Conditions: Binge-Eating Disorder
Keywords: eating disorder, pharmacotherapy
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 36
Healthy volunteers: no

Brief summary:
The study is a 17-week, single-center, double-blind, parallel-group, randomized placebo controlled trial that will test the efficacy of liraglutide 3.0 mg/d as compared to placebo in reducing the number of binge episodes per week, achieving remission from binge episodes, and in changes in body weight, global BED symptom improvement, cognitive restraint of food intake, dietary disinhibition, perceived hunger, quality of life, and depressed mood at treatment end.

Detailed description:
All applicants will be initially screened by phone and/or electronically to determine whether they potentially meet eligibility criteria. Those who appear to meet eligibility criteria and remain interested in the trial will be scheduled for an in-person interview.

The in-person interview will be conducted by a psychologist or Masters' level staff member, who will obtain informed consent and evaluate subjects' behavioral eligibility (i.e., willingness and appropriateness to participate) using structured and semi-structured clinical interviews including: an examination of the applicants' BED symptoms, their mood, suicidality, and other general psychopathology. Participants will also be asked to complete questionnaires assessing eating behavior, demographic characteristics, frequency of specific eating behaviors related to loss of control, risk of substance dependence with the consumption of high fat/sugar foods, alexithymia, night eating syndrome, sleep patterns and quality, and attitudes towards food cravings.

Subjects who remain interested and pass this portion of the assessment will proceed to meet with the study physician or nurse practitioner, who will obtain a medical history and conduct a physical examination to determine medical eligibility. Subjects will also have an electrocardiogram (EKG), fasting blood test, and a urine pregnancy test (for females of child bearing age) to confirm eligibility.

Upon successful completion of the screening visit, subjects will be asked to eat as they normally would for 2 weeks. Once per week over these two weeks they will receive a brief survey through REDcap to assess their binge eating episodes for eligibility.

Subjects who continue to meet eligibility criteria assessed at the screening visit and during the run-in period will be scheduled for a randomization visit at the Center within 3 weeks of their screening.

Subjects will be randomly assigned to the two interventions in equal numbers (i.e., 1:1 ratio). The subject's weight, blood pressure, and pulse will then be measured. Following randomization, all subjects will have a medical visit with the study physician or nurse practitioner who will instruct them in the use of liraglutide 3.0 (as described later) and provide the first month's supply of medication.

After randomization, subjects will return at week 1 to assess rate of response. Subjects will return for study visits every two weeks thereafter, at weeks 3, 5, 7, 9, 11, 13, 15, and 17.

These study visits include a brief medical visit (10-15 minutes) with a physician or nurse practitioner to monitor their response to the medication or any changes in health. Vitals and weight will be taken. Additionally, binge episodes, mood, suicidality, and symptom improvement will be assessed by the psychologist or Masters' level trained study staff. Participants will be asked also to complete questionnaires assessing quality of life, obsessions related to food, and food cravings prior to each treatment visit for the secondary outcomes:

In summary, study visits will consist of the medical visit, completion of written surveys, review of structured interviews with the study staff and review of medication adverse events. These visits are expected to last about 30-40 minutes. The study assessments at week 17 will consist of the previously listed procedures and measures in addition to the questionnaires and blood tests conducted at baseline.

Arms:
arm 1: Pre-filled, multi-dose pen that delivers doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg, or 3 mg via subcutaneous injection. Matching the recommended dosage and administration guidelines of the FDA-approved labeling for the use of liraglutide (Saxenda), the medication will be initiated at 0.6 mg daily for 1 week, and then increased by 0.6 mg/day in weekly intervals until a dose of 3.0 mg/day is achieved. Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist. arm 2: Pre-filled, multi-dose pen that delivers doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg, or 3 mg of placebo via subcutaneous injection. The placebo will be initiated at 0.6 mg daily for 1 week, and then increased by 0.6 mg/day in weekly intervals until a dose of 3.0 mg/day is achieved.The inactive ingredients include: disodium phosphate dihydrate, 1.42 mg; propylene glycol, 14 mg; phenol, 5.5 mg; and water for injection.

Interventions: intervention 1: Liraglutide (Saxenda) 6Mg/Ml Inj Pen 3Ml intervention 2: Placebo
Intervention descriptions: intervention 1: subcutaneous injection, pre-filled, multi-dose pen that delivers doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg, or 3 mg (6 mg/mL, 3 mL). Matching the recommended dosage and administration guidelines of the FDA-approved labeling for the use of liraglutide (Saxenda), the medication will be initiated at 0.6 mg daily for 1 week, and then increased by 0.6 mg/day in weekly intervals until a dose of 3.0 mg/day is achieved. intervention 2: subcutaneous injection, pre-filled, multi-dose pen that delivers doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg, or 3 mg (6 mg/mL, 3 mL). It is designed to be identical to the pen used for liraglutide (Saxenda). Placebo product inactive ingredients: disodium phosphate dihydrate, 1.42 mg; propylene glycol, 14 mg; phenol, 5.5 mg; and water for injection

