Accelerated rTMS as a Treatment for Post-stroke Depression in the Subacute Phase: an Open Label Pilot Study
Phase: NA
Conditions: Post-stroke Depression
Sponsor: Amelia Adcock

1 
 
PROTOCOL and ICF COVER PAGE: 
 
 
Accelerated Repetitive Transcranial Magnetic Stimulation (rTMS) as a treatment 
for post-stroke depression in the subacute phase: an open label pilot study 
Ameila Adcock, MD 
 
NCT04093843 
 
September 25, 2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

2 
 
Protocol Number & Study Protocol Title 
 
Accelerated rTMS as a treatment for post‐stroke depression in the subacute phase: an open label pilot study 
IRB # 1804090922 
PI Signature  
 
Abbreviations List 
Date   
 
 
AAQP = Amino Acids, Quantitative, Plasma 
AIS = Acute Ischemic Stroke 
ASRM = Altman Self‐Rating Mania Scale 
BP = Blood Pressure 
CT = Computed Tomography 
DLPFC = Dorsolateral prefrontal cortex 
DSMB = Data Safety Monitoring Board 
EKG = electrocardiogram 
FDI = First Dorsal Interosseous 
FIM = Functional Independence Measures 
HAMD = Hamilton Depression Rating Scale 
HR = Heart Rate 
Hz = Hertz 
IR = Interventional Radiology 
MINI = Mini International Neuropsychiatric Interview 
MRI = Magnetic Resonance Imaging 
mRS = Modifed Rankin Scale 
NIHSS= National Institutes of Health Stroke Scale 
NLR = Neutrophil to Lymphocyte Ratio 
PSD = Post Stroke Depression 
RMT = Resting Motor Threshold 
rTMS = repetitive Transcranial Magnetic Stimulation 
tPA = tissue Plasminogen Activator 

3 
 
 
 
Study Team Composition 
 
Research Summary 
Study Population – 
Goal subject recruitment N for this study = 20 patients 
Patients are NOT recruited from vulnerable populations (eg children, prisoners, pregnant women, and/or mentally 
handicapped individuals). Selection of subjects will be equitable addressing gender, race, and ethnicity because all 
patients who have radiographic evidence of stroke and meet eligibility criteria will be considered for enrollment. 
All patients must meet the following inclusion criteria: 
1. Ages 22‐85 years old. 
2. Radiographic evidence of acute or subacute ischemic stroke (typically on MRI or CT). 
3. Ischemic stroke diagnosed within the last 2 weeks to 6 months. 
4. HAMD depression score 8 or greater. 
5. Agrees and is able to provide written informed consent. 
6. Agrees and is able to participate in all study procedures. 
Exclusion Criteria: 
1. Metallic objects or neurostimulators implanted intracranially. 
2. Stroke in the Left DLPFC. 
3. Known history of epilepsy or seizure disorder. 
4. Clinically significant EKG abnormalities including QTC prolongation >450 ms in men or > 480 ms in women. 
5. A woman who is pregnant or breastfeeding. 
6. History of psychiatric hospitalization unrelated to current PSD 
7. Current SI or MINI suicide scale > 8. 
8. ASRM > 6 
9. Current illicit drug use. 
10. History of head trauma resulting in loss of memory >5 minutes or requiring hospitalization. 
11. Evidence of hemorrhage in the brain at the time of study. 
Role: Principal Investigator 
1 
Amelia Karen Adcock 
Contact information: akadcock@hsc.wvu.edu 304‐598‐6127 
Role: Co‐Investigator 
2 
3 
4 
Jessica Elizabeth Frey 
Role: Co‐Investigator 
Ashley Brooke Petrone Role: Co‐Investigator 
Umer Najib 
Role: Co‐Investigator 
Role: Study Coordinator: 
1 
Jay Michael Sherman 
2 
Louise Ann Moore 
Role: Study Personnel: 
1 
Padmashree Srinivasan Tirumalai 
Section I: Team and Research Summary 

4 
 
Section II: Design 
12. Have other mental or physical conditions that are inappropriate for study participation at PI's discretion. 
Study Design – 
This is an open label trial meaning that all participants (stroke patients with depression) will be given the intervention, 
which in this case is rTMS. 
The purpose of this study is to find alternative treatments for patient's suffering from depression after having a 
stroke. The specific treatment this study will be looking at is Transcranial Magnetic Stimulation (TMS). TMS is a non‐ 
invasive process where a patient reclines in a chair and a magnetic coil is placed near the patient's head. The coil will 
be pointed at specific target in the patient's brain and will give pulsations to that area of the brain. These pulsations 
can change the patient's brain activity. After the pulsations are done, the patients will be immediately able to resume 
their normal daily activities. After the TMS sessions, the patients' quality of life, measure of depression, and stroke 
deficits will be assessed. The patients will then follow up at their regularly scheduled stroke follow up appointments in 
the outpatient clinic and these same measures will be reassessed. Past studies have shown that TMS is safe and 
effective for treating major depression as well as motor recovery in stroke, but there are fewer studies looking at TMS 
in post‐stroke depression. This study aims to show that accelerated rTMS is a safe, effective, and convenient 
treatment for patient's suffering from post‐stroke depression in the acute to subacute phase. This will be an open 
label trial and thus all participants will receive the active rTMS intervention. This is a pilot study with a small sample 
size (20 patients) and the information gathered from this study will help to generate future randomized controlled 
studies on similar topics. 
Study Duration –3 years total, with patients accrued and data analyzed on a rolling basis. 
 
 
 
 
Background & Significance 
 
TMS has been well studied in major depression and has shown significant benefit for patients suffering from MDD, with 
more benefit seen in younger patients who already respond well to antidepressants (Dumas, Brunelin). TMS has also 
been well studied as an effective treatment for post‐stroke motor recovery by either stimulating the affected 
hemisphere or sending inhibitory pulsations to the unaffected hemisphere in order to promote plasticity (Hoyer). Post‐ 
stroke depression (PSD) is a phenomenon that affects up to 30‐50% of stroke survivors (Paolucci). It is a prevalent 
condition that not only affects mood but can translate into poorer motor recovery and overall quality of life. As acute 

5 
 
stroke management continues to improve through the use of tPA and IR thrombectomy, there are more stroke survivors 
and as a consequence, a higher population of survivors suffering from PSD. Currently the mainstay of treatment for PSD 
is the use of antidepressants. However, many patients cannot tolerate antidepressants due to side effects or drug‐drug 
reactions. In addition, antidepressants are not always effective for patients. Therefore, an alternative treatment for PSD 
such as rTMS as needed. However, the downside for TMS is that it typically takes 4‐6 weeks of nearly daily session 
before a clinically significant benefit is seen and this is a barrier due to patient location, transportation, and compliancy 
(Janicak, Holtzheimer). Thus, a new protocol that accelerates the time period in which the patient receives the rTMS 
sessions within a reasonable time frame is needed. Studies have shown that an accelerated protocol is a safe and 
effective treatment tool for patients suffering from major depressive disorder as well as in patients suffering from 
alcohol withdrawal craving symptoms (Baeken, Herremans). Studies have also shown that rTMS is safe in the acute 
stroke period (Conforto, Khedr, Rossi). It follows then that an accelerated rTMS protocol would also be effective in 
patients suffering from post‐stroke depression. Please see attachments section for cited references. 
Objectives 
 
Purpose – Overall purpose is to improve an otherwise poorly and incompletely treated common complication of stroke; 
PSD. rTMS is a promising alternative as an effective and practical tool to combat PSD. 
 
