Clinical trial NCT02737930
Conditions: Acute Stroke Visual Field Loss
Keywords: Acute ischemic stroke Homonymous hemianopia Homonymous quadrantanopia Visual field loss Post-stroke recovery Fluoxetine Selective serotonin reuptake inhibitor
Sponsor: Bogachan Sahin
Start date: 2016-05-01; Completion date: 2020-08-01
Enrollment: 17 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine whether fluoxetine, a selective serotonin reuptake inhibitor commonly used for depression, enhances visual recovery after an acute ischemic stroke.

Detailed description:

Arms: arm 1: 20 mg fluoxetine capsule by mouth once daily for 90 days arm 2: Matching placebo
Interventions: intervention 1: Fluoxetine intervention 2: Placebo
Intervention descriptions: intervention 1: None intervention 2: None

Protocol documents:
Prot_SAP_000.pdf: 
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March 15, 2016 
NCT02737930
Fluoxetine for Visual Recovery after Ischemic 
Stroke 
(FLUORESCE) 
Principal Investigator 
Bogachan Sahin, MD, PhD 
Department of Neurology 
601 Elmwood Avenue, Box 681 
Rochester, New York 14642 
1.
PURPOSE AND BACKGROUND
1.1. Purpose 
Primary Objective: 
To test whether fluoxetine, a selective serotonin reuptake inhibitor (SSRI) previously 
demonstrated to enhance post-stroke motor recovery, also enhances post-stroke visual 
recovery in ischemic stroke survivors.  
Secondary Objectives: 
(1) To understand whether a putative fluoxetine effect is mediated through a drug-specific
mechanism (e.g. a fluoxetine-dependent increase in neural plasticity), or rather through
indirect mechanisms, such as general improvements in mood and motivation to
participate in rehabilitation, resulting from the antidepressant actions of the drug.
(2) To track the natural history of post-stroke visual recovery using a combination of
clinical and radiographic approaches, including standard neuro-ophthalmologic
evaluations, measures of retinal nerve fiber layer (RNFL) thickness, visual and general
disability measures, neuropsychological testing, and functional magnetic resonance
imaging (fMRI).
(3) To estimate the feasibility of larger future clinical trials studying the effects of various
pharmacological or behavioral interventions on the rate and degree of post-stroke
visual recovery.
(4) To use the information gathered from the above objectives to study the physiologic
mechanisms of spontaneous post-stroke visual recovery, with the goal of identifying
better targets for therapeutic interventions.
1.2. Background 
Current strategies in the treatment of ischemic stroke 
Despite major advances in acute stroke care over the last two decades, ischemic stroke 
remains a leading cause of serious long-term disability (1), with 800,000 strokes expected 
in the United States this year alone.  Some form of visual impairment, such as 
homonymous hemianopia, is present in one to two thirds of all stroke patients (2).  Visual 
impairment, and in particular homonymous hemianopia, is associated with poor prognosis 
after stroke (3).  Complete spontaneous recovery is uncommon (4) although there is some 
gradual return of visual function due to endogenous repair mechanisms in the first few 
months (5).  At present, there are no proven treatments beyond the first several hours after 
a stroke that substantially improve functional outcomes.  Two decades on, thrombolysis 
with intravenous (IV) recombinant tissue plasminogen activator (rt-PA) remains the gold 
standard of acute stroke care in the United States and elsewhere (6).  Unfortunately, only 
10% of ischemic stroke patients are eligible for this therapy, as the overwhelming majority 


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of stroke survivors do not present to a hospital within 3 to 4.5 hours of symptom onset.  
Furthermore, given that not all eligible patients are treated with IV rt-PA (e.g. 77% in 
2011) (7), and only 12% of treated patients benefit (6), less than 1% of all ischemic stroke 
patients may ultimately owe their functional recovery to this time-sensitive treatment.  
Therapies that enhance recovery beyond the hyperacute stage of the injury have the 
potential to help a much larger proportion of stroke patients.  However, no subacute 
therapy capable of enhancing post-stroke recovery across the spectrum of stroke etiology, 
severity, and symptomatology is currently available. 
 
A possible role for SSRIs in improving functional outcomes in stroke survivors 
Several lines of evidence suggest that SSRIs, and in particular fluoxetine, may improve 
functional outcomes in stroke survivors with moderate to severe motor deficits (8).  We 
hypothesize that SSRIs mediate these effects by modulating neural plasticity and 
promoting cortical reorganization.  One of the major shortcomings of previous studies 
investigating a role for SSRIs in post-stroke functional recovery has been their focus on 
clinical outcomes at the expense of physiologic outcomes.  As a result, it has been difficult 
to attribute clinical benefits to mechanisms independent of the antidepressant and 
activating effects of these medications.  In the Fluoxetine for Motor Recovery after Acute 
Ischemic Stroke (FLAME) trial (8), arguably one of the most compelling studies in this 
field of inquiry to date, the authors were careful to exclude patients with a history of 
depression and those on antidepressants at the time of their strokes.  At 90 days, patients in 
the fluoxetine group had less depression, suggesting that these patients may have been 
more motivated to recover, but the apparent clinical benefit from fluoxetine in terms of 
motor recovery was still significant after the authors adjusted their analysis for the onset of 
depression during the study period.  While suggestive of an independent role for fluoxetine 
in post-stroke recovery, these results do not constitute direct evidence of a separate, 
intervenable mechanism by which fluoxetine may enhance the recovery process in a 
manner independent of its antidepressant actions.  Similarly another SSRI, escitalopram, 
has shown promise in improving post-stroke cognitive outcomes, specifically short-term 
memory, in ischemic stroke survivors (9), but the authors did not elucidate the physiologic 
mechanism of this apparent clinical benefit.  We hope to resolve this issue by conducting a 
randomized clinical trial in which we will follow clinical and physiologic outcomes 
longitudinally in acute ischemic stroke patients with isolated visual field deficits treated 
with fluoxetine vs. placebo. 
 
Using visual recovery to study the mechanisms of post-stroke functional recovery 
The visual cortex offers the ideal model system for testing hypotheses about mechanisms 
of neural plasticity that may be engaged by SSRIs in the post-stroke recovery period.  First, 
in contrast to motor recovery, motivation probably plays a less prominent role in post-
stroke visual recovery, as most spontaneous recovery probably occurs early (10) and 
rehabilitative interventions typically focus on teaching patients compensatory techniques.  
Second, it is known that fluoxetine can reopen critical periods of neural plasticity in the 
adult rodent visual system (11).  Third, structure-function relationships in the visual system 
are well understood.  The early visual cortex in particular has a highly regular retinotopic 
organization.  Post-stroke changes in this retinotopic map can be characterized and 
followed by fMRI.  Furthermore, cerebral infarction can lead to retinal ganglion cell 
degeneration through a retrograde trans-neuronal mechanism (12), providing another 
window through which post-stroke changes in the visual pathway can be monitored and 
quantified using non-invasive techniques such as optical coherence tomography (OCT).  
Our research team has demonstrated expertise in characterizing early visual system 
organization in clinical populations (13).  Thus, we are well positioned to assess whether 


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any observed effects of fluoxetine on post-stroke recovery are due to quantifiable changes 
in neuronal survival and neural plasticity.   
 
Potential future directions 
Fulfillment of this research program has the potential to alter our clinical approach to 
ischemic strokes affecting the visual system.  In addition, answering these questions in the 
visual system may have more general implications.  An understanding of the dynamics and 
limits of neural plasticity in the post-stroke visual cortex will likely enable us to formulate 
and test specific hypotheses about how therapeutic interventions like fluoxetine may 
promote recovery from ischemic strokes affecting other higher-order cognitive functions, 
including language, praxis, memory, attention, and executive function.   
 
 
2. STUDY DESIGN  
 
2.1. Overview 
This will be a single-center randomized double-blind placebo-controlled clinical trial in 
which ischemic stroke patients with isolated hemianopia or quadrantanopia will be 
identified during their acute hospitalization and randomly assigned to a course of 
fluoxetine vs. placebo for 90 days.  Baseline visual function will be assessed during the 
initial hospital admission using a battery of neurologic, ophthalmologic, behavioral, and 
radiographic measures.  As post-stroke recovery tends to plateau by 6 months, patients will 
be followed for 6 months and evaluated using the same set of measures at 30 days, 90 
days, and 6 months post-stroke in order to determine whether fluoxetine improves visual 
recovery.  
 
2.2. Rationale for Study Design 
Given the growing evidence that SSRIs may improve motor recovery in stroke survivors, 
we hypothesize that fluoxetine will also enhance post-stroke functional recovery in the 
visual system.  We further hypothesize that this effect will be mediated through a 
mechanism independent of the antidepressant and activating effects of fluoxetine.  In order 
to investigate these hypotheses, we have designed a clinical trial in which acute ischemic 
stroke patients with visual field deficits will be randomized in a 1:1 ratio to fluoxetine vs. 
placebo.  The degree of improvement in visual function will then be directly compared 
between the treatment group and the control group.  Because visual recovery after stroke 
usually plateaus in the first 6 months, we have chosen to treat study subjects for 90 days 
with fluoxetine vs. placebo to determine if exposure to SSRIs during the peak time of 
recovery improves the rate or degree of recovery.  This is also the duration of treatment 
that was used in the FLAME trial (8). 
 
2.3. Rationale for Dosage 
Study subjects will be randomized to 20 mg of fluoxetine vs. placebo by mouth, taken on a 
daily basis for 90 days, starting within 72 hours of admission to the hospital.  This dosage 
was chosen because it was shown to have an effect on post-stroke motor recovery in the 
FLAME trial (8).  Furthermore, stroke patients tend to be older and therefore more likely 
to develop side effects at higher doses of the drug. 
 
 
3. CHARACTERISTICS OF THE RESEARCH POPULATION 
 
3.1. Subject Characteristics 


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a) Number of Subjects: The planned enrollment is 40 patients over 12 months in order 
to achieve a final sample size of 30 subjects, assuming a dropout rate of 25% during 
the course of the study.  This projected sample size and time frame represent a 
conservative estimate based on the 56 acute ischemic stroke patients who were 
admitted to Strong Memorial Hospital with an isolated visual field deficit between 
January 1, 2015 and December 31, 2015.  This sample size is comparable to equivalent 
pilot trials evaluating the efficacy of an approved drug for a novel indication.  If any 
subjects withdraw from the study, they will be replaced to meet this enrollment goal.   
 
b) Gender and Age of Subjects: Men and women between 18 and 85 years of age will 
be enrolled in the study.  Patients older than 85 will be excluded because advanced age 
is associated with increased risk of adverse side effects from SSRIs.  Furthermore, the 
ability to fixate and produce reliable visual field measurements deteriorates with 
increasing age.  
 
c) Racial and Ethnic Origin:  Subjects of all racial and ethnic backgrounds will be 
enrolled in the study. 
 
d) Vulnerable Subjects: Subjects who are vulnerable to coercion or undue influence will 
not be enrolled, including children, pregnant women, students, employees, prisoners, 
and persons with decisional impairments. 
 