Protocol document:
Prot_SAP_000.pdf: 
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Protocol: A Randomized Controlled Trial of Liraglutide 3.0 
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mg/d for Binge Eating Disorder 
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PI: KELLY C. ALLISON, PHD 
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VERSION 5.20.2019 
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A Randomized Controlled Trial of Liraglutide 3.0 mg/d for 
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Binge Eating Disorder  
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INVESTIGATOR-INITIATED STUDY PROPOSAL 
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UNIVERSAL TRIAL NUMBER (UTN): U1111-1172-4315 
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Department of Psychiatry 
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Perelman School of Medicine, University of Pennsylvania 
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3535 Market St # 3029 
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Philadelphia, PA 19104 
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Correspondence to:  
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Kelly C. Allison, Ph.D. 
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Director, Center for Weight and Eating Disorders 
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Perelman School of Medicine at the University of Pennsylvania  
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3535 Market St., Suite 3029 
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Phone: 215-898-2823, fax: 215-898-2878; kca@pennmedicine.upenn.edu 
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Table of Contents  
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BACKGROUND AND SIGNIFICANCE: .......................................................................... 4 
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SPECIFIC OBJECTIVES: ............................................................................................... 6 
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PRIMARY OBJECTIVE ....................................................................................................... 6 
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SECONDARY OBJECTIVES .................................................................................................6 
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RESEARCH DESIGN AND METHODS:........................................................................... 6 
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STUDY HYPOTHESES: ....................................................................................................... 6 
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ENDPOINTS: ..................................................................................................................... 7 
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STUDY TYPE: .................................................................................................................... 7 
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RATIONALE FOR STUDY DESIGN ...................................................................................... 8 
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STUDY POPULATION: ................................................................................................ 8 
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INCLUSION CRITERIA ....................................................................................................... 9 
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EXCLUSION CRITERIA ...................................................................................................... 9 
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RATIONALE FOR STUDY POPULATION ........................................................................... 10 
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WITHDRAWAL CRITERIA ................................................................................................ 10 
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SUBJECT REPLACEMENT ................................................................................................ 11 
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VISIT PROCEDURES .................................................................................................. 11 
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FIGURE 1. STUDY FLOW DIAGRAM ................................................................................ 12 
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SCREENING PROCEDURES .............................................................................................. 12 
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RUN-IN PERIOD .............................................................................................................. 13 
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TABLE 1. SCHEDULE OF STUDY ASSESSMENTS AND LIFESTYLE INTERVENTION………..….15 
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RANDOMIZATION VISIT .................................................................................................. 16 
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FIGURE 2. DOSING SCHEDULE FOR LIRAGLUTIDE .......................................................... 16 
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MEDICAL ASSESSMENT…………........................................................................................ 17 
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ASSESSMENTS FOR EFFICACY ................................................................................... 17 
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ASSESSMENTS FOR SAFETY ...................................................................................... 18 
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SUBJECT COMPLIANCE ............................................................................................. 18 
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ASSESSING ADVERSE EVENTS…………………………………………………………………………………..18 
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STATISTICAL CONSIDERATIONS: .............................................................................. 19 
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SAMPLE SIZE CALCULATION .......................................................................................... 19 
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STATISTICAL METHODS ................................................................................................. 19 
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DATA HANDLING AND RECORD KEEPING: ............................................................... 2 
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ETHICS: ................................................................................................................... 20 
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STUDY SCHEDULE: .................................................................................................. 21 
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STUDY DRUGS AND MATERIALS: ............................................................................ 22 
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STUDY MEDICATION .................................................................................................... 22 
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PACKAGING AND LABELLING OF STUDY MEDICATION ................................................ 22 
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STORAGE AND DRUG ACCOUNTABILITY OF STUDY MEDICATION ............................... 22 
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RANDOMIZATION AND BLINDING .......................................................................... 23 
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BREAKING OF BLINDED CODES .................................................................................... 23 
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CONCOMITANT ILLNESSES AND MEDICATIONS: ..................................................... 23 
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ADVERSE EVENTS: ................................................................................................. 24 
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LIABILITY AND SUBJECT INSURANCE: ..................................................................... 26 
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EVALUABILITY OF SUBJECTS: ................................................................................. 26 
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PREMATURE TERMINATION OF STUDY: ................................................................ 27 
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PUBLICATION PLAN: ............................................................................................. 27 
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REFERENCES: ........................................................................................................ 28 
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BACKGROUND AND SIGNIFICANCE: 
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Binge eating disorder (BED) was first described in 1959 by the founder of our Center for Weight 
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and Eating Disorders, Dr. Stunkard [1], who, along with Co-I Dr. Wadden, was involved in 
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establishing the first diagnostic criteria for BED [2]. BED is a serious psychiatric condition that 
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often co-occurs with mood, anxiety, and/or substance abuse disorders [3,4]. In the Diagnostic 
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and Statistical Manual 5 (DSM 5)[5], the Feeding and Eating Disorders section has been revised 
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and expanded. BED previously was categorized under eating disorder not otherwise specified 
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(ED-NOS), but is now a stand-alone disorder. With this new recognition, it is likely that more 
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patients will be seeking treatment, and, consequently, more healthcare providers will need 
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efficacious treatments for BED.  
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BED is characterized by the consumption of an objectively large amount of food in a short 
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period (≤ 2 hours), accompanied by feeling a loss of control over eating [5]. Persons typically eat 
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more rapidly than usual, eat until uncomfortably full, eat large amounts when not physically 
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hungry, eat alone due to embarrassment, and feel disgust or upset about these episodes after they 
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occur. Binge episodes must occur once per week for an average of 3 months for a diagnosis of 
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BED. The prevalence of BED in the general population is 1.6% of women and 0.8% of men, 
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based on DSM-IV criteria [6], but these numbers will likely increase given the decreased 
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threshold to one binge episode required per week (as compared to the previous criteria of two 
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episodes per week). For example, a recent study of a representative sample of Australian late 
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adolescents and adults reported a prevalence range of 5.6 – 6.9% for BED using the DSM 5 
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diagnosis [7]. The prevalence also increases as body mass index (BMI) increases including 
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persons seeking weight loss treatment [8] and those seeking bariatric surgery [e.g., 9]. BED is 
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also associated with significant health complications independent of BMI, including increased 
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risk for chronic neck and back pain, diabetes, hypertension, and chronic headaches [10].  
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As stated above, persons with BED are more likely to have co-morbid psychiatric diagnoses, 
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such as mood disorders, anxiety disorders, and substance use disorders as compared to persons 
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without an eating disorder [4].  A recently published meta-analysis has also confirmed that 
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quality of life is significantly lower among individuals with BED as compared to those without it 
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[11].  Treatment for BED often improves co-morbid mood and anxiety symptoms, as well as 
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quality of life [12].  
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Aside from the core behavior of engaging in binge episodes, BED is associated with a range of 
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eating disordered attitudes and behaviors.  Previous studies have established that persons with 
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BED experience higher levels of disinhibition over eating and perceived hunger [13].  In 
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addition, food cravings are often extreme among those with BED, typically described as 
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experiencing obsessions with food and feeling compelled to act on those thoughts.  Thus, these 
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extreme thoughts regarding food interfere with one’s ability to resist binge episodes.  Successful 
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treatment of BED should help improve these psychological correlates of disordered eating 
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behavior, as well as reduce the actual occurrence of binge episodes. However, data regarding the 
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impact of liraglutide has not been published (to our knowledge) that demonstrate its impact on 
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these psychological factors related to eating behavior. 
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Lisdexamfetamine is the only medication currently approved by the FDA for the treatment of 
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BED [14], although other medications, including selective serotonin re-uptake inhibitors (SSRIs) 
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[15-16], topirimate [17], and sibutramine [18] have been tested for this disorder.  McElroy and 
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colleagues tested several dosing levels of lisdexamfetamine as compared to placebo, using a 3- 
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week titration period and 8 week trial at full strength.  They found reductions in the frequency of 
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binge episodes per week for placebo and the 30-, 50-, and 70-mg/d treatment groups of [mean 
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(SD)] -3.3 (2.04), -3.5 (1.95), -4.1 (1.52), and -4.1 (1.57), respectively.  These reductions were 
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significantly greater in the 50- and 70-mg/d groups as compared to placebo.  The percentage of 
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participants who achieved cessation from binge episodes for four weeks at the end of the trial 
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was 42% of those on placebo vs. 50% across all treatment groups. Reductions in body weight 
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were -0.1 (3.09), -3.1 (3.64), -4.9 (4.43), and -4.9 (3.93) kg for placebo, and the 30-, 50-, and 70-
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mg/d groups, respectively. (All treatment groups differed significantly from the placebo group.) 
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Examining the effects of a weight loss agent, sibutramine (15 mg/d), as compared to placebo 
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over 24 weeks, Wilfley et al. showed significant reductions in binge episodes per week among 
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those taking sibutramine, with a mean (SD) of -2.7 (1.7) as compared to -2.0 (2.3) for those on 
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placebo [18].  (Our study physician, Dr. Berkowitz was an investigator for this trial.) Of those on 
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sibutramine, 58.7% achieved cessation of binge episodes for four weeks as compared to 42.8% 
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of the placebo group.  Weight loss was also significantly greater in the sibutramine group with a 
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mean (SD) = - 4.3 (4.8) kg as compared to that with placebo, +0.8 (3.5) kg.   
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However, sibutramine is no longer available on the market in Europe or the United States due to 
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medical complications.  Randomized controlled trials of some SSRIs have shown significant 
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reductions in binge episodes per week as compared to placebo, but weight loss has not generally 
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been significant or long-lasting on these agents. In addition, sexual functioning is often adversely 
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impacted on SSRI agents. While topiramate has shown successful reductions in both binge 
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episodes and weight [17], its side effect profile, particularly its negative effect on cognitive 
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functioning, often makes this medication difficult to tolerate. Thus, more medications are needed 
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that produce significant reductions in binge eating, as well as weight, among this population. 
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In sum, BED is a serious disorder associated with distress and medical co-morbidities. Cognitive 
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behavior therapy is considered the most effective treatment for BED [19], but it is expensive, 
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time-consuming, and not available in many geographical regions.  Thus, effective 
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pharmacotherapies are needed for this patient population, particularly medications that do not 
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increase weight or negatively affect sexual functioning, as found with SSRIs, or cognitive 
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functioning, as often seen with topiramate. Finally, as a stimulant, lisdexamfetamine poses the 
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potential for abuse, which may be problematic for a significant proportion of persons with BED, 
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given the elevated rate of substance use disorders among persons with BED [3,4].   
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The proposed study will test the efficacy of liraglutide 3.0 mg/d (Saxenda) for the treatment of 
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BED.  Although data do not seem available regarding liraglutide’s effect on dampening the drive 
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to eat in previously published weight loss trials [20, 21], there is some evidence that liraglutide 
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could help significantly reduce the urge to engage in binge eating, and also suppress appetite.  
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Only one previous study has tested liraglutide in the treatment of BED, to our knowledge [22].  
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This study was an open-label administration of liraglutide 1.8 mg/d with minimal diet and 
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lifestyle advice, as compared to diet and lifestyle advice only among patients in Malaysia.  BED 
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symptoms were assessed with the self-reported Binge Eating Scale (BES) [23]. Participants 
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assigned to liraglutide significantly decreased their BES scores at 6 and 12 weeks (study end).  
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These participants also showed significant decreases in weight (95.5 to 90.1 kg), waist 
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circumference, systolic blood pressure, fasting glucose, and total cholesterol.  However, there 
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were several weaknesses with this study, including its lack of a placebo group and its reliance on 
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a global self-report measure of binge eating, as compared to specific assessment of the frequency 
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of binge episodes per week.  As such, a randomized controlled trial (RCT) would be a logical 
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next step to test whether liraglutide 3.0 mg/d is superior to placebo.   
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SPECIFIC OBJECTIVES: 
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Primary Objective:  
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To test the efficacy of liraglutide 3.0 mg/d as compared to placebo in reducing the number of 
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binge episodes per week during a 17-week, randomized, placebo-controlled trial. 
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Secondary Objectives:  
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To compare the proportion of participants on liraglutide 3.0 mg/d as compared to placebo who 
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achieve remission from binge episodes at week 17, defined as having no binge episodes for the 
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previous 4 weeks.  
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To compare differences between the liraglutide 3.0 mg/d and placebo groups in changes in body 
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weight, global BED symptom improvement, cognitive restraint of food intake, dietary 
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disinhibition, perceived hunger, quality of life, and depressed mood at treatment end. 
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Of note: the Eating Inventory (cognitive restraint of food intake, dietary disinhibition, and 
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perceived hunger) was administered at baseline and at study end. With the small number of 
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completers, it may not be possible to run the mixed models analyses on these outcome variables. 
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RESEARCH DESIGN AND METHODS 
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Study Hypothesis (hypotheses): 
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The trial has the following primary aim and hypothesis: 
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Aim 1. The primary aim is to test the efficacy of liraglutide 3.0 mg/d in reducing the number of 
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binge episodes per week during a 17-week, randomized, placebo-controlled trial. 
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H1: We hypothesize that participants randomized to liraglutide 3.0 mg/d (n =76) will show 
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significantly greater reductions in the number of binge episodes per week as compared to those 
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on placebo (n = 76).  
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Of note, the final sample size is n=36 total.  
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The trial has the following secondary aims and hypotheses. 
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Aim 2. We will compare the proportion of participants in the two groups who achieve remission 
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from binge eating at week 17, defined as having no binge episodes for the previous 4 weeks.  
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H2: We hypothesize that significantly more participants in the liraglutide 3.0 mg/d group will 
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achieve remission at week 17 as compared to the placebo group.  
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Aim 3. We will compare differences between the liraglutide 3.0 mg/d and placebo groups in 
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changes in body weight, global improvement BED symptom improvement, cognitive restraint of 
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food intake, dietary disinhibition, perceived hunger, quality of life, and depressed mood at week 
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17. 
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H3: We hypothesize that participants randomized to liraglutide 3.0 mg/d as compared to those 
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assigned to placebo, will lose significantly more weight, and show greater improvements in 
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investigator-rated global BED symptoms, cognitive restraint of food intake, dietary disinhibition, 
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hunger, quality of life, and depressed mood. (We note that these latter comparisons, Aims 2 and 
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3, are considered exploratory. The study is not powered to determine significant differences 
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among groups on these outcomes.) 
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We note that the Eating Inventory subscales (restraint, disinhibition, and hunger) were 
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completed at baseline and treatment end only, and we may not have enough completers to run 
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the final analyses for this secondary outcome.  
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Endpoints: 
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Primary 
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The primary endpoint is change in binge episodes per week from randomization (week 0) to 
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study end (week 17).    
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Secondary 
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The secondary endpoints include examining the proportion of participants who have achieved 
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remission from binge-eating (no binge episodes between weeks 13 – 17), week 17 rating on the 
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interviewer-based Clinical Global Impression of Improvement Scale (CGI-I)[24] for global 
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assessment of BED symptoms, and changes in body weight, cognitive restraint of food intake, 
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dietary disinhibition, perceived hunger, quality of life, and depressed mood.  
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(See note above regarding restraint, disinhibition, and hunger variables.) 
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Study type: 
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We propose a 17-week, single-center, double-blind, randomized placebo-controlled trial with 
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parallel groups.  There are two treatment arms: a) liraglutide titrated over 5 weeks to 3.0 mg/d, 
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followed by 12 weeks on full dose, and b) placebo for the full 17 weeks.  Seventy-six 
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participants will be randomized to each of the two groups, for a total of 152 participants with 
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BED. 
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Of note, the final sample size for analyses will be 36 participants.  
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Rationale for Study Design 
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We have considered the design of this study at length based on the literature and our group’s 
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experience with clinical trials for BED [e.g. 18, 25].  Most previous RCTs for BED, and 
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certainly all of the initial trials for each individual agent, have used a simple double-blind, 
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randomized placebo control design to demonstrate efficacy [see 26 for review].  Cross-over 
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designs have not been used in any of these trials to date.  As reviewed above, only one open label 
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trial of liraglutide 1.8 mg/d has been published [22], so this would be the first placebo-controlled 
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trial testing the efficacy of liraglutide for BED. 
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Of note, previous studies have shown 30 – 60% of persons with BED are responsive to placebo.  
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Those with mild symptom profiles tend to be most susceptible to placebo response [27].  
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Therefore, many BED trials include a run-in period [28-30], typically for a duration of 1-4 
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weeks, where participants self-monitor their binge episode frequencies or are administered 
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placebo in a single-blind fashion.  If participants’ binge episodes persist over the course of this 
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run-in period, they have demonstrated stability of symptoms and are typically less responsive to 
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placebo [27].  We plan to use a 2-week run-in period consisting of daily monitoring of binge 
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episodes in the proposed study to ensure the stability of BED in our participants. Participants will 
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not be using a placebo during this run-in. After this run-in period, we will use a 17-week double-
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blind placebo-controlled trial to test the efficacy of liraglutide compared to placebo in reducing 
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binge eating episodes, along with our secondary outcomes.  The 17-week duration will allow for 
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titration to the 3.0 mg dose over 5 weeks, followed by a 12 week trial at the full dose, which 
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would allow for adequate time to test for efficacy of the medication on reduction in BED 
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symptoms. This duration is longer than the trial of 11-weeks (3-week titration, 8 week full dose) 
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for lisdexamfetamine [14] and the Malaysian group’s 12-week (total) trial of liraglutide [23].  
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Study population: 
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We will randomly assign 152 participants with BED to either placebo or liraglutide 3.0 mg/d 
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(Saxenda) for the first phase of the trial.  We expect to screen about 500 persons by phone.  Of 
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these, we expect 220 to attend the screening visit.  We expect about a third of these to not meet 
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criteria for BED after the 2-week run-in period, leaving 152 to be randomized to start the 
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intervention (medication or placebo).  We will recruit these participants at a single site – the 
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Center for Weight and Eating Disorders at the University of Pennsylvania, Philadelphia, PA, 
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USA - through local media advertisements and news shows/outlets, as well as Internet-based 
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advertising outlets and flyers around our community. We will be utilizing the university-based 
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website iConnect, which allows access to their volunteer registry data of interested research 
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volunteers.   We have extensive experience recruiting for studies of BED and other forms of 
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disordered eating, and believe that enrolling 152 participants with BED over the course of 36 
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months is highly feasible.  
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UPDATE: We received 1,016 contacts for screening and completed 305 phone screens.  
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However, we were only able to randomize 36 participants who entered the study successfully. 
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(We randomized 37, but one participant told us after starting the protocol that she was already 
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taking metformin, an exclusion criteria, so she was censored).  
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Inclusion Criteria 
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1. BMI > 30 kg/m2 or BMI ≥ 27 - 29.9 kg/m² in the presence of at least one weight-related 
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comorbid condition, such as binge eating disorder, hypertension, or dyslipidemia. There 
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is no upper BMI limit for this trial. 
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2. Age ≥ 21 years and ≤ 70 years 
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3. Meet full DSM 5 criteria for BED 
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a. Recurrent episodes of binge eating characterized by both consuming an 
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abnormally large amount of food in a short period of time compared with what 
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others might eat in the same amount of time under the same or similar 
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circumstances and experiencing a loss of control over eating during the episode. 
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b. These episodes feature at least 3 of the following:  
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i. consuming food more rapidly than normal;  
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ii. eating until uncomfortably full;  
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iii. consuming large amounts of food when not hungry;  
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iv. consuming food alone due to embarrassment;  
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v. feeling disgusted, depressed, or guilty after eating a large amount of food. 
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c. Significant distress about the binge episodes is present. 
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d. Binge episodes must occur, on average, at least once per week for 3 months. 
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4. All races and ethnicities are included 
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5. Eligible female subjects will be: 
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 non-pregnant, evidenced by a negative urine dipstick pregnancy test 
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 non-lactating 
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 surgically sterile or postmenopausal, or they will agree to continue to use an 
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accepted method of birth control during the study 
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6. Ability to provide informed consent before any trial-related activities 
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7. Subjects must: 
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 have a primary care provider (PCP) who is responsible for providing routine care 
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 have reliable telephone or Internet service to communicate with study staff  
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 understand and be willing to comply with all study-related procedures and agree 
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to participate in the study by giving written informed consent 
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 plan to remain in the Philadelphia area for the next 6 months or more 
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Exclusion Criteria 
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1. Pregnant or nursing, or plans to become pregnant in the next 6 months, or not using 
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adequate contraceptive measures 
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2. Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia 
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syndrome type 2 
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3. Uncontrolled hypertension (systolic blood pressure ≥ 160 mm Hg or diastolic blood 
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pressure ≥ 100 mm Hg) 
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4. Type 1 diabetes 
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5. Type 2 diabetes 
361 
6. A combination of fasting glucose ≥ 126 mg/dl, combined with an HbA1c >6.5, will be 
362 
used to indicate the presence of diabetes, an exclusion criterion 
363 
7. Recent history of cardiovascular disease (e.g., myocardial infarction or stroke within the 
364 
past 6 months), congestive heart failure, or heart block greater than first degree 
365 
8. Clinically significant hepatic or renal disease 
366 


