSE and quadriceps muscle performance in patients recovering from ACLR.  We will incorporate two measures 
of quadriceps performance, isometric strength and rate of torque development (RTD) as both measures are altered and 
related to functional outcomes after ACLR.  However, to the best of my knowledge, no studies have determined the 
effectiveness of tDCS on CSE and quadriceps performance in patients after ACLR, and no studies to date have evaluated 
the relationship between multiple measures of quadriceps performance and CSE in patients after ACLR. Evaluating new 
interventions with potential to mitigate alterations in CSE (i.e. active motor thresholds (AMT) and slope of the 
recruitment curve (SLOPE)) and quadriceps muscle performance (i.e. isometric strength and RTD) in patients recovering 
from ACLR are critical to improving outcomes in this population. Therefore, the aims of this study are to: 
 
Aim 1: Determine the effects of a single session of tDCS on two measures of CSE and two measures of quadriceps 
performance in patients after ACLR. 
Hypothesis 2.1: Patients after ACLR will demonstrate increased CSE (lower AMTs and steeper SLOPEs) after one session 
of active tDCS and no changes in CSE after placebo tDCS. 
Hypothesis 2.2: Patients after ACLR will demonstrate greater RTD/isometric strength after one session of active tDCS 
and no changes in RTD/isometric strength after placebo tDCS.   
 
Aim2: Determine the relationship between two measures of CSE and two measures of quadriceps muscle performance in 
patients after ACLR.  
Hypothesis 1.1: Greater CSE will be associated with greater quadriceps isometric strength and greater RTD. 
Hypothesis 1.2: The correlation between CSE and RTD will be greater than the correlation between CSE and isometric 
strength.   
 
Current outcomes following ACLR are less than optimal with patients demonstrating chronic quadriceps dysfunction 
related to altered movement patterns and the development of post-traumatic knee OA.  Emerging evidence suggests that 
quadriceps dysfunction after ACLR is related to alterations in CSE. Therefore, interventions targeting CSE have the 

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potential to mitigate chronic quadriceps dysfunction, improve movement patterns, and improve outcomes. The proposed 
study is a logical and essential first step in determining the effect of tDCS, an intervention known to induce changes in 
excitability, on CSE and quadriceps performance in patients after ACLR.  Upon completion of this study, I will have 
obtained the pilot data needed to apply for a larger grant to investigate the effects of multiple sessions of tDCS on CSE 
and quadriceps muscle performance, generating the evidence needed to introduce this intervention into the clinical 
practice.   
 
 
2. Data Use (Select all that apply):  
☐ Dissertation, Thesis, Undergraduate honors project 
☒ Publication/journal article, conferences/presentations 
             ☐ Results released to agency or organization 
             ☒ Results released to participants/parents 
             ☐ Results released to employer or school 
             ☐ Other Click here to enter text. 
 
3. External IRB: 
a) Is this proposal currently under review or has it been reviewed and approved by another institution’s 
IRB? IF YES, include a copy of the proposal and if available, IRB approval from that institution. If the 
proposal has not yet been submitted to the other institution, please note an anticipated date of submission and 
a copy of the other institution’s review guidelines. 
 
☐ Yes 
☒ No 
 
Anticipated date of Submission:  
 
b) Is this a collaboration with another institution (if yes, please move to section 3 c)? 
 
☐ Yes 
☒ No 
 
c) Is each institution doing their own review or will one institution serve as the primary IRB through an 
Authorization Agreement? 
                  ☐ Each institution will complete their own review. 
                  ☐ An Authorization Agreement will be signed. 
 
4. Study Population - Are the human subjects involved in the proposed activity included in the following 
categories? (check all that apply, at least one box must be checked) 
Yes. Human subjects are included in this study.   
☒Minors                                                                                     ☐ Pregnant women, human fetuses, neonates 
             ☐Prisoners                                                                                  ☐ AIDS/HIV-positive subjects 
             ☐ Terminally ill subjects                                                            ☐ Subjects with intellectual disabilities 
             ☐ Economically and/or educationally disadvantaged persons   ☐ Minorities 
             ☐ None of the above                                                                   ☐ Other Click here to enter text. 
 
5.  Inclusion and Exclusion Criteria - Describe the criteria that define who will be included or excluded in 
your study sample. If you are conducting data analysis only describe what is included in the data set you 
propose to use. 
 

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ACLR Group: Individuals between the ages of 13 and 55 years with a history of ACLR (4 months to 5 years) will 
be recruited.   
 
