Clinical trial NCT02528409
Conditions: Binge Eating Disorder
Sponsor: University of Chicago
Start date: 2016-06-01; Completion date: 2018-11-01
Enrollment: 80 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The aim of the present study is to examine the efficacy and safety of vortioxetine vs placebo in adults with moderate to severe Binge eating disorder, as indicated by at least 3 binge eating days per week for the 2 weeks before the baseline visit.

Detailed description:
Binge-eating disorder recently included in the Diagnostic and Statistical Manual, 5th Edition, is now recognized as a serious public health problem. Binge-eating disorder is associated with obesity and psychiatric comorbidities, including depression, and may be predictive of metabolic syndrome. Many patients are undertreated despite functional impairments and personal and social difficulties leading to a poor quality of life. Binge-eating disorder is characterized by recurrent episodes of excessive food consumption accompanied by a sense of loss of control and psychological distress but without the inappropriate compensatory weight-loss behaviors of bulimia nervosa. Binge eating is seen in 23-46% of obese individuals seeking weight loss treatment and its severity relates to body mass index and predicts regain of lost weight.

Current treatments for binge eating disorder are often inadequate. Cognitive behavioral therapy has been shown to reduce binge eating but finding trained psychologists is difficult. Lisdexamfetamine was recently approved by the Food and Drug Administration for binge eating disorder but it carries risk of addiction and diversion and so will likely not be prescribed by most family physicians or psychiatrists. Other currently available medications, used off-label for binge eating disorder, include anticonvulsants, which may reduce binge eating but are often poorly tolerated. Therefore, additional clinical trials are needed to identify effective pharmacotherapies.

Consuming food is necessary for life and involves brain regions that are quite ancient in evolutionary terms. The intestinal tract itself is almost like a "second brain" in that it contains vast amounts of neurons used to transmit and process sensory information; indeed the intestinal tract contains more of the neurotransmitter serotonin than the brain itself. Peripheral signals from the body (including from the intestinal tract, but also from the blood stream - e.g. glucose levels) are transmitted to brain regions such as the hypothalamic nuclei to help regulate appetite/hunger and maintain equilibrium. Another key aspect of circuitry involved in eating involves the brain reward system, including the nucleus accumbens, which is regulated by neurotransmitters such as dopamine, opioids, noradrenaline, and serotonin. In humans, but to a lesser degree in other animals, there is also top-down control from the prefrontal cortices, which serve to regulate our behaviors and suppress our tendencies to crave rewards, and allow us to flexibly adapt our behavior rather than get stuck in repetitive habits. Thus, binge-eating most likely involves dysregulation of all three above domains regulating behavior: the primitive 'peripheral-hypothalamic' feedback system, reward circuitry, and top-down control circuitry. On a neurochemical level, binge eating may be related to dysfunction of the serotonergic, dopamine, glutamatergic, and norepinephrine systems. Thus, a medication to target binge eating needs to be multi-modal in terms of its pharmacology.

Arms: arm 1: 10 milligrams per day for the first week and 10 milligrams per day for the final taper week 20 milligrams per day for 10 weeks between taper periods. arm 2: 10 milligrams per day day for the first week and 10 milligrams per day for the final taper week 20 milligrams per day for 10 weeks between taper periods.
Interventions: intervention 1: Vortioxetine intervention 2: Placebo
Intervention descriptions: intervention 1: Medication currently approved for major depression. intervention 2: None

Protocol documents:
Prot_SAP_000.pdf: 
 
1 
 
IISR GUIDE (to be completed in English) 
STUDY INFORMATION 
Date:  April 19th, 2017 
Protocol Version:3.1 
Country(s) the study will be conducted 
in:  
United States 
Compound/Product: <Generic Drug 
Name> 
Vortioxetine 
Study Type :{ie, clinical interventional, 
clinical non-interventional, 
observational} 
Clinical interventional 
Study Title:  
A Double-Blind, Placebo-Controlled Study 
of Vortioxetine in the Treatment of Binge 
Eating Disorder. 
Indication:List therapeutic area: 
{Gastroenterology, Diabetes/Metabolism, 
Hypertension, Central Nervous System, 
Respiratory, Other} 
Central nervous system 
 
INVESTIGATOR CONTACT INFORMATION 
Number of Sites: (if there are sites 
multiple countries, name each country 
and number of sites in each country) 
1 – United States 
Principal Investigator Contact: 
 
Principal Investigator Name 
Jon Grant, JD, MPH, MD 
Organization Name 
University of Chicago 
Address 
5841 S. Maryland Avenue 
Telephone 
773-834-1325 
Fax 
773-834-6761 
E-mail address 
jongrant@uchicago.edu 
Co or Sub-Investigator(s) Contact (if 
applicable): 
 
Sub-Principal Investigator Name 
Royce Lee, MD 
Organization Name 
University of Chicago 
Address 
5841 S. Maryland Avenue 
Telephone 
773-834-5673 


updated 19APR2017 
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Fax 
E-mail address 
773-834-6761 
rlee@yoda.bsd.uchicago.edu 
Study Assistant(s)/Coordinator(s) 
Contact: 
 
Name 
(address, phone number, email) 
Eric Leppink 
5841 S. Maryland Avenue 
Tel: 773-834-3778 
Email: eleppink@yoda.bsd.uchicago.edu 
Institution’s Contracts or Grants office 
contact: 
 
Name 
(address, phone number, email) 
Ms. Janet Nelson  
Research Section Manager  
Department of Psychiatry and Behavioral 
Neuroscience 
The University of Chicago Biological 
Sciences 
5841 South Maryland Avenue  
Room B-354, MC 3077  
Chicago, Illinois 60637 
Tel: 773/834.1324 
Fax:  773/834.6761 
Email: jnelson@yoda.bsd.uchicago.edu 
Name and contact information of 
person completing this form: 
(name, address, phone number, email) 
Jon Grant, JD, MPH, MD 
University of Chicago 
5841 S. Maryland Avenue 
Tel: 773-834-1325 
Fax: 773-834-6761 
Email: jongrant@uchicago.edu 
 


updated 19APR2017 
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RESOURCES REQUESTED 
Resource Requested: {Drug, funding or 
drug & funding} 
Drug and Funding 
 
Estimated Study Budget: 
(Enter total here – including direct, indirect 
cost and institutional overhead)  
$401,776 
Do you have additional funding sources 
for this project? 
(If yes, please explain) 
No 
Dosage and Formulation: 
10mg tablets and 20mg tablets 
 
Estimated Total Drug Supply for Study:  
(number of tablets, capsules, vials)  
10mg po qday (or placebo) for the first 
week and 10mg po qday (or placebo) for 
the final taper week (this means 14 days 
total taking 10mg tablets for 80 subjects = 
1120 tablets [560 10-mg tablets and 560 
placebos]) and 
20mg po day for 11 weeks for 80 subjects 
(means 3080 tablets and 3080 placebos) 
Total # of Subjects:  
80 subjects (40 assigned to vortioxetine 
and 40 assigned to placebo) 


updated 19APR2017 
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Study Timeline: 
Planned StudyActivation: (month/year) 
Study activation is final regulatory authority 
approved protocol and fully executed 
contract  
 