V 3 5.20.19 
11
9. Thyroid disease, not controlled 
367 
10. History of malignancy (except for non-melanoma skin cancer) in past 5 years 
368 
11. The presence of current anorexia nervosa or bulimia nervosa 
369 
12. Current major depressive episode, active suicidal ideation, or history of suicide attempts 
370 
within the past 5 years. We will exclude participants who have a Patient Health 
371 
Questionnaire-9 (PHQ-9) [31] score > 15, or a score of > 1 on the suicidal ideation item, 
372 
as well as any risk of suicidality as measured by a score of 4 or 5 on the Columbia-
373 
Suicide Severity Rating Scale (C-SSRS)[32]. 
374 
13. Psychiatric hospitalization within the past 6 months 
375 
14. Self-reported alcohol or substance abuse within the past 12 months, including at-risk 
376 
drinking (current consumption of ≥ 14 alcoholic drinks per week) 
377 
15. Current or past psychosis 
378 
16. Use in past 3 months of medications known to treat BED (such as lisdexamfetamine), 
379 
induce significant weight loss (i.e., prescription weight loss medications), or induce 
380 
weight gain (e.g., chronic use of oral steroids, second generation antipsychotics) 
381 
17. Currently receiving behavioral or pharmacological treatment for BED 
382 
18. Loss of ≥ 10 lb of body weight within the past 3 months 
383 
19. Known or suspected allergy to trial medication(s), excipients, or related products 
384 
20. Hypersensitivity to liraglutide or any product components  
385 
21. The receipt of any investigational drug within 6 months prior to this trial 
386 
22. Previous participation in this trial (e.g., randomized and failed to participate) 
387 
23. History of pancreatitis 
388 
24. History of gastrointestinal surgery (With the exception of individuals who have 
389 
previously had an adjustable gastric band but subsequently have had it removed at least 
390 
six months prior to the study.  These individuals would not be excluded). 
391 
 