Primary Objective – 
Determine the feasibility and tolerability of repetitive transcranial magnetic stimulation (rTMS) in patients with post‐ 
stroke depression (PSD) in the subacute recovery period. 
 
Hypothesis: This study design and its execution will support the feasibility of a 4 day accelerated rTMS protocol and 
that PSD patients will tolerate this accelerated protocol in the subacute recovery period following an ischemic stroke. 
 
Secondary Objective(s) – 
Determine the efficacy of repetitive transcranial magnetic stimulation (rTMS) in patients with post‐stroke depression 
(PSD) in reducing depressive symptoms during the subacute recovery period. 
 
Hypothesis: PSD patients who are treated with rTMS in the subacute recovery period following an ischemic stroke will 
experience amelioration of their depressive symptoms compared with PSD patients who do not receive rTMS. 
 
Tertiary objective‐ 
Investigate the role the immune system plays in patients who undergo rTMS for PSD. 
 
Hypothesis: The NLR will be positively correlated with the HAM‐D scale score and is an accurate prognostic marker to 
identify stroke patients at risk for PSD. Second, rTMS will decrease the NLR in stroke patients with PSD, and this 
reduction in NLR will correlate with a decrease in depression symptoms, as measured by the HAM‐D scale score. 
 
 
Study Design & Methodology 
 
This is an open label study. The intervention that is being studied is rTMS in PSD patients. 
1. Patients will have a radiographic study of the brain that shows evidence of ischemic stroke (this step represents 
routine care in their stroke evaluation). 
2. Patients who meet the inclusion/exclusion criteria and have a HAMD or ≥ 8 will be offered to participate. 
3. Enrolled patients will be scheduled for their 4 day sessions of neurostimulation. 

6 
 
Prior to stimulation (typically on Day 1): 
a. Screen subject with: 
a. ASRM 
b. MINI 
c. NIHSS 
d. mRS 
e. FIM 
f. 
HAMD 
g. Vitals (EKG and BP) 
h. Blood draw 
i. 
Assess whether psychiatric medication was changed within the preceding 10 days 
j. 
Mapping procedure (where to place the stimulator): 
i. the patient's resting motor threshold (RMT) will be identified visually as muscle twitching in 
the First Dorsal Interosseous (FDI) muscle in 5 out of 10 stimuli provided. RMT can vary 
between patients, so this will be used to ensure that patients are all getting the same 
strength of TMS treatment. 
4. The following protocol will be applied on days 1‐4: 
High frequency (20 Hz)‐ rTMS will be applied to the patients. There will be five sessions per day over the course 
of 4 days for a total of 20 sessions. Neurostimulation will be applied with a figure of eight coil. There will be 40 
trains of 2.0 second duration (39 pulses) with a 12 second intertrain interval for a total of 1560 pulses per 
session. Each session will be separated by 10‐20 minutes (based on subject discretion). Stimulation will be 
provided at up to 110% of the resting motor threshold over the left DLPFC. Patient will be able to immediately 
resume normal activities after the stimulation session and their safety will be monitored throughout the study. 
 
5. Subjects’ vitals will be checked prior to 1st rTMS stimulation session of the day as well as after the day’s last 
session. 
 
6. General adverse event screens will be conducted following each day. Self‐harm will be assessed before and after 
each stimulation treatment. In addition to general and mood‐related significant adverse events will be defined 
as hospitalization that was a result of a psychiatric condition throughout the 12 months of enrollment (per 
subject). 
 
7. Following day 4’s stimulation, a follow up HAMD, FIM, mRS, NIHSS, ASRM and MINI will be conducted and 
bloodwork obtained. 
 
8. A follow up phone call within 24‐72 hours following Day # 4 to further assess for any adverse events will be 
completed. 
 
9. Subjects will return for follow‐up visits at 3, 6 and 12 months post stimulation. Patients will be surveyed with the 
HAMD scale, FIM scale, NIH stroke scale, mRS, MINI suicide scale, and ASRM prior to the intervention and then 
directly afterwards at the end of the 4th day as well as at their stroke follow up appointments at 3 months, 6 
months, and 1 year. Patients will additionally have CBC/diff, Pax Gene tube, Sodium EDTA tubes, green top tube 
for AAQP drawn prior to TMS treatment, after TMS treatment, and at their 3 month follow up appointment to 
measure neutrophil‐lymphocyte ratios and arginase levels, in addition to glutamate levels and validation of any 
unique proteins (included in the kits) in order to characterize the immune response in patients with acute stroke 
and PSD. 

7 
 
10. The blood samples will be drawn before the 4 days of TMS, after the 4 days of TMS sessions, and during their 3 
month follow up. Four tubes of blood will be collected during the blood draws described: CBC/diff (lavender 
top), PaxGene tube, Sodium EDTA tube, and AAQP (green top). The samples will be given a de‐identified sample 
number and then stored for processing serum and WBC isolation. Once fully processed, the sample will be 
stored in a locked ‐80 freezer in a locked room to complete analysis of blood work. Patients will have the ability 
to opt out of the blood storage portion and this will be specified in the consent form. 
 
11. General variables about the subject’s background will also be recorded in our de‐identified secure database 
(RedCap): age, gender, ethnicity, handedness, stroke risk factors, etiology of stroke, mRS prior, antidepressant 
use prior and if an SSRI was initiated post stroke. 
 
12. In addition to the specific tools used to monitor for adverse events describes above, eg the ASRM (for mania) 
and the MINI (for suicidality), adverse events will include any hospitalization for psychiatric disease. Any death 
and cause, when known, occurring during the study period of 12 months, will be recorded. Tolerability of the 
study will be assessed by asking participants to report any discomfort or side effect to the treatments during the 
4 days of active rTMS treatment. 
 
13. Concomitant medications: all psychiatric medications will be recorded at each study visit. A participant will not 
undergo rTMS if a modification in their psychiatric medications in the preceding 10 days or less has occurred. 
 
14. rTMS administration will be supervised by adequately trained personnel and the number of pulses and times 
received will be documented in the subject’s binder. 
15. Prespecified stopping rule: if 1) a seizure in a patient or 2) a patient attempts/completes suicide occurs. Either of 
these events would trigger a Data Safety Monitoring Board Review. This would also generate an IDE supplement 
for FDA review. 
The address of the DSMB is as follows: 
West Virginia University Cancer Institute 
1801 Health Sciences South 
PO Box 9300 
304‐293‐0781 
 
The Data Safety and Monitoring Board is comprised of 3 WVU faculty who all have extensive research experience and 
have committed to serving in the role as monitors for this study. They are familiar with the protocol and specifically with 
the prespecified timelines and events necessary that will trigger their analysis. While they all have expertise conducting 
research; both in the clinical and pre‐clinical arenas, as well as trial design and data analysis, none of these members 
have any involvement in this trial or stake in its outcome. They are completely independent and impartial. 
 
 
1. Muhammed Alvi, M.D.: Dr. Alvi is a vascular neurologist. He has been Co‐I or PI in multiple investigator‐initiated 
institutional studies as well as large multi‐center clinical trials and is currently PI on 4 multicenter trials . 