September 1, 2015 
 
Study Activation to FirstPatient In (days, 
weeks, months):  
September 7, 2015 (within one week of 
study activation) 
First Patient In to Last Patient In  
(days, weeks, months) 
20 months 
Last Patient In to Last Patient Out 
(days,weeks, months) 
13 weeks 
Monthly enrollment rate:(days) 
4 subjects per month 
Treatment duration:(in months) 
3 months (12 weeks of treatment and 1 
week taper off) 
Number of Study Sites/Depots: (depots 
are defined as shipment facilities for sites) 
1 
Completion of Data Analysis: (# months) 
2 months 
Completion of Final Study 
Report/Manuscript: (month/year) 
October, 2017 
Publication Plan: (target journal, target 
conference) 
American Journal of Psychiatry 
ACNP 


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STUDY PROPOSAL 
Background 
Binge-eating disorder recently included in the DSM-5, is now recognized as a serious 
public health problem (Kessler et al., 2013). Binge-eating disorder is associated with 
obesity and psychiatric comorbidities, including depression, and may be predictive of 
metabolic syndrome (Mathes et al., 2009). Many patients are undertreated despite 
functional impairments and personal and social difficulties leading to a poor quality of 
life (Hudson et al., 2007). Binge-eating disorder is characterized by recurrent episodes 
of excessive food consumption accompanied by a sense of loss of control and 
psychological distress but without the inappropriate compensatory weight-loss 
behaviors of bulimia nervosa. Binge eating is seen in 23–46% of obese individuals 
seeking weight loss treatment and its severity relates to body mass index and predicts 
regain of lost weight.   
Current treatments for binge eating disorder are often inadequate. Cognitive behavioral 
therapy has been shown to reduce binge eating but finding trained psychologists is 
difficult. Lisdexamfetamine was recently approved by the FDA for binge eating disorder 
(McElroy et al., 2015) but it carries risk of addiction and diversion and so will likely not 
be prescribed by most family physicians or psychiatrists. Other currently available 
medications, used off-label for binge eating disorder, include anticonvulsants, which 
may reduce binge eating but are often poorly tolerated (McElroy et al., 2012). Therefore, 
additional clinical trials are needed to identify effective pharmacotherapies. 
Consuming food is necessary for life and involves brain regions that are quite ancient in 
evolutionary terms. The intestinal tract itself is almost like a “second brain” in that it 
contains vast amounts of neurons used to transmit and process sensory information; 
indeed the intestinal tract contains more of the neurotransmitter serotonin than the brain 
itself. Peripheral signals from the body (including from the intestinal tract, but also from 
the blood stream – e.g. glucose levels) are transmitted to brain regions such as the 
hypothalamic nuclei to help regulate appetite/hunger and maintain equilibrium. Another 
key aspect of circuitry involved in eating involves the brain reward system, including the 
nucleus accumbens, which is regulated by neurotransmitters such as dopamine, 
opioids, noradrenaline, and serotonin. In humans, but to a lesser degree in other 
animals, there is also top-down control from the prefrontal cortices, which serve to 
regulate our behaviors and suppress our tendencies to crave rewards, and allow us to 
flexibly adapt our behavior rather than get stuck in repetitive habits. Thus, binge-eating 
most likely involves dysregulation of all three above domains regulating behavior: the 
primitive ‘peripheral-hypothalamic’ feedback system, reward circuitry, and top-down 
control circuitry. On a neurochemical level, binge eating may be related to dysfunction 
of the serotonergic, dopamine, glutamatergic, and norepinephrine systems (David et al., 
2009; Johnson and Kenny, 2010; Latagliata et al., 2010).  Thus, a medication to target 
binge eating needs to be multi-modal in terms of its pharmacology. 
Rationale:  
Rationale for evaluating this compound in this population/target organ. Provide overall 
reason the study is being proposed, including past study results that may have led to a 
decision to propose this study. 
Vortioxetine has distinctive properties that make it a promising option for patients with 


updated 19APR2017 
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binge eating disorder. In vitro studies indicate that vortioxetine is an inhibitor of the 5-HT 
transporter and is a 5-HT1D, 5-HT3 and 5-HT7 receptor antagonist, a 5-HT1A receptor 
agonist and a 5-HT1B receptor partial agonist. Animal and in vitro studies indicate that 
several neurotransmitter systems may be impacted by vortioxetine, with the drug 
enhancing levels of 5-HT, noradrenaline, dopamine, acetylcholine and histamine in 
certain areas of the brain, as well as modulating γ-aminobutyric acid and glutamate 
neurotransmission (Gibb and Deeks, 2014). In addition, vortioxetine appears to improve 
executive functioning which in turn has the potential to improve top-down cognitive 
control (Mahableshwarkar et al., 2015). This suggests that vortioxetine could improve 
the symptoms of binge eating disorder by two complementary pathways. Finally, 
because of low rates of side effects, low likelihood of sexual dysfunction, and the 
potential for improved cognitive performance, vortioxetine should be a well-tolerated 
and in fact desired medication approach to binge eating. 
Given the serious public health problems associated with binge eating disorder, and the 
likelihood of success of vortioxetine in treating the disorder, the aim of the present study 
was to examine the efficacy and safety of vortioxetine vs placebo in adults with 
moderate to severe Binge eating disorder, as indicated by at least 3 binge eating days 
per week for the 2 weeks before the baseline visit 
Hypothesis:  
State hypothesis for study objectives. 
We hypothesize that vortioxetine will be more effective than placebo in reducing the 
number of binge eating days per week after 12 weeks of treatment when compared to 
baseline. 
Primary Aim/Objective: 
For clinical studies– eg, To evaluate the safety and efficacy of interventions with test 
medication on symptoms, signs and quality of life in patients with target condition. 
The aim of the present study is to examine the efficacy and safety of vortioxetine vs 
placebo in adults with moderate to severe Binge eating disorder, as indicated by at least 
3 binge eating days per week for the 2 weeks before the baseline visit.  
 
 
Secondary Aim/Objective:(if applicable) 
A secondary aim of the study is to examine the effects of vortioxetine vs placebo con 
overall functioning and quality of life. 
 
Primary Endpoint(s):  
The primary efficacy measure is the number of binge eating days per week based on 
clinician interview and confirmation of identified Binge eating episodes in self-reported 
Binge eating diaries. The primary efficacy end point is the change from baseline to week 
12 on the log-transformed scale (Binge eating days per week) + 1. 
 


updated 19APR2017 
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Secondary Endpoint(s): (if applicable) 
Secondary efficacy measures include the number of Binge eating episodes per week, 1-
week Binge eating episode response status, and 4-week cessation from Binge eating 
(free from Binge eating episodes). Other secondary endpoints include the change in 
weight/BMI between baseline and study endpoint, the Clinical Global Impressions–
Improvement Scale (CGI-I) rated global improvement of symptoms over time (results 
will be dichotomized as improved [CGI-I ratings of 1 or 2 very much/much improved] or 
not improved [CGI-I ratings of 3-7]). The self-reported Eating Inventory, also known as 
the Three-Factor Eating Questionnaire, the self-reported Binge Eating Scale, the Yale-
Brown Obsessive Compulsive Scale modified for Bing Eating (YBOCS-BE), the Quality 
of Life Inventory, the Hamilton Depression Rating Scale and the Hamilton Anxiety 
Rating Scale. 
 
Study Plan: 
Eighty individuals with binge eating disorder will be recruited for a double-blind, 
placebo-controlled pilot study in which Vortioxetine or placebo is administered in a 1:1 
fashion. All 80 subjects will have binge eating disorder per DSM-5 criteria for at least a 
year. Following baseline measures, subjects will receive Vortioxetine (10mg for one 
week and then 20mg thereafter) or inactive placebo. Participants will be seen one week 
after the baseline visit (assessing the 10mg dose), one week after that (assessing the 
20mg dose), and then every 2 weeks for the remainder of the 12-week period. At week 
12, subjects will start a 1-week taper off the medication and will be seen at week 13. 
Efficacy and safety measures will be performed at each visit.   
 