392 
Rationale for Study Population 
393 
Exclusion criteria include children or adolescents, as liraglutide is not indicated for use in these 
394 
groups. Persons older than 70 years will be excluded as little is known about the occurrence of 
395 
BED in this age group.  BMI criteria will be set at > 27 kg/m2 to capture overweight and obese 
396 
patients with BED. Given that BED confers medical risks independent of BMI, we propose 
397 
including BED as a co-morbidity that would qualify those with a BMI between 27 – 29.9 kg/m2 
398 
for treatment.  Persons with BED who also have diabetes will be excluded as diabetes can 
399 
independently influence the timing and degree of food intake. In this first trial, we would like to 
400 
examine the impact of liraglutide on BED independently of any effects of medical conditions on 
401 
eating.  Similarly, we would like to focus on the effect of liraglutide on BED symptoms, so we 
402 
will exclude persons with other significant psychiatric diagnoses, as listed above.  We will 
403 
exclude participants who have a Patient Health Questionnaire-9 (PHQ-9) [31] score > 15, or a 
404 
score of > 1 on the suicidal ideation item, as well as any risk of suicidality as measured by a 
405 
score of 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS)[32]. We also would 
406 
like to study persons free of diabetes and without any other uncontrolled significant medical 
407 
problems that could influence their eating patterns and outcomes. Those who are currently 
408 
receiving weight loss or BED treatment, or have taken medications for weight loss or BED 
409 
treatment in the past 3 months will be excluded as we would like to examine the impact on BED 
410 
independently of any other treatments that may affect the study outcomes.  Finally, we will 
411 
exclude persons who have had previous gastrointestinal surgery, including sleeve gastrectomy, 
412 