8 
 
2. Ann Murray, M.D.: Dr. Murray specializes in treating people with inflammatory disorders of the CNS and is 
director of our neuromodulation center with a focus on Deep Brain Stimulation (DBS). She has been involved 
with multiple clinical trials and is currently PI on 3 clinical trials. 
 
3. Cheryl Smith, M.D.,PhD: Dr. Smith earned her doctorate in neuroanatomy. Clinically, she is a neuromuscular 
specialist. She has over 20 years of research experience. Dr. Smith heads the Department of Neurology’s 
research division and is currently PI/Co‐I of 6 active clinical trials. 
 
 
 
Schedule of Activities 
 
Procedures 
Screening 
Day 1 to 
170 
Enrollment/Baseline 
Visit 1, 
TMS Day 1 
Study 
Visit 
2 
TMS 
Day 2 
Study 
Visit 
3 
TMS 
Day 
3 
Study 
Visit 
4 
TMS 
Day 4 
Follow 
up Phone 
Call 
(within 
72 hours 
of 
Day 4) 
Study 
Visit 5 
3 
month 
follow 
up 
Study 
Visit 6 
6 
months 
follow 
up 
Final 
Study 
Visit 7 
12 
month 
follow 
up 
Informed consent# 
Demographics 
Medical history 
Variable Collectiona 
Administer rTMS 
Concomitant psychiatric 
medication review1 
Depression Screen (HAMD 
or PHQ 9)# 
Vital signs1,2 
mRS a,b 
FIM a,b 
NIHSS a,b 
MINI a,b 
rTMS documented2 
EKG (as indicated)1,2 
Pregnancy testa 

9 
 
Key: 
#: can either be completed during screening phase or during visit 1, prior to TMS 
a: before TMS on day 1 
b: after TMS on day 4 
1: before each TMS treatment 
2: after each TMS treatment 
Procedures 
Screening 
Day 1 to 
170 
Enrollment/Baseline 
Visit 1, 
TMS Day 1 
Study 
Visit 
2 
TMS 
Day 2 
Study 
Visit 
3 
TMS 
Day 
3 
Study 
Visit 
4 
TMS 
Day 4 
Follow 
up Phone 
Call 
(within 
72 hours 
of 
Day 4) 
Study 
Visit 5 
3 
month 
follow 
up 
Study 
Visit 6 
6 
months 
follow 
up 
Final 
Study 
Visit 7 
12 
month 
follow 
up 
Adverse event review and 
evaluation (post 
treatment)1,2 
ASRM a,b 
Other assessments(e.g., 
bloodwork)a,b 
Psychiatric medication 
review 
 
 
 
 
 
Target Population & Recruitment Methods 
See above. 
Goal subject recruitment N for this study = 20 patients. 
 
Patients are NOT recruited from vulnerable populations (eg children, prisoners, pregnant women, and/or mentally 
handicapped individuals). Selection of subjects will be equitable addressing gender, race, and ethnicity because all 
patients who have radiographic evidence of stroke and meet eligibility criteria will be considered for enrollment. 
 
Inclusion & Exclusion Criteria – All patients must meet the following inclusion criteria: 1. Ages 22‐85 years old. 2. 
Radiographic evidence of acute or subacute ischemic stroke (typically on MRI or CT). 3. Ischemic stroke diagnosed 
within the last 2 weeks to 6 months. 4. HAMD depression score 8 or greater. 5. Able and agrees to provide written 
informed consent. 6. Able and agrees to participate in all study procedures. 7. If subject has child bearing potential 
will have a negative urine pregnancy test prior to enrollment. Exclusion Criteria: 1. Metallic objects or 
neurostimulators implanted intracranially. 2. Stroke in the L DLPFC. 3. Known history of epilepsy or seizure disorder. 4. 
Clinically significant EKG abnormalities including QTC prolongation >450 ms in men or > 480 ms in women. 5. A 
woman who is pregnant or breastfeeding. 6. History of psychiatric hospitalization unrelated to current PSD 7. Current 
SI or MINI suicide scale > 8. 8. ASRM > 6 9. Current illicit drug use. 10. History of head trauma resulting in loss of 
memory >5 minutes or requiring hospitalization. 11. Evidence of hemorrhage in the brain at the time of study. 12. 
Have other mental or physical conditions that are inappropriate for study participation at PI's discretion. 

10 
 
 
 
Risk & Benefit 
Risk – Currently there are no standard safety guidelines for TMS in stroke, although it is generally thought that high 
frequency TMS carries a higher risk of seizure since high frequency (>1 Hz) generates cortical excitability (Rossi). 
However, it has also been reported that TMS is a focal process and if the area of seizure susceptibility (whether that is 
an ischemic stroke or epileptogenic focus) is not directly stimulated by TMS, the risk for seizure is not any higher in 
the stroke population that in the regular healthy adult population (Rossi, Jorge, Fregni). In addition, there have been 
several studies looking at various high frequency, high stimulation intensity protocols in stroke patients (for various 
outcomes such as motor recovery and grip strength) that have been shown to be safe, with similar side effect profiles 
to the general population (Guo, Sasaki, Hosomi, Guan). These studies have been summarized in the table below 
references. Of note, the only major adverse effect reported in all of the aforementioned studies was one patient with 
attempted suicide‐ it should also be noted that this adverse effect was in a study that was specifically studying suicidal 
ideation and thus all patients in the study were at high risk for suicidal ideation. All other reported side effects 
summarized in the table below involve transient pain or feelings of discomfort at the site of stimulation. Accelerated 
rTMS has not been tested for PSD, which is part of the novelty of our proposed study. However, given the above 
studies demonstrating safety and efficacy of accelerated protocols for depression and high frequency, high 
stimulation protocols in acute stroke timelines (as early as 5 days post‐stroke), it follows that an accelerated rTMS 
protocol would also be an effective and safe method in patients suffering from post‐stroke depression (when 
stimulation will be performed much later, in the subacute period). Lastly, the most current and complete meta‐ 
analyses of rTMS in our population of interest (PSD) which compared 25 RCTs (n = 1,804 patients with n = 520 with 
safety data available) failed to show any significant incidence of a serious adverse event (including seizure) in the 
actively treated patients (Shen 2017, McIntyre 2016). 
Due to the theoretical risk of higher seizure risk in a patient with stroke, we will follow similar protocols for clinical 
monitoring of seizure signs and symptoms as outlined in the studies mentioned above. Our study will have vitals 
closely monitored before and after each TMS session. Patients will be clinically monitored for signs of seizure and 
clinicians trained to diagnose and manage seizures will be immediately available at the study site. AEDs will also be 
immediately available should any patients have a seizure during the study. 
Study 
Site of 
Stimulation 
Frequency 
Trains 
per 
session 
Sessions 
per day 
# of days 
Total # 
of 
pulses 
Intertrain 
interval 
Intersession 
interval 
# of 
patients 
AEs 
Baeken 2014 
(Unipolar 
depression) 
Left DLPFC 
20 Hz 
40 
5 
4 consecutive 
31,2000 
12 sec 
15-20 min 
15 
Transient 
headache 
and 
transient 
fatigue 
Herremans 
2015 
Right DLPFC 
20 Hz 
40 
5 
3 consecutive 
23,400 
12 sec 
15 minutes 
26 
1 dropped 
out due to 
temporary 
Recruitment – 1. Patients who have radiographic evidence of an acute stroke and are currently on the stroke service 
(or in the outpatient clinic) will be screened for depression with the HAMD scale during routine stroke care, including 
admission to the hospital and at their follow up stroke appointments or other outpatient appointments. Potential 
candidates are pre‐screened by the study coordinator via the electronic medical record. MyChart messages may also 
be sent to qualified candidates and West Virginia Practice Based Network providers are aware of this study. They may 
refer an appropriate candidate for more information. Participants may also be pre‐screened over the phone for those 
patients who were identified as potential study subjects. 2. The study will be explained to patients that meet the 
inclusion/exclusion criteria. 3. Patients who wish to enroll and participate and who have decision making capacity will 
be consented during their hospitalization, at their outpatient neurology follow up appointment, depending on the 
timeline for that particular patient. TriNetX will also be used to identify potential candidates via chart review. Families 
will be invited to participate in the discussion regarding enrollment in this study. 