The study will be conducted in accordance with the International Conference on 
Harmonization Guideline for Good Clinical Practice, all local ethical and legal 
requirements, and the World Medical Assembly (Declaration of Helsinki). The study 
protocol and procedures will be approved by the University of Chicago’s institutional 
review board prior to any  recruitment. Written informed consent will be required for 
study participation. 
Study Population 
80 male and female outpatients aged 18-65 with a primary diagnosis of binge eating 
disorder. 
 
Subjects 
 
Inclusion criteria:  
1) Men and women age 18-65;  
2) Primary diagnosis of Binge eating disorder;  
 
3) At least 3 binge eating days per week for the 2 weeks before the baseline visit; 
4) Ability to understand and sign the consent form. 


updated 19APR2017 
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Exclusion criteria:  
1) Unstable medical illness based on history or clinically significant abnormalities 
on baseline physical examination (history of medical illness which is currently 
stable is allowed such as diabetes well controlled, treated hypothyroidism, 
hypertension, etc)  
2) Current pregnancy or lactation, or inadequate contraception in women of 
childbearing potential 
 
3) Subjects considered an immediate suicide risk based on the Columbia Suicide 
Severity rating Scale (C-SSRS) (www.cssrs.columbia.edu/docs)  
4) Past 12-month DSM-5 major psychiatric disorder (psychotic disorder, bipolar 
disorder, major depressive disorder) 
5) Past 6-month alcohol or substance use disorders 
6) Illegal substance use based on urine toxicology screening  
7) Initiation of psychological or weight-loss interventions within 3 months of 
screening  
8) Use of any other prescription psychotropic medication (except a PRN hypnotic 
or PRN benzodiazepine) 
9) Previous treatment with Vortioxetine 
10) Currently taking OTC weight loss medications. If willing to stop these 
medications, the participant will not be excluded based on this criterion. 
10) Cognitive impairment that interferes with the capacity to understand and self-
administer medication or provide written informed consent  
Stable medical conditions (‘stability’ based on history and clinical and physical 
examination) will not be reason for exclusion. 
Concomitant medications, that have no psychotropic qualities, will be allowed.  
Participants can be receiving psychotherapy if they have been in treatment for at least 3 
months prior to study entry.  
Concurrent formal weight loss interventions will not be allowed. 
 
Study Drug(s):  
Drugs, Dosages, and Regimens  
Baseline visit will consist of all evaluations. For subjects who meet inclusion/exclusion 
criteria, they will be randomized at the end of their baseline visit.  
All 80 subjects who are randomized to Vortioxetine (1:1 randomization) will receive 
10mg/day or placebo during the first week of the study (the first dose will be started the 
day immediately after the baseline visit).  All subjects will receive 10mg or placebo for 7 
days and then will be evaluated with all measures at week 1 (7 days after baseline). 


updated 19APR2017 
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At the week 1 visit, subjects will be started on 20mg/day (or remain on placebo) for the 
remainder of the study. They will return at week 2 (corresponding to having been on 
20mg/day for one week) and be evaluated with all measures. After week 2 visit, all 
subjects will be seen every two weeks for the remainder of the 12-week study period 
(this corresponds to visits at week 4, 6, 8, 10, and 12). Week 12 evaluation will be the 
study endpoint for purposes of efficacy. 
All visits are as outpatients and include in-person assessments. 
After study conclusion (at week 12), the dose will be tapered off during a 1-week follow-
up period. All subjects will return at week 13 for final safety evaluation only. 
Dosage changes/reductions will not be permitted. Because nausea, and possibly 
headache, are the most likely side effects anticipated at the 20mg dose, participants will 
be allowed the use of over-the-counter options such as Tylenol prn for headaches, or 
bismuth subsalicylate for nausea. The use of over-the-counter options will be tracked at 
each visit. If side effects continue and are intolerable, the participant will have to 
discontinue treatment. If that occurs, a detailed ‘final visit’ assessment will be conducted 
and the participant will be contacted two weeks following to assess side effect 
outcomes. 
Treatment Duration, Visit Frequency, and Procedures   
This is a 13-week study (12 weeks of acute treatment followed by a 1-week tapering 
phase). Subjects will be seen for a total of 9 study visits. All visits will include the full 
battery of assessments except week 13 which is only a safety evaluation.  
 
Randomization 
Participants are randomized (1:1) to receive placebo or vortioxetine by the 
investigational pharmacy at the University of Chicago. The study blind will be 
maintained by over-encapsulation, making placebo and active treatments appear 
identical in size, weight, shape, and color. Dosage changes and reductions will not 
permitted during the study and participants will be discontinued if they experienced 
intolerance. 
 
Baseline Visit Assessments  
Those subjects who appear appropriate for the study, based on telephone screening, 
will be invited for a baseline assessment. The duration of the baseline assessment will 
be approximately 2-3 hours and will include the following: Informed consent, 
Demographic data, Concomitant medications (no psychotropic medications will be 
allowed), Family history data, Medical evaluation including physical examination, EKG, 
weight, and vital signs, Urine pregnancy test (for women of childbearing years) and 
urine drug screen, and a psychiatric evaluation (using the following measures: MINI 
International Neuropsychiatric Interview (Sheehan et al., 1998); Neurocognitive 
assessments of impulsivity; Depressive symptoms will be rated with the 24-item 
Hamilton Depression Rating Scale (HAM-D) (Hamilton, 1960); Anxiety symptoms will be 
assessed using the Hamilton Anxiety Rating Scale (HAM-A) (Hamilton, 1959); 
Psychosocial functioning will be evaluated using the patient-rated version of the 


updated 19APR2017 
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Sheehan Disability Scale (SDS) (Sheehan, 1983); Quality of Life Inventory (QOLI) 
(Frisch et al., 1993); Compulsivity will be assessed using the Cambridge Chicago Trait 
Scale (Cambridge CHI-T Scale) (Grant & Chamberlain, 2016), the Lie Acceptability 
Scale (Goosie, 2014), The Narcissistic Personality Inventory (Raskin & Terry, 1988), 
The Social Desirability Scale (Crowne & Marlowe, 1960), and the Columbia Suicide 
Severity Rating Scale (C-SSRS)). If subjects consent, a blood sample will be collected 
to check for diabetes by measuring blood glucose levels. 
At baseline, binge eating will be assessed using the following: Binge eating diary, 
Clinical Global Impressions–Severity Scale, the Three-Factor Eating Questionnaire, 
Self-Reported Binge Eating Scale, and the Yale-Brown Obsessive Compulsive Scale 
modified for Binge Eating (YBOCS-BE). Baseline labs, as well as interim labs, may be 
ordered based on clinical and medical evaluation. 
Weight will be recorded using a calibrated scale with the participants not wearing shoes, 
rounded to the nearest 0.5 pounds, and converted to kilograms (to convert, multiply by 
0.45) for data reporting. 
Following-Up Visit Assessments 
All follow-up visits will include safety measures (adverse events, vital signs, C-SSRS), 
weight, binge eating measures, Clinical Global Impressions–Improvement Scale, and 
other psychiatric measures. 
Medical evaluation including physical examination will be performed again at study 
endpoint. 
At study completion, participants will be made aware of all available options for follow-
up care in the community. 
 
