Balance Training With Transcranial Direct Current Stimulation (tDCS) for Chronic Ankle Instability (CAI)
Phase: NA
Conditions: Ankle Injuries and Disorders
Sponsor: University of Miami

IRB Study Number:20200090
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1) Protocol Title

Title of Study: Balance Training with Transcranial Direct Current Stimulation for 
Chronic Ankle Instability

eProst ID Number: 20200090

Version Number: 1

Version Data: 07/13/2023

Principle Investigator: Brian Arwari, PhD, Associate Professor, University of 
Miami Kinesiology and Sport Sciences, Merrick Building 317-1

5202 University Drive

Coral Gables, Fl, 33124

Ph. 305-284-5418

b.arwari@umiami.edu

National Clinical Trial Number: NCT04390048.
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2) Objectives*
The purpose of this study is to investigate the effect of balance training with 
transcranial direct current stimulation (tDCS) on postural balance, self-reported 
functions, and neural functions in individuals with chronic ankle instability (CAI). 
3) Background*
Ankle sprain is the most common injury in physically active individuals.[1] A 
significant proportion of ankle sprain patients suffer from residual symptoms and 
recurrent injuries, and develop a chronic disease, clinically termed as chronic ankle 
instability (CAI).[2-4] CAI is a multifactorial condition involving a variety of 
predisposing factors for CAI: muscle weakness [5], muscle activation failure [6], 
postural control impairments [7], and altered joint mechanics [8-9]. However, among 
these factors, it is well known that postural control plays an essential role in ankle 
instability. For this reason, discovering the underlying mechanisms of impaired 
postural control has been a primary focus in the CAI literature. With recent advances 
in neurophysiological technology, sport medicine researchers have begun to examine 
specific mechanisms regarding impaired postural control following ankle injuries. 
Recent studies [10-16] have demonstrated altered neural functions in CAI patients. 
Patients with CAI demonstrated deficits in spinal excitability [11, 14], cortical 
excitability [10, 12, 14, 15], smaller excitable cortical areas of lower leg muscle [17], 
and higher fluctuations of cortical activation [13] compared to healthy individuals. 
These findings [10-16] indicate the alteration of neural functions in patients with 
CAI, which may be related with postural control deficit, and clearly suggest a new 
therapeutic target, not just treating the ankle joint, but the brain control in CAI 
patients.
Balance training (BT) has been frequently used by clinicians for improving postural 
control in CAI patients.[18-21] However, recent research with advanced analysis 
techniques for postural control found that the current BT may not be ideal, as only 
one third of CAI patients presented clinically meaningful improvements.[22] Besides, 
BT was not strong enough to restore the decreased cortical activation [23] that is 
potentially linked to poor postural control in CAI patients. These results [22, 23] 
suggest that the need for potential adjunctive rehabilitation that is capable of altering 
the ongoing maladaptive brain plasticity in order to supplement the clinical efficacy 
of BT for CAI patients. 
Transcranial direct current stimulation (tDCS) is an non-invasive electrical 
stimulation technique over the brain that safely influences the cortical excitability, 
and it is a painless and portable.[24-29] It is thought that a subtle electrical current 
(up to 2.0 mA) can induce facilitatory effects on cortical excitability of the primary 
motor cortex: The anodal (+) stimulation is known to increase cortical excitability 
while cathodal (-) stimulation decreases the excitability.[31-33] Given these positive 
outcomes and high applicability (safe, portable, and easy-to-use), tDCS has been 
extensively used in the neuroscience literature[34-38] to address neurological 
symptoms including impaired postural control and motor dysfunction in a wide range 
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of neurological patients such as stroke[38], Parkinson’s disease[36], and spinal cord 
injury[37]. 
There are emerging interests in tDCS to address musculoskeletal conditions. A recent 
study [39] has examined its efficacy for patients with chronic low back pain and 
confirmed its effects on pain and postural control. Anodal tDCS was applied to the 
motor cortex area during 20 minutes of balance training: It was found that pain and 
postural control were significantly improved after the intervention (tDCS with 
balance training).[39] Besides, tDCS has been used in patients with CAI. The tDCS 
was applied to the patients before they began their strength training. The use of tDCS 
in combination with strength training was found superior to strength training alone 
CAI patients.[40] This tDCS study for CAI clearly shows that CAI patients are 
responsive, and raise the potential that tDCS can be incorporated into other CAI 
rehabilitation programs such as balance training. Thus, it is possible to hypothesize 
that BT with tDCS would improve postural control and patients reported outcome 
along with enhancement in neural excitability, which induces superior improvements 
to BT alone. 
4) Inclusion and Exclusion Criteria*
 Below are characteristics of the subject population 