3.2. Inclusion and Exclusion Criteria 
 
a) Inclusion Criteria: Patients between 18 and 85 years of age who are admitted to 
Strong Memorial Hospital with an MRI-confirmed acute ischemic stroke resulting in a 
clinically verifiable isolated right-sided or left-sided homonymous hemianopia or 
quadrantanopia will be eligible for inclusion in the study. 
  
b) Exclusion Criteria:  
 
Known hypersensitivity reaction to fluoxetine or other SSRIs 
 
National Institutes of Health Stroke Scale (NIHSS) score greater than 5 
 
Premorbid modified Rankin Scale (mRS) score greater than 2 
 
Premorbid monocular or binocular visual field deficits 
 
Premorbid retinopathy or optic neuropathy 
 
Premorbid depression 
 
History of cognitive impairment, dementia, or neurodegenerative disorder 
 
History of seizure disorder 
 
History of mania or hypomania 
 
History of hyponatremia 
 
History of angle-closure glaucoma or elevated intraocular pressure 
 
Current alcohol abuse or impaired liver function 
 
Current use of an antidepressant medication 
 
Current use of a medication likely to have an adverse interaction with fluoxetine 
 
Current use of a medication likely to impair post-stroke recovery 
 
Contraindication to MRI 
 
Pregnancy or lactation 
 
Hemorrhagic transformation of the index stroke, resulting in mass effect 
 
Enrollment in another clinical trial at the time of the index stroke 


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3.3. Discussion of Subject Population 
 
In order to minimize risks to our study population, potential subjects will be excluded from 
participation in the study if they have a known contraindication to a component of the 
study protocol, such as a drug allergy to fluoxetine or other SSRIs, concomitant use of a 
medication that may interact with SSRIs, or contraindication to MRI.  Because of potential 
risks to the fetus and nursing infants, pregnant and lactating women will also be excluded.  
Pre-menopausal women will only be included if the initial urine pregnancy test is negative 
and they commit to using birth control for the duration of the drug administration phase of 
the study (first 90 days).  Patients with impaired liver function or advanced age (greater 
than 85 years old) will be excluded due to the possibility of impaired fluoxetine 
metabolism.   
 
Additionally, we will exclude any subject with a condition that may interfere with the 
interpretation of the study results, such as premorbid depression, previously identified 
visual field deficit of any cause, concurrent use of medications known to impair post-stroke 
recovery, high initial NIHSS score, or hemorrhagic transformation of the index stroke 
resulting in a hematoma large enough to cause mass effect (corresponding to an ECASS 
score of PH1 or PH2) (14), as these conditions are associated with poor functional 
outcome. 
 
Finally, because automated Humphrey perimetry requires the subject to be able to follow 
multi-step commands and maintain visual fixation for 20 minutes, potential subjects with 
impaired cognition or attention, or premorbid mRS score greater than 2, will be excluded.  
 
 
4. SUBJECT IDENTIFICATION, RECRUITMENT, AND CONSENT 
 
4.1. Method of Subject Identification and Recruitment 
 
Potential subjects will be identified by Neurology and Ophthalmology residents, fellows, 
and attending physicians at Strong Memorial Hospital.  When a candidate is identified, a 
member of the medical team will ask the patient if he or she would be interested in being 
approached by study personnel during the hospital admission in order to find out more 
about the study.  If the patient expresses interest, the study coordinator and one of the 
investigators will meet with the patient and family to describe the study and obtain 
consent.  In order to minimize undue influence, members of the medical team (i.e. the 
attending physician of record and the on-service stroke fellow) will not be involved in the 
consent process.  Instead, an investigator not directly involved in the patient’s care will be 
responsible for discussing the study with the potential subject and obtaining consent. 
 
 
4.2. Process of Consent 
 
An investigator will obtain written informed consent from each subject before the 
performance of any procedure related specifically to the study protocol.  The protocol will 
be reviewed with each candidate, highlighting the differences between study-specific 
procedures and routine studies performed as part of standard care, so that he or she can 
make an informed decision about participation in the study.  When possible, potential 
study participants will be approached early during their hospital course to ensure sufficient 
time to address any questions or concerns.  We do not anticipate enrolling any non-English 
speaking subjects. 


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Each signed consent form will be kept in the study binder in a locked drawer in the 
Principal Investigator’s office (Room 5.5722A).  This is a locked room in an office suite 
that requires badge access for entry.  A separate fMRI consent form will be used for any 
fMRI studies performed at the Rochester Center for Brain Imaging (RCBI).  This consent 
will be administered by RCBI staff on the day of the procedure and stored securely in 
accordance with RCBI protocols. 
 
 
5. METHODS AND STUDY PROCEDURES 
 
Subjects will be evaluated at five time points as indicated in the Table: at baseline (i.e. 
during the acute hospitalization immediately after enrollment in the study) and at 7 days, 30 
days, 90 days, and 6 months after randomization.  They will be contacted by phone 7 days 
after the initiation of the study drug to screen for any adverse events using an adverse event 
questionnaire (Appendix H).  This questionnaire will be administered in the hospital if the 
patient has not been discharged yet, and repeated at the remaining time points. 
 
At baseline, the premorbid mRS, Patient Health Questionnaire-9 (PHQ-9), and Visual 
Function Questionnaire-25 (VFQ-25) scores will be determined for each subject.  As part of 
standard care, subjects will undergo a formal neuro-ophthalmological examination to 
confirm and characterize their visual field deficits.  This will also help to rule out ocular, 
motor, or cognitive deficits likely to impair their ability to perform the visual function tests 
required by the study protocol.  In addition, subjects will be evaluated by ocular coherence 
tomography to determine baseline RNFL thickness, neuropsychological testing to assess 
their ability to perform certain visual tasks, and fMRI for retinotopic mapping of the early 
visual cortex.  To ensure that potential subjects do not have any hematologic abnormalities 
(e.g. thrombocytopenia) or metabolic derangements (e.g. hyponatremia, hepatic 
insufficiency) that may affect the safety of taking fluoxetine, all candidates will have a 
complete blood count (CBC) and comprehensive metabolic panel (CMP) drawn at baseline.  
Women of childbearing age will have a urine pregnancy test to make sure they are not 
pregnant.  Finally, because some SSRIs like citalopram have been associated with QT 
interval prolongation, each patient’s baseline electrocardiogram (ECG) will be assessed for 
possible arrhythmias prior to randomization. 
 
Subjects will be started on fluoxetine vs. placebo within 5 days of the index stroke and no 
later than 72 hours after their admission to the hospital.  Seven days after randomization, 
they will be called by telephone and assessed for any adverse events using a questionnaire.  
If the subject has not been discharged from the hospital yet, this assessment will be 
performed in person in the hospital.  Subjects will return for study-specific and routine 
evaluations at 30 days, 90 days, and 6 months following the initiation of treatment.  During 
these visits, they will undergo assessments that constitute standard care as well as study-
specific evaluations and monitoring, as indicated in the Table.   
 
5.1. Treatment Dosage and Administration 
 
Subjects will be randomized in a 1:1 ratio to 20 mg of fluoxetine vs. placebo.  Fluoxetine is 
an oral medication and is usually taken in the morning because of its possible stimulant 
effects.  The University of Rochester Medical Center Investigational Drug Service will 
prepare and provide fluoxetine or placebo to all subjects.  They will administer the study 
drug to each study participant during the hospital admission.  At discharge, each study 


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participant will be given enough study drug to last until the end of the study.  The study 
drug will be discontinued without a taper at the end of 90 days.  Drug accountability logs 
will be updated during routine follow-up visits at 30 and 90 days. 
 
5.2. Efficacy Assessments 
 
To assess the effect of fluoxetine on post-stroke visual recovery, subjects will be evaluated 
by a formal neuro-ophthalmologic examination, automated Humphrey perimetry, OCT, 
neuropsychological testing, fMRI, and various clinical scales and questionnaires (mRS, 
PHQ-9, and VFQ-25) following the schedule outlined in the Table.  Functional vision will 
be assessed by calculating the functional vision score as described in the Guide for the 
Evaluation of Visual Impairment, prepared on behalf of the International Society for Low 
Vision Research and Rehabilitation (15). 
 
1. Modified Rankin Scale (mRS): The most commonly used outcome measure in stroke 
clinical trials, the mRS is a tool designed to quantify disability in stroke patients based 
on their level of independence in the activities of daily living (Appendix E).  It requires 
5 minutes to perform and will be administered by certified faculty, fellows, and 
residents from the Department of Neurology.  Scores range from 0 (no symptoms) to 6 
(death).  Documentation of the mRS score at baseline and outpatient follow-up is part 
of standard care. 
 
2. Neuro-ophthalmologic examination: This is a standardized clinical evaluation to be 
performed by study investigator, Dr. Zoe Williams, at the University of Rochester 
Flaum Eye Institute.  It consists of an external eye exam, pupillary exam, dilated 
fundoscopic exam, standard neurologic exam, and an evaluation of visual acuity, 
refraction, color vision, sense of brightness, visual field size, and ocular motility.  A 
baseline neuro-ophthalmologic evaluation represents standard care in the assessment of 
patients with new visual field deficits attributable to an acute ischemic stroke. 
 
3. Automated Humphrey perimetry: Humphrey perimetry is an automated non-invasive 
clinical test performed in most routine ophthalmologic evaluations to characterize and 
monitor a patient’s peripheral vision, using normative data from healthy age-matched 
controls as a reference.  In this study, we will use Swedish Interactive Threshold 
Algorithm (SITA) standard 24-2 visual field testing to assess each subject’s peripheral 
vision at the specified time points.  This form of automated Humphrey perimetry 
requires 7 ½ minutes of testing time.  Testing will be performed by a qualified 
ophthalmic technician or physician at the University of Rochester Flaum Eye Institute.  
During each test, the subject will place his or her chin on a chin rest, fixate on a central 
point, and respond with a push-button when he or she sees a test spot presented briefly 
in the peripheral visual field.  Baseline, 90-day, and 6-month assessments represent 
standard care, whereas the 30-day assessment is for research purposes only. 
 
4. Optical coherence tomography (OCT): This is a standardized non-invasive clinical test 
that uses light waves to measure the thickness of the RNFL in patients with a wide 
range of visual problems.  It requires 30 seconds of testing time.  It will be performed 
by a qualified ophthalmic technician or physician at the University of Rochester Flaum 
Eye Institute.  OCT is not part of standard care for this patient population. 
 
5. Patient Health Questionnaire-9 (PHQ-9): This is a self-report inventory used as a 
screening and diagnostic tool for depression (Appendix F).  The 9 items are based on 


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the 9 diagnostic criteria for depression included in the Diagnostic and Statistical 
Manual of Mental Disorders IV.  It takes 5-10 minutes to complete.  It will be 
administered at baseline, 30 days, 90 days, and 6 months.  The 30- and 90-day 
assessments will be performed during routine follow-up in the University of Rochester 
Stroke and Cerebrovascular Disorders Clinic.  The 6-month assessment will be 
performed by phone interview.  Screening for depression by PHQ-2, a shorter version 
of PHQ-9, is part of standard care for this patient population at baseline.  However, 
screening by PHQ-9 is not part of standard care at baseline or at any other study time 
point. 
 
6. Functional vision assessment: This will be done by calculating the functional vision 
score for each subject as described in the Guide for the Evaluation of Visual 
Impairment (15), a clinical and research tool designed to measure functional vision in 
adults with acquired vision loss.  Calculation of a functional vision score using this 
tool requires visual field and visual acuity assessments, so it will be done at baseline 
and at 6 months by study investigator, Dr. Zoe Williams, at the University of 
Rochester Flaum Eye Institute.  Ophthalmologic follow-up at these time points is part 
of standard care. 
 
7. Visual Function Questionnaire-25 (VFQ-25): This is a 25-item survey designed to 
provide a vision-targeted assessment of health-related quality of life by measuring the 
influence of visual disability on daily visual functioning, emotional well-being, and 
social functioning (Appendix G).  It takes 10 minutes to complete.  It will be 
administered at baseline and 6 months.  The 6-month assessment will be performed by 
phone interview.  Assessing vision-related quality of life by VFQ-25 is not part of 
standard care for this patient population. 
 
8. Neuropsychological testing: The neuropsychological assessment will consist of picture 
naming tasks, face memory tasks, and other simple tests of low- and high-level visual 
processing, such as indicating whether a stimulus is seen on a screen.  The 
participant’s eye position will be monitored using special cameras during certain tests.  
Some tests will require participants to indicate the location of a stimulus on a screen 
with their fingers.  For these tests, finger position during the pointing motion will be 
tracked using a special camera system.  Neuropsychological testing will be performed 
at baseline, 30 days, 90 days, and 6 months by study investigator, Dr. Bradford Mahon, 
and members of his laboratory.  The baseline assessment will be completed before 
discharge from the hospital and require approximately 45 minutes.  Subsequent 
sessions will occur at the RCBI and will require approximately 90 minutes each.  
Neuropsychological testing is not part of standard care for this patient population. 
 