Safety Assessments 
Safety and tolerability will be assessed using spontaneously reported adverse events 
data, Columbia–Suicide Severity Rating Scale (C-SSRS) vital signs, and by evaluating 
premature termination. Safety assessments (C-SSRS, sitting blood pressure, heart rate, 
adverse effects, and concomitant medications) will be documented at each visit. 
Subjects who are an immediate suicide risk will be removed from the study and 
appropriate clinical intervention (e.g. hospitalization) will be arranged. Urine pregnancy 
tests will be performed at the initial visit. Subjects who have a positive urine pregnancy 
test will be excluded from the study. Assessment of side effects will be done at each 
visit. AEs will be coded by system organ class (SOC) and preferred term (PT) using the 
Medical Dictionary for Regulatory Activities (Med- DRA) Version11.1. The incidences of 
all AEs will be summarized descriptively. 
 
Safety Reporting (please do not change the safety section of the template) 
Institution/Investigator is solely responsible for reporting all Adverse Events and Serious 
Adverse Events to regulatory authorities, investigators, IRBs or IECs and Takeda, as 
applicable, in accordance with national regulations in the countries where the study is 
conducted.  


updated 19APR2017 
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Regardless of expectedness or causality, all SAEs and pregnancy reports must also be 
reported in English by facsimile to Takeda Pharmacovigilance or designee: 
Fatal and Life Threatening SAEs within 24 hours of the sponsor-investigator’s 
observation or awareness of the event 
All other serious (non-fatal/non-life threatening) events within 4 calendar 
days of the sponsor-investigator’s observation or awareness of the event 
 
Takeda Safety Reporting Contact Information 
 
Takeda requires that all information be communicated to Takeda’s 
Pharmacovigilance Department as outlined in the study contract. 
 
All reported adverse drug reactions and safety issues related to Takeda compound 
must be included in the final study report. 
Describe procedures for reporting Adverse Events and Serious Adverse Events. 
 
Reporting Adverse Events and Serious Adverse Events 
 Any unanticipated problem will be reported by telephone within 24 hours to 
Takeda.  A full written report will be sent to the Institutional Review Board (IRB) 
at the University of Chicago and Takeda within 10 working days of the event. 
 Any other adverse event will be summarized in the IRB and Takeda annual 
progress reports. 
 The PI will inform either Takeda or the IRB at the University of Chicago of actions 
taken by the other organization as a result of their continuing review. 
 
Definitions: 
Adverse event (AE) means any untoward medical occurrence in a patient or subject 
administered a medicinal product; the untoward medical occurrence does not 
necessarily have a causal relationship with this treatment.  An AE can therefore be any 
unfavorable and unintended sign (including an abnormal laboratory finding), symptom, 
or disease temporally associated with the use of a medicinal (investigational) product 
whether or not it is related to the medicinal product.  This includes any newly occurring 
event, or a previous condition that has increased in severity or frequency since the 
administration of study drug. 
An abnormal laboratory value will not be assessed as an AE unless that value leads to 
discontinuation or delay in treatment, dose modification, therapeutic intervention, or is 
considered by the investigator to be a clinically significant change from baseline. 
 
An adverse drug reaction (ADR) is a response to a medicinal product which is noxious 
and unintended. Response in this context means that a causal relationship between a 
medicinal product and an adverse event is at least a reasonable possibility. This 
includes adverse reactions which arise from: use of a medicinal product within the terms 
of the marketing authorization; use outside the terms of the marketing authorization, 


updated 19APR2017 
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including overdose, misuse, abuse and medication errors; and occupational exposure*. 
* This corresponds to the exposure to a medicinal product for human use as a result of 
one’s occupation, such as nurses who may handle products routinely in their 
occupational setting. 
 
Serious AE (SAE) means any untoward medical occurrence that at any dose: 
 Results in death. 
 Is life-threatening (refers to an AE in which the patient was at risk of death at 
the time of the event.  It does not refer to an event which hypothetically might 
have caused death if it were more severe). 
 Requires inpatient hospitalization or prolongation of an existing 
hospitalization . 
 Results in persistent or significant disability or incapacity. (Disability is 
defined as a substantial disruption of a person’s ability to conduct normal life 
functions). 
 Is a congenital anomaly/birth defect. 
 Is a medically important event.  This refers to an AE that may not result in 
death, be immediately life threatening, or require hospitalization, but may be 
considered serious when, based on appropriate medical judgment, may 
jeopardize the patient, require medical or surgical intervention to prevent 1 of the 
outcomes listed above, or involves suspected transmission via a medicinal 
product of an infectious agent.   Examples of such medical events include 
allergic bronchospasm requiring intensive treatment in an emergency room or at 
home, blood dyscrasias or convulsions that do not result in inpatient 
hospitalization, or the development of drug dependency or drug abuse; any 
organism, virus, or infectious particle (e.g., prion protein transmitting 
Transmissible Spongiform Encephalopathy), pathogenic or nonpathogenic, is 
considered an infectious agent.   
 
An IMPORTANT MEDICAL EVENT also includes any event described in Takeda 
Medically Significant AE List below: 
Acute respiratory failure/acute respiratory distress 
syndrome 
Anaphylactic shock 
Torsade de pointes/ventricular fibrillation/ventricular 
tachycardia 
Acute renal failure 
Malignant hypertension 
Pulmonary hypertension 
Convulsive seizures 
Pulmonary fibrosis 
Agranulocytosis 
Confirmed or suspected endotoxin shock 
Aplastic anemia 
Confirmed or suspected transmission of infectious agent 
by a medicinal product 
Toxic epidermal necrolysis/Stevens-Johnson 
syndrome 
Neuroleptic malignant syndrome/malignant hyperthermia 
Hepatic necrosis 
Spontaneous abortion/stillbirth and fetal death 
Acute liver failure 
  
 
Clarification should be made between a serious AE (SAE) and an AE that is considered 
severe in intensity (Grade 3 or 4), because the terms serious and severe are NOT 


updated 19APR2017 
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synonymous.  The general term severe is often used to describe the intensity (severity) 
of a specific event; the event itself, however, may be of relatively minor medical 
significance (such as a Grade 3 headache).  This is NOT the same as serious, which is 
based on patient/event outcome or action criteria described above, and is usually 
associated with events that pose a threat to a patient’s life or ability to function.  A 
severe AE (Grade 3 or 4) does not necessarily need to be considered serious.  For 
example, a white blood cell count of 1000/mm3 to less than 2000 is considered Grade 3 
(severe) but may not be considered serious.  Seriousness (not intensity) serves as a 
guide for defining regulatory reporting obligations. 
 
Procedures for Reporting Drug Exposure during Pregnancy and Birth Events 
If a woman becomes pregnant or suspects that she is pregnant while participating in 
this study, she must inform the investigator immediately and permanently discontinue 
study drug.  The sponsor-investigator must fax a completed Pregnancy Form to the 
Takeda Pharmacovigilance or designee immediately.  The pregnancy must be followed 
for the final pregnancy outcome (i.e., delivery, still birth, miscarriage)and Takeda 
Pharmacovigilance or designee will request this information from the sponsor-
investigator. Please refer to study contract for Takeda pharmacovigilance contact 
information. 
If a female partner of a male patient becomes pregnant during the male patient’s 
participation in this study, the sponsor-investigator must also immediately fax a 
completed Pregnancy Form to the Takeda Pharmacovigilance or designee. Every effort 
should be made to follow the pregnancy for the final pregnancy outcome. Please refer 
to study contract for Takeda pharmacovigilance contact information. 
 