Anticipated number: 60 human subjects with chronic ankle instability 

Age: 18-45

Sex: Both

Race: All
 Criteria for inclusion:

Subjects should be neurologically sound.                                                                                                

Subjects should have abilities to maintain single leg stance at least for 10 
seconds.

A history of ankle sprain

A history of ankle joint giving ways 

Current feelings of ankle joint instability
 Criteria for exclusion:

Individuals with a clinically defined neurological disorder, with an increased risk 
of seizure for any reason, with a history of treatment with TMS, deep brain 
stimulation for any disorder will be excluded.

Patients with cardiac pacemakers, implanted medication pumps, intracardiac 
lines, or acute, unstable cardiac disease, with intracranial implants (e.g. aneurysm 
clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal 
object within or near the head, excluding the mouth, that cannot be safely 
removed will be excluded.

A history of balance or vestibular disorder

A history of previous surgeries to the musculoskeletal structures in either limb of 
the lower extremity 

A history of a fracture in either limb of the lower extremity requiring realignment
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
A history of acute injuries to the lower extremity joints in the previous 3 months, 
which impacted joint integrity and function (i.e., sprains, fractures) resulting in at 
least 1 interrupted day of desired physical activity 

A history of herniated disc

Poorly controlled headache

Hypersensitivity to electrical or magnetic stimulation
The study will not recruit any of the special classes of subjects as shown below. 

Adults unable to consent

Individuals who are not yet adults (infants, children, teenagers)

Pregnant women

Prisoner
5) Procedures Involved*
Study Overview
The proposed study is a double-blinded, randomized-control design which examines 
the efficacy of tDCS with balance training (BT) for patients with chronic ankle 
instability (CAI). Participants will be randomly allocated to one of two groups 
including (1) anodal tDCS + BT and (2) sham tDCS + BT. Outcome measures allow 
us to measure effects on postural balance, neural functions, and self-reported physical 
function. 
General Procedures
Figure 1 illustrates the study flow, procedures and design. Participants will undergo 
brief screening over the phone or email to ensure they meet inclusion criteria. A face-
to-face baseline assessment will be scheduled for eligible individuals at the Sports 
Medicine Laboratory in the Max Orovitz Building. Potential participants will be 
given a full description of the study procedures and asked to read and sign an IRB-
approved informed consent form before any study procedures or assessments are 
conducted. Consent will take place in a private office and will be conducted by 
trained staff, including the principal investigator, co-investigator, research assistant. 
All participants who provide written consents will be screened for their current health 
status to determine whether they qualify for participating in the study. The screening 
involves several questionnaires to be administered by a certified athletic trainer to 
ensure eligibilities and safety of participants (Appendices A-C). For qualified 
participants, the certified clinician will perform a standard physical exam of the ankle 
joint and quantify a current level of physical activity using physical activity 
questionnaire (Appendix D-E). During the preintervention measurement, eligible 
participants will complete a battery of assessments including postural control, self-
reported functions, and neural functions. 
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Figure 1. Flowchart of Overall Study Design and Procedure
There will be one screening day and 2 separate testing days (Figure 2). On the 
screening day, participants will fill out the CAIT and health questionnaire to 
determine the presence of CAI. On the first testing day, self-reported function 
(FAAM), static postural control, and neural excitability (H-reflex, TMS) will be 
measured. On the second testing day, dynamic postural control (SEBT and side hop) 
will be measured. The testing days will be separated by at least 24 hours (Figure 2). 
The testing will repeat at post-2-weeks and post 4-weeks of intervention 
measurement.                  
 