Uninjured Group:  Individuals between the ages of 13 and 55 years without a history of major knee injury or 
surgery will be recruited for the uninjured group.  These participants will be matched to participants in the ACLR 
group by sex, age, and activity level.     
 
Both groups must participate (or participated in prior to surgery) in sports involving jumping, pivoting, cutting 
on a regular basis to be included.  Individuals < 18 years of age will only complete strength testing and 
questionnaires at one testing session.  They will not participate in TMS testing or the intervention (tDCS with 
stationary bike riding).   
 
Subjects recruited for either group will also be excluded if: (1) they are currently on anti-epileptic medication or 
have a history of epilepsy or seizures (2) have a first-degree family member with a history of epilepsy (3) had a 
prior head injury that required hospitalization or concussion in the past 6 months (4) have any metal in the head, 
eyes, neck or face (with the exception of dentures) (5) have a history of brain surgery (6) have skull abnormalities 
or fractures (7) have implantation of electrical devices such as (but not limited to) cardiac pacemaker, cardiac 
defibrillator, cochlear implants or nerve stimulators (8) history or recurring or severe headaches/migraines (9) 
known neurological disorders or muscle diseases (10) pregnancy (11) lower extremity botulinum injections in 
past 6 months (12) baclofen pumps (13) taking any medications that act on the central nervous system.  Potential 
participants will be screened verbally of  via email for these exclusion criteria prior to consent.  At time of 
consent, the TMS Adult Safety Screen will completed in writing by each potential participant to again screen for 
these criteria.15  Yes answers to questions 1, 3, 5,6,7,8,9,10,12,13 are absolute exclusions.  Yes answers to 
2,4,11,14,15 will trigger follow up questions.  Individuals with a chronic history of syncope, ringing in the ears 
(yes answer to 2,4) will be excluded.  Individuals taking any medications affecting the CNS will be excluded.  
Individuals with previous adverse reactions to TMS and/or MRI (questions 14,15) will be excluded.   
 
6. Number of Participants - Indicate the total number of anticipated participants to be recruited and enrolled. 
 
Thirty subjects without a history of major knee injury/surgery and 30 subjects with a history of ACLR will be 
recruited for this study. 
 
7. Recruitment Method - Describe who will be doing the recruitment of participants.  Describe when, where, 
and how potential participants will be identified and recruited.  Describe and attach materials that will be 
used to recruit participants (attach documents or recruitment script with the application). 
 
The following recruitment methods will be used for this study. 
a. Two flyers have been created for recruitment (see attached, one flyer for uninjured participants and one 
for participants after ACLR).  These flyers will be posted on bulletin boards at Arcadia University, posted 
on social media, emailed to students, and emailed to local physical therapists.     
b. Individuals with a history of ACL reconstruction will be recruited from local physical therapy clinics.  
Physical therapists will be notified of the study via email and/or phone and asked to have interested 
participants complete the “consent to contact form”.  Email/phone scripts are below.  Good 
Sheppard/PENN Partners (GSPP) has a physical therapy clinic on campus.  GSPP requires that a 
specific consent to contact form.  Therefore, two consent to contact forms will be attached to this 
protocol.  The physical therapists will only be informing the patients or patients guardians (if  under 18 
years old)  that they may be eligible for a study being conducted at Arcadia University and having the 
patients/guardians complete the consent to contact form.  Patients who complete the consent to contact 
form will be contacted by the PI who will determine eligibility and explain the study in more detail.  Only 
the PI will be gaining consent with each subject.   
 

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                           Email script 
Dear __________, 
 
My name is Ryan Zarzycki.  I am a physical therapist and faculty member in the Physical Therapy 
Department at Arcadia University.  I am running a study to test quadriceps strength and function after 
ACL reconstruction.  For this study, I need to recruit participants without a history of major knee injury 
and participants with a history of ACL reconstruction.  Please have any interested participants complete 
the “consent to contact form” attached to this email.   
 
Sincerely, 
Ryan Zarzycki 
 
 
                          Phone script 
Hello.  My name is Ryan Zarzycki.  I am a physical therapist and faculty member in the Physical Therapy 
Department at Arcadia University.  I am running a study to test quadriceps strength and function after 
ACL reconstruction.  For this study, I need to recruit participants without a history of major knee injury 
and participants with a history of ACL reconstruction.  Can you provide me with your email so I can send 
you additional information regarding the study?   
 