Product Complaints and Medication Errors  
A product complaint is a verbal, written, or electronic expression that implies 
dissatisfaction regarding the identity, strength, purity, quality, or stability of a drug 
product.  Individuals who identify a potential product complaint situation should 
immediately contact Takeda and report the event.   
A medication error is a preventable event that involves an identifiable patient and that 
leads to inappropriate medication use, which may result in patient harm.  While 
overdoses and underdoses constitute medication errors, doses missed inadvertently by 
a patient do not.  Individuals who identify a potential medication error situation should 
immediately contact Takeda (see below) and report the event. 
 
Phone: 1-877-TAKEDA7 (1-877-825-3327) 
E-mail: medicalinformation@tpna.com 
FAX: 1-800-247-8860 
Product complaints and medication errors in and of themselves are not AEs.  If a 
product complaint or medication error results in an SAE, an SAE form should be 
completed and sent to Takeda Pharmacovigilance. 


updated 19APR2017 
Page 14 of 19 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


updated 19APR2017 
Page 15 of 19 
Statistical Analysis: 
Design/Randomization 
The study is a double-blind, placebo-controlled study. Participants will be randomized 
(1:1) to receive vortioxetine or placebo by the University of Chicago Investigational 
pharmacy in block sizes of eight, using computer-generated randomization with no 
clinical information.  
Efficacy Analysis 
For statistical analysis, the full-analysis set will be defined as all participants who took at 
least 1 dose of the study drug and had at least 1 post-baseline primary efficacy 
assessment. The safety-analysis set will be defined as all randomized participants who 
took at least 1 dose of the study drug and completed at least 1 follow-up safety 
assessment.  
We will compare the baseline characteristics of both groups using Fisher’s exact test for 
categorical variables and the t test for continuous variables. We will calculate 
adherence to treatment, based on the number of capsules returned at each visit, as the 
number of capsules taken divided by the number of days in the study × 100%. 
 
Primary endpoint analysis 
 
The primary outcome measure will be the change from baseline in frequency of binge 
eating episodes (binges/week), defined as the mean number of binges per week in 2-
week intervals. If the visit interval is less than 2 weeks, the mean number of binges 
per week will be estimated based on the number of binge days in the interval since the 
last visit.  
 
Between group comparisons will use a mixed-effects model for repeated measures, 
including fixed factors for treatment and visit, the interaction of treatment and visit, a 
covariate of the log-transformation ([baseline number of BE days per week] + 1), and the 
interaction of the baseline covariate and visit using visit as a categorical variable. 
Mixed-effects models for repeated measures estimates differences from placebo in the 
change from baseline of the log-transformed scale ([BE days per week] + 1) at week 12 
(primary end point). Based on previous research, log-transformation should reduce 
skewness (McElroy et al., 2007).  
 
Secondary endpoints analyses 
 
Secondary outcome measures will include the change from baseline in frequency of 
binge days (or mean days per week when the participant had one or more binges), 
weight, body mass index, global improvement, Three-Factor Eating Questionnaire, and 
Impact of Weight on Quality of Life.  
We will also analyze changes from baseline in log-transformed BE episodes, TFEQ 
factor scores, and YBOCS-BE total score to week 12 using the mixed-effects model for 
repeated measures. Pairwise χ2 statistical tests will evaluates dichotomized CGI-I 
ratings at week 12 for placebo vs treatment group. 
 


updated 19APR2017 
Page 16 of 19 
Response categories will be tabulated based on the percentage decrease in frequency 
of binges from baseline to endpoint, which will defined as follows: complete=cessation 
of binges; marked=75% to <100% decrease; moderate=50% to <75% decrease; and 
none=<50% decrease.  
 
We will calculate effect sizes for the primary analysis of binges per week and weight 
using Cohen’s d. Finally, we will perform a Spearman rank correlation to assess the 
association between the change in frequency of binges from baseline to week 12 and 
the change in weight from baseline using completers. 
 
Safety analyses 
 
Adverse events will be collected at baseline visit. We will evaluate differences between 
groups in the incidence of treatment-emergent adverse events using Fisher’s exact test. 
Descriptive statistics will be used to evaluate changes in laboratory values, blood 
pressure and heart rate.  
 
Sample Size 
The sample size was calculated for the primary endpoint of change from baseline in 
binge eating days per week. For 80% power to compare the change from baseline in 
binge eating days per week on the log-transformed scale, assuming an effect size of 0.6 
to 0.7 between treatment group and the placebo group, 40 participants will needed in 
each treatment group based on a 2-group t test at the .05 level of significance. Given 
the particularly low rates of adverse events reported with Vortioxetine, as well as its 
more positive side effect profile in terms of sexual side effects compared to other 
antidepressants used in binge eating disorder, we expect few drop-outs from the study 
and therefore a smaller sample is needed.  
 
Feasibility 
Given our past experience and the pacing of the study, we feel the goal to enroll 80 
subjects in 20 months is practical and attainable. Given no-shows and rescheduling, 
and the time required for recruitment, telephone and in-person screening, and related 
issues inherent in any human study, the current goal of averaging at least 4 subjects 
per month is reasonable based on the fairly high prevalence of binge eating disorder, 
the number of subjects calling our outpatient clinic, and the large recruitment area of 
metropolitan Chicago. We will also employ our standard participant friendly provisions, 
including scheduling sessions in late afternoon/early evening and weekends, 
incorporating technological advances for contacts and reminders, and providing 
adequate compensation for participants’ time.  
 
 Data Management Plan: 
Data collected will consist of demographic data, subjective (self-report questionnaires, 
interview responses, ratings), and physiological (weight, heart rate and blood pressure). 
Access to individually identifiable private information about human subjects will be 
limited to Drs. Grant and Lee and their staff and will be collected specifically for the 
proposed research project. All collected data will be stored utilizing a 4-digit subject 
identification code, linked to separately stored identifying information via a coded log 


updated 19APR2017 
Page 17 of 19 
only available to the PIs.  
The gender ratio of adult binge eating disorder has been estimated to be approximately 
1:1  We will also make every effort to include a racially/ethnically diverse study 
population. The year 2010 Chicago census is 2,695,598 (US Census Bureau, 2011).  
The year 2010 Chicago race distribution is as follows: white 47.1%, African/African-
American 33.9%, Asian/Asian-American 6.2%, Native American 1.0%, or other race/not 
identified (11.8%). A total of 28.9% of the population also identified as Hispanic/Latino 
allowing for a diverse population sample (year 2010, US Census Bureau, Chicago, IL). 
We will make every effort to ensure that members of both genders and diverse racial, 
ethnic, and socioeconomic groups are adequately represented in the proposed study. 
The PI will implement the following procedures to ensure data integrity and the safety of 
participants during the study: A number of elements of the research plan are intended to 
minimize the risks of study participation. For example, the study exclusion criteria 
exclude patients who are experiencing clinically significant suicidality or require a higher 
level of care than outpatient. If this is indicated, the PI will evaluate them and refer them 
for immediate non-study treatment (for example, inpatient or additional pharmacologic 
treatment).  The PI will carefully monitor ratings on the Columbia Suicide Severity 
Rating Scale and the Hamilton Depression rating Scale; any participant endorsing 
suicidal thoughts, will be immediately evaluated by the PI and referred to a higher level 
of care if clinically indicated. The PI will evaluate patient safety at each visit and resolve 
any safety issues more frequently if necessary, as such issues arise.  The PI will also 
be responsible for preparing written summary reports of adverse events and will 
prepare a written report summarizing any decisions that are made pertaining to 
participant disposition. Data integrity and confidentiality will be safeguarded as 
discussed above in the Data Management and Statistical Analysis section under 
Methods. 
Timetable: Our research team has a history of excellent recruitment for research 
studies Our university clinic has active impulsivity and eating disorders clinics. The 
current goal of averaging at least 4 subjects per month is based on the number of calls 
we receive each month asking for treatment for this disorder. Generally the clinic 
received 10-15 calls per month for BED. Of these calls, we anticipate that approximately 
30% would meet criteria for study entry.  The study will recruit in month 1 of YR1 and 
end recruitment in month 20 of YR2. We estimate that immediately upon having IRB 
approval, we will embark on full data collection, including recruitment, telephone and in-
person screening. We estimate averaging 4 subjects per month. Recruitment will be 
until month 20 for 80 subjects.  
 