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Figure 2. Outcome measures at testing day 1 and 2.
The first testing day: Once participants arrive at the lab, they will complete health 
questionnaire, including the Foot and Ankle Ability Measures (FAAM). Then, they 
will be asked to do 5~10 minutes of a warm-up. After the warm-up, the investigator 
will assess double leg balance and a single-leg balance. The static postural control 
testing requires 3 successful trials of balance for each task. During the static postural 
control assessment, concomitant assessments of ankle muscle activation (soleus, 
fibularis longus, and tibialis anterior) will be assessed. Once a participant finishes the 
static postural control assessment, neural excitability testing will be performed in the 
counterbalanced order of TMS and H-reflex to prevent the order effect. 
The second testing day: Once participants arrive at the lab, they will be asked to do 
the warm-up. After the warm-up, participants will perform dynamic postural control 
tests (star excursion balance test and side hop). The detailed procedures for each 
outcome measure are described in the following subsections.  
Outcome Measures
Spinal Excitability (H-reflex): The cathode (2 mm shield disk electrode, BIOPAC 
Systems Inc., Goleta CA, USA) will be secured over in the superior popliteal fossa 
proximal to the bifurcation the tibial and common peroneal nerve with a strip of 
hypoallergenic tape and the dispersive electrode (circular carbon-impregnated 
dispersive pad) will be positioned on the anterior thigh just above the patella. The 
soleus H-reflex will be elicited by a 1-ms square-wave electrical stimulus applied to 
the sciatic nerve at increasing intensities until a maximal Hoffmann reflex (H-reflex) 
and maximal motor response (M-response) are found. The soleus muscle was selected 
due to its functional role in postural control. Five maximal H-reflex and M-response 
measurements will be recorded. The averages of both responses will be used to 
calculate the Hmax/Mmax ratio as an outcome variable representing the spinal 
excitability. Corticospinal Excitability (TMS): The participant will be accustomed 
to the stimulus by progressively increasing the TMS stimulator (Magstim Company 
Ltd, Wales, UK) intensity up to the intensity that results in motor response. The 
participant may feel minimal sensations at the point of application (like a puff of air 
on the scalp). After a brief introduction of the stimulation, participants will be asked 
to wear a Lycra swim cap that has a dot grid line (1cm x 1cm squares) and a straight 
line in the middle sagittal plane in order to navigate the brain area. A series of TMS 
stimuli of 1.0 Tesla will be delivered to identify the location of the motor cortex 
where the investigator observes the largest amplitude (hotspot). Once the hotspot is 
determined, a magnetic field will be introduced to the scalp at a location in the 
primary motor cortex where cortical neurons innervating the soleus muscle are 
located. When the magnetic field is received at the primary motor cortex at the 
appropriate area, motor signals are sent to the soleus muscle. We will record these 
signals with surface electrodes that are on the soleus muscle. As the intensity of the 
TMS increases, the soleus muscle will briefly contract/twitch that is known as motor-
evoked potential (MEP). The contraction is comparable to what would be felt during 
standard medical reflex testing. The active motor threshold (AMT) will be defined as 
the stimulator intensity required to elicit a peak-to-peak MEP amplitude above 3 
standard deviations of mean soleus EMG activity during10-sec of both single and 
double leg stance. AMT will be determined by using a software that runs the 
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maximum-likelihood threshold tracking algorithm, Parameter Estimation by 
Sequential Testing (PEST). Ten trials of TMS will be delivered at two different TMS 
intensities of AMT110% and 120% in order to assess motor neuron activity at the 
supra-spinal level. TMS tests will be performed while participants maintain single 
and double leg balance. The averages of responses at each intensity will be used as an 
outcome variable representing the corticospinal excitability. Electromyography 
(EMG): For measurements of H-reflex and TMS responses, it requires EMG signals 
from muscles to be recorded. A total of 4 EMG Ag-AgCl electrodes will be placed 
over the lower leg muscles including soleus, fibularis longus, and tibialis anterior and 
the one reference electrode on the lateral malleolus. The surface EMG electrode will 
be placed based on the SENIAM recommendations. Static Postural Control: The 
static postural control will be measured at unipedal and bipedal stance on a force plate 
(Accusway Plus, AMTI, Waterfront, MA). For bipedal stance, participants will be 
asked to maintain a barefoot stance with their shoulder-width apart and crossed arms 
on the chest. The foot positions will be outlined with tape. Participants will be asked 