 
8. Procedures Involved -  Describe procedures including:  
 
Procedures 
This study will consist of two collections separated by at least 48 hours.  Each testing session will take 
approximately 2.5 hours to complete.  All testing procedures will be administered pre and post a session of 
transcranial direct current stimulation (tDCS).  The primary investigator (Ryan Zarzycki) will collect all data.  
Doctoral students will assist data collection.  The PI retains the right to stop testing if he determines that any 
aspect of the protocol puts the participant at more than minimal risk.   
 
Individuals <18 years old will only complete strength testing and questionnaires at one testing session.   
 
Demographic Data 
Each participant will be asked to self-report their leg and hand dominance, describe sport participation, date of 
birth, age, height, weight, and sex.   
 
Central Nervous System testing 
Cortical excitability (via TMS) and cortical activation (via fNIRS) will be evaluated during 2 different tasks: 1) 
While seated in a dynamometer (strength testing device) and activating their quadriceps muscle at 5% of their 
maximal torque, and 2) during a single limb stance position.  Participants will be secured into a harness system 
during the single limb stance task to prevent loss of balance.  See next 2 sections for specific TMS and fNIRS 
procedures.  Participants < 18 years old will not undergo TMS testing.  A separate consent form has been created 
for participants < 18 years excluding the TMS procedure.   
 
TMS testing 
TMS will be delivered using a MagStim 200 Stimulator with a double circular coil (Magstim Ltd, Wales, UK). All 
TMS testing procedures will be performed for both hemispheres and during both of the tasks mentioned above.  
Electrical activity from multiple lower extremity muscles will be collected using surface EMG electrodes placed 
on the skin.  One or more of the following muscle groups will be collected: quadriceps, hamstrings, triceps surae.  
Subjects will wear a closely fitting cap. First, the site on the scalp where a TMS pulse of ~50% maximum 
stimulator output produces the greatest muscle response (hotspot) will be identified.  The active motor threshold 

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(AMT) will be determined by finding the amount of stimulator output needed to generate at least 5/10 motor 
evoked potentials that exceed 100 µV.  Patients will be activating the target muscle at 5% their MVIC during each 
pulse by receiving visual feedback of their force.  After determining the AMT, 10 pulses at intensities between 
80% AMT and 140% AMT (at 10% intervals) will be delivered. 
 
Each time the stimulus intensity is changed, a test stimulus will be triggered away from the participant to ensure 
the correct intensity and that no noise is present in the EMG signal.   
 
Strength testing 
Testing will take place in the Exercise Testing Lab (Room 109, Health Sciences Building).  Strength testing will 
consist of maximal voluntary contractions of the quadriceps muscles of both legs.  This testing is performed 
routinely during physical therapy for individuals with knee pathology.  Participants will be seated upright in a 
dynamometer (HUMAC NORM), a device that secures their pelvis and limbs and resists the patient’s attempt to 
straighten the knee from 90 degrees of knee flexion. The participant will be asked to kick as hard as they can 
against the arm of the dynamometer to calculate their maximum volitional isometric contraction (MVIC).  The 
amount of force/torque produced will then be recorded.  Prior to the MVICs, a series of three sub-maximal 
practice trials will be performed to familiarize each participant with the task. Three MVICs will then be 
performed and recorded for analysis.  Two additional (one warm up and one test set) sets of five repetitions will 
be performed to test both quadriceps and hamstring strength through the patients full available range or motion.   
 
Questionnaires 
Multiple questionnaires will be administered to examine pain, knee function, emotions and fear of reinjury, and 
activity level.  See appendix B. 
 
Transcranial direct current stimulation (tDCS) 
a-tDCS (Soterix 1x1, Soterix Medical Inc, NY, NY) will be delivered over the primary motor cortex 
contralateral to the surgical limb (i.e. hot spot for the vastus medialis muscle representation found 
during TMS testing).  A pair of carbon electrodes placed in saline-soaked sponges (surface area: 5 x 7 
cm2) will be secured to the scalp using straps (Soterix EASYstrap).  The anode will be centered over the 
hotspot while the cathode will be placed on the right supraorbital area.  a-tDCS will be administered 
while the participant rides a stationary bike for 20 minutes. The bike seat will be adjusted for each 
participant so that maximal knee flexion range of motion will be 90 degrees.  Participants will also be 
instructed to maintain a neutral ankle angle.  Verbal feedback provided by an investigator will be 
provided throughout the intervention to maintain the neutral ankle position.  The standardized seat 
position and ankle position is to prevent the participant from using their ankle plantarflexors during the 
pedaling motion.  Stationary bike riding was chosen as this task is commonly performed early after 
ACLR with minimal stress to the healing graft and requires quadriceps activity. The first 5 minutes will 
serve as a warmup with the patient maintaining a rate of perceived exertion (RPE) of light or 1 out of 
10.  Over the next 10 minutes, the resistance will be increased to maintain a RPE of moderate or 3/10.  
The last 5 minutes will serve as a cool down at the same intensity/resistance as the warm up.  Active a-
tDCS will be applied at an intensity of 2mA with a 30-second ramp-up and 30-second ramp-down for 
the entire duration of bike riding, while the sham a-tDCS will be applied for only the first 30 seconds.   
 