V 3 5.20.19 
12
gastric bypass, or an adjustable gastric band, as these surgeries affect the amount of food that can 
413 
be consumed at one sitting.  
414 
 
415 
Withdrawal Criteria 
416 
A subject may voluntarily withdraw from the study at any time for any reason. The sponsor-
417 
investigator, Dr. Allison, also may withdraw the subject from further participation at any time, if 
418 
it is considered in the best interest of the subject or the study, without prejudice to the subject’s 
419 
future medical care.  
420 
 
421 
The primary reason for a subject’s premature discontinuation from the study will be selected 
422 
from the following standard categories and documented in the source documents: 
423 
 
424 
Adverse event (AE): One or more clinical or laboratory events which, in the medical judgment of 
425 
the investigator, are grounds for discontinuation, even if the event does not appear to be related 
426 
to study drug. The subject may withdraw because of an AE even if the investigator does not feel 
427 
that it is grounds for discontinuation. This category includes subject death. 
428 
 
429 
Withdrawal of consent: The subject desires to withdraw from further participation in the study. 
430 
 
431 
Lost to follow-up: In the case of subjects who do not return to the center for study procedures and 
432 
cannot be contacted, study personnel will make vigorous and repeated attempts (minimum of 3) 
433 
to contact the subject. These attempts will include at least 1 certified mail receipt. If all attempts 
434 
to contact the subject fail, that subject will be considered to be lost to follow-up and discontinued 
435 
from the study. 
436 
 
437 
Protocol violation: The subject’s laboratory or other findings, or the subject’s conduct, fail to 
438 
meet the protocol entry criteria or fail to adhere to the protocol requirements. Subject pregnancy 
439 
or intention of becoming pregnant would also be a violation. 
440 
 
441 
The Stopping Criteria for individual subjects include: 
442 
 
443 
The Principal Investigator, study physician, and/or nurse practitioner conclude it is unsafe for the 
444 
subject to continue. These reasons may include: 
445 
 A new diagnosis is made of a significant medical condition which could influence the 
446 
response to liraglutide (e.g., renal failure). 
447 
 A medication is begun that could alter the subject’s responses to liraglutide. 
448 
 
449 
Subjects meeting individual stopping criteria will be withdrawn from the trial. 
450 
 
451 
Subject Replacement 
452 
 
453 
Subjects who prematurely discontinue from the study or become ineligible will not be replaced 
454 
once they have been randomized. 
455 
 
456 
Visit Procedures 
457 
 
458 


V 3 5.20.19 
13
Figure 1 shows the flow of subjects through randomization. Table 1 presents the schedule of 
459 
study assessments and treatment visits.  
460 
 
461 
Figure 1. Study Flow Diagram 
462 
 
463 
Screening Procedures  
464 
 
465 
All applicants will be screened by phone and questions administered through REDCap (the 
466 
University of Pennsylvania’s research data capture system) to determine whether they potentially 
467 
meet eligibility criteria. We will obtain a waiver of written documentation of consent for the 
468 
telephone and electronic questionnaire screen. Those who appear to meet eligibility criteria and 
469 
remain interested in the trial will be scheduled for an in-person interview. 
470 
 
471 
The in-person interview will be conducted by a psychologist or Masters’ level staff member, 
472 
who will obtain informed consent and evaluate subjects’ behavioral eligibility (i.e., willingness 
473 
and appropriateness to participate). Individuals who do not wish to participate in the research 
474 
study will receive recommendations for alternative treatments for binge eating disorder if they 
475 
are interested.  Assessment of eligibility will include  examination of the applicants’ BED 
476 
symptoms, as measured by the Eating Disorder Examination (interview version, 16th edition) 
477 
[33], their mood (using a cut score of 15 on the PHQ-9)[31], suicidality (including history of 
478 
suicidal ideation and behavior), as assessed at screening by a score of 4 or 5 on the Columbia-
479 
Suicide Severity Rating Scale [32]), and other general psychopathology, as measured by the 
480 
Mini International Neuropsychiatric Interview 7.0 (MINI) [34].  Participants will be asked to 
481 
complete additional questionnaires including the Eating Inventory (EI) [35], a questionnaire 
482 
assessing demographic characteristics, Loss of Control Eating Scale (LOCES) [36] to measure 
483 
frequency of specific eating behaviors related to loss of control, Yale Food Addiction Scale [37] 
484 
to identify those most likely to be at risk for substance dependence with the consumption of high 
485 


V 3 5.20.19 
14
fat/sugar foods, Toronto Alexithymia Scale (TAS-20) [38] as a self-report measure of features 
486 
associated with Alexithymia, Night Eating Questionnaire (NEQ) [39] to assess the behavioural 
487 
and psychological symptoms of night eating syndrome, Pittsburgh Sleep Quality Index (PSQI) 
488 
[40] to measure sleep patterns and sleep quality, the Food Craving Questionnaire – State (FCQ-
489 
S) [41] and the Food Craving Questionnaire – Trait (FCQ-T) [41] to assess state and trait 
490 
attitudes towards food cravings. 
491 
 