to stand as still as possible during testing. Participants will complete three trials of 
bipedal stance with eyes open and eyes closed condition for 10 seconds each trial. 
After the bipedal balance testing, the participant will be asked to perform unipedal 
balance testing. Participants will be asked to stand on their involved limbs of CAI. 
The stance foot will be put on the midlines of the forceplate. The participant will be 
asked to maintain their unipedal stance. Participants will complete three trials of 
unipedal stance with eyes open and eyes closed condition for 10 seconds each trial. If 
a participant touches down with the opposite limb, contacts the stance limb, or is 
unable to maintain standing posture during the 10-second trial, the trial would be 
terminated and repeated. Successful trials of each balance testing will be recorded. 
Dynamic Postural Control: Star Excursion Balance Test (SEBT): SEBT is a 
clinical assessment for functional deficits of lower extremity balance. Participants 
will be asked to stand barefoot on a firm surface. Participants will stand on a single 
leg with the CAI involved limb placed at the center of different lines (anterior (A), 
posteromedial (PM), postero-lateral (PL). Participants will be asked to reach the 
furthest point on the line with extending their contralateral foot. Participants will be 
asked not to move their stance foot from their center position, with hands on the hip. 
The distance from the center of the grid to the furthest reach point will be manually 
measured in cm with a measuring tape. Three testing trials with 4 practice trials will 
be performed with each participant in each direction on each side. The mean of three 
trials will be used for the analysis. Side Hop: All participants will be instructed to 
hop on their CAI-involved limbs. Participants will be instructed to hop laterally over 
a 30-cm distance by alternating sides from lateral direction back to the starting 
location with an involved limb. One repetition will be the ability to hop laterally and 
return to the starting location. Participants will be instructed to complete 10 
repetitions as quickly as possible. Testing trials will be repeated until 3 successful 
ones. If a participant falls, put the contralateral foot on the ground, and do not follow 
the course outline, the trial will be considered “a failed trial.” The examiner will 
record the total time to complete the trial, using the stopwatch, to the nearest 0.01 
second. Participants will perform three practice trials, followed by 3 testing trials. The 
average of 3 testing trials will be recorded and used for analysis. Self-reported 
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functions: The Foot and Ankle Ability Measure (FAAM) is a self-reported 
measurement designed to examine ankle function for patients with foot and ankle 
related impairments. FAAM is divided into two subscales, such as Activities of Daily 
Living (ADL) and Sports Subscale. The FAAM-ADL consists of 21-item 
questionnaire and assesses various ankle activities such as standing, walking, 
stepping, and squatting. The FAAM-Sports consist of 8-items questionnaire and 
assess more challenging activities related to sport such as running, jumping, landing, 
starting-stopping quickly, cutting movements and sports specific movement. Both 
FAMM-ADL and Sports will be administered to each of participants. The investigator 
will guide participants how to fill out the ankle questionnaire. Once participants 
complete the questionnaire, the investigator will score each questionnaire. Each item 
is scored on a 5-point scale from “no difficulty at all” being 4 points to “unable to do” 
being 0 points. The total score for FAAM-ADL is 84, and FAAM-Sport is 32, which 
will be transformed into percentage scores. A higher percentage represents higher 
levels of ankle function. These percentage scores provide perceived ankle dysfunction 
in patients with CAI. The FAAM is a reliable and valid measure for patients with 
CAI.    
Study Interventions
Transcranial Direct Current Stimulation: Participants in the active and sham tDCS 
groups will receive tDCS while performing balance exercises (about 20-min 
application). An anodal surface electrode will be attached to the contralateral motor 
cortex (M1) of the CAI-involved side and the reference electrode will be placed on 
the ipsilateral side of the supraorbital ridge. These electrode placements (stimulation 
sites) were consistent with previous studies.[39, 40] Anodal tDCS will deliver a low 
electrical current stimulation at 2 mA, while for sham tDCS, the stimulator will be 
turned off automatically 30 s following the application. The sham stimulation mimics 
the transient scalp sensation perceived when the stimulator is initially switched on. 
This technique is currently state-of-the-art for conducting convincing sham 
stimulation in the tDCS field. For tDCS treatment set-up, participants will sit on the 
chair. Sponge electrodes will be placed and secured with a head strap: Active 
electrode over the motor cortex area and the reference electrode on the contralateral 