9. Functional magnetic resonance imaging (fMRI): Visual processing will be assessed 
using fMRI.  Dependent measures will consist of high-resolution measurements of 
cortical thickness and representation, functional activity during visual tasks as 
measured by blood oxygen level-dependent (BOLD) responses, and measurements of 
the structural integrity of nerve fibers in the brain using diffusion tensor imaging.  
Subjects will be asked to view and respond to a visual stimulus according to the 
specific task description.  For example, they may be asked to name common objects 
depicted in a picture, or estimate the number of dots in a display.  Typically subjects 
will be asked to perform a task in the MRI machine for 45 minutes, although sessions 
may go up to 70 minutes depending on the comfort and compliance of the study 
participant.  Tasks will be broken up into shorter runs of 5 to 10 minutes in order to 


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allow participants to rest during the testing session.  Scanning will occur on MRI 
machines at Strong Memorial Hospital, the University of Rochester Stroke and 
Cerebrovascular Disorders Clinic, or the RCBI.  Study integrity will not be 
compromised by scanning a given patient on different scanners at different times.  We 
will compute contrasts only between experimental conditions tested on the same 
machine during the same scan, so the key effects we measure will be orthogonal to any 
scanner variation.  Finally, fMRI data will be retained in an anonymized form for 
future use by other researchers as part of this study. 
 
5.3. Safety Assessments 
 
Subjects will be instructed to exercise caution when drinking alcohol or taking any 
previously prescribed sedating medications, such as diphenhydramine or cyclobenzaprine, 
while on the study drug.  Additionally, they will be advised to contact their primary care 
physicians or the study team before starting any new prescription or over-the-counter 
medications, or any new herbal or nutritional supplements.  Primary care physicians will 
be provided with a list of medications and supplements to avoid while their patients are on 
the study drug. 
 
Laboratory studies: A CBC and CMP will be repeated 30 days after the initiation of the 
study drug to monitor for any hematologic or metabolic abnormalities.  This will require a 
total of 9 mL of blood to be collected from each subject. 
 
ECG: An ECG will be obtained at baseline and at 30 days to measure each subject’s QT 
interval and monitor for QTc prolongation or other arrhythmias. 
 
Adverse event survey: A questionnaire to screen for adverse events will be administered by 
study personnel at 7 days by phone interview (Appendix H).  This 7-day evaluation will be 
done in person if the patient has not been discharged from the hospital yet.  The same 
questionnaire will be administered when the subjects return to the University of Rochester 
Stroke and Cerebrovascular Disorders Clinic for their follow-up visits at 30 and 90 days.  
Finally, the same questionnaire will be administered at 6 months by phone interview. 
 
5.4. Data and Specimen Banking for Future Research Use 
 
The data generated in this study may be used in future research in an anonymized form that 
cannot be connected to any individual subject.  Data may also be shared with other 
researchers, but only after all identifying information has been removed to ensure subject 
confidentiality.  Information recorded on paper will be stored inside a locked cabinet in a 
locked office as previously described.  All digital data will be password-protected and 
stored on a firewalled server.   
 
5.5. Costs to the Subject 
 
There will be no planned costs to the subject for participation in this study.  All study drugs 
will be provided free of charge.  Neurological and neuro-ophthalmological evaluations 
performed as part of standard care at baseline, 30 days, 90 days, and 6 months will be 
billed to the patient’s insurance.  Additional study-specific evaluations that fall outside 
standard care (see Table) will be covered by the research program.  Should a subject suffer 
any adverse outcomes as a result of participation in the study, the subject and/or the 
subject’s insurance may need to cover the costs of any additional medical treatment 


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required. 
 
5.6. Payment for Participation 
 
Upon completing the study, each subject will receive a $50 Visa® prepaid debit card as a 
token of appreciation for his or her participation.  In addition, parking expenses will be 
covered for all follow-up visits. 
 
5.7. Return of Individual Research Results 
 
Individual research results will not be routinely made available to study subjects.  
However, they will have access to many of their test results upon request or through the 
online patient medical record access system, MyChart.  With the exception of the serial 
fMRI studies, baseline and 60-day OCT studies, the PHQ-9, VFQ-25, and adverse event 
questionnaires, and the ECG, CBC, CMP, and Humphrey visual field testing performed at 
30 days, all proposed evaluations are part of the routine care and work-up of stroke patients 
with visual field deficits.  Results of these evaluations will be included in the medical 
record.  Any incidental findings of potential clinical significance, discovered in the course 
of a study-specific evaluation that falls outside standard care, will be immediately 
disclosed to the patient and his or her primary care physician.  Follow-up studies or 
consultations will also be recommended to the primary care physician as appropriate.  
 
 
6. CONCOMITANT AND DISALLOWED MEDICATIONS 
 
Subjects will be randomized to 20 mg of fluoxetine vs. placebo as previously described.  During 
the course of the study, they will not be allowed to take higher doses of fluoxetine or any other 
SSRIs.  Additionally, in order to reduce the risk of any adverse events due to drug-drug 
interactions, they will not be allowed to take medications contraindicated in combination with 
SSRIs, including other SSRIs, non-selective serotonin reuptake inhibitors, monoamine oxidase 
inhibitors, tricyclic antidepressants, and QTc-prolonging agents.  
 
 
7. SUBJECT WITHDRAWALS 
 
Subjects will be advised on the written informed consent form (Appendix A) that they have the 
right to withdraw from the study at any time without prejudice.   Subjects may also be withdrawn 
from the study by study investigators if they have a recurrent stroke, a symptomatic hemorrhagic 
transformation of the index ischemic stroke, or another major illness requiring hospitalization, if 
they become pregnant, or if they are not able to comply with the study protocol or return for 
routine and study-specific neurological or ophthalmological assessments.  Subjects withdrawn 
from the study will be replaced.  
 
 
8. STUDY DRUG ADMINISTRATION AND ASSIGNMENT 
 
8.1. Study Drug 
 
Fluoxetine is an antidepressant medication approved by the U.S. Food and Drug 
Administration (FDA) for use in several conditions, including major depressive disorder 
and obsessive-compulsive disorder.  During the study, each subject will take 20 mg of 


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fluoxetine or a matching placebo daily for 90 days.  Blinded capsules, identical in 
appearance and containing either an active dose or a placebo, will be prepared by over-
encapsulation.  Active doses will consist of a single 20-mg fluoxetine capsule placed inside 
a larger opaque colored capsule and backfilled with inert lactose powder.  Placebo doses 
will consist of the same opaque colored capsule filled only with lactose.  Exemption from 
Investigational New Drug (IND) regulations was granted by the FDA for the use of 
fluoxetine in this study on August 18, 2015. 
 
8.2. Dosage of Study Drug 
 
Fluoxetine will be administered by mouth at a daily dose of 20 mg for 90 days.  There are 
no plans to increase or decrease the dose of the drug during the course of the study. 
 
8.3. Subject Enrollment and Randomization 
 
Subjects will be randomized in a ratio of 1:1 to fluoxetine vs. placebo by computer 
randomization.  All study personnel will remain blinded to treatment assignments until the 
conclusion of the entire study, with the exception of the pharmacist and the statistician.  
These individuals will not disclose any information regarding the treatment assignment of 
individual subjects to the study investigators.  
 
8.4. Accountability of Investigational Drug Supplies 
 
The active drug and placebo will be prepared by the University of Rochester Medical 
Center Investigational Drug Service, which will also administer the drug to study 
participants during their hospital admission.  Remaining doses of the drug will be given to 
each subject at the time of hospital discharge.  From that point forward, the subject will be 
responsible for storing and administering the drug as an outpatient. 
 
8.5. Discontinuation of Study Drug by Subject 
 
Subjects will be free to stop the study drug at any time.  Should they do so, they will be 
withdrawn from the study. 
 
8.6. Emergency Drug Disclosure 
 
The University of Rochester Medical Center Investigational Drug Service will maintain a 
list of treatment assignments for each subject and disclose this information upon request in 
case of a medical emergency.  Should drug disclosure occur, the subject in question will be 
withdrawn from the study.  
 
 
9. SAFETY AND REPORTABLE EVENTS 
 
9.1. Adverse Event Definition 
 
An adverse event is any symptom, sign, illness, or medical experience that develops or 
worsens during the course of the study, whether it is attributable to the study drug or not. 
 
9.2. Serious Adverse Event 
 


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March 15, 2016 
A serious adverse event is defined as an adverse medical experience that is life-threatening, 
results in death, requires hospitalization or prolongs an ongoing hospitalization, results in 
persistent or significant disability or incapacity, and/or requires a medical or surgical 
intervention to prevent permanent injury or impairment. 
 
9.3. Recording Adverse Events 
 
As specified in the Table, study personnel will screen each subject for adverse events at 7 
days, 30 days, 90 days, and 6 months by recording all voluntary complaints of the subject, 
administering the adverse event questionnaire, and evaluating any available objective 
clinical findings.  
 
All adverse events, whether observed by study personnel, or elicited from or volunteered 
by the subject, will be documented.  Documentation will include a brief description of the 
experience, the date of onset, the date of resolution, the duration and type of experience, 
the severity, any relationship to the study drug, any contributing or alleviating factors, and 
any action taken with respect to the study drug. 
 
9.4. Responsibilities for Reporting Serious Adverse Events 
 
The Principal Investigator will record all serious adverse events that occur during the study 
period in an adverse event log.  The study period for reporting serious adverse events will 
be from the time of signing consent until the final study visit at 6 months (i.e. 3 months 
after stopping the study drug).  The Principal Investigator will comply with all RSRB 
policies and regulations regarding the reporting of adverse events.   
 
 
10. RISK/BENEFIT ASSESSMENT 
 
10.1. Potential Risks and Protection against Risks 
 
Fluoxetine: Potential risks associated with the use of fluoxetine include allergic reaction, 
anaphylactic shock, depression, suicidal behavior, mania, seizures, serotonin syndrome, 
neuroleptic malignant syndrome, QT interval prolongation, acute angle-closure glaucoma, 
abnormal bleeding due to impaired platelet function, hypotension, hyponatremia, and 
priapism.  More commonly, patients report insomnia, headache, anxiety, irritability, dry 
mouth, tremor, decreased libido, delayed ejaculation, and gastrointestinal symptoms such 
as nausea, indigestion, constipation, or diarrhea.  These side effects typically resolve upon 
discontinuation of the drug.  Subjects will be screened for depression during their 
enrollment in the study.  If, at any point, they are diagnosed with depression, they will be 
referred to a health care provider for counseling and treatment.  If they report suicidal 
thoughts, they may be directed to the Emergency Department for further evaluation. 
 
Automated Humphrey perimetry, OCT, and neuropsychological testing: The risk 
associated with these procedures is minimal, the main risk being slight stress, fatigue, or 
boredom.  To minimize these risks, subjects will be encouraged to take breaks, stop the 
evaluation, or leave the study at any time as they feel necessary.  They will also be allowed 
to bring a family member or companion to the visit.  These options will be explained 
clearly to all subjects prior to enrollment and during the course of the study.  
 