 
Data Analysis 
Independent t-tests will be used to examine demographic differences between the two groups.  A 2 (limb) x 2 
(group) ANOVA will be used to evaluate differences in strength, TMS, and fNIRS measures.  Regression analyses 
will be used to determine the relationship between the CNS measures and quadriceps strength, and the 
relationship between the TMS and fNIRS measures. 

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9. Compensation or Credit - Describe the amount and timing of any compensation or credit to participants.  
Identify the source of the funds to compensate participants 
 
Each participant (≥18 years of age) will be paid $100 for their participation in this study.  Participants must 
complete both sessions to receive the compensation. 
 
Each participant (<18 years of age) will receive $50 for their participation in this study as they will only 
complete one session.   
 
10. Risk to Participants - List the reasonably foreseeable risks, discomforts, or inconveniences related to 
participation in the research. Consider physical, psychological, social, legal, and economic risks. 
 
Risks associated with Testing Procedures (TMS, strength testing) 
 
There are no known long term risks of TMS.  There is a very small risk of seizure, syncope, and change in 
auditory thresholds.  A recent study examining adverse events of TMS concluded: “Our data suggest that 
single/paired-pulse and repetitive TMS, conducted within the published guidelines pose a very small increment 
over the background risks of everyday life to subjects without known risk factors.”8 Screening potential 
participants for a prior history of seizures, syncope, and hearing impairments will allow us to exclude individuals 
at increased risk.  Participants with be offered ear plugs if the sound from the TMS pulse is uncomfortable.   
 
In the very unlikely event of a seizure, the following steps will be taken:  1) The participant will be positioned in 
the safest position to maintain an open airway (i.e. laying supine or side lying), 2) emergency personal will be 
contacted by dialing 911 (research assistant), 3) any objects will be moved away from the participant to prevent 
additional injury, 4) monitor vitals until emergency personal arrive.   
 
Most subjects report no discomfort from TMS although some do report mild discomfort over the site of 
stimulation.  Some subjects report a mild headache following the procedure.  This typically resolves within 24 
hours and can be treated with over the counter analgesics (i.e. Tylenol, ibuprofen).  If subjects do experience 
discomfort over the stimulation site, the intensity of the stimulator can be reduced to minimize this.  The session 
will be terminated immediately if the subject reports discomfort that is beyond their tolerance.  Subjects may 
experience mild muscle soreness 24-48 hours after the testing session.  This is a normal physiologic response to 
strength testing and strength training.  There are no risks or discomfort associated with strength testing.  Strength 
testing is performed at regular intervals after ACL reconstruction.   
 
Risks associated with transcranial direct current stimulation (tDCS) 
 
TDCS have been used in a growing number of laboratories worldwide since 1985. In the present protocol, only a 
non-significant risk protocol is being employed by using tDCS. TDCS is very safe and there have been very few 
incidences of adverse events with tDCS.  A recent meta-analysis of adverse effects associated with tDCS reviewed 
209 experiments (3836 subjects).11  The main adverse events were itching, tingling, headache, discomfort, and 
burning sensation.  Poreisz et al summarized findings from 567 sessions involving 102 participants to 
demonstrate that adverse effects were quite minor in severity.2 For example, mean ratings of itching during 
stimulation were 1.6 out of 5. Similar ratings were given for tingling (1.74), burning (1.59), headache (1.4), pain 
(1.41), difficulties in concentrating (1.73), nervousness (1.0), and unpleasant sensation (1.24). The highest rated 
adverse effect was fatigue (2.17), although the authors note that this factor was likely influenced by the 
completion of sometimes monotonous tasks while also receiving tDCS. 
 