side of the upper forehead. The tDCS set-up will take approximately 10 minutes. 
Participants will undergo 12 sessions (20-min each) of active or sham tDCS using 
2mA current. This constant current device ramps up to the desired amplitude and 
ramps the amplitude back to 0mA at the end of the treatment duration. tDCS (real or 
sham) will be delivered from beginning of balance training to the end of the training. 
After each training session, an aloe cream will be applied to the skin under the 
electrodes to reduce risks associated with skin drying. Balance training: All groups 
will receive the same progressive balance training (BT). BT will be implemented 3 
times a week over 4 weeks, each training session lasting about 20 minutes. The 4 
weeks of BT has been shown effective in enhancing postural control in patients with 
CAI. The BT will consist of 3 types of balance exercises: (A) single-leg stance 
exercise with eyes open and closed and on stable and unstable surfaces, (B) single-leg 
deadlift exercise with eyes open and on stable and unstable surface, and (C) balance 
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exercise on wobble board. Participants will be asked to perform a progressive level of 
exercise in each session.   
The single-leg exercise is static balance exercise. Participants will be instructed to 
maintain their single leg balance with their CAI involved limb as still as possible. 
There will be 6 levels of difficulty. Participants will advance to the next level if they 
demonstrate error-free performance. The error includes falling, touching down with 
the opposite limb, bracing the non-stance limb against the stance limb, and opening 
the eyes during the eyes-closed condition. 
Single leg deadlift is a semi-dynamic balance exercise that involves a hip-hinge 
movement while maintaining a single-leg balance. Participants will be instructed to 
stand with their feet hip-width apart and parallel, Then, they will be asked to lean 
forward in their torso by shifting the weight onto the involved leg while the non-
weight bearing leg extends backward. The extended leg will be lifted, and the torso 
will be shifted forward until the “T” shape is formed. There will be 6 levels of 
difficulty. Participants will advance to the next level if they perform the deadlift 
without errors including excessive trunk motion (more than 30 degrees of lateral 
flexion), removing the hands from the hips for the related activities, and missing the 
target. 
The wobble board exercise is a dynamic balance exercise. The wobble board is a 
circular plate (30 inches) with different sides of domes that screw into the bottom of 
the board to make balance exercises challenging. Participants will perform the 
exercise near a wall and be only allowed to touch fingertips to the wall for stability. A 
balance exercise will be performed on the board, and then clockwise and 
counterclockwise rotations of the rim of the board will be completed. The dome with 
the shortest diameter will be considered the lowest level (e.g., level 1) and all 
participants will begin performance on this level. Five levels will be used for training, 
and height of each level increased by half inches. Thus, heights ranged between 1 and 
3 inches. The initial direction of rotation will be selected by participants and will be 
changed every 10 seconds of the 40-second trial. There will be 5 difficulty levels. 
Participants will be progressed to the next level if they perform balance on the board 
with smooth transitions between and within rotation directions as well as self-
reported feelings of “easiness.
6) Data and Specimen Banking*
All data collected from this study will be stored on password protected computers at 
the Sports Medicine Laboratory in the Max Orovitz Building. Participants will be 
assigned own identification number at the time of participation. Our laboratory is in a 
locked building with limited key card swipe access. Only investigators for this study 
will have access to the data.
7) Data Management*
Data will be stored in a personal computer which is in locked research offices and is 
encrypted and password protected. The means and standard deviations will be 
calculated for one pre and two post outcome measures and will be used for statistical 
analysis. The normal distribution of data will be assessed by using the Shapiro-Wilk 
tests. For each outcome measures (postural control, neural measures, and self-
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reported function), 2 (group: anodal tDCS+BT and sham tDCS+BT) by 3 (time: pre-
intervention, 2 weeks post-, 4 weeks post-intervention) ANOVA with repeated 
measures will be performed to determine effects of tDCS for each outcome measure. 
In the presence of a significant group-by-time interaction, a post-hoc analysis using 
Sidak adjustment will be conducted. The level of significance will be set a priori at 
0.05. All statistical analyses will be performed using SPSS 26.0 statistical software 
(SPSS Incorporated, Chicago, IL, USA).
 