Page 13 of 31 
March 15, 2016 
MRI: There are no immediate risks associated with exposure to magnetic fields of 3.0 
Tesla.  Since the MR gantry is a small opening approximately 3 feet in diameter, the 
subject may experience anxiety, claustrophobia, or dizziness once he or she is placed 
inside the MRI machine.  In addition, the functional scanning coil closely encloses the 
subject’s head, potentially increasing the likelihood of claustrophobia.  To mitigate these 
risks, the MR gantry is equipped with a camera allowing continuous monitoring of the 
subject from the control room at all times.  In addition, the subject is given a pneumatic 
bulb that initiates an alarm in the control room when squeezed by the subject in case of an 
emergency.  Furthermore, the subject is able to communicate through an intercom with the 
operator.  Should the subject feel any discomfort, the experiment will be terminated 
promptly upon his or her request. 
 
Subjects will be screened for magnetic material before each study using an MRI safety 
screening form (Appendices D1, D2, and D3).  Those with pacemakers, implantable 
cardiac defibrillators, aneurysm clips, penile implants, metallic prostheses including heart 
valves and cochlear implants, and bullet or shrapnel fragments are at risk of injury in an 
MR environment.  Welders and metal workers are also at risk because of possible metal 
fragments in their eyes.  Those at risk will be excluded from the study.   
 
Scanning by MRI produces a loud tone that can cause injury to the inner ear if appropriate 
protection is not used.  Earplugs or close-fitting silicone-padded headphones will be 
provided to each subject to prevent ear injury. 
 
The long-term health risks of MRI are unknown.  This study will use a magnetic field 
strength of 3.0 Tesla, which is commonly used in clinical practice and research.  This field 
strength has been used in the clinical setting for nearly a decade, and so far no detrimental 
long-term effects have been identified. 
 
Phlebotomy: Risks associated with phlebotomy include pain or stinging when the needle is 
inserted and throbbing and/or bruising at the puncture site after the blood is drawn.  To 
reduce the risk of bruising, subjects will be instructed to hold pressure on the puncture site 
for several minutes after the needle is withdrawn.  Rarely the vein may become inflamed 
after the blood sample is obtained.  This is treated with a warm compress applied several 
times a day.  Finally, there is a small risk of infection at the puncture site.  This risk will be 
minimized by the use of proper sterile technique. 
 
10.2. Potential Benefits to Subjects 
 
Patients randomized to the fluoxetine arm of the study may have improved visual recovery.  
They also may benefit from the antidepressant effects of fluoxetine.  All subjects, whether 
they are in the fluoxetine or placebo arm, may benefit from depression screening, as 
depression is common after stroke and associated with poor recovery.  
 
10.3. Alternatives to Participation 
 
Patients may choose not to participate in the study.  Unfortunately there are no proven 
therapies known to enhance post-stroke visual recovery at this time.  Standard care for 
stroke patients with visual field deficits includes occupational and cognitive rehabilitation, 
which will be offered to all patients regardless of their participation in the study.  
 
 


Page 14 of 31 
March 15, 2016 
11. CONFIDENTIALITY OF DATA AND INFORMATION STORAGE  
 
Subjects’ names or initials will not be used when working with the data.  Each subject will be 
assigned a label to maintain confidentiality.  While we will make every effort to maintain 
confidentiality, it cannot be absolutely guaranteed as consent forms and other records that 
identify study subjects may be inspected by the Department of Health and Human Services 
and/or authorized officials of the University of Rochester.  However, in no case will personal 
information be shared with other individuals or groups without written prior authorization from 
the subject.  The results of this study may be presented at scientific meetings, published, shared 
with other researchers, or used in future studies, but data will be maintained in an anonymized 
form that cannot be connected to any individual subject.  Information recorded on paper will be 
stored inside a locked cabinet in a locked office.  All digital data will be password-protected and 
stored on a firewalled server. 
 
 
12. RESEARCH INFORMATION IN MEDICAL RECORDS 
 
Most of the data collected during this study will be part of the subject’s medical record, including 
the initial diagnostic MRI, all automated Humphrey perimetry and OCT studies, all ECG studies, 
and all clinical exam and laboratory findings.  The subject’s participation in the study will also be 
documented in the medical record.  The results of the neuropsychological assessment, fMRI 
testing, adverse event questionnaire, PHQ-9 and VFQ-25 questionnaires, and functional vision 
assessment will not be included in the medical record, but stored in the subject’s study binder.  
 
 
13. DATA ANALYSIS AND MONITORING 
 
13.1. Sample Size Determination 
 
The currently planned enrollment target of 40 subjects (i.e. 20 subjects per arm) is intended 
to achieve a final sample size of 30 and assumes a dropout rate of 25% during the course of 
the study.  In turn, this estimate is based on the number of acute ischemic stroke patients 
who presented to Strong Memorial Hospital with an isolated visual field deficit in the 
previous calendar year (56 patients between January 1, 2015 and December 31, 2015).  
Previous studies indicate that 50% of patients will experience an improvement in their 
visual field deficit by 3 months.  Based on this rate of spontaneous recovery, a final sample 
size of 15 subjects per group will provide 80% power to detect an improvement rate of 
90% in the actively treated group (i.e. a 40% difference between the fluoxetine and placebo 
groups), using a one-sided 2 test with  = 0.05.  Thus, the planned sample size will be 
sufficient to detect a moderately large effect and is comparable to sample sizes used in 
equivalent pilot trials evaluating the efficacy of an FDA-approved drug for a novel 
application.  
 
13.2. Planned Statistical Analysis 
 
The primary endpoint will be an improvement in peripheral vision of at least 15 degrees in 
the affected visual field as measured by automated Humphrey perimetry at 6 months.  The 
primary outcome will be compared between the treatment groups using an upper-tailed 
two-sample t test with  = 0.05.  Secondary outcome measures will include degree of 
cortical reorganization as assessed by fMRI, RNFL thickness as assessed by OCT, the 
functional vision score as assessed by the Guide for the Evaluation of Visual Impairment, 


Page 15 of 31 
March 15, 2016 
performance on neuropsychological testing, and scores on the mRS, PHQ-9, and VFQ-25.  
 
13.3. Data and Safety Monitoring 
 
A data and safety monitoring plan appropriate to the nature, size, and complexity of the 
study will be used to ensure: 1) an adequate process is in place for the oversight and 
monitoring of the conduct and progress of the study; 2) important information that may 
affect the safety or welfare of study subjects is noted and addressed as quickly as possible; 
and 3) the validity and integrity of the data are protected.  The monitoring of data quality 
and subject safety will follow the National Institute of Neurologic Disorders and Stroke 
Guidelines for Data and Safety Monitoring in Clinical Trials.  
 
The Principal Investigator will monitor the following elements of the study as part of this 
data and safety monitoring plan: 
 
 
Flow of data acquisition 
 
Timeliness and completeness of reporting 
 
Recruitment rates 
 
Protocol violations 
 
Serious adverse events 
 
The number and nature of adverse events will be reviewed on a monthly basis by the 
Principal Investigator, and data will be un-blinded if there is serious concern about either 
of the treatment groups. 
 
 
14. REFERENCES 
 
1) Go, A.S., Mozaffarian, D., Roger, V.L., Benjamin, E.J., Berry, J.D., Blaha, M.J., Dai, S., 
Ford, E.S., Fox, C.S., Franco, S., Fullerton, H.J., Gillespie, C., Hailpern, S.M., Heit, J.A., 
Howard, V.J., Huffman, M.D., Judd, S.E., Kissela, B.M., Kittner, S.J., Lackland, D.T., 
Lichtman, J.H., Lisabeth, L.D., Mackey, R.H., Magid, D.J., Marcus, G.M., Marelli, A., 
Matchar, D.B., McGuire, D.K., Mohler, E.R. 3rd, Moy, C.S., Mussolino, M.E., Neumar, 
R.W., Nichol, G., Pandey, D.K., Paynter, N.P., Reeves, M.J., Sorlie, P.D., Stein, J., 
Towfighi, A., Turan, T.N., Virani, S.S., Wong, N.D., Woo, D., Turner, M.B. (2015). Heart 
disease and stroke statistics--2014 update. A report from the American Heart Association. 
Circulation, 129:e28-e29. 
2) Lawrence, E.S., Coshall, C., Dundas, R., Stewart, J., Rudd, A.G., Howard, R., and Wolfe, 
C.D.A. (2001). Estimates of the prevalence of acute stroke impairments and disability in a 
multiethnic population. Stroke, 32:1279-1284. 
3) MacIntosh, C. (2003). Stroke re-visited: visual problems following stroke and their effect on 
rehabilitation. British Orthoptic Journal, 60:10-14.  
4) Zhang, X., Kedar, S., Lynn, M.J., Newman, N.J., and Biousse, V. (2006). Natural history of 
homonymous hemianopia. Neurology, 66: 901-905. 
5) Ali, M., Hazelton C., Lyden P., Pollock A., and Brady M. (2013). Recovery from poststroke 
visual impairment: evidence from a clinical trials resource. Neurorehabilitation and Neural 
Repair, 27(2):133-141. 
6) The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group 
(1995). Tissue plasminogen activator for acute ischemic stroke. New England Journal of 
Medicine, 333:1581-1587.  


Page 16 of 31 
March 15, 2016 
7) Schwamm, L.H., Ali, S.F., Reeves, M.J., Smith, E.E., Saver, J.L., Messe, S., Bhatt, D.L., 
Grau-Sepulveda, M.V., Peterson, E.D., and Fonarow, G.C. (2013). Temporal trends in 
patient characteristics and treatment with intravenous thrombolysis among acute ischemic 
stroke patients at Get With The Guidelines-Stroke hospitals. Circulation: Cardiovascular 
Quality and Outcomes, 6:543-549. 
8) Chollet, F., Tardy, J., Albucher, J.F., Thalamas, C., Berard, E., Lamy, C., Bejot, Y., Deltour, 
S., Jaillard, A., Niclot, P., Guillon, B., Moulin, T., Marque, P., Pariente, J., Arnaud, C., and 
Loubinoux, I. (2011). Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): 
a randomised placebo-controlled trial. Lancet Neurology, 10:123-130. 
9) Jorge, R.E., Acion, L., Moser, D., Adams, H.P. Jr., and Robinson, R.G. (2010). Escitalopram 
and enhancement of cognitive recovery following stroke. Archives of General Psychiatry, 
67:187-196. 
10) Pambakian, A.L.M. and Kennards, C. (1997). Can visual function be restored in patients with 
homonymous hemianopia? British Journal of Ophthalmology, 81:324-328. 
11) Maya Vetencourt, J.F., Sale, A., Viegi, A., Baroncelli, L., De Pasquale, R., O’Leary, O.F., 
Castrén, E., and Maffei, L. (2008). The antidepressant fluoxetine restores plasticity in the 
adult visual cortex. Science, 320:385-388.  
12) Park, H.Y.L., Park Y.G., Cho, A.H., Park C.K. (2013). Transneuronal retrograde 
degeneration of the retinal ganglion cells in patients with cerebral infarction. Ophthalmology, 
120:1292-1299. 
13) Paul, D.A., Gaffin-Cahn, E., Hintz, E.B., Adeclat, G.J., Zhu, T., Williams, Z.R., Vates, G.E., 
and Mahon, B.Z. (2014). White matter changes linked to visual recovery after nerve 
decompression. Science Translational Medicine, 6:1-12. 
14) Renou, P., Sibon, I., Tourdias, T., Rouanet, F., Rosso, C., Galanaud, D., Drier, A., Coudert, 
M., Deltour, S., Crozier, S., Dormont, D., Samson, Y. (2010). Reliability of the ECASS 
radiological classification of postthrombolysis brain haemorrhage: A comparison of CT and 
three MRI sequences. Cerebrovascular Diseases, 29:597-604. 
15) International Society for Low Vision Research and Rehabilitation (ISLRR). Guide for the 
Evaluation of Visual Impairment. (1999). 
 