 
 


updated 19APR2017 
Page 18 of 19 
Ethical and Regulatory Considerations: 
Prior to initiating the study, the Investigator must obtain written approval to conduct the 
study from appropriate institutional ethical and/or regulatory committee and send a copy 
to Takeda (gma.externalresearch@takeda.com). Should changes to the study become 
necessary, copies of written approvals from appropriate institutional ethical and/or 
regulatory committees must be sent to Takeda (gma.externalresearch@takeda.com). 
If research involves human subjects, the Investigator must register the study with 
clinical trials.gov and other appropriate entities, as necessary. 
An IND or CTA may be required.  The investigator is responsible to work with regulatory 
authority to obtain or prove exemption 
References: 
Davis  CA, Levitan  RD, Reid  C,  et al. (2009). Dopamine for “wanting” and opioids for  
“liking”: a comparison of obese adults with and without binge eating. Obesity (Silver 
Spring). 17(6):1220-1225. 
 
Frisch MB, Cornell J, Villaneuva M (1993). Clinical validation of the Quality of Life 
Inventory: a measure of life satisfaction for use in treatment planning and outcome 
assessment. Psychol Assess 4:92-101. 
 
Gibb A, Deeks ED. (2014) Vortioxetine: first global approval. Drugs. 74(1):135-45. 
 
JE, Chamberlain SR. (2016) Cambridge Chicago Trait Scale (Cambridge CHIT-T Scale). 
Available Upon Request. 
ton M (1959) The assessment of anxiety states by rating. Br J Med Psychol 32:50-55  
 
Hamilton M (1960). A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56-
62.  
 
Hudson  JI, Hiripi  E, Pope  HG  Jr, Kessler  RC. (2007) The prevalence and correlates 
of eating disorders in the National Comorbidity Survey Replication. Biol Psychiatry 
61(3):348-358. 
 
Johnson  PM, Kenny  PJ. (2010). Dopamine D2 receptors in addiction-like reward 
dysfunction and compulsive eating in obese rats. Nat Neurosci 13(5):635-641. 
 
Kessler  RC, Berglund  PA, Chiu  WT,  et al. (2013). The prevalence and correlates of 
binge eating disorder in the World Health Organization World Mental Health Surveys. 
Biol Psychiatry. 73(9):904-914. 
 
Latagliata  EC, Patrono  E, Puglisi-Allegra  S, Ventura  R.  Food seeking in spite of 
harmful consequences is under prefrontal cortical noradrenergic control. BMC Neurosci. 
2010;11:15. doi:10.1186/1471-2202-11-15. 
 
Mahableshwarkar AR, Zajecka J, Jacobson W, Chen Y, Keefe RS. A Randomized, 


updated 19APR2017 
Page 19 of 19 
Placebo-Controlled, Active-Reference, Double-Blind, Flexible-Dose Study of the 
Efficacy of Vortioxetine on Cognitive Function in Major Depressive Disorder. 
Neuropsychopharmacology. 2015 Jul;40(8):2025-37 
 
Mathes  WF, Brownley  KA, Mo  X, Bulik  CM.  The biology of binge eating. Appetite. 
2009;52(3):545-553. 
 
McElroy  SL, Hudson  JI, Capece  JA, Beyers  K, Fisher  AC, Rosenthal  NR; 
Topiramate Binge Eating Disorder Research Group.  Topiramate for the treatment of 
binge eating disorder associated with obesity: a placebo-controlled study. Biol 
Psychiatry. 2007;61(9):1039-1048. 
 
McElroy  SL, Guerdjikova  AI, Mori  N, O’Melia  AM.  Pharmacological management of 
binge eating disorder: current and emerging treatment options. Ther Clin Risk Manag. 
2012;8:219-241. 
 
McElroy SL, Hudson JI, Mitchell JE, Wilfley D, Ferreira-Cornwell MC, Gao J, Wang J, 
Whitaker T, Jonas J, Gasior M. Efficacy and safety of lisdexamfetamine for treatment of 
adults with moderate to severe binge-eating disorder: a randomized clinical trial. JAMA 
Psychiatry. 2015 Mar;72(3):235-46 
 
Sheehan DV (1983). The Anxiety Disease. New York: Scribner's. 
 
Supporting documentation/tables and graphs: 
Timetable of visits is attached. 
Detailed Budget for all study related costs: 
Please refer to the budget template accompanied with the notification letter from 
Takeda and include with your protocol submission. 
 

ICF_001.pdf: 
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Version Date: August 8, 2017 
 
The UNIVERSITY OF CHICAGO 
The Division of the Biological Sciences  The University of Chicago Medical Center 
 
CONSENT/AUTHORIZATION BY SUBJECT FOR PARTICIPATION IN A 
RESEARCH PROTOCOL 
 
Protocol Number: 15-1115 
Name of Subject:   
 
 
 
 
 
__ 
 
 
 
 
Medical History Number:   
 
 
 
 
__ 
 
STUDY TITLE:  
“A Double-Blind, Placebo-Controlled Study of Vortioxetine in the Treatment of Binge Eating 
Disorder” 
 
Doctors Directing Research: Dr. Jon Grant & Dr. Royce Lee  
Address: 5841 S. Maryland Ave, Chicago, IL 60637 
Telephone Number: 773-834-1325 
 
You are being asked to participate in a research study. A member of the research 
team will explain what is involved in this study and how it will affect you. This consent 
form describes the study procedures, the risks and benefits of participation, as well as how 
your confidentiality will be maintained. Please take your time to ask questions and feel 
comfortable making a decision whether to participate or not. This process is called 
informed consent.  If you decide to participate in this study, you will be asked to sign this 
form.   
 
WHY IS THIS STUDY BEING DONE? 
 
The aim of the present study is to examine the efficacy and safety of vortioxetine vs 
placebo (a pill that contains no medicine) in adults with Binge Eating Disorder. This 
research is being done because the researchers want to find out if vortioxetine works in 
reducing the symptoms of Binge Eating disorder significantly more than a placebo.  The 
study drug, vortioxetine, is an experimental drug that has been approved by the FDA for 
the treatment of Major Depressive Disorder but is not approved to treat Binge Eating 
Disorder.  The use of vortioxetine in this study is therefore considered experimental. 
 
HOW MANY PEOPLE WILL TAKE PART IN THE STUDY? 
About 80 people will take part in this study at the University of Chicago. 
 
WHAT IS INVOLVED IN THE STUDY? 
Based on your telephone screening, you may be eligible for this study. We have asked 
you to come in for a screening visit.  After signing this consent form, you will undergo 
the following to determine if you are eligible:  
 A review of your medical history, a review of medications you have taken and any 
past treatments for binge eating will be completed.  
 You will undergo a psychiatric interview, which entails a structured clinical interview 
of psychiatric disorders with a research team member.   


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 You will be asked to give a urine sample that will be tested for drug use. This test 
must be negative for you to participate in the study.  
 If you are a female capable of having a child, you will be given a urine pregnancy test 
to ensure that you are not pregnant at the time of study entry. This test must be 
negative for you to participate in the study, and you also must be using appropriate 
contraceptives during the course of the study. Additionally, you must not be 
breastfeeding.    
 