492 
The Eating Disorders Examination (EDE, 16th edition) [33] is a standardized interview devised 
493 
for the assessment of the psychopathology specific to eating disorders. It is considered the gold 
494 
standard for assessment of BED. Specifically, the EDE assesses the frequency of different forms 
495 
of overeating during the previous 28 days, including objective binge episodes (i.e., consuming 
496 
unusually large quantities of food with a subjective loss of control), subjective binge episodes 
497 
(i.e., subjective loss of control while eating a quantity of food not judged to be large given the 
498 
context) and objective overeating episodes (overeating without a loss of control). It also assesses 
499 
inappropriate compensatory behaviors that have occurred in the previous 28 days associated with 
500 
eating disorder psychopathology. The EDE yields four subscales rated on 7-point scales (0-6) 
501 
with higher scores indicating greater pathology: Dietary Restraint, Eating Concern, Shape 
502 
Concern, and Weight Concern.  A Global EDE score is averaged across these four subscales.  
503 
The EDE will be administered by a trained rater at baseline and week 17.  It takes approximately 
504 
an hour to administer.  The binge eating section of the EDE will be used to assess frequency of 
505 
binge episodes at each medical visit. 
506 
 
507 
The Eating Inventory (also known as the Three Factor Eating Questionnaire) consists of 51 items 
508 
that assess three factors: Cognitive Restraint, Disinhibition, and Hunger [35]. Scores increase 
509 
positively with endorsement of items for each factor. Higher disinhibition scores have been 
510 
linked to greater frequency of binge eating, while higher cognitive restraint and lower hunger 
511 
scores are associated with larger weight losses among overweight persons in weight loss 
512 
programs. The Eating Inventory will be administered at baseline and week 17. 
513 
 
514 
The MINI 7.0 [34] assesses most Axis I disorders, such as major depressive disorder, bipolar 
515 
disorder, the anxiety disorders, attention deficit-hyperactivity disorder, and psychosis.  It will be 
516 
used to characterize the sample and to identify psychiatric conditions that are listed as exclusions 
517 
to participation.  The MINI will be administered at baseline and takes approximately 15-25 
518 
minutes.   
519 
 
520 
Subjects who remain interested and pass this portion of the assessment will proceed to meet with 
521 
the study physician or nurse practitioner, who will obtain a medical history and conduct a 
522 
physical examination to determine medical eligibility. Persons who continue to remain eligible 
523 
will proceed to have an electrocardiogram (EKG) and fasting blood test to determine that final 
524 
eligibility criteria are met. As detailed below, safety screening labs include a comprehensive 
525 
metabolic panel (including glucose), lipids, hemoglobin A1c, and a urine pregnancy test (for 
526 
females of child-bearing age). These labs will be repeated at week 17. 
527 
 
528 
The following procedures will be completed at the screening visit as discussed above: informed 
529 
consent; behavioral evaluations; assessment of criteria for BED; medical history; full physical 
530 
exam; review of medication; 12-lead EKG; blood draw (approximately 1 tablespoon - i.e., 15 ml 
531 


V 3 5.20.19 
15
of blood); weight; height; and sitting blood pressure and pulse rate. For women of childbearing 
532 
potential, a urine pregnancy test also will be performed. Results of these tests will be reviewed 
533 
by the study physician or nurse practitioner to determine whether the subject has any 
534 
contraindications to the use of liraglutide, as detailed in the inclusion/exclusion criteria.  
535 
 
536 
Run-In Period 
537 
Upon successful completion of the screening visit, subjects will be asked to not change anything 
538 
and eat as they normally would for 2 weeks.  Once per week over these two weeks they will 
539 
receive a brief survey through REDcap to assess their binge eating episodes.  For those without 
540 
internet access, study staff will call the participant to ask this information over the phone.  If 
541 
participants report having at least one binge episode per week (a total of two or more during the 
542 
two weeks), they will be included in the trial.  Subjects will be trained at the screening visit on 
543 
general guidelines for the definition of a binge episode.  
 
544 


V 3 5.20.19 
16
Table 1. Timeline and Procedures 
545 
 
546 
 
Screening 
RCT 
 
Weeks 
 
Screen 
2-week 
run-in 
Randomization/ 
Week 0 
1 
3 5 7 9 11 13 15 17 
Procedures 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent 
x 
 
 
 
 
 
 
 
 
 
 
 
Adverse events actively 
collected 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Behavioral evaluation 
x 
 
 
 
 
 
 
 
 
 
 
 
History and physical 
x 
 
 
 
 
 
 
 
 
 
 
 
EKG 
x 
 
 
 
 
 
 
 
 
 
 
 
Blood draw 
x 
 
 
 
 
 
 
 
 
 
 
x 
Labs 
x 
 
 
 
 
 
 
 
 
 
 
x 
Log of BED behaviors 
 
x 
 
 
 
 
 
 
 
 
 
 
Self-reported outcomes 
 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Medical visit 
 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Psychological assessment of 
BED symptoms 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Vital signs 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
547 
Note: Shaded weeks are formal assessment weeks. Data regarding binge episodes, weight, vital signs, mood and suicide risk, and other 
548 
self-reported outcomes will be collected at each medication visit, as well.   
549 
 
 
550 


V 3 5.20.19 
17
Randomization Visit 
551 
 
552 
Subjects who continue to meet eligibility criteria assessed at the screening visit and during the 
553 
run-in period will be scheduled for a randomization visit at the Center within 3 weeks of their 
554 
screening.  
555 
 
556 
Subjects will be randomly assigned to the two interventions in equal numbers (i.e., 1:1 ratio). 
557 
This will be accomplished using a computer-generated algorithm operated by the Investigational 
558 
Drug Service of the University of Pennsylvania. Assignment will be made from randomly varied 
559 
block sizes (2, 4, or 6), realizing that this method may require slightly more than 152 participants 
560 
to be randomized in order to achieve perfect balance between the two groups. 
561 
 
562 
The subject’s weight, blood pressure, and pulse will then be measured, following the methods 
563 
described later (see Assessment for Efficacy). 
564 
 
565 
Following randomization, all subjects will have a medical visit with the study physician or nurse 
566 
practitioner who will instruct them in the use of liraglutide 3.0 (as described later) and provide 
567 
the first month’s supply of medication.  
568 
 
569 
Subjects will be provided liraglutide 3.0 (Saxenda) or placebo after being randomized at week 0. 
570 
Liraglutide 3.0, a glucagonlike peptide-1 receptor agonist, is a once-daily self-administered, 
571 
subcutaneous injection [42].  Liraglutide 3.0 mg or placebo will be provided as pre-filled, 
572 
disposable, personal injectors. Subjects will be taught (by the study physician or nurse 
573 
practitioner) how to properly perform subcutaneous injections into their abdomen, thigh, or 
574 
upper arm. In addition, subjects will be given an instruction card about how to administer the 
575 
medication. To reduce the likelihood of gastrointestinal symptoms (e.g., nausea, vomiting), the 
576 
medication will be initiated at 0.6 mg daily for 1 week, and then increased by 0.6 mg/day in 
577 
weekly intervals until a dose of 3 mg/day is achieved (please see below for dosing schedule). 
578 
Subjects will be instructed that if they miss a dose, to resume the once-daily regimen with the 
579 
next scheduled dose and not to take an extra dose or higher dose. If subjects miss more than 3 
580 
days, they will be instructed to contact the physician or nurse practitioner who will initiate 
581 
therapy at 0.6 mg/day to avoid gastrointestinal symptoms. Subjects who do not tolerate an 
582 
increased dose during escalation will have a delayed dose escalation by up to 7 days. Study 
583 
medical staff also will help subjects develop a medication schedule, based on when and where 
584 
subjects will take the medication each day and how they will remind themselves to do so. 
585 
Figure 2. Dosing Schedule for Liraglutide 
586 
 