11 
 
(cravings of 
alcohol 
dependent 
patients) 
pain at 
stimulation 
site 
Seok 2015 
(MDD) 
Not available 
Not 
available 
Not 
available 
5 
3 consecutive 
Not 
available 
Not 
available 
Not available 
20 
No major 
AEs 
Holtzheimer 
2010 
Left DLPFC 
10 Hz 
20 
5 on day 
1 and 10 
on day 2 
2 consecutive 
15,000 
25 sec 
0 
14 
1 patient 
had 
possible 
increase in 
SI 
Guo 2017 
(acute stroke 
for motor 
recovery) 
Ipsilesional 
motor cortex 
(same side as 
acute stroke) 
10 Hz 
30 
1 
10 
15,000 
25 sec 
NA 
15 
none 
Fitzgerald 
2018 
(MDD) 
Left DLPFC 
10 Hz 
83-84 
3 
6 
63,000 
15 sec 
15-30 min 
58 
2 
withdrew 
due to 
treatment 
discomfort 
and 1 
withdrew 
due to 
migraine 
Duprat 2016 
(medication 
resistant 
depression) 
Left DLPFC 
iTBS 
54 triplet 
bursts 
5 
4 consecutive 
32,400 
8 sec 
15 min 
50 
3 dropped 
out due to 
discomfort 
at 
stimulation 
site 
Desmyter 
2016 
(suicide risk 
in refractory 
MDD) 
Left DLPFC 
iTBS 
54 triplet 
bursts 
5 
4 consecutive 
32,400 
8 sec 
15 min 
50 
1 suicide 
attempt 
(patients 
had SI 
prior to 
study 
enrollment 
because 
study was 
assessing 
suicide 
risk) 
Conforto 
2012 
(acute stroke 
treatment of 
hemiparesis) 
Contralesional 
motor cortex 
1 Hz 
Not 
reported 
1 
10 
15,000 
Not 
reported 
NA 
15 
Transient 
head pain, 
no serious 
AEs 
Khedr 2005 
(acute stroke 
for motor 
recovery) 
Ipsilesional 
motor cortex 
3 Hz 
10 
1 
10 
15,000 
50 sec 
NA 
52 
none 
Hosomi 2016 
(subacute 
stroke for 
upper limb 
paresis) 
Ipsilesional 
motor cortex 
5 Hz 
10 
1 
10 
50,000 
50 sec 
NA 
39 
none 
Sasaki 2017 
(acute stroke 
for leg 
weakness 
recovery) 
Ipsilesional 
motor cortex 
10 Hz 
10 
2 
5 
10,000 
50 sec 
Not reported 
21 
none 
Blesneag 
2015 
Contraslesional 
motor cortex 
1 Hz 
Not 
reported 
1 
10 
12,000 
Not 
reported 
NA 
16 
None 
reported 
Young Gu 
2017 
Population: 
PSD 
Left DLPFC 
10 Hz 
20 
1 
10 
(consecutive) 
10,000 
60 sec 
NA 
24 
None 
Jorge 2004 
Population: 
PSD 
L DLFPC 
10 Hz 
20 
1 
10 
(consecutive) 
10,000 
60 sec 
NA 
20 
Transient 
headache, 
local pain 
and 
anxiety. 
 

12 
 
Insomnia 
in one 
patient. No 
serious AE 
Carey 2008 
Population: 
PSD 
Contraslesional 
motor cortex 
6 Hz 
20 
1 
1 
1000 
25 sec 
NA 
10 
Transient 
fatigue, 
headache, 
neck pain. 
No serious 
AE 
reported. 
El Etribi 
2010 
Population: 
PSD 
L DLPFC 
1 Hz 
10 
1 
10 
1000 
2 sec 
NA 
20 
Transient 
mild 
headache 
Narushima 
2010 
Population: 
PSD or at 
least 3 
vascular risk 
factors) 
L DLPFC 
(excluded 
patients with 
stroke at this 
location) 
10 Hz 
20 
1 
10 
18,000 
60 sec 
NA 
31 
None 
Benefit ‐The current options for treating post‐stroke depression include stroke support groups, cognitive therapy, and 
anti‐depressants. Although these options are available and will be offered to all the patients in this trial, there is not 
one particular option that is currently considered the standard of care. There was one trial which showed that 
fluoxetine showed mild improvement in motor recovery for stroke patients, so fluoxetine is often prescribed for 
stroke patients to enhance motor recovery, though it is not specifically used for PSD. Thus, patients previously on 
antidepressants or that have been started on antidepressants, particularly fluoxetine, will not be excluded from the 
study. However, patients will be asked to remain on current treatment (not to stop, start, or change antidepressants) 
throughout the duration of the study, unless medically necessary to adjust, so as to not influence results of the study. 
If a patient changes their antidepressant regimen within 10 days of TMS (pt will be rescheduled if possible for 
stimulation sessions to begin or, if this change occurs within the 10 days following TMS treatment, it will be noted in 
our statistical analysis). Patients will also be informed of all the options available to them to treat their post‐stroke 
depression, and support groups, cognitive therapy, and antidepressants will be offered to all patients in addition to 
the TMS therapy to patients in this study. 
Participants in this study may note a benefit in their mood, functional status, and motor recovery. Prior studies have 
shown TMS to improve motor recovery after stroke and prior studies have also shown TMS to improve depression in 
patients with major depression as well as post‐stroke depression (Dumas, Brunelin, Shen). It follows then that some 
form of TMS in the acute to subacute phase will additionally benefit patient's mood, motor recovery, and cognitive 
recovery. 
In order to compensate for time spent or transportation costs, participants will be reimbursed with a $50 gift card 
following completion of all 4 sessions. If a participant lives remotely or cannot reasonably drive to Morgantown daily 
for 4 days of treatments, hotel accommodations locally will be provided. 
The potential benefits to society include novel and efficient approaches to treating post‐stroke depression. The goal is 
to find an alternative treatment to post stroke depression since many patients cannot tolerate antidepressants due to 
side effects or drug‐drug interactions. Thus TMS potentially represents a safe and convenient alternative or adjunctive 
therapy to antidepressants for patients with post‐stroke depression. It also represents an alternative or adjunctive 
treatment to therapy or support groups, treatments that rely heavily on a patient's intrinsic motivation for recovery, 
whereas TMS does not depend on patient's motivation for effectiveness. This data will be used to support a larger, 
randomized controlled project comparing accelerated rTMS to sham TMS. 
 