 
 


Page 17 of 31 
March 15, 2016 
TABLE.  Schedule of tests and procedures 
 
            
     Procedure 
                Baseline  7 days  
    30 days         90 days        6 months 
 
History & Physical 
 
 
 
 
 
Brain MRIa 
 
 
 
 
 
Urine pregnancy testb 
 
 
 
 
 
Complete blood count 
 
 
 
 
 
Comprehensive metabolic panel 
 
 
 
 
 
Electrocardiogram 
 
 
 
 
 
Modified Rankin Scale 
 
 
 
 
 
Neuro-ophthalmological exam 
 
 
 
 
 
Automated Humphrey perimetry 
 
 
 
 
 
Optical coherence tomography 
 
 
 
 
 
Functional vision score 
 
 
 
 
 
Visual Function Questionnaire-25 
 
 
 
 
 
Neuropsychological testing 
 
 
 
 
 
Functional MRI 
 
 
 
 
 
Patient Health Questionnaire-9 
 
 
 
 
 
Adverse event questionnaire 
 
 
 
 
 
 
a Magnetic resonance imaging  
 
 
 Standard care 
b For women of childbearing age only 
 
 Study-related procedure 
 
 


Page 18 of 31 
March 15, 2016 
APPENDICES. 
 
A. Consent form (included separately) 
 
B. Fluoxetine package insert (included separately) 
 
C. Letter to primary care physicians 
 
D. MRI safety screening forms  
 
D1. Strong Memorial Hospital  
D2. University Medical Imaging 
D3. Rochester Center for Brain Imaging 
 
E. Modified Rankin Scale 
 
F. Patient Health Questionnaire-9 
 
G. Visual Function Questionnaire-25 
 
H. Adverse event questionnaire 
 
I. Authorization to release medical information 
 
J. List of study personnel 
 
 
 


Page 19 of 31 
March 15, 2016 
APPENDIX A.  Consent form 


Page 20 of 31 
March 15, 2016 
APPENDIX B.  Fluoxetine package insert 


Page 21 of 31 
March 15, 2016 
APPENDIX C.  Letter to primary care physicians 
 
601 Elmwood Avenue, Box 681 
Rochester, New York, 14642 
Phone: (585) 275-2530 
Fax: (585) 273-1026 
 
Primary care physician’s name 
Address line 1 
Address line 2 
Address line 3 
 
 
Date 
 
Dear Dr. _____________, 
 
Mr./Ms. _____________ was admitted to Strong Memorial Hospital recently for an acute ischemic 
stroke resulting in a visual field deficit.  He/She has consented to participate in a randomized double-
blind placebo-controlled clinical trial testing the effect of fluoxetine (20 mg administered daily for 90 
days) on post-stroke visual recovery.  The study protocol involves serial visual field testing, optical 
coherence tomography, and functional magnetic resonance imaging studies to track the recovery 
process over the first 6 months after stroke.   
 
In order to minimize the risk of any serious drug-drug interactions, Mr./Ms. _____________ was 
advised to contact you or the study team before starting any new prescription or over-the-counter 
medications, or any new herbal or nutritional supplements.  For your convenience, we have attached 
a list of medications and supplements that should be avoided while your patient is on the study drug 
during the first 90 days of the study.  In addition to these medications, the use of any pharmaceutical 
agents likely to impair post-stroke recovery, including benzodiazepines and barbiturates, should also 
be avoided in the first 6 months.   
 
Thank you in advance for your time and assistance.  Please do not hesitate to contact me with any 
questions or concerns. 
 
Sincerely, 
 
 
 
 
 
 
[Signature] 
 
 
Bogachan Sahin, MD, PhD 
Principal Investigator, FLUORESCE Study 
Assistant Professor, Department of Neurology 
University of Rochester School of Medicine and Dentistry 
 
 
 
 


Page 22 of 31 
March 15, 2016 
List of medications to be avoided during the study 
To minimize the risk of serious drug-drug interactions and possible impairment of post-stroke 
recovery, the following medications, herbs, and supplements should be avoided while your patient is 
in this study.  If, in your opinion, the patient develops an indication for one of these medications 
during the first 90 days of the study, he or she may need to stop taking the study drug and withdraw 
from the study. 
 
Selective and non-selective serotonin reuptake inhibitors, including citalopram, duloxetine, 
escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, trazodone, venlafaxine, vilazodone. 
Monoamine oxidase inhibitors, including isocarboxazid, linezolid, methylene blue, moclobemide 
phenelzine, procarbazine, rasagiline, selegiline, tranylcypromine. 
Tricyclic antidepressants, including amitriptyline, nortriptyline, desipramine, imipramine. 
Medications that prolong the QT interval, including amiodarone, azithromycin, ciprofloxacin, 
dofetilide, dronedarone, erythromycin, haloperidol, levofloxacin, moxifloxacin, pimozide, 
quetiapine, sotalol, thioridazine, ziprasidone. 
Medications that may enhance the levels or toxic effects of fluoxetine, including abiraterone 
acetate, alfalfa, anise, aripiprazole, bilberry, buspirone, cimetidine, clarithromycin, dapoxetine, 
dextromethorphan, ethanol, fosphenytoin, ivabradine, linezolid, lithium, methylene blue, 
metoclopramide, mifepristone, ondansetron, propafenone, St. John’s wart, tramadol, tryptophan, 
ziprasidone. 
Medications that may diminish the levels or therapeutic effects of fluoxetine, including 
carbamezapine, dabrafenib, non-selective non-steroidal anti-inflammatory drugs. 
Medications whose levels or toxic effects may be enhanced by fluoxetine, including aripiprazole, 
atomoxetine, carbamezapine, chlorpromazine, cilastazol, clozapine, dosulepin, conventional 
doxorubicin, flecainide, fosphenytoin, haloperidol, mequitazine, methadone, metoprolol, mexiletine, 
non-selective non-steroidal anti-inflammatory drugs, propafenone, tizanidine, tramadol, vinblastine, 
vortioxidine. 
Medications whose levels or therapeutic effects may be diminished by fluoxetine, including 
clopidogrel, codeine, iobenguane I 123, tamoxifen. 
Medications that may impair post-stroke recovery, including phenytoin, benzodiazepines, and 
barbiturates.


Page 23 of 31 
March 15, 2016 
APPENDIX D1.  MRI safety screening form (Strong Memorial Hospital) 


Page 24 of 31 
March 15, 2016 
APPENDIX D2.  MRI safety screening form (University Medical Imaging) 


Page 25 of 31 
March 15, 2016 
APPENDIX D3.  MRI safety screening form (Rochester Center for Brain Imaging) 
 


Page 26 of 31 
March 15, 2016 
APPENDIX E.  Modified Rankin Scale 
 
 
0 
No symptoms 
 
1 
No significant disability, able to perform previous activities despite some symptoms 
 
2 
Slight disability, able to look after own affairs, but unable to perform previous activities 
 
3 
Moderate disability, requiring some amount of help, but able to walk without assistance 
 
4 
Moderately severe disability, unable to walk or attend to bodily needs without assistance 
 
5 
Severe disability, requiring constant care, bedridden, incontinent 
 
6 
Death 


Page 27 of 31 
March 15, 2016 
APPENDIX F.  Patient Health Questionnaire-9 (PHQ-9) 
 
 


Page 28 of 31 
March 15, 2016 
APPENDIX G.  Visual Function Questionnaire (VFQ-25)


Page 29 of 31 
March 15, 2016 
APPENDIX H.  Adverse event questionnaire 
 
Please indicate if you have had any of the following symptoms since starting the study drug by 
placing a check mark  in the appropriate box. 
 
☐Weight gain  
 
☐Cough 
 
 
☐Dry hair 
☐Weight loss  
 
☐Wheezing 
 
 
☐Dry skin 
☐Poor appetite  
 
☐Shortness of breath 
 
☐Hair loss  
☐Increased appetite 
 
☐Rapid breathing 
 
☐Easy bruising 
☐Fatigue 
 
 
☐Recurrent colds 
 
☐Sun sensitivity 
☐Night sweats  
 
☐Coughing up blood 
 
☐Rash  
☐Cold sweats during the day 
☐Ankle swelling 
 
☐Itching 
☐Excessive daytime sweating ☐Palpitations  
 
☐Painful urination 
☐Hot or cold spells 
 
☐Rapid or irregular pulse 
☐Difficulty starting urination  
☐Abnormal sensitivity to heat ☐Chest pain 
 
 
☐Loss of bladder control 
☐Abnormal sensitivity to cold ☐High blood pressure  
☐Urine with unusual odor 
 
☐Excessive sleeping 
 
☐Low blood pressure  
☐Cloudy urine 
☐Excessive daytime sleepiness ☐Headache 
 
 
☐Blood in urine 
☐Excessive thirst 
 
☐Neck pain or stiffness ☐Decreased sexual desire 
☐Excessive urination  
☐Sore throat 
 
 
Women 
☐Flu-like symptoms 
 
☐Blurry vision  
 
☐No menses 
☐Vague sick feeling 
 
☐Double vision 
 
☐Irregular menses 
☐Restlessness  
 
☐Sensitivity to light 
 
☐Painful periods 
☐Depressed mood 
 
☐Seeing spots or shadows 
☐Heavy periods 
☐Suicidal thoughts 
 
☐Hearing loss  
 
☐Abnormal vaginal bleeding 
☐Forgotten periods of time 
☐Ringing in the ears 
 
☐Abnormal vaginal discharge 
☐Loss of conscioussness 
☐Disturbance in sense of smell ☐Painful intercourse (sex) 
☐Imbalance 
 
 
☐Runny nose  
 
Men 
☐Incoordination 
 
☐Dry mouth 
 
 
☐Inability to have an erection 
☐Light-headedness 
 
☐Sore tongue  
 
☐Inability to maintain an erection  
☐Spinning sensation   
☐Difficulty swollowing 
☐Inability to ejaculate (orgasm) 
☐Memory impairment  
☐Nausea or vomiting  
☐Delayed ejaculation  
☐Seizures or convulsions 
☐Abdominal pain 
 
☐Early ejaculation  
☐Tics  
 
 
☐Constipation  
 
☐Scrotal pain  
☐Tremors 
 
 
☐Diarrhea 
 
 
☐Abnormal penis discharge  
☐Muscle spasms 
 
☐Loss of bowel control 
☐Numbness 
 
 
☐Frequent belching or gas 
☐Other 
☐Tingling 
 
 
☐Vomiting blood 
 
 
☐Slurred speech 
 
☐Bloody (red or black) stools Explain: _____________________ 
☐Word-finding difficulty 
☐Yellowing of the skin  
_____________________________ 
☐Impaired attention 
 
☐Back pain or stiffness  
_____________________________ 
☐Impaired concentration 
☐Joint pain or stiffness  
_____________________________ 
☐Confusion 
 
 
☐Bone pain 
 
 
_____________________________ 
☐Limb weakness 
 
☐Muscle pain  
 
_____________________________ 
☐Falls  
 
 
☐Muscle cramps 
 
_____________________________ 


Page 30 of 31 
March 15, 2016 
APPENDIX I.  Authorization to release medical information 
 


Page 31 of 31 
March 15, 2016 
APPENDIX J.  List of study personnel 
 
 
Principal Investigator 
Bogachan Sahin, MD, PhD 
Assistant Professor, Department of Neurology 
 
 
Co-Principal Investigators 
Bradford Mahon, PhD 
Assistant Professor, Departments of Brain and Cognitive Science and Neurosurgery 
 
Zoe Williams, MD 
Associate Professor, Department of Ophthalmology 
 
 
Sub-Investigators 
Curtis Benesch, MD, MPH 
Professor, Department of Neurology 
 
Jeffrey Burdett, MD 
Assistant Professor, Department of Neurology 
 
Ania Busza, MD, PhD 
Experimental Therapeutics Fellow, Department of Neurology 
 
 
Michael Chilungu, MD 
Assistant Professor, Department of Neurology 
 
Fulvio Gil, MD 
Vascular Neurology Fellow, Department of Neurology 
 
Todd Holmquist, MD 
Assistant Professor, Department of Neurology 
 
Adam Kelly, MD 
Associate Professor, Department of Neurology 
 
Anthony Noto, MD 
Vascular Neurology Fellow, Department of Neurology 
 
 
Study Coordinator 
Ann Leonhardt, NP 
Research Coordinator, Department of Neurology 
 