587 
 
588 
 
589 


V 3 5.20.19 
18
After randomization, subjects will return at week 1 to assess rate of response.  Subjects will 
590 
return for study visits every two weeks thereafter, at weeks 3, 5, 7, 9, 11, 13, 15, and 17. Study 
591 
staff will review the individual’s medication adherence at each study visit, determining the 
592 
number of days that liraglutide was used each week and identifying reasons for missed doses. 
593 
The number of doses of medication taken each week will be tracked.  
594 
 
595 
Medical assessment: Study visits include a brief medical visit (10-15 minutes) with a physician 
596 
or nurse practitioner. These visits are needed for subjects to monitor their response to the 
597 
medication. At each medical visit, subjects’ weights and vital signs will be measured and their 
598 
response to the medication will be assessed. Subjects will be asked whether there have been any 
599 
changes in their health or medications. For all non-study-related medical events, subjects will be 
600 
referred to their own PCPs.  
601 
 
602 
Assessments for Efficacy 
603 
An assessment of binge frequency since the participant’s last visit will be completed by the 
604 
psychologist or Masters’ level trained study staff by interview at each study visit based on the 
605 
binge eating section of the EDE.  Subjects also will be asked about their mood or any thoughts of 
606 
harming themselves, as assessed by the Patient Health Questionnaire, 9 item version (PHQ-9) 
607 
[31] and the Columbia-Suicide Severity Rating Scale (C-SSRS) [32]. In the event of reports of 
608 
suicidal ideation or disturbances in mood, subjects will be referred to the study’s psychologist or 
609 
psychiatrist for further evaluation, as appropriate.  
610 
  
611 
The Clinical Global Impression of Improvement scale (CGII) [24] will be used by the 
612 
psychologist or master’s level study staff to rate level of overall symptom improvement based on 
613 
the information gathered at each treatment visit. This is a 7-point scale ranging from 1 – very 
614 
much improved to 7 – very much worsened.    
615 
 
616 
Additionally, participants will be assessed using several assessments at the randomization visit 
617 
and each study visit for the secondary outcomes: 
618 
1. In addition to a safety assessment, the Patient Health Questionnaire 9-Item version (PHQ-9) 
619 
[31] will be used to assess changes in mood during treatment.   
620 
2. The Quality of Life, Enjoyment and Satisfaction Questionnaire (Q-LES-Q) [43] is a face-valid 
621 
survey of a broad range of quality of life items that we have used in several previous treatment 
622 
trials for eating disorders.    
623 
3.  The Yale-Brown Obsessive Compulsive Scale modified for BE (YBOCS-BE)[44] assesses 
624 
the degree of obsessions that are focused on BE thoughts and compulsions that are focused on 
625 
BE behaviors. 
626 
4.  Weight will be measured at each visit, without shoes and in light clothing, on a calibrated 
627 
Tanita scale measured to the nearest 0.1 kg.   
628 
 
629 
In summary, study visits will consist of the vital sign and weight assessment, medical 
630 
assessment with a physician or nurse practitioner, completion of written surveys (PHQ-9, QLES-
631 
Q, YBOCS-BE), review of the binge eating module of the EDE, C-SSRS, and CGII by study 
632 
staff, and review of medication adverse events.  All measurements and assessments will be 
633 
recorded in the patient case report form.  These visits are expected to last about 30-40 minutes. 
634 
The study assessments at week 17 will consist of the full EDE, Eating Inventory, Loss of Control 
635 


V 3 5.20.19 
19
Eating Scale, Yale Food Addiction Scale, FCQ-T, FCQ-S, NEQ, and PSQI in addition to the 
636 
previously listed measures. 
637 
 
638 
Assessments for Safety 
639 
Safety endpoints include physical examination, adverse events (AEs), standard laboratory tests, 
640 
and mental health as assessed by the C-SSRS [32]. As detailed above, all subjects also will have 
641 
brief medical visits (10-15 minutes) with a physician or nurse practitioner at weeks 0, 1, 3, 5, 7, 
642 
9, 11, 13, 15, and 17. These visits are to monitor subjects’ response to the medication. Subjects 
643 
will be asked whether there has been any change in their health or medications. They also will be 
644 
asked about their mood (PHQ-9) or any thoughts of harming themselves, as determined by the C-
645 
SSRS. In the event of significant adverse mental health events, subjects will be referred to the 
646 
study’s psychologist or psychiatrist for further evaluation, if required. For all non-study-related 
647 
medical events, subjects will be referred to their own primary care provider.  
648 
 
649 
Subjects will have fasting blood draws (comprehensive metabolic panel, lipids, hemoglobin A1c) 
650 
at screening and week 17. Vital signs (blood pressure and pulse) and weight will be measured at 
651 
screening and weeks 0, 1, 3, 5, 7, 9, 11, 13, 15, and 17.  
652 
 
653 
As stated above, safety labs will be assessed at baseline and week 17.  Fasting blood samples 
654 
(i.e., following an 8 hour overnight fast) will be drawn on each of these occasions, including a 
655 
complete blood count (CBC), comprehensive metabolic panel (CMP; including glucose), 
656 
hemoglobin A1c (to identify pre-existing or the occurrence of diabetes mellitus), (for women) a 
657 
urine pregnancy test, and assayed for triglycerides, total cholesterol, and LDL and HDL 
658 
cholesterol. (Samples will be drawn and spun at our center, and shipped to be analyzed by Quest 
659 
Diagnostics.) Each blood draw will require approximately 1 tablespoon (i.e., 15 mls) of blood. 
660 
Blood pressure and pulse will be measured on each occasion using an automated monitor 
661 
(Dinamap, model 9300). Two readings will be taken on each occasion (at 1-minute intervals), 
662 
after participants have been seated for at least 5 minutes.  
663 
 
664 
At baseline screening, participants will complete a history and physical examination and have an 
665 
EKG.  Interpretation of results will use the categories “normal”, “abnormal”, not clinically 
666 
significant” or “abnormal, clinically significant”.  Subjects will be screened extensively (by a 
667 
physician or nurse practitioner) to determine that they have no contraindications to the use of 
668 
liraglutide or to possible weight loss.   
669 
 
670 
Other Assessments 
671 
n/a 
672 
 
673 
Subject Compliance 
674 
Subjects will be instructed to keep a medication diary to be reviewed at each visit, and they will 
675 
be asked if they have missed any doses since their last visit. We will also measure subjects’ 
676 
medication adherence using injection counts from visual inspection of the dose counter taken 
677 
from subjects’ injection pens. Subjects will be instructed to bring the pen to each session, and we 
678 
will record missed doses and problem solve with subjects if they are missing doses.  
679 
 
680 
 
681 


V 3 5.20.19 
20
Assessing Adverse Events 
682 
All information regarding adverse events will be actively collected from the point of the first 
683 
study-related activity (i.e., completion of the informed consent procedure), through to each 
684 
participant’s study endpoint.  This includes adverse events that may be related to any study 
685 
procedure (i.e., laboratory tests or ECGs) that may not have been performed during normal 
686 
management of the participant, in addition to his/her use of liraglutide.  
687 
 