Statistical Analysis Plan 
 
Analyses will be conducted using SPSS, version 22. Descriptive and frequency data will be analyzed for Adverse Events. 
T‐tests will be used to determine differences in BP/HR pre‐ and post‐rTMS. While not sufficiently powered to provide 

13 
 
 
 
Safety Monitoring & Unanticipated Event Reporting 
If an adverse event is noted or any other question surrounding the eligibility of a patient, the PI will be immediately 
contacted. Any IRB reporting is done as a study team including the PI, the study coordinator (s) and regulatory liaison 
in accordance with the requirements outlined by the IRB/IDE. 
 
Data Safety Monitoring – 
This study will be stopped prior to its completion if: (1) the intervention is associated with adverse effects that call 
into question the safety of the intervention; (2) difficulty in study recruitment or retention will significantly impact the 
ability to evaluate the study endpoints; (3) any new information becomes available during the trial that necessitates 
stopping the trial; or (4) other situations occur that might warrant stopping the trial. 
 
Relationship to TMS Procedure: 
 
Definitely related – the AE can be fully explained by administration of theprocedure. 
Probably related – the procedure is more likely the cause of the AE than other factors. 
Possibly related – there is a reasonable possibility that the procedure is the cause of the AE, including that the 
procedure and another factor(s) are equally likely as causes of the AE. 
Unrelated – another factor is clearly (incontrovertibly) the cause of the AE. 
 
Severity Rating 
Definition 
Grade 1 = Mild 
Usually transient, requiring no special treatment 
Does not interfere with usual status or activities 
Awareness of the event, but easily tolerated 
Grade 2 = Moderate 
May be ameliorated by simple therapeutic measures 
May cause enough discomfort to interfere with usual activities 
Grade 3 = Severe 
Causes inability to perform usual activities 
Requires close monitoring and/or intervention 
Grade 4 = Very Severe/ 
Life Threatening 
Significantly debilitating or incapacitating despite symptomatic therapy 
Requires immediate intervention or emergency treatment 
May be life threatening 
 
Participants who meet 4 AE severity criteria will be medically monitored and then discontinued from the study. 
Participants who meet Grade 1, 2, or 3 AE severity criteria will be medically monitored and determination of 
continuation/discontinuation will be made at the discretion of the study physician. 
conclusive results, mixed‐model, repeated measures analysis of variance (ANOVA) will be used to evaluate 
preliminary efficacy effects of rTMS on HAMD score, FIM score, and NIH scores. This latter analysis will serve as pilot 
data for future studies. 
Sample Size –This is an open label, pilot study intended to gather data about safety and logistics of using accelerated 
rTMS in the subactue stroke phase as a treatment for post‐stroke depression. We hope to gather data about subjects' 
response to accelerated rTMS in preparation to eventually conduct a larger, randomized controlled trial comparing 
rTMS to sham rTMS. However, this study will look at a smaller sample size of intervention only patients to monitor 
safety and efficacy in this population. 

14 
 
 
 
Study Duration & Timeline 
 
 
 
 
Protected Health Information (PHI) 
 
 
Confidentiality & Privacy 
 
Confidentiality – All data collected must be kept for a minimum of 3 years after the conclusion of the research project. 
It may be decided upon by the research team to keep the data for a longer time frame. Physical copies of data 
collected must be locked in a drawer or file cabinet, within a locked room or office. Digital data should be encrypted or 
on a password protected database. All participant identifiers should be stored separately from the data collected (ex. 
ICFs should not be in the same locked drawer as the survey results collected). 
Data will be kept for 3 years. The data will be secured in a password protected database on a password protected 
tablet in a locked office. The Department of Neurology has a protocol in place for destroying PHI if in paper form. It is 
a locked box in a staff only area. Electronic data will be deleted from the protected files. 
Data is only accessible to the PI, research team members, or IRB. 
Participants will be "de‐identified" and assigned a participant number. Their information will be kept on an encrypted 
drive. Consent forms will be kept in a separate, locked cabinet in a separate, locked room. Participants will be 
consented in their individual hospital rooms where nonessential personnel will not be given access during the 
consenting process. Similarly, all questionnaires and the TMS procedures will be completed in a private, secure room 
in individual sessions with no other participants and/or nonessential staff present. 
Yes, this research will deal with protected health information (PHI). However, participants will be "de‐identified" and 
assigned a participant number in our secure database (RedCap). 
Nov 2018‐Nov 2021: Study recruitment and execution. Parallel data analysis and dissemination. 
Adverse events will be monitored via the adverse events screening forms and patients will be routinely asked 
if they are experiencing any side effects during the treatment process. Any of the following scenarios would trigger an 
immediate review with the Data Safety Monitoring Board: 
‐a seizure in a patient 
‐a patient who attempts or completes suicide 
The Data Safety Monitoring Board will also meet when 50% target patient accrual is achieved, and quarterly 
thereafter. The Board will review adverse events and trial progress. All serious adverse events will be immediately 
discussed and if at any time the Board determines one of the above 4 criteria have been met, the study will be 
stopped prior to its completion. 

15 
 
 
 
 
 
 
 
 
 
 
Conflict of Interest 
 
 
Publications, Presentations, & References 
 
 
References 
 
 
Baeken, C, D Marinazzo, GR Wu, P Van Schuerbeek, J De May, I Marchetti, MA Vanderhasselt, J Remue, R Luypaert, R 
De Raedt. “Accelerated HF-rTMS in treatment-resistant unipolar depression: insights from subgenual anterior cingulate 
functional connectivity.” The World Journal of Biological Psychiatry. 12: 2014. 
 
Blesneag AV, Slavoaca DF, Popa L, Stan AD, Jemna N, Isai Moldovan F, Mursenau DF. Low frequency rTMS in 
patients with subacute ischemic stroke: clinical evaluation of short and long term outcomes and neurophysiological 
assessment of cortical excitability. J Med Life 2015;8(3):378-387. 
 
Brunelin, J, E Poulet, C Boeuve, H Zeroug-vial, T d’Amato, M Saoud. “Efficacy of repetitive transcranial magnetic 
stimulation (rTMS) in major depression: a review.” L’Encephale. 33(2): 2007, 126-134. 
 
Conforto AB, SM Anjos, G Sapsonik, EA Mello, EM Nagaya, W Santos, KN Ferrero, ES Melo, FI Reis, M Scaff, LG 
Cohen. “Transcranial magnetic stimulation in mild to severe hemiparesis early after stroke: a proof of principle and novel 
approach to improve motor function.” Journal of Neurology. 259(7): July 2012, 1399-1405. 
 
Desmyter, S, R Duprat, C Baeken, S Van Autreve, K Audenaert, K van Heerigen. “Accelerated intermittent theta burst 
stimulation for suicide risk in therapy-resistant depressed patients: A randomized, sham-controlled trial.” Frontiers in 
Human Neuroscience. Sept 2016. 
 
Dumas, R, R Padovani, R Richieri, C Lancon. “Repetitive Transcranial Magnetic Stimulation in Major Depression: 
Response Factor.” L’Encephale. 38(4): Sep 2012, 360-368. 
 