8) Risks to Subjects*
tDCS risks and safety plan
The risks associated with tDCS are minimal. There is no documented risk of seizure 
associated with tDCS, but participants with a history of seizure disorder will be 
excluded to ensure optimum safety. Side effects associated with tDCS include mild 
headache, tingling, itching, or stinging under the electrodes, and skin irritation. After 
each therapy session, an aloe cream will be applied to the skin under the electrodes to 
reduce risks associated with skin drying.
Balance training and safety plan
There is a small risk that balance training cause injury during balance training, but 
participants may feel mild muscle soreness during and after balance training 
activities. For the safety of participants, all exercise sessions will be supervised by a 
certified athletic trainer. If participants perform an activity in a way that may hurt 
them, they can take a rest anytime they want, and we will demonstrate a proper form 
of exercise.  
TMS risks and safety plan
TMS is a safe procedure that has been used on many people to study the brain. Most 
people do not find the stimulation painful, but occasionally strong contractions of 
scalp muscles can cause some discomfort or headache. TMS-induced headaches are 
mild and brief (less than 1 hour).
If a headache or mild scalp discomfort occurs, subjects will be directed to use over 
the counter pain medication at their own discretion. The symptoms usually go away 
promptly with nonprescription medication.
The noise of the TMS magnet may affect hearing, so subjects will be required to wear 
disposable earplugs during TMS session.
The risk of inducing a seizure with single-pulse TMS* is considered very low. 
Seizures from single-pulse TMS have only been reported in subjects with medically-
intractable epilepsy very rarely (0.0-3%).
In the unlikely event of a seizure, a standard seizure protocol will be followed.
1. First thing: REMOVE THE COIL FROM SUBJECT’S BRAIN
2. Remove harmful objects from the subject’s surrounding area
3. Cushion the head as possible and the area so subject does not injure themselves
4. If the subject is having trouble breathing, turn the subject on their side 
5. Monitor the duration of the seizure
6. If the seizure ends in less than 60 seconds, monitor and contact primary care doctor 
to rule out predisposing factors
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7. If seizure lasts more than 60 seconds, activate emergency services.
Precautions: 
Do not place anything or any fingers anywhere near the mouth
Do not attempt to hold the subject down
Remain calm, seizures almost always stop after a few minutes
TMS can interfere with implanted medical devices and will not be done in people 
who have pacemakers, implanted pumps, or stimulators, such as cochlear implants or 
in people who have metal objects inside the eye or skull. All participants will be 
screened before enrollment to assure that they meet study criteria and that there are no 
contraindications to TMS, subjects will be instructed that they can discontinue the 
TMS experiment at any time
* The amount of energy introduced to the body is considered safe. The duration of the 
stimulus is extremely brief (less than 1 millisecond) and the maximum intensity is 1.4 
Tesla (less than magnetic resonance imaging). The magnetic stimulation in this study 
feels similar to a gentle tap on the head. Please note the proposed study will utilize 
the single-pulse TMS that has been considered safer than other types of TMS 
techniques such as paired-pulse or repetitive TMS. FDA has approved repetitive TMS 
to treat depression. 
H-reflex and M-response risks and safety plan
H-reflex and M-response are also considered a safe procedure that has been used on 
many people to study the peripheral nerves. Most people do not find the stimulation 
painful, but occasionally strong contractions of tested muscles can cause some 
discomfort or pain. Stimulation-induced pain is mild and short (less than 4 hours). 
The pain is usually manageable with nonprescription pain medication. 