 

ICF_001.pdf: 
RSRB Case Number: 00058133/Study #781 Page 1 of 19
Version Date: 03/19/2019
NCT02737930
CONSENT FORM
Fluoxetine for Visual Recovery after Ischemic Stroke (FLUORESCE)
Principal Investigator: Bogachan Sahin, MD, PhD
Co-Principal Investigator: Bradford Z. Mahon, PhD
Co-Principal Investigator: Zoe R. Williams, MD
This consent form describes a research study.  It explains what you may 
expect if you decide to take part.  It contains important information to help 
you make your decision.  Please read it carefully.
The study staff will explain this study to you.  Please ask questions about 
anything that is not clear before you agree to participate.  Before you make a 
decision, you may discuss this consent form with your family, friends, and 
members of your health care team, including your primary care physician.
Being in this study is voluntary – it is your choice.
If you join this study, you can change your mind and stop at any time.
If you choose not to take part, your routine medical care will not be affected in
any way.
There are risks associated with participation in any research study, and you
should understand what these mean to you.
Introduction
You are being asked to take part in this study because you have had an ischemic 
stroke that affected your vision.  An ischemic stroke is a condition where blood 
flow to part of your brain is cut off, usually because of a clot inside a blood 
vessel.  This leads to tissue injury.  In your case, the part of the brain that was 
damaged by the stroke played an important role in vision.  As a result, your ability 
to see has been affected by your stroke.
This study is being conducted by Bogachan Sahin, MD, PhD and Zoe R. 
Williams, MD from the Departments of Neurology and Ophthalmology at the 
University of Rochester. This study is also being conducted at Carnegie Mellon 
University by Dr. Bradford Mahon of the Psychology Department at Carnegie 
Mellon University and the Department of Neurosurgery at the University of 
Rochester Medical Center.
DEPARTMENT of NEUROLOGY
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Purpose of Study
The purpose of this study is to determine if a medication called fluoxetine (also 
known by the brand name, Prozac®) can improve recovery from vision loss due 
to a stroke.  Fluoxetine is a selective serotonin reuptake inhibitor (SSRI), a type 
of medication commonly used to treat depression.  It has also been found to help 
with recovery of brain function after a stroke.  In one recent clinical trial, stroke 
patients with severe weakness or paralysis affecting one side of the body were 
treated with fluoxetine for the first 3 months after their strokes.  At the end of the 
3-month treatment period, they had more strength on the side affected by the 
stroke compared to patients who had not taken fluoxetine.  This study, the 
“Fluoxetine for Visual Recovery after Ischemic Stroke” (FLUORESCE) trial, is 
designed to see if fluoxetine can also help patients with vision loss due to a 
stroke.
Fluoxetine is not approved by the U.S. Food and Drug Administration (FDA) to 
help improve recovery after a stroke.  Moreover, there are important differences 
between the parts of the brain involved in limb movement and those involved in 
vision.  At this time, it is not known whether fluoxetine will help stroke patients 
with vision loss.
Description of Study Procedures
THERE ARE A NUMBER OF POTENTIAL DRUG INTERACTIONS WITH THE 
STUDY DRUG.  BEFORE YOU START TAKING ANY NEW PRESCRIPTION 
OR OVER-THE-COUNTER MEDICATIONS, OR ANY NEW HERBAL OR 
NUTRITIONAL SUPPLEMENTS, YOU MUST CHECK WITH YOUR PRIMARY 
CARE PHYSICIAN OR THE STUDY DOCTOR FIRST.
Please also note that you cannot be enrolled in another interventional study such 
as a clinical trial investigating a drug or device while you are participating in this 
study. If you know you are currently participating in another research study, or if 
you are considering enrolling in another study at any time, please contact a 
member of our study team. 
Please see the Appendix at the end of this consent form and the Table on page 9 
for a study timeline and a summary of all routine and study-related procedures.
Before you begin the treatment part of the study...
If you agree to take part in this study, your study doctor will check whether you 
meet all the required conditions to participate, including the results of any tests or 
procedures you have already had as part of your routine medical care in the 
hospital.  The study team will also perform some additional tests, as indicated in 
bold in this section and all subsequent sections:
1.
A complete physical examination and medical history, including any 
medications you are currently taking.
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2.
An assessment of your level of independence in your daily activities 
prior to your stroke, based on the modified Rankin Scale.
3.
A magnetic resonance imaging (MRI) scan of your brain to confirm that 
you have had a stroke.
4.
A psychological assessment called the Patient Health Questionnaire-
9 (PHQ-9) to screen for depression.
5.
A urine pregnancy test.  If you are a woman of childbearing potential, 
we will obtain a urine sample to see if you are pregnant.  Fluoxetine can 
adversely affect a fetus, so pregnant women may not participate in this 
study.  If you are a woman of childbearing potential, you must use an 
acceptable method of birth control to avoid pregnancy while on the 
study drug.  Acceptable methods of birth control include hormonal 
contraceptives, intrauterine device, abstinence, or spermicide and 
barrier.
6.
A formal eye exam by a neuro-ophthalmologist (an eye doctor who 
specializes in nerve and brain problems that affect vision) and a vision 
test called automated Humphrey perimetry to determine how much of 
your vision has been affected by the stroke.
7.
Functional vision score.  This is an assessment of how your vision 
loss has affected your ability to perform your daily activities.  It is 
calculated by the neuro-ophthalmologist using information already 
gathered as part of the formal eye exam.  It does not require any 
additional testing.
8.
A questionnaire called the Visual Function Questionnaire-25 to 
determine if your vision affected your health-related quality of life in any 
way before your stroke.
9.
An electrocardiogram (ECG) to make sure you do not have an 
abnormal heart rhythm.
10. Blood tests to measure your complete blood count and make sure your 
kidneys and liver are working well (comprehensive metabolic panel).
You will not be included in this study until all of these tests and procedures have 
been completed, and the study team has reviewed the results.
During the treatment part of the study...
If you are found eligible for this study after these tests and procedures are 
completed, you will be randomly assigned, or randomized, to one of the two 
groups described below.  Randomization means that you are put into a group by 
chance, like tossing a coin.  You will have an equal chance of being placed in 
one group or the other.  This is a double-blind study, which means that neither 
you nor your study doctor will know which of the study groups you have been 
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assigned to.  However, this information will be readily available in case of an 
emergency. 
Group A: If you are assigned to this group, you will take a capsule 
containing 20 mg of fluoxetine by mouth every day for 90 days. 
Group B: If you are assigned to this group, you will take a capsule 
containing an inactive substance (placebo, or sugar pill) by mouth every 
day for 90 days.
You will be started on fluoxetine or placebo during your hospital admission.  (We 
will refer to them as the study drug from this point forward.)  While you are taking 
the study drug, you will need to avoid certain medications that may have drug 
interactions with fluoxetine.  A list of these medications will be provided to your 
primary care physician.  If, in the opinion of your primary care physician or other 
treating doctors, you need to start taking one of these medications at any point 
during the 90-day treatment part of the study, the study drug will be stopped and 
you will be taken out of the study.
Several additional tests will be done to assess the function of your visual system 
before you leave the hospital, including:
1. Neuropsychological assessment: Participation in the study will involve 
approximately 5 ½ hours of neuropsychological testing spread over 4 
sessions, as indicated in the Table on page 9.  You will complete a 
neuropsychological examination lasting 45 minutes before your discharge 
from the hospital.  This will be followed by sessions lasting 90 minutes 
each at 30 days, 90 days, and 6 months.  These outpatient sessions will 
be conducted in Dr. Bradford Mahon’s laboratory at the Rochester Center 
for Brain Imaging, where most fMRI studies will also take place (see 
below).
Neuropsychological testing will consist of picture naming tasks, face 
recognition tasks, and other simple tests of visual processing, such as 
indicating whether a particular visual target is displayed on a screen or 
not.  Your eye position may be monitored using special cameras during 
certain tasks.  Some tests may require you to indicate the location of an 
object or visual target on a screen with your finger.  For these tests, finger 
position during the pointing motion will be tracked using a special camera 
system.
2. Functional MRI (fMRI): You will have a special MRI scan that looks at the 
activity of different parts of your brain while you perform certain visual 
tasks inside the MRI machine, such as viewing visual stimuli.  You may be 
asked to participate in as much as 5 hours of fMRI testing, but any given 
session will only last 45 to 60 minutes, and sessions will take place over 
the span of 6 months as described in the Table on page 9.  Sessions may 
take place at Strong Memorial Hospital, the University of Rochester Stroke 
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and Cerebrovascular Disorders Clinic, or the Rochester Center for Brain 
Imaging.  
First you will be asked to fill out a safety screening form to assess whether 
it is safe for you to enter the MRI room.  You will then be asked to remove 
any metal objects you may be carrying (e.g. wallets, watches, earrings, or 
piercings) and possibly to change into a gown that we will provide in case 
of large metal parts attached to your clothing, such as large zippers.  
The MRI scanner is a large, tunnel-shaped machine.  It produces a 
constant magnetic field that orients the water molecules in your body.  
Pulses of radio waves are then used to interact with the magnetic field and 
produce detailed pictures of the inside of the body.
You will first be asked to lie down on a table outside the MRI scanner.  
Your head will be kept still with padding so it cannot move; you should, 
however, feel comfortable at all times.  Once you are comfortable, the 
table on which you are lying will be moved inside the MRI scanner.  From 
this point forward, you will be asked to lie still when the MRI scanner is 
collecting images of your body.  The MRI scanner does not collect images 
at all times.  You will know when the MRI scanner is collecting images 
because you will hear the thumping noise from the electrical switching of 
the magnetic field and feel the associated vibrations.  Please make sure to 
stay as still as possible during these times (no sneezing, scratching, 
stretching etc.).  Between these periods of image collection, feel free to 
stretch or move as needed.  You will be able to communicate with us at all 
times through a built-in intercom.  You will also be holding an emergency 
rubber bulb that you can squeeze at any time to let us know you want to 
come out of the MRI scanner.
As part of this study, your fMRI data will be stored for future research.  
The data will be stored and shared only after all information that may 
identify you has been removed.
3. Optical coherence tomography (OCT): This is a test to measure the 
thickness of your retina, the light-sensitive inner surface in the back of 
your eyeball where visual perception begins.  It is a non-invasive test (a 
retinal scan) that uses light waves and takes about 30 seconds per eye.  
This test will be performed once at the beginning of the study and once at 
the end, as described in the Table on page 9.  Testing will take place at 
the University of Rochester Medical Center Flaum Eye Institute.
Before your discharge from the hospital, you will be given a sufficient supply of 
the study drug to last you until the end of the study.  In addition, an appointment 
for your next study visit will be made, and information about how to contact your 
study doctor will be provided.  You will be asked for your contact information, 
including your email address and any alternate contacts, so that we can keep in 
touch with you throughout the study.  You do not have to provide any alternate 
contacts if you do not wish to do so.  You will also be asked to confirm the name 
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of your primary care physician so that he or she can be informed that you are 
participating in this study. 
Study visits and phone calls: 
1 week
About one week after you start the study, the study coordinator will call you, or 
ask you in person, if you have been taking the study drug and collect 
information about any new symptoms or side effects you may be 
experiencing.  The study coordinator will also collect information about your other 
medications. 
30 days
You will return to the University of Rochester 30 days after starting the study.  
You will be asked to bring your bottle of the study drug with you so that we can 
confirm how many doses of the study drug you have taken since your discharge 
from the hospital.  
Parts of this visit will be for your routine care as a stroke patient.  Other parts will 
be for study purposes only, as indicated in bold below.  At this 30-day follow-up 
visit:
1.
You will be seen by your neurologist, who will review your medications 
and evaluate the progress of your recovery, the severity of your stroke 
symptoms, and your level of disability.
2.
You will answer a questionnaire about any new symptoms or side 
effects you may be experiencing since starting the study;
3.
You will have a repeat psychological assessment (PHQ-9) to screen 
for depression.
4.
You will have your vision re-tested by automated Humphrey 
perimetry;
5.
You will have a repeat ECG;
6.
You will have repeat laboratory tests, and;
7.
You will have a repeat fMRI study for us to understand if and how your 
brain is healing from the injury caused by the stroke.  If this brain scan 
takes place at the Rochester Center for Brain Imaging, you will be 
asked to sign a separate consent form there immediately before the 
study.
8.
You will have a repeat neuropsychological evaluation to assess your 
ability to perform certain tasks requiring different levels of visual 
processing.
90 days
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You will return to the University of Rochester 90 days after starting the study. 
Once again, you will be asked to bring your bottle of the study drug with you so 
that we can confirm how many doses of the study drug you have taken since 
your discharge from the hospital.  
Parts of this visit will be for your routine care as a stroke patient.  Other parts will 
be for study purposes only, as indicated in bold below.  At this 90-day follow-up 
visit:
1.
You will be seen again by your neurologist, who will review your 
medications and evaluate the progress of your recovery, the severity of 
your stroke symptoms, and your level of disability.
2.
You will answer a questionnaire about any new symptoms or side 
effects you may be experiencing since starting the study.
3.
You will have a repeat psychological assessment (PHQ-9) to screen 
for depression.
4.
You will have your vision re-tested by automated Humphrey perimetry;
5.
You will have a repeat fMRI study for us to understand if and how your 
brain is healing from the injury caused by the stroke.  If this brain scan 
takes place at the Rochester Center for Brain Imaging, you will be 
asked to sign a separate consent form there immediately before the 
study.
6.
You will have a repeat neuropsychological evaluation to assess your 
ability to perform certain tasks requiring different levels of visual 
processing.
At the 90-day study visit, we will remind you that the treatment part of the 
study is complete and you should stop taking the study drug.
6 months
You will return to the University of Rochester 6 months after starting the study. 
Parts of this visit will be for your routine care as a stroke patient.  Other parts will 
be for study purposes only, as indicated in bold below.  At this 6-month follow-up 
visit, 
1.
You will have your vision re-tested by automated Humphrey perimetry.
2.
You will have a repeat retinal scan (OCT) to measure the thickness of 
your retina in each eye.
3.
Your functional vision score will be calculated again to assess how 
your vision loss has affected your ability to perform your daily activities.
4.
You will again answer the Visual Function Questionnaire-25 for us to 
determine how your vision loss has affected your health-related quality 
of life.
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5.
You will answer a questioannaire about any new symptoms or side 
effects you may be experiencing since starting the study.
6.
You will have a repeat psychological assessment (PHQ-9) to screen 
for depression.
7.
You will have a repeat fMRI study for us to understand if and how your 
brain is healing from the injury caused by the stroke.  If this brain scan 
takes place at the Rochester Center for Brain Imaging, you will be 
asked to sign a separate consent form there immediately before the 
study.
8.
You will have a repeat neuropsychological evaluation to assess your 
ability to perform certain tasks requiring different levels of visual 
processing.
If you miss your follow-up visits, we will attempt to contact you by phone.  If we 
are unable to reach you, we will ask your alternate contact and/or review your 
medical chart.  
The following information about your participation in the study will be included in 
your electronic medical record.
Documentation that you are in this study
A copy of your signed consent form
Results of your pregnancy test, if applicable
Results of your 30-day blood tests
Results of your 30-day ECG
Results of any study-related visual exams
The fMRI studies are being done for research purposes only.  The results of your 
fMRI studies will not be given to you or to your doctor, nor will they be included in 
your medical record.  
If at any time during the study you feel that you may be experiencing new 
symptoms or side effects, please contact the study team immediately or 
seek emergency medical care.
Number of Subjects
A total of 40 patients will be included in this study.  
Duration of the Study
The total length of your participation in this study is approximately 6 months.  The 
amount of time needed to evaluate you and assign you to a treatment group 
during your hospital admission is about 2 ½ hours beyond what would normally 
be required for your care as a stroke patient.  The telephone follow-up at day 7 
will take about 15 minutes.  The follow-up visits at 30 days and 90 days after your 
enrollment in the study will take about 2 hours of standard follow-up care, plus an 
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additional 3 or 4 hours to review any new symptoms or possible side effects, and 
perform additional laboratory and imaging tests.  The final follow-up visit at 6 
months will take 1 hour of standard follow-up care, plus 3 hours of additional 
testing.  Therefore, a total of about 12 additional hours of participation will be 
needed from you if you decide to take part in the study. 
Risks of Participation 
1. Risks from the study drug:  All medications have possible side effects, 
including those that have been approved by the FDA.  You may experience side 
effects while you are on the study drug.  Everyone taking part in the study will be 
watched carefully for any side effects.  Side effects may be mild or very serious.  
Many side effects will go away once you stop taking the study drug.  However, in 
some cases, side effects can be serious and long-lasting, or may never go away.  
Known side effects of the study medication are listed below.  The study drug may 
have side effects that no one knows about yet.  The study team will let you know 
if they learn anything about the study drug during the study that might make you 
change your mind about participating.  You should talk to your study doctor about 
any side effects you experience while you are taking part in the study.
TABLE.  Schedule of tests and procedures
           