688 
STATISTICAL CONSIDERATIONS: 
689 
Sample Size Calculation 
690 
A power analysis was conducted for the primary outcome, reduction in binge episodes per week 
691 
(i.e., last 7 days). Estimated variances and clinically relevant treatment differences were derived 
692 
from the literature using previous randomized controlled trials for BED [14, 45]. The common 
693 
standard deviation used was 4.1 [45], and the clinically relevant change in binge episode used 
694 
was 1.6 binge episodes per week [45].  Furthermore, a mixed effects model design assuming a 
695 
compound symmetry covariance structure (congruent with the primary analytic plan) with a total 
696 
of 10 assessment points and an ICC parameter equal to 0.59 (this is the value that was used as the 
697 
auto correlation rho in PASS), estimated based on data collected from similar populations within 
698 
our Center for Weight and Eating Disorders [46], i.e., reduction in nocturnal ingestions per week 
699 
among patients with night eating syndrome with an SSRI. There is often overlap between 
700 
persons with night eating syndrome and BED and we believe that the variance in improvements 
701 
from week to week in core symptoms of these disorders would be similar.  Based on these 
702 
estimates, a baseline sample size of 152 participants (76 per group) with a 15% attrition rate 
703 
(actual total n=132) will give 80% power to detect a clinically relevant mean difference in degree 
704 
of reduction in binge episodes of 1.6 per week (effect size: 0.39) to be significant at alpha = 0.05, 
705 
based on a two-sided test.  All secondary outcomes will be considered exploratory and evaluated 
706 
at the alpha=0.05 level. However, those exploratory analyses will provide valuable findings on 
707 
changes in weight and other clinically meaningful changes in eating disordered attitudes and 
708 
behaviors that have not been examined previously in relation to the use of liraglutide.  The power 
709 
analysis was conducted using the PASS software, Version 11 NCSS LLC, Kaysville, UT [47]. 
710 
 
711 
Statistical Methods 
712 
Preliminary and descriptive analyses. All data will first be assessed for missing and out-of-range 
713 
values with basic statistical procedures such as univariate statistics (means, confidence intervals, 
714 
standard deviations, ranges, frequencies, proportions, percentiles) and graphs such as histograms, 
715 
box and whisker plots, scatter plots and Q-Q plots. All questions of data quality will be 
716 
investigated and resolved before any statistical modelling, as complete and accurate data are 
717 
essential for unbiased estimates and confidence intervals.     
718 
 
719 
Baseline and demographic characteristics will be summarized overall for all subjects and by 
720 
treatment group.  Means and confidence intervals will be provided for continuous variables and 
721 
frequencies and percentages for categorical variables.  Graphical methods mentioned above will 
722 
be used to examine distributions and identify potential influential points. The balance of baseline 
723 
measures across the two treatment groups will be compared using appropriate 2-sample tests, 
724 
including Wilcoxon rank-sum and t-tests for continuous variables, and Fisher's exact and Pearson 
725 
Chi-square tests for categorical variables. Any baseline variables found to be associated with 
726 
treatment condition will be added to the outcome analysis as a covariate.   
727 


V 3 5.20.19 
21
 
728 
Primary analysis. The primary outcome is the degree of reduction in binge episodes per week.  
729 
It is count data that is likely to be skewed, so a shifted log transformation will be considered to 
730 
stabilize the distribution to better meet the normality assumptions. To address the primary aim 1, 
731 
a mixed effects model will be fit with Treatment Group (liraglutide 3.0 mg/d and placebo) as a 
732 
between subjects factor and Time (Weeks 1 through 17) as a categorical within-subjects factor. 
733 
Time is treated as a categorical factor so that we can use the group-time interactions with the 
734 
time main effect to estimate and test intention-to-treat (ITT) treatment group differences at each 
735 
time point, with the 17-week time point as our primary ITT test. In fitting a mixed effects model 
736 
with maximum likelihood, a variance-covariance structure must be selected.  We will begin by 
737 
assuming a compound symmetry structure, but also consider criteria such as the Akaike’s 
738 
Information Criterion (AIC) for selecting the best form of the variance-covariance structure 
739 
using Residual Maximum Likelihood (REML) (e.g., Compound Symmetry, Toeplitz, first-order 
740 
autoregressive, and unstructured). Furthermore, we will include as baseline covariates those 
741 
variables that have been established to be associated with the outcome based on prior literature, 
742 
including sex and age.  The results from the mixed model will be summarized by mean (SE) 
743 
change from baseline for each treatment group at each time point.   
744 
 
745 
Given the above definition of the ITT tests under the mixed effects model, the main interest in 
746 
this study is the to the test of the primary hypotheses that participants randomized to liraglutide 
747 
3.0 mg/d (N=76) will show superior improvements from baseline to treatment end (week 17) in 
748 
the number of binge episodes per week as compared to those on placebo (N=76).  The primary 
749 
hypothesis will be evaluated at the alpha = 0.05 level and all other contrasts and 
750 
secondary/tertiary outcomes/hypotheses will be considered exploratory and those results will be 
751 
interpreted with caution at alpha equal to 0.05 level. Analyses will be conducted using the 
752 
statistical software package, SAS for Windows (SAS Institute, Inc., Cary, NC) [48]. 
753 
 
754 
As a sensitivity analysis, we will alternatively use a negative binomial distribution to model the 
755 
rate of binge eating episodes per week (taking into account the trial duration for individual 
756 
subjects) and will count r as a number of binge eating episodes. The binge eating episodes per 
757 
week ratio will be compared between the liraglitude and placebo groups.   
758 
 
759 
Of note, the analysis plan for the primary outcome variable will remain the same, but the final 
760 
sample size will be 36 instead of 152.  
761 
 
762 
Analyses for Aim 2. To assess differences among the two conditions in the percentage of 
763 
participants who were in remission (2 binary outcomes), generalized estimating equation (GEE) 
764 
models will be fit with the same between group, within group, and interaction terms as presented 
765 
above, as well as, any relevant baseline covariates. A binomial distribution will be specified 
766 
using a logit link function, and the unstructured covariance matrix will be considered to adjust 
767 
for the within subject clustering of repeated measures data. From the GEE models, odds ratios 
768 
and 95% confidence intervals will be computed to compare the treatment groups at each time 
769 
point. 
770 
 
771 
Of note, this analysis will also be completed as proposed with the reduced sample. 
772 


V 3 5.20.19 
22
Analyses for Aim 3. The mixed effects model approach described for the primary analysis will 
773 
also be utilized to compare changes in body weight, global BED symptom improvement, 
774 
cognitive restraint of food intake, dietary disinhibition, perceived hunger, quality of life, and 
775 
depressed mood between treatment groups. Changes in these outcomes will also be summarized 
776 
by mean(SE) for each treatment group at each time point.  If violations in the normality 
777 
assumption are observed, log transformations, as well as alternative distributions such as Poisson 
778 
and Negative binomial will be considered.  
779 
 
780 
Of note, cognitive restraint, disinhibition, and hunger will only be available for completers, so it 
781 
is unlikely that this