Based on the result of this interview, we will determine if you qualify the study. If so, we will 
ask you to complete the following Baseline Visit procedures at this same visit: 
 
 You will have a physical exam and your sitting and standing blood pressure, pulse, 
temperature, weight and height will be recorded. 
 You will be asked if you are willing to provide an optional blood sample (3 
teaspoons) to measure blood glucose level (blood sugar) to check for diabetes. If you 
consent, your blood will be drawn one time. If you do not consent to having your 
blood drawn, you are still eligible to participate in this study. 
 
I agree to have an optional blood draw to measure my blood glucose level to 
check for diabetes.          
 
_____YES               _____NO          __________________________ 
                                                                                  Initials and date 
 
 An Electrocardiogram (EKG- an electrical tracing of your heart) will be obtained to 
check your heart activity if your medical history suggests cardiac problems. 
 You will be asked about how you are feeling and if you have recently started taking 
any new medications or had any other changes to other medications recently.   
 You will be asked to complete several forms related to binge eating, including both 
self-report and clinician administered inventories. 
 You will also be asked to complete questionnaires about anxiety, depression, mood 
and other behaviors. 
 You will be asked to complete a series of computer tasks measuring attention and 
impulsivity. 
 You will be asked to complete a binge eating diary, which includes writing down the 
time of day the binge occurred, the number of binges, the time spent on the binge, the 
estimated calories of each binge, and what you ate during the binge. You will be 
given information sheets where you can keep track of this information and we will 
review the diary at each visit. 
 You will receive the study drug you have been randomly assigned to for the study.  
The study drug is provided in the form of a pill which you take by mouth. 
 
This baseline visit will require approximately 2-3 hours. 
 
Study Drug Administration 
 


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Following the baseline visit, the study drug administration phase will begin.  You will be 
randomly assigned to receive either the active study drug vortioxetine or the placebo. The 
placebo does not contain any active drug. The random assignment is based on a 50/50 
chance, like flipping a coin.  Neither the study personnel nor you will know whether you 
are taking vortioxetine or the placebo. This is what is meant by “blinding.”  The study 
will last up to 13-weeks and involves up to 9 study visits, including the baseline visit.  
You will take your assigned study drug for the duration of the 13 weeks.  
 
You will start by taking 10mg of vortioxetine or placebo for the first 7 days of the study. 
After the first 7 days, you will go up to 20mg of the vortioxetine (or remain on placebo). 
You will remain on 20mg of vortioxetine or placebo until the last week of the study (for a 
total of 11 weeks). Then you will taper off of the study drug by going down on dose to 
10mg during the last 7 days of the study. 
 
The study doctor will discuss the next study visit scheduling with you during each of 
your current visits.  
 
For the first 3 visits (Visit 1, Visit 2, and Visit 3), visits will be scheduled one week apart. 
Visits 4-8 will be scheduled two weeks apart. 
 
During Visits 2-7, the following will occur: 
 
Your weight and vital signs will be checked. 
 
You will be given the study drug or placebo. 
 
You will be asked to complete several questionnaires to assess binge eating behavior 
and mood since the last visit. 
 
These visits will take approximately 30 minutes to one hour each.   
 
Visit 8 will be scheduled two weeks after Visit 7, and the following will occur: 
 You will have a physical exam and your sitting and standing blood pressure, pulse, 
temperature, weight and height will be recorded. 
 You will be asked about how you are feeling and if you have started taking any new 
medications or had any other changes to other medications you may be taking since 
your last visit.   
 You will be asked to complete the same forms administered during the first visit, 
including the cognitive tasks on the computer. 
 
The final visit (Visit 9) will be scheduled one week after Visit 8 and we will ask about 
any problems or side effects you might be experiencing. 
 
During this study, Dr. Grant and his research team will collect information about you for 
the purposes of this research.  This information will include the following: your name, 
contact information, social security number (for payment purposes), basic demographic 
information (such as your age, gender, and race), relationship status, sexual orientation, 
family and other history, medical and medication history, and responses from 
questionnaires. This information is being collected so that we are able to later evaluate 
your information and other participants’ to find correlations between certain 


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characteristics and mood and treatment outcomes. This information is also being 
collected so that we are able to compare those results to different outcomes and to other 
participants. All of the data collected will be completely confidential.  
 
HOW LONG WILL I BE IN THE STUDY? 
 
We think you will be in the study for about 13 weeks.    There is no long-term follow-up 
in the study after you stop the study drug. 
 
Dr. Grant may decide to take you off of the study without your consent if: 
 You are unable to meet the requirements of the study; 
 Your medical condition changes; 
 The study drug is no longer available; 
 New information becomes available that indicates that participation in this study is 
not in your best interest; or 
 If the study is stopped. 
 
WHAT ARE THE RISKS OF THE STUDY? 
You may experience side-effects while taking the drug used in this study.  Your condition 
may remain the same or worsen if this treatment does not work for you.  
 
The most common side effects associated with vortioxetine include (percentages are the 
expected frequency):  
 nausea (30%) 
 diarrhea (7%) 
 constipation (6%) 
 vomiting (6%) 
 dry mouth (8%) 
 flatulence (1%) 
 dizziness (9%) 
 sexual dysfunction (5% in males, 2% in females) 
 
Vortioxetine and other similar drugs may increase suicidal thoughts or actions in some 
children, teenagers, or young adults within the first few months of treatment or when the 
dose is changed. Notify study staff immediately if you experience these symptoms.  
 
There may be risks to taking vortioxetine that are not now known. If new information 
becomes available which could influence your willingness to continue, this new 
information will be discussed with you. 
 
The use of drugs that modulate serotonin, including vortioxetine, may increase the risk of 
bleeding events. Using aspirin, nonsteroidal anti-inflammatory drugs (NSAIDS), 
warfarin, and other anticoagulants along with vortioxetine may further increase this risk. 
If you have questions about what medications you can or cannot take with the study drug, 
feel free to ask Dr. Grant or the research staff at any time. 
 


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There have been reports of serious, sometimes fatal, reactions between drugs that 
modulate serotonin, such as vortioxetine, and monoamine oxidase inhibitors (MAOI) 
(another type of drug commonly used for depression). Therefore, it is recommended that 
vortioxetine should not be used in combination with an MAOI, or within 14 days of 
stopping treatment with an MAOI. Similarly, at least 14 days should be allowed after 
stopping vortioxetine before starting an MAOI.  Again if you have questions about this, 
please ask Dr. Grant. 
 
If you consent to having your blood drawn, the needle stick may cause discomfort, pain, 
burning sensation, or bruising. 
 
If you are asked to get an EKG, you may have some discomfort when the electrodes (soft 
patches attached using adhesive tape) are removed from your chest and limbs. There is a 
possibility you could develop a minor rash when the electrodes were placed. This rash 
should go away without treatment. 
 
It is possible that some of the questions may cause discomfort or mental stress, such as 
“do you feel down or sad?” and specific questions that involve your binge eating habits. 
If that should happen, we would be happy to talk about any thoughts or problems you 
may have. The study doctor may remove subjects from this study who have suicidal 
thoughts. In such a case, the study doctor may refer you for additional help.  
 
ARE THERE ANY BENEFITS TO TAKING PART IN THE STUDY? 
If you agree to take part in this study, there may or may not be direct medical benefit to 
you for your binge eating behavior. We hope the information learned from this study will 
benefit other individuals with binge eating disorder in the future.  
 