 Procedure
                             Baseline   1 week    30 days    90 days  6 months
Physical examination & medical history

MRIa scan of the brain

Urine pregnancy testb

Complete blood count


Comprehensive metabolic panel


Electrocardiogram (ECG)


Modified Rankin Scale (mRS)



Formal eye exam

Automated Humphrey perimetry




Optical coherence tomography (OCT)


Functional vision score


Visual Function Questionnaire-25 (VFQ-25)


Neuropsychological testing




Functional MRI




Patient Health Questionnaire-9 (PHQ-9)




Adverse event questionnaire
 




a Magnetic resonance imaging 
 Standard care
b For women of childbearing age only
 Study-related procedure
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Patients who have a known allergic reaction to fluoxetine or other SSRIs may not 
participate in this study.  The most common side effects of fluoxetine include 
abdominal pain, upset stomach, diarrhea, headache, irritability, and difficulty 
sleeping.  Fluoxetine can also cause easy bruising and increase bleeding risk.  In 
some people, it can cause drowsiness, dizziness, decreased sex drive, or 
impotence (decreased ability to have or maintain an erection).  It can also cause 
liver abnormalities, heart rhythm irregularities, and hyponatremia (low sodium 
level in the blood).  This is why we will monitor all patients in the study with 
repeat laboratory tests and ECG at 30 days.  In rare cases, fluoxetine can cause 
dangerous side effects including anaphylactic shock (a severe life-threatening 
allergic reaction), seizures, acute angle-closure glaucoma (increased pressure in 
the eye), or serotonin syndrome or neuroleptic malignant syndrome (high blood 
pressure, rapid heart rate, fever, sweating, rigidity, muscle twitching, confusion, 
agitation, and hallucinations that can result from too much serotonin activity in 
the brain).  
During the trial, you must immediately tell your study doctor about any abnormal 
or unexpected symptoms, and in particular about any irritability, hyperactivity, 
aggressive behavior, depression or suicidal thoughts, skin rash, difficulty 
breathing, chest pain, tremors, stomach ache, severe diarrhea, or jaundice 
(yellow discoloration of the skin). 
If you are a woman of childbearing potential, you must not be pregnant or 
currently nursing a child, and you must use an acceptable method of birth control 
to avoid pregnancy while on the study drug.  Acceptable methods of birth control 
include hormonal contraceptives, intrauterine device, abstinence, or spermacide 
and barrier.  If you should become pregnant while on the study drug, you should 
notify your study doctor immediately.
You will be screened for depression during your enrollment in the study.  If, at 
any point, you are diagnosed with depression, you will be referred to a health 
care provider for counseling and treatment.  If you report any suicidal thoughts, 
you may be directed to the Emergency Department for further evaluation.
If you are hospitalized for any reason at another hospital, you must inform your 
study doctor as soon as possible. 
2. Risks associated with MRI: 
A. Metal: The MRI scanner produces a strong and constant magnetic 
field.  There are no immediate risks associated with exposure to 
strong magnetic fields.  However, if you have any metal in your body, 
the magnetic field may cause the metal in your body to heat up or 
shift position.  You will be screened for the presence of metal in your 
body before each study session using a questionnaire.  If you have a 
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cardiac pacemaker, implantable cardiac defibrillator, aneurysm clip, 
surgical wires, penile implant, metallic prosthesis, mechanical heart 
valve, cochlear implant, pump, shunt, or bullet or shrapnel fragments, 
or if you have a high risk of having metal fragments in your eyes as a 
result of working as a welder or metal worker, you will be excluded 
from the study.  
B. Claustrophobia: When you are inside the MRI machine, the scanner 
will surround your body and a close-fitting scanning coil with surround 
your head.  If you feel anxious in confined spaces, you may not want 
to participate.  If you decide to participate and feel claustrophobic 
later, you will be able to tell us through the intercom or squeeze the 
emergency rubber bulb in your hand, and we will stop the study and 
remove you from the scanner immediately.
C. Inner ear damage: The MRI machine produce a loud tone that can 
cause injury to the inner ear if appropriate ear protection is not used.  
Earplugs or close-fitting silicone-padded headphones will be provided 
to protect your ears.
D. Burns: In rare cases, contact with the MRI transmitting and receiving 
coil, contact with conductive materials such as wires, or skin-to-skin 
contact that forms conductive loops, may cause excessive heating 
and result in burns.  The MRI operator will take steps, such as using 
foam pads when necessary, to minimize this risk.  You should report 
any heating or burning sensation during the scan to the MRI operator 
immediately.
E. Pregnancy: Exposure to strong magnetic fields may be harmful to a 
pregnant woman or unborn child.  Although there are no established 
guidelines at this time about MRI during pregnancy, there is a 
possibility of an as-of-yet undiscovered pregnancy-related risk.  You 
will not be included in the study if you are pregnant, or if you are 
unwilling or unable to use an acceptable method of birth control. 
Acceptable methods of birth control include hormonal contraceptives, 
intrauterine device, abstinence, or spermacide and barrier.  If you 
should become pregnant during the study, you should notify your 
study doctor immediately.
F. Long-term risks: The long-term health risks of MRI are unknown.  
Strong magnetic fields have been used in clinical practice and 
research for nearly 15 years, and so far no detrimental long-term 
effects have been identified, but this does not mean that we will not 
become aware of adverse long-term effects in the future.  If new 
information about the risks of MRI become available during the 
course of the study, we will let you know.
G. Acute ischemic stroke: Exposure to strong magnetic fields in the 
days and weeks immediately after a stroke may pose a slightly 
higher risk compared to magnetic field exposure months or years 
after a stroke.  This risk is unlikely to be greater than minimal.  
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Nonetheless, in anticipation of any possible increase in risk during 
the study period, a neurologist familiar with your care will be on call 
during each fMRI session.
3. Risks associated with blood draws: These include pain or stinging when 
the needle is inserted and throbbing and/or bruising at the puncture site after 
the blood is drawn.  To reduce the risk of bruising, you will be asked to hold 
pressure for several minutes at the puncture site after the the needle is 
removed.  Rarely the vein may become inflamed after the blood is drawn.  
This is treated with a warm compress applied several times a day.  Finally, 
there is a small risk of infection at the puncture site.  This risk is minimal 
because your blood will be drawn by a trained health professional using 
proper sterile technique, including cleaning the puncture site with an alcohol 
swab before the needle gets inserted into your skin. 
4. Risks associated with questionnaire completion: Common risks include 
possible boredom, mental fatigue, embarrassment at poor performance, 
frustration, or emotional discomfort when answering questions about one’s 
health and well-being.  You will be free to take breaks or stop completing the 
questionnaire at any time.  As a result of responding to a health-related 
questionnaire, some people may rightly or wrongly conclude that they have a 
disease, disorder, or disturbance.  Should you have such concerns, you will 
have a chance to discuss them with your study doctor.
5. Risks associated with optical coherence tomography: This is a 
noninvasive test that uses light waves to look inside the eye.  It usually takes 
30 seconds to perform.  It does not involve radiation, ultrasound, radio waves, 
or magnetic fields.  It has no known risks or harmful side effects other than 
possible boredom, fatigue, anxiety, or discomfort resulting from waiting and 
holding still while the test is being performed.
6. Risks associated with automated Humphrey perimetry: This is a 
noninvasive test that uses brief light signals to test your peripheral vision.  It 
usually takes less than 10 minutes to perform.  There are no known risks or 
harmful side effects other than possible boredom, fatigue, anxiety, or 
discomfort resulting from waiting while the test is being performed.
7. Risks associated with neuropsychological testing: This assessment 
consists of noninvasive tests that evaluate your ability to perform simple 
visual tasks requiring different levels of visual processing, such as naming 
objects, recognizing faces, and pointing at visual targets on a screen.  It takes 
45-90 minutes to complete.  There are no known risks or harmful side effects 
other than possible boredom, mental fatigue, emotional discomfort as a result 
of being reminded of the visual impairment caused by your stroke; or 
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frustration, embarrassment, or anxiety due to real or perceived poor 
performance on the visual tasks in question.
8. Confidentiality: Because this study involves collecting personal, identifiable 
information about you, there is a potential for invasion of privacy or breach in 
confidentiality.  To minimize this risk, we will assign you a study number 
instead of labeling the information we collect from you with your name or 
medical record number.  All of the information we collect will be stored in a 
secure manner and only study team members will have access to it.
The study team may be notified if you receive other health care services at 
the University of Rochester Medical Center (URMC) or its Affiliates (e.g. visit 
to the emergency room).  In addition, the following individuals may know you 
participated in research and may see results of testing conducted for this 
study if it is included in your medical record:

Staff at the University of Rochester Medical Center and its Affiliates 
(i.e. Strong Memorial Hospital, Highland Hospital, URMC primary 
care and specialist physician offices) who have a reason to access 
your electronic health record. 

Individuals who request a copy of information from your health record 
for activities such as treatment or payment (e.g. medical insurance 
companies, worker’s compensation). 
A description of this clinical trial will be available on 
http://www.ClinicalTrials.gov, as required by U.S. law.  This website will not 
include information that can identify you.  At most, the website will include a 
summary of the results.  You can search this website at any time. 
Benefits of Participation
You might not benefit from being in this study.  If you are assigned to Group A, 
the recovery of your vision may be enhanced as a result of being on fluoxetine.  If 
you are assigned to Group A, you may also benefit from the antidepressant effect 
of fluoxetine, as depression does occur in some stroke survivors.  
New Study Findings 
If we discover anything that might make you change your mind about continuing 
in the study, we will let you know.
Alternatives to Participation
You do not have to be in this study.  If you choose not to participate in this study, 
you will still get the full care required by your condition.  Currently there are no 
proven treatments to enhance visual recovery after a stroke.  The standard of 
care for stroke patients with vision loss is occupational and cognitive 
rehabilitation, which will be offered to all patients whether they choose to 
participate in the study or not.  
RSRB Approval Date: 8/27/2019
Expiration Date: 8/26/2020


RSRB Case Number: 58133 Page 14 of 19
Version Date: 09/07/2018
Costs 
Some of the tests and procedures you will receive during the course of this study 
are standard care (indicated in the Table on page 9 as blue squares).  You 
and/or your insurance company will be responsible for paying for any tests, 
procedures, or exams that are done as part of your standard care.  You are 
encouraged to discuss your coverage with your insurance provider.
The study drug and all study-related tests and procedures (indicated in the Table 
on page 9 as red circles), including all fMRI studies and retinal scans, all 
neuropsychological testing, the automated Humphrey perimetry study at 30 days, 
and the follow-up ECG and laboratory studies at 30 days, will be provided to you 
free of charge.
Payments 
Upon completing the study, you will receive a $50 prepaid debit card for 
participating in this study.  
Reimbursement for Travel Expenses 
You will be issued a pre-paid parking pass for your visits at 30 days, 90 days, 
and 6 months.
Circumstances for Dismissal 
You may be withdrawn from the study if the study team feels that staying in the 
study is harmful to your health.  Additionally, you may be withdrawn from the 
study if you do not keep appointments for the study visits, or if you cannot 
complete study activities.  
Compensation for Injury 
If you are directly injured by the drug that is being studied, or by the clinical 
procedures solely required to participate in the study, you may need to pay for 
treatment of your injuries, but you will not be required to pay for emergency 
medical treatment provided at Strong Memorial Hospital or Highland Hospital.  
The University may seek payment for this care from your health insurer or third 
parties.  Decisions regarding care and compensation for any other research-
related injury will be made on a case-by-case basis.
Confidentiality of Records and Authorization to Use and Disclose 
Information for Research Purposes 
The University of Rochester makes every effort to keep the information collected 
from you private.  In order to do so, you will only be identified by a study number 
(not by your name or initials) in the study records.  Paper records will be kept in a 
locked file cabinet in a secure room, and computerized records will be kept on a 
secure server accessible only by authorized members of the study team. 
RSRB Approval Date: 8/27/2019
Expiration Date: 8/26/2020


RSRB Case Number: 58133 Page 15 of 19
Version Date: 09/07/2018
Sometimes, however, researchers need to share information that may identify 
you to people that work for the University or to regulators.  If this does happen, 
we will take precautions to protect the information you have provided.  Results of 
the research may be presented at meetings or in publications, but your name will 
not be used.
At your request, information collected about you from your participation in this 
study may be given to your primary care doctor.
If you have never received a copy of the University of Rochester Medical Center 
and Affiliates Notice of Privacy Practices, please ask the study team for one. 
What information may be used and given to others?
The study doctor will get your personal and medical information.  For example: 

Research records

Records about phone calls made as part of this research

Records about your study visits

Past and present medical records related to the study 

Results of medical tests 
Who may use and give out information about you?

The study doctor and the study team

University of Rochester Medical Center and its Affiliates

Carnegie Mellon University
Your information may be given to: 

The Department of Health and Human Services

The University of Rochester 

Carnegie Mellon University

The U.S. Food and Drug Administration (FDA) may also need to inspect 
study records at some point during the study or even after it has been 
completed.  In the event that this should occur, every effort will be made to 
keep identifying information about you private.  
Why will this information be used and/or given to others?

To do the research 

To study the results 

To see if the research was done right  
If the results of this study are made public, information that identifies you will not 
be used.
What if I decide not to give permission to use and give out my health 
information?
Then you will not be able to participate in this research study.
RSRB Approval Date: 8/27/2019
Expiration Date: 8/26/2020


RSRB Case Number: 58133 Page 16 of 19
Version Date: 09/07/2018
May I review or copy my information?
Yes, but only after the research is over.
How long will this permission be valid?
This permission will last indefinitely. 
May I cancel my permission to use and disclose information?
Yes, you may cancel your permission to use and disclose your health information 
at any time.  You do this by sending written notice to the study doctor.  Upon 
receiving the written notice, the study team will no longer use or disclose your 
health information, and you will not be able to stay in the study.  Information that 
has already been gathered may need to be used and given to others for the 
validity of the study.  
May I withdraw from the study?
Yes. If you withdraw your permission to be in the study, no new health 
information identifying you will be gathered after that date.  Information that has 
already been gathered may still be used and given to others.  
Is my health information protected after it has been given to others?
No.  There is a risk that your information will be given to others without your 
permission.
Contact Persons
For more information concerning this research, or if you feel that your 
participation has resulted in any research-related injury, or emotional or physical 
discomfort, please contact Bogachan Sahin, MD, PhD by telephone at (585) 
275-2530, or by email at bogachan_sahin@urmc.rochester.edu.
Please contact the University of Rochester Research Subjects Review Board at 
265 Crittenden Blvd, CU 420315, Rochester, NY 14642; phone: (585) 276-0005 
or (877) 449-4441 for any of the following reasons:

You wish to talk to someone other than the research team about your 
rights as a research subject;

You wish to voice concerns about the research;

You wish to provide input concerning the research process;

You are unable to reach the study team.
Voluntary Participation
Taking part in this study is voluntary.  You are free not to take part or to withdraw 
at any time, for whatever reason.  No matter what decision you make, there will 
be no penalty or loss of benefit to which you are entitled.  In the event that you do 
withdraw from this study, the information you have already provided will be kept 
in a confidential manner.
RSRB Approval Date: 8/27/2019
Expiration Date: 8/26/2020


RSRB Case Number: 58133 Page 17 of 19
Version Date: 09/07/2018
Signatures/Dates
After reading and discussing the information in this consent form, you should 
understand:

Why this study is being done;

What will happen during the study;

Any possible risks and benefits to you;

Other options you may have instead of being in the study; 

How your personal information will be protected;

What to do if you have problems or questions about this study.
Subject Consent
I have read (or have had read to me) the contents of this consent form and have 
been encouraged to ask questions.  I have received answers to my questions.  I 
agree to participate in this study.  I have received (or will receive) a signed copy 
of this form for my records and future reference.
Subject Name (Printed by Subject)
Signature of Subject
Date
Alternate Contacts
Please place your initials in the “YES” box to the right if you agree to 
allow study team members to contact your alternate contacts to 
discuss your participation in this study and find out how you are 
doing if you are unreachable.  Place your initials in the “NO” box if you do not 
wish to allow study team members to contact your alternate contacts.
YES
NO
RSRB Approval Date: 8/27/2019
Expiration Date: 8/26/2020


RSRB Case Number: 58133 Page 18 of 19
Version Date: 09/07/2018
Primary care physician
Please place your initials in the “YES” box to the right if you agree to 
allow study team members to share information collected about you 
from your participation in this study with your primary care doctor.  
Place your initials in the “NO” box if you do not wish to allow study team 
members to share this information with your primary care doctor.
 
Person Obtaining Consent
I have read this form to the subject and/or the subject has read this form.  I will 
provide the subject with a signed copy of this consent form.  An explanation of 
the research was given and questions from the subject were solicited and 
answered to the subject’s satisfaction.  In my judgment, the subject has 
demonstrated comprehension of the information.  I have given the subject 
adequate opportunity to read the consent before signing.
Name and Title (Print)
Signature of Person Obtaining Consent
Date
YES
NO
RSRB Approval Date: 8/27/2019
Expiration Date: 8/26/2020


RSRB Case Number: 58133 Page 19 of 19
Version Date: 09/07/2018
APPENDIX
Schedule of tests and procedures
       Procedure
     Baseline     1 week     30 days     90 days    6 months
Physical examination & 
medical history

MRIa scan of the brain

Urine pregnancy testb

Complete blood count


Comprehensive metabolic panel


Electrocardiogram (ECG)


Modified Rankin Scale (mRS)



Formal eye exam

Automated Humphrey perimetry




Optical coherence tomography 
(OCT)


Functional vision score


Visual Function Questionnaire-25 
(VFQ-25)


Neuropsychological testing




Functional MRI




Patient Health Questionnaire-9
(PHQ-9)




Adverse event questionnaire
 




a Magnetic resonance imaging 
 Standard care
b For women of childbearing age only
 Study-related 
procedure
RSRB Approval Date: 8/27/2019
Expiration Date: 8/26/2020