Duprat, R, S Desmyter, R de Rudi, K van Heerigen, D Van den Abbeele, H Tandt, J Bakic, G Pourtois, J Dedoncker, M 
Vervaet, S Van Autreve, GM Lemmes, C Baeken. “Accelerated intermitten theta burst stimulation treatment in 
medication-resistant major depression: A fast road to remission?” Journal of Affective Disorders. 200: Aug 2016, 6-14. 
North American Conference on Neuromodulation (NANS) Las Vegas Jan 2019. Poster presentation. Study Design. 
Van Liere Research Day. West Virginia University, Morgantown, WV. Poster Presentation, first place award. 
CTSI Annual Conference. Greenbrier Resort, WV, April 2019. Poster presentation. Preliminary Results. 
NONE 
Section IV: Other Considerations 

16 
 
Fitzgerald PB, Hoy KE, Elliot D, McQueen RNS, Wambeek LE, Daskalakis ZJ. Accelerated repetitive transcranial 
magnetic stimulation in the treatment of depression. Neuropsychopharmacology 2018; 
 
Fregni F, Boggio PS, Valle AC, Rocha RR, Duarte J, Ferreira MJL, Wagner T, Fecteau S, Rigonatti SP, Riberto M, 
Freedman SD, Pascual-Leone A. A sham-controlled trial of a 5 day course of repetitive transcranial magnetic stimulation 
of the unaffected hemisphere in stroke patients. Stroke 2006;37:2115-2122. 
 
Guan YZ, Li J, Zhang WH. Effectiveness of repetitive transcranial magnetic stimulation (rTMS) after acute stroke: a one 
year longitudinal randomized trial. CNS Neuroscience & Therapeutics 2017;23(12):940-946. 
 
Guo Z, Jin Y, Peng H, Xing G, Liao X, Wang Y, Chen H, He B, McClure MA, Mu Q. Ipsilesional high frequency 
repetitive transcranial magnetic stimulation add-on therapy improved diffusion parameters of stroke patients with motor 
dysfunction: a preliminary DTI study. Neural Plasticity 2016;2016:11. 
 
Herremans, SC, P Van Schuerbeek, R De Raedt, F Matthys, R Buyl, J De May, C Baeken. “The impact of accelerated 
prefrontal high-frequency repetitive transcranial magnetic stimulation (rTMS) on cue-reactivity: an fMRI study on craving 
in recently detoxified alcohol-dependent patients.” PLoS One. 10(8): 2015. 
 
Holtzheimer, PE, WM McDonald, M Mufti, ME Kelley, S Quinn, G Corso, and CM Epstein. “Accelerated repetitive 
transcranial magnetic stimulation (aTMS) for treatment-resistant depression.” Depression and Anxiety. 27(10): Oct 2010, 
960-963. 
 
Hosomi K, Morris S, Sakamoto T, Taguchi J, Maruo T, Kageyama Y, Kinoshita Y, Goto Y, Shimokawa T, Koyama T, 
Saitoh Y. Daily repetitive transcranial magnetic stimulation for poststroke upper limb paresis in the subacute period. 
Journal of Stroke and Cerebrovascular Diseases 2016;25(7):1655-1664. 
 
Janicak, PG, and ME Dokucu. “Transcranial magnetic stimulation for the treatment of major depression.” 
Neuropsychiatric Disease and Treatment. 11: 2015, 1549-1560. 
 
Jorge, RE, RG Robinson, A Tateno, K Narushima, L Acion, D Moser, S Arndt, E Chemerinski. “Repetitive transcranial 
magnetic stimulation as treatment of poststroke depression: a preliminary study.” Biological Psychiatry. 55(4): Feb 
2004, 398-405. 
 
Khedr, EM, MA Ahmed, N Fathy, JC Rothwell. “Therapeutic trial of repetitive transcranial magnetic stimulation after 
acute ischemic stroke.” Neurology. 65: 2005, 466-468. 
 
Oberman, L, D Edwards, M Eldaief, and A Pascual-Leone. “Safety of theta burst transcranial magnetic stimulation: A 
systematic review of the literature.” Journal of Clinical Neurophysiology. 28(10): Feb20 11, 67-74. 
 
Rossi, S, M Hallett, PM Rossini, A Pascual-leone. “Safety, ethical considerations, and application guidelines for the 
use of transcranial magnetic stimulation in clinical practice and research.” Clinical Neurophysiology. 120(12): Dec 
2009, 2008-2039. 
 
Seok JH, Chung MH. The efficacy and safety of accelerated repetitive transcranial magnetic stimulation in major 
depressive disorder: single-blind, randomized study. Brain Stimulation 2015;8:378-394. 
 
Sasaki N, Abo M, Hara T, Yamada N, Niimi M, Kakuda W. High-frequency rTMS on leg motor area in the early phase of 
stroke. Acta Neurologica Belgica 2016;117:189-194. 
 
Shen, XY, MY Liu, Y Cheng, C Jia, XY Pan, QY Gou, XL Liu, H Cao, LS Zhang. “Repetitive Transcranial Magnetic 
Stimulation for the treatment of Post-stroke depression: a systemic review and meta-analysis of randomized and 
controlled clinical trials.” Journal of Affective Disorders. 211: 2017, 65-74. 

17 
 
 
 
Key Information for: 
Accelerated Repetitive Transcranial Magnetic Stimulation (rTMS) as a treatment 
for post-stroke depression in the subacute phase: an open label pilot study 
You are being asked to participate in the research described below. This page provides key information that may 
help you to make this decision; more detailed information can be found after this section. 
 
Why is this research being done and what is involved? 
The purpose of this study is to find alternative treatments for patient's suffering from depression after having a 
stroke. 
 
The specific treatment this study will be looking at a procedure called Transcranial Magnetic Stimulation 
(TMS). During an TMS session, an electromagnetic coil is placed against your scalp. The electromagnet 
painlessly delivers a magnetic pulse that stimulates nerve cells in the region of your brain involved in mood 
control and depression. 
 
In this study, you will receive 5 sessions of TMS per day over the course of 4 days for a total of 20 sessions, each 
day lasting for a 2-4 hours.In addition you will have blood draws, ECG, vital signs, and tests to assess your stroke 
and depression status. You will then follow up at regularly scheduled stroke follow up appointments at, 3, 6 and 
12 months in the outpatient clinic and some of these same measures will be reassessed. There may be phone calls 
following your treatment. 
 
Do I have to participate and what are the risks, benefits and alternatives? 
Participation in this research study is completely voluntary and you are free to withdraw from the research at 
any time.  You may or may not directly benefit from participating in this research. 
Side effects such as headache and light headedness are generally mild to moderate and improve shortly after an 
individual session and decrease over time with additional sessions. 
Rare but serious risks from participation in this study include temporary or permanent hearing loss, seizure, and 
mania. There may be other study related risks that are currently not known. 
You do not have to participate in this study and your post-stroke care will not be affected if you choose not to 
participate. Alternative treatment options for post-stroke depression include antidepressants and 
counseling/therapy. 
 
Who can I talk to if I have questions or concerns? 
If you have any questions or concerns about this research or would want to withdrawal from the study, you can 
contact Dr. Amelia Adcock at 304 598 -6127 or AKADCOCK@hsc.wvu.edu from the Dept. of Neurology at 
West Virginia University. 
 
 
For more information, please see the Informed Consent Form. 
 