WHAT OTHER OPTIONS ARE THERE? 
Instead of being in this study, you have these options: 
 Receive standard of care medication given for your condition, such as Vyvanse 
(lisdexamfetamine dimesylate)  
 Receive psychotherapy 
 No treatment and/or therapy 
 
There are a select number of treatment options which have been found to be helpful for 
the treatment of binge eating disorder.  Dr. Grant and his research team can provide you 
with information on resources in Chicago where you could potentially find other options 
for care.   
 
The decision whether or not you wish to participate in this study will not affect your care 
at the University of Chicago Medical Center. 
 
WHAT ARE THE COSTS? 
Clinical services provided during a clinical trial are either research-related or related to 
usual medical care. Research-related services are done to complete the research and the 
costs are not the responsibility of you or your insurance.  


6 of 9 
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The costs that are considered research-related for this study include the following:  all 
vortioxetine/placebo for the duration of the study, all visits with the study team (including 
Dr. Grant or Dr. Lee), pregnancy tests, urine drug tests, physical exams, blood draws, 
EKG, and psychiatric evaluations. 
 
Usual medical care costs include any and all services that are considered medically 
necessary for your disease, such as medications or treatments. The cost of this usual, 
ongoing medical care will be the responsibility of you or your insurance, and may include 
deductibles and co-payments. Similarly, this care will be subject to all the same 
requirements and restrictions of your insurance. Once the study has concluded, the 
continuation of care from a mental health provider will be the responsibility of you and/or 
your insurance. This would include the cost of vortioxetine, if you wish to continue 
taking one of them after your participation in the study has ended.  
 
If you suffer an unanticipated injury as a direct result of this research and require 
emergency medical treatment, treatment will be provided at the University of Chicago 
Medical Center at no cost to you.  You must notify Dr. Grant as promptly as possible 
after your injury in order to receive this care.  An injury is “unanticipated” if it is not one 
of the known effects of vortioxetine, and is not the result of your disease or condition. 
The costs of any non-emergency care for such an injury will be billed to you or your 
insurance in the ordinary manner.  If you think that you have suffered a research related 
injury, you must let Dr. Grant know right away. 
 
WILL I BE PAID FOR MY PARTICIPATION? 
For participation in this study you will receive $20 per visit. The total amount you could 
receive for this study is $180 if you complete all nine study visits. All payment for your 
participation will be provided in the form of cash after every visit. You will also be 
compensated for your travel in the form of a parking voucher or bus voucher, which you 
will receive at the conclusion of each visit. 
 
The policies at the University of Chicago may require that you to complete a tax form in 
order to receive compensation. If this is the case, we will be collecting personal 
information about you including your name, address, and social security number.   
 
WHAT ABOUT CONFIDENTIALITY? 
Study records that identify you will be kept confidential.  All records will be kept in a 
secure office in a locked cabinet of the Psychiatry Department at the University of 
Chicago. Only study staff will have access to study records. The data collected in this 
study will be used for the purpose described in the form.  By signing this form, you are 
allowing the research team access to your medical records, which include Protected 
Health Information.  Protected Health Information (PHI) consists of any health 
information that is collected about you, which could include your medical history and 
new information collected as a result of this study.  The research team includes the 
individuals listed on this consent form and other personnel involved in this study at the 
University of Chicago.  


7 of 9 
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As part of the study, Dr. Grant and his research team will report the results of your study-
related procedures and tests explained above to Takeda Pharmaceuticals. These include 
any serious adverse effects that may occur during the course of the study. This 
information is being sent because the sponsor needs to be informed of any serious 
problems that may occur with the study drug for monitoring and drug labeling purposes. 
The study sponsor or their representatives, including monitoring agencies, may also 
review your medical record.  Please note that these individuals may share your health 
information with someone else.   
 
Your records may be reviewed by federal agencies whose responsibility is to protect 
human subjects in research including the Food and Drug Administration (FDA) and 
Office of Human Research Protections (OHRP).  In addition, representatives of the 
University of Chicago, including the Institutional Review Board, a committee that 
oversees the research at the University of Chicago, may also view the records of the 
research.  If your research record is reviewed by any of these groups, they may also need 
to review your entire medical record.  
 
If health information is shared outside the University of Chicago, the same laws that the 
University of Chicago must obey may not protect your health information. 
 
During your participation in this study, you will have access to your medical record. Dr. 
Jon Grant is not required to release to you research information that is not part of your 
medical record. 
 
This consent form will be kept by the research team for at least six years. The study 
results will be kept in your research record and be used by the research team indefinitely.  
At the time of study completion, either the research information not already in your 
medical record will be destroyed or information identifying you will be removed from 
study results.  Any research information in your medical record will be kept indefinitely. 
 
Data from this study may be used in medical publications or presentations.  Your name 
and other identifying information will be removed before this data is used.  If we wish to 
use identifying information in publications, we will ask for your approval at that time. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as 
required by U.S. Law. This Web site will not include information that can identify you. 
At most, the Web site will include a summary of the results. You can search this Web site 
at any time. 
 
WHAT ARE MY RIGHTS AS A PARTICIPANT? 
Taking part in this study is voluntary.  If you choose not to participate in this study, your 
care at the University of Chicago/University of Chicago Medical Center will not be 
affected. You may choose not to participate at any time during the study.  Leaving the 
study will not affect your care at the University of Chicago/University of Chicago 
Medical Center. 


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If you choose to no longer be in the study and you do not want any of your future health 
information to be used, you must inform Dr. Grant in writing at the address on the first 
page.  Dr. Grant may still use your information that was collected prior to your written 
notice.  
 
We will tell you about significant new information that may affect your willingness to 
stay in this study.  
 
You will be given a signed copy of this document. This consent form document does not 
have an expiration date. 
 
WHOM DO I CALL IF I HAVE QUESTIONS OR PROBLEMS? 
You have talked to Dr. Grant about this study and you had the opportunity to ask 
questions concerning any and all aspects of the research.  If you have further questions 
about the study, you may call Dr. Grant at 773-834-1325. 
 
If you have a research related injury, you should call Dr. Grant (the study doctor) 
immediately at 773-834-1325. 
 
If you have any questions concerning your rights in this research study you may contact the 
Institutional Review Board, which is concerned with the protection of subjects in research 
projects.  You can reach the Committee office between 8:30 am and 5:00 pm, Monday 
through Friday, by calling (773) 702-6505 or by writing:  University of Chicago, 
Institutional Review Board, 5841 S. Maryland Ave., MC7132, I-624, Chicago, IL 60637. 
 
CONSENT 
 
SUBJECT 
The research project and the procedures associated with it have been explained to me.  
The experimental procedures have been identified and no guarantee has been given about 
the possible results. I will receive a signed copy of this consent form for my records. 
 
I agree to participate in this study.  My participation is voluntary and I do not have to sign 
this form if I do not want to be part of this research study. 
 
Signature of Subject:   
 
 
 
 
 
 
 
Date:    
 
 
Time:    
   AM/PM (Circle) 
 
PERSON OBTAINING CONSENT 
I have explained to                                                                            the nature and purpose 
of the study and the risks involved.  I have answered and will answer all questions to the 
best of my ability.  I will give a signed copy of the consent form to the subject. 
 
Signature of Person Obtaining Consent:   
 
 
 
 
 


9 of 9 
Version Date: August 8, 2017 
 
 
Date:    
 
 
Time:    
   AM/PM (Circle) 
 
INVESTIGATOR/PHYSICIAN: 
Signature of Investigator/Physician    
 
 
 
 
 
Date:    
 
 
Time:    
   AM/PM (Circle)