 There is a strong evidence that tDCS is extremely safe. A recent review reported that “To date, based on over a 
total 33,000 sessions and over 1000 subjects who received repeated tDCS sessions, there is no evidence for 

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irreversible injury produced by conventional tDCS protocols within a wide range of stimulation parameters (≤40 
min, ≤4 mA, ≤7.2 C).”1 In our protocol, the dose of tDCS is significantly below the dose (≤2mA, 20 min) 
described here. An even more recent systematic review (2018) concluded that “Little evidence was found to 
suggest that repeated sessions of active tDCS poses increased risk to participants compared to sham tDCS within 
the limits of parameters used to date.”11  However, in case of an unlikely adverse event, we will have appropriate 
measures to ensure participant safety and comfort. If there is any discomfort during the tDCS procedure, we will 
double-check our electrodes and machine settings. In case of a headache/neck pain after tDCS, the participant 
will be advised to take an over-the-counter pain medication. In an unlikely event of skin burn, participant will be 
referred/ directed to a physician for medical management. Patient and/or his/her medical insurance will pay for 
the care. This will be made clear in the informed consent. 
 
We will assess any discomfort or adverse event before, during or after tDCS in patients and age-matched 
controls. We do not anticipate any major adverse events. Only minor discomfort in less than 5% of subjects 
undergoing tDCS experience is transient headaches or soreness at the site of stimulation.  These side-effects are 
believed to be due to stimulation of muscles and nerves near the stimulating coil. During and following every 
tDCS session, we will ask the participant about any incidence of headache. If the participant complains of any 
discomfort or pain during the tDCS session, the session will be terminated at once. Participants will be informed 
that if they should feel a tingling sensation below the electrodes. If they feel any other uncomfortable sensation 
such as burning, they should inform the investigators.  If the participant informs us of uncomfortable sensation, 
we will ensure electrode/machine settings are correct. If the uncomfortable sensation continues, we will stop the 
procedure. 
 
In order to ensure participant safety following the session, we will use the questionnaire proposed by Brunoni et 
al. 2011 after each session to record any adverse effects, and follow-up with participants the day after each 
session if they report scores of 3 (moderate) or 4 (severe) for any of the symptoms or side effects.2 Anyone self-
reporting a severe effect (4) will be withdrawn from the study.   
 
Risks associated with stationary bike riding 
 
There is very minimal risk involved with stationary bike riding in our population of athletic individuals.  
Additionally, stationary bike riding is part of standard physical therapy early (prior to 4 months which is the 
earliest time that we would recruit a participant) after ACLR. During the intervention (stationary bike with 
tDCS), participant tolerance will be assessed subjectively (rating of perceived exertion, symptoms) at regular 
intervals, and the exercise will be terminated if signs or symptoms indicate poor tolerance.  In addition, the 
protocol will include warm-up and cool down phases to minimize the risk of musculoskeletal injury. If required, 
the participants will be provided with water before, during or after the exercise.    
 
 
 
11. Potential Benefits to Participants - Realistically describe the potential benefits that individual participants 
may experience from taking part in the research. Indicate if there is no direct benefit. Do not include 
benefits to society or others. 
 
Results of the strength test will be provided to participants in both groups.  The results of the strength test will 
benefit participants in the ACLR group as the findings indicate whether additional strengthening is required and 
if progression into the next stage of rehabilitation is warranted.  The results do not provide any benefits to 
participants in the uninjured group.   
 
 

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12. Confidentiality - Describe the following measures to ensure the confidentiality of data: Who will have 
access to the data?  Where and how data will be stored?  How long the data will be stored? How and when 
will data be de-identified? 
 
The primary investigator (Ryan Zarzycki), coinvestigator (Shailesh Kantak), and doctoral students working as 
research assistants will have access to the data.  Electronic data will be stored on the hard drive of the computer 
that runs the HUMAC NORM and a password protected University maintained server only assessable to Dr. 
Zarzycki.  Paper data records will be locked in file cabinets in Dr. Zarzycki’s office.  All data will be de-
identified.  A unique two-digit identifier will be randomly assigned to each participant.  This code will be 
utilized on all of the data collection materials. De-identified data will be stored indefinitely.   
 
 
13. Consent Process - Describe the process and procedures process you will use to obtain consent. Include a 
description of: who will be responsible for completing the consent process with participants, where the 
consent process will take place, how consent will be obtained; and if participants who do not speak English 
will be enrolled, describe the process to ensure that the oral and/or written information provided to those 
participants will be in their preferred language. Indicate the language that will be used by those obtaining 
consent. 
 