Page 1 of 9 
 

Page 2 of 9 
 
 
Informed Consent | More than Minimal Risk Research (Version date December 
20, 2018) 
 
Site Version 25 Sept 2019 
 
 
Principal Investigator (PI) | Amelia Adcock, MD 
Department | 
Neurology 
Co-Investigator(s) | 
Jessica Frey, MD; Ashley Petrone, PhD; Umer Najib, MD, 
Patrick Marshalek, MD 
Coordinators 
Jay Sherman, RN Louise Moore, RN, Jennifer Krupp, MPH 
 
Funding Source | 
None 
WVU IRB Protocol # | 
1804090922 
Study Title | 
Accelerated Repetitive Transcranial Magnetic Stimulation (rTMS) as a treatment 
for post-stroke depression in the subacute phase: an open label pilot study 
 
Contact Persons 
If you experience any injury or side effects from being in this research, you should contact Dr. Adcock at 304 598 
-6127. 
If an injury occurs outside of business hours and is related to your participation in this research, please contact 
Dr. Adcock at 304 598-6000. 
If you have any questions, concerns, or complaints about this research, you can contact Dr. Amelia Adcock at 
304 598 -6127. 
For information regarding your rights as a person in research or to talk about the research, contact the WVU 
Human Research Protection Program (HRPP) at (304) 293-7073 or by email at IRB@mail.wvu.edu. 
 
Introduction 
You, 
, have been asked to participate in this research study, which has been 
explained to you by 
 
. This study is being conducted by Dr. Adcock in the 
Department of Neurology at West Virginia University, along with Jessica Frey, MD; Ashley Petrone, PhD; Umer 
Najib, MD, Patrick Marshalek, MD. 
 
Purpose 
The purpose of this study is to determine if repetitive Transcranial Magnetic Stimulation (rTMS) is an effective 
treatment for post-stroke depression (PSD). Post-stroke depression affects up to 30- 50% of stroke patients. TMS 
may reduce depressive symptoms in stroke patients by changing electrical activity in the brain, and may 
additionally improve strength and thinking in stroke patients. WVU expects to enroll up to 20 subjects. 
 

Page 3 of 9 
 
 
Description of Procedures 
If you are enrolled in this study, you will be evaluated with several scales: 
  
Hamilton Depression Screen (HAMD): measures level of depression 
   Functional Independence Measures (FIM): measures level of independence 
   NIH stroke scale: measures severity of stroke symptoms using a neurologic exam 
  
MINI Suicide Scale: measures risk of suicide 
   Altman Self-Rating Mania Scale (ASRM): measures tendency toward mania 
After that, you will receive an experimental protocol using TMS. The protocol involves 20 
total sessions over the course of 4 consecutive days. A brief description of the actual rTMS 
procedure is as follows: 
 
   Step One: You will recline comfortably in the treatment chair, awake and alert 
   Step Two: A small curved device containing the magnetic coil rests lightly on your head 
  
Step Three: The device delivers pulses directly to the target areas of your brain 
   Step Four: You can immediately resume normal activities 
During treatment, you will hear a clicking sound and feel a tapping sensation on the head. 
 
Study Procedures 
The study procedures will be as follows: 
   After reviewing and signing this consent form, you will be screened with a survey to ensure you meet all 
inclusion and exclusion criteria as well as the surveys listed above 
   Any personal information will be de-identified 
   Bloodwork will be drawn along with your routine labs to check for signs related to post stroke 
depression. 
We will obtain basic vital signs including EKG, blood pressure, and heart rate prior to the start of the TMS 
sessions. 
All participants will receive rTMS using the following experimental protocol: 
   5 sessions of TMS per day over the course of 4 days for a total of 20 sessions, each day lasting for 
approximately 2-4 hours. 
   Prior to the first session, we will determine the correct TMS settings for you by looking for a twitch of the 
hand muscles. 
   Prior to and following all TMS treatments, your blood pressure and heart rate will be monitored and EKGs 
will be performed 
You are asked to report any side affects you may experience throughout this protocol. Within 72 hours of your 
Day 4 visit you will receive a follow-up phone call to determine if you experienced any side effects following 
the treatments. 
After the 4 total days of TMS, you will again be evaluated based on the HAMD, FIM, and 
neurologic exam. The same assessments will be measured during your routine outpatient stroke follow-up 
appointments at 3 months, 6 months, and 1 year. Treatment will be stopped at your request or if your physician 
determines that this treatment is not in your best interest. 
 

Page 4 of 9 
 
 
 
You will have routine blood work drawn at specific time points in this study. Blood samples will be drawn 
before the 4 days of TMS, after the 4 days of TMS sessions and during your 3 month follow up appointments. 
Once these samples have been processed, the samples will be given a unique identification number, will not be 
labeled with your name or any other personally identifying information and stored for future testing. The testing 
will look at gene and protein markers of depression. You can opt out of having the samples stored for future 
testing and will still be able to participate in the main study. 
Please indicate if you would like us to store your sample for testing. 
1 I do want to have my blood sample stored for future testing. 
1 I do NOT want to have my blood samples stored for future testing. 
 
 
 
 
Risks and Discomforts 
Common Side Effects: 
   Temporary pain or discomfort at stimulation site 
  
Headache 
   Eye pain 
  
Toothache 
   Muscle twitch 
  
Facial pain 
   Neck stiffness 
Acetaminophen or other medications for treatment will be available and provided to you if the 
above side effects occur. 
Uncommon Side Effects: 
   Temporary or permanent hearing loss 
  
Seizure (less than 0.1% of the time) 
  Mania 
In order to minimize the rare risk of hearing loss, the following procedures will be followed: 
  
You will wear earplugs during the TMS sessions 
   Study staff will discuss with you the risk of permanent hearing loss if earplug falls out 
   Study staff will ask you to immediately report any loosening of an earplug duringTMS 
   Investigators will immediately stop TMS if you report or if an investigator observes that an earplug has 
loosened or has fallen out. 
In order to minimize the rare risk of seizure, the following procedures will be followed: 
   You will be monitored at all times for signs of seizure by a trained physician or nurse who has 
experience treating seizures 
 

Page 5 of 9 
 
 
   Equipment such as oxygen, suction, blood pressure monitor, CPR equipment, and anti seizure 
medications will be available on site if needed 
   Given the social implications of seizure and convulsive syncope (i.e. adverse impact on future 
employability, insurability, and/or eligibility to drive), in the event of seizure, the 
investigators will provide you with a letter documenting that the event was experimentally produced. 
 
In order to minimize the rare risk of mania, you will be monitored with the Altman Self-Rating Mania Scale and a 
score concerning for manic symptoms will halt further TMS trials and you will be provided with appropriate 
psychiatric care should these symptoms occur. 
 
There is no known adverse effect of TMS on cognitive functioning. The long-term effects of TMS are 
unknown. 
 
If you are a woman of child bearing age, you will be asked to provide a pregnancy test prior to enrollment in the 
study. 
 
Starting any treatment for depression, you may become more depressed before getting better. Your depression 
symptoms will be closely monitored throughout the study. Any signs of self-harm or suicidal ideation will lead 
to removal from the study and immediate and appropriate psychiatric care for these symptoms. Any increased 
risk of self-harm will be assessed via a standardized questionnaire known as the M.I.N.I. Suicide Scale. 
 
You will be asked to report any adverse reactions you may experience throughout the study. You may choose to 
discontinue the study at any time. 
 
In addition, this study will involve some routine blood draws. Some adverse reactions to blood draws include 
pain from inserting a needle under the skin surface (common), fainting at or about the time of blood drawing 
(infrequent), bruising at the site (infrequent), and infection at the site (rare). 
 
Alternative 
You do not have to participate in this study and your post-stroke care will not be affected if you choose not to 
participate. Alternative treatment options for post-stroke depression include antidepressants and 
counseling/therapy, which have been discussed with you and you are welcome to partake in as well. 
 