** The amount of energy introduced to the body is not significant. The duration of the 
stimulus is extremely brief (1 millisecond) and the maximum intensity is 200V. The 
shocks in this study feel like a shock of static electricity, like when you are walking 
across a carpet and then touch a door knob, except the voltage is much lower (A 
shock of static electricity can provide up to thousands of volts of electricity).
9) Potential Benefits to Subjects*
There will be no guarantee of a specific benefit to individual participants; however, 
successful completion of this study will open a new class of therapeutic approaches 
for individuals with chronic ankle instability.
10)
Vulnerable Populations*
     N/A
11)
Setting
Data collection will take place at the Sports Medicine and Motion Analysis 
Laboratory at University of Miami.
12)
Resources Available
All necessary equipment is available in the Sports Medicine and Motion Analysis 
Laboratory, and the investigators have considerable experience to safely conduct the 
proposed study.
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13)
Prior Approvals
This project has been approved by the Department of Kinesiology and Sports Sciences 
in the School of Education as a dissertation research project.
14)
Recruitment Methods
Subjects will be recruited from the University of Miami’s Medical and Coral Gables 
campuses as well as community centers and local sports medicine and orthopedic 
clinics. Flyers and emails approved by the University of Miami’s Institutional Review 
Board (IRB) for the Use and Protection of Human Subjects will be used when 
permitted. We will be seeking permission to send an email to potential people by 
identifying in-charge person/officer in each university unit (i.e., departments, club 
sports teams, athletics) or building, who can provide us with a list of email addresses 
or can send an email for us. We will do the same for other places outside the 
university community.
15)
Local Number of Subjects
Sixty human subjects with chronic ankle instability will be recruited and enrolled in 
the study. A statistical power analysis was performed to estimate sample size, based 
on the previous tDCS study [40] on CAI patients with similar dependent variables 
(e.g., corticospinal excitability). The effect size (f=0.55) in this study was large using 
Cohen’s criteria. With an alpha=0.05 and power = 0.80, the projected sample size 
needed is approximately 8 participants for each group with a total of 24 CAI patients. 
Thus, the proposed sample size of 20 for each group with a total of 60 CAI patients 
will be more than adequate and should also allow for expected attrition.
16)
Confidentiality
All collected data will be kept in a locked cabinet at the laboratory (Room 123 in the 
Max Orovitz, 1507 Levante Ave. Coral Gables, FL). Only the principal researcher 
and his research staff will be allowed access. All electronic data will be stored in a 
password-locked computer that is kept in the locked cabinet, and only the principal 
researcher and his research staff will have the password. All records will be identified 
using only ID numbers and no information than may reveal the subject’s identity will 
be attached to these records. The ID list and the signed consent forms will be kept in a 
separate locked cabinet in the room 120, only accessible by the principal researcher.
17)
Provisions to Protect the Privacy Interests of Subjects
All interactions will be limited to the principal investigator and study team.
18)
Consent Process
A signed informed consent form will be required from all subjects participating in the 
study. The consent form will be in plain language and describe all aspects of the 
study: the purpose, procedure, time requirements, and any potential risk factors 
associated with participation. Informed consent will be obtained from subjects upon 
during the first visit to the lab (University of Miami, Coral Gables). Informed consent 
will be reviewed by the subject and explained by researcher. This will include 
answering any questions the subject has. The PI will obtain consent.  
19)
Process to Document Consent in Writing
Consent form attached
20)
References
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