Consent forms will be used and are attached for review.  The PI will obtain consent from all participants.   
 
14. HIPAA:  
a)  Is any of the data coming from covered entities* under HIPAA? 
 
       ☐ Yes 
☒ No 
 
IF YES, please describe: 
 
 
 
b) Is a data use agreement** required? 
 
☐ Yes 
☒ No 
 
c) Is a HIPAA Waiver of authorization*** requested? 
 
☐ Yes 
☒ No 
 
* Covered Entity- A health plan, a health care clearinghouse, or a health care provider who transmits health 
information in electronic form in connection with a transaction for which HHS has adopted a standard. 
 
** Data Use Agreement- An agreement into which the covered entity enters with the intended recipient of a 
limited data set that establishes the ways in which the information in the limited data set may be used and how 
it will be protected. 
 
*** Waiver of Authorization- The documentation that the covered entity obtains from a researcher or an 
IRB or a Privacy Board has waived or altered the Privacy Rule's requirement that an individual must 
authorize a covered entity to use or disclose the individual's PHI for research purposes. 
 
15. Conflicts of Interest 

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a)  Do you or any member of your research group, spouses or any dependent children have any interest 
(i.e. any property of financial interest including stock in the sponsor company, patents, trademarks, 
copyrights or licensing, supplemental research grants or consulting arrangements) in the test 
drug/product, device, or research procedure that is the subject of this study that could affect any of the 
following: the study outcome, data analysis, enrollment of subjects, study design. 
 
☐ Yes 
☒ No 
 
IF NO, please move on to section 16. 
 
IF YES, please disclose below and the ways in which the researchers will minimize harm to research subjects 
and/or the objectivity of research.  Please discuss how these conflicts will be managed during the period of the 
trial.  Include language disclosing such interest in the consent form for the use by research subjects.  
 
In addition, for industry-sponsored trials, please attach the documentation submitted to the sponsor as 
required by 21CFR54.1, if applicable. 
 
 
 
b) If related to a grant, have all investigators filed a current annual Significant Financial Interest Form? 
 
☐ Yes 
☐ No 
 
c) Among the research team, is there any financial interest that could affect any of the following: the 
study outcome, data analysis, enrollment of subjects, study design?   
 
☐ Yes 
☐ No 
 
IF YES, please describe and disclose in the consent form. 
 
d) Are there any plans for commercial development related to the findings of this study?    
 
☐ Yes 
☐ No 
 
IF YES, please describe 
 
 
 
e) Will participants financially benefit if the findings are commercialized? 
 
☐ Yes 
☐ No 
 
IF YES, please describe 
 
 
 

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16. CITI Training- Have the Principal Investigator, Co-PI(s), and faculty advisor (if PI is a student) taken the 
on-line CITI Course in the Protection of Human Research Subjects?  (IF YES, enter dates of certification 
on IRBNet) 
 
☒ Yes ☐ No 
 
Ryan Zarzycki (PI) 5/19/20 
Shailesh Kantak (co-investigator)  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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References 
1.  
Bikson M, Grossman P, Thomas C, et al. Safety of Transcranial Direct Current Stimulation: Evidence Based 
Update 2016. Brain Stimul. 2016;9(5):641-661. doi:10.1016/j.brs.2016.06.004. 
2.  
Brunoni AR, Amadera J, Berbel B, Volz MS, Rizzerio BG, Fregni F. A systematic review on reporting and 
assessment of adverse effects associated with transcranial direct current stimulation. Int J Neuropsychopharmacol. 
2011;14(8):1133-1145. doi:10.1017/S1461145710001690. 
3.  
Davis HC, Troy Blackburn J, Ryan ED, et al. Quadriceps rate of torque development and disability in individuals 
with anterior cruciate ligament reconstruction. Clin Biomech. 2017;46(November 2016):52-56. 
doi:10.1016/j.clinbiomech.2017.04.011. 
4.  
Eitzen I, Holm I, Risberg MA. Preoperative quadriceps strength is a significant predictor of knee function two 
years after anterior cruciate ligament reconstruction. Br J Sports Med. 2009;43(5):371-376. 
doi:10.1136/bjsm.2008.057059. 
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                                      Institutional Review Board (IRB)                                                             
                         Application for Expedited/ Full Board Review  
 
  
 
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