Benefits 
Possible benefits include the improvement of your health, including improvement of your depression as well as 
motor recovery and improved quality of life. Since this study is using TMS in a novel way, it is not known 
whether rTMS will be effective in your case, and you may not receive any benefit or your condition may 
worsen. The knowledge gained from this study may eventually benefit others. 
 
Financial Considerations 
There are no special fees for participating in this study. 
All participants will a receive card to compensate for their time ($10 for each TMS procedure completed with 
an additional $10 for subjects who complete all four TMS). Additional compensation is available for lodging 
 

Page 6 of 9 
 
 
and or transportation for all participants who either live more than 1 hour away or have significant barriers 
securing transportation to trial appointments (including the TMS session days). 
You may be asked to provide your Social Security Number and/or verification of U.S Citizenship or Permanent 
Resident Status to receive payment. 
Your information may be provided to the appropriate parties for billing and/or payment purposes. Please be 
advised that any compensation received for participation in a research study, including a gift card, is considered 
taxable income and must be reported to the IRS. If you are a WVU employee or a WVU student-employee, you are 
required to report the total amount of compensation received for your participation in a research study to the WVU 
Tax Services Office upon receipt of payment. 
 
Voluntary Compensation 
In the event that you are physically injured as a result of participating in this research, care will be available and 
we will connect you with a medical professional who will examine and treat you if needed. Unless an injury 
happened because of an error directly related to the study, we will not compensate for any medically related 
charges. You should realize, however, that you have not released this institution from liability for negligence. 
Please contact the investigator, Dr. Amelia Adcock at 304 598-6127 if you are injured or for further 
information. 
 
Confidentiality 
Any information about you that is obtained as a result of your participation in this research will be kept as 
confidential as legally possible. Information or bio specimens collected as part of the study will not be used or 
distributed for future studies, even if the identifiers are removed. Your research records and test results, just like 
hospital records, may be subpoenaed by court order or may be inspected by the study sponsor or federal 
regulatory authorities, including the Food and Drug Administration (FDA), without your additional consent. 
In addition, there are certain instances where the researcher is legally required to give information to the 
appropriate authorities. These would include mandatory reporting of infectious diseases, mandatory reporting of 
information about behavior that is imminently dangerous to your child or to others, such as suicide, child abuse, 
etc. 
In any publications that result from this research, neither your name nor any information from which you might 
be identified will be published without your consent. 
 
Voluntary Participation 
Participation in this study is voluntary. You are free to withdraw your consent to participate in this study at any 
time. If you choose to withdraw your participation from the study, the data collected on you up until that time 
remains a part of the study database and may not be removed. No additional information will be added to the study 
database after your withdrawal. 
Refusal to participate or withdraw will not affect your future care at West Virginia University. 
In the event new information becomes available that may affect your willingness to participate in this study, this 
information will be given to you so that you can make an informed decision about whether or not to continue 
your participation. 
 

Page 7 of 9 
 
 
 
Genetic Information Nondiscrimination Act (GINA) 
A Federal law, called the Genetic Information Nondiscrimination Act (GINA), generally makes it illegal for 
health insurance companies, group health plans, and most employers to discriminate against you based on your 
genetic information.  This law generally will protect you in the following ways: 
 
• Health insurance companies and group health plans may not request your genetic information that we 
get from this research. 
• Health insurance companies and group health plans may not use your genetic information when making 
decisions regarding your eligibility or premiums. 
• Employers with 15 or more employees may not use your genetic information that we get from this 
research when making a decision to hire, promote, or fire you or when setting the terms of your 
employment. 
 
All health insurance companies and group health plans must follow this law by May 21, 2010. All employers 
with 15 or more employees must follow this law as of November 21, 2009. Be aware that this Federal law does 
not protect you against genetic discrimination by companies that sell life insurance, disability insurance, or long-
term care insurance. 
West Virginia's genetic discrimination laws protect patients from discrimination by health insurers or 
employers. This means that a health plan or insurance company cannot raise your rates based on genetic 
information about you or commit any other form of illegal discrimination, nor can employers in West Virginia 
use your genetic information to inform decisions related to hiring or firing you. 
 
 
HIPAA Authorization 
We know that information about your health is private. We are dedicated to protecting the privacy of that 
information. Because of this promise, we must get your written authorization (permission) before we may use or 
disclose your protected health information or share it with others. 
You can decide to sign or not to sign this authorization section. However, if you choose not to sign this 
authorization, you will not be able to take part in the research study. Whatever choice you make about this 
research study will not have an effect on your access to medical care. 
 
 
Persons/Organizations Providing the Information 
Patient (data are from the participant)/West Virginia University Hospitals/ WVU Medicine/ WVUHS (data are from 
records) 
 
 
Persons/Organizations Receiving the Information 
   The research site(s) carrying out this study. This includes UHA or UHA Affiliates, WVU, WVU Hospitals, 
WVUHS. It also includes each site’s research staff and medical staff. 
 

Page 8 of 9 
 
 
   Health care providers who provide services to you as part of this research study. 
   Laboratories and other people and groups that look into your health information as part of this study in 
agreement with the study protocol. 
   The members and staff of any institutional review board that oversees this research study. 
   The West Virginia University Human Research Protection Program and/or Compliance and the Office of 
Sponsored Programs. 
   WVCTSI Clinical Trials research staff 
The Following Information Will Be Used 
Information from your existing medical records, and new information about you that is created or collected 
during this study, such as: history and physicals, clinic visit notes, nursing and staff notes, laboratory results, x- 
rays, EKG results, demographic data, pulmonary tests, imaging scans, and study forms. 
The Information is Being Disclosed for the Following Reasons 
   Review of your data for quality assurance purposes 
  
Publication of study results (without identifying you) 
   Other research purposes such as reviewing the safety or effectiveness of the study drug and other products 
or therapies; conducting performance reviews of the study drug; evaluating other products or therapies for 
patients; developing a better understanding of disease; improving the design of future clinical trials 
 
You may cancel this Authorization at Any Time by Writing to the Principal Investigator: 
Amelia Adcock 
1 Medical Center Drive 
Morgantown, WV 26505 Email: 
akadcock@hsc.wvu.edu Phone: 
304 598-6127 
 
If you cancel this authorization, any information that was collected already for this study cannot be withdrawn. 
Once information is disclosed, according to this authorization, the recipient may re-disclose it and then the 
information may no longer be protected by federal regulations. 
You have a right to see and make copies of your medical records. You will not be able to see or copy your records 
related to the study until the sponsor has completed all work related to the study. At that time, you may ask to see 
the study doctor’s files related to your participation in the study and have the study doctor correct any information 
about you that is wrong. 
 
This authorization will expire at the end of the study unless you cancel it before that time. 
ClinicalTrials.gov 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law. 
This Web site will not include information that can identify you. At most, the Web site will include a summary of 
the results.  You can search this Web site at any time. 
 

Page 9 of 9 
 
 
 
 
 
 
Signatures 
You have been given the opportunity to ask questions about the research, and you have received answers 
concerning areas you did not understand. Upon signing this form, you will receive a copy. 
I willingly consent to participate in this research. 
 
 
 
Signature of Subject or Subject’s Legal Representative 
 
 
Printed Name 
Date 
 
 
The participant has had the opportunity to have questions addressed. The participant willingly agrees to be in the 
study. 
 
 
 
Signature of Person Obtaining Informed Consent 
 
 
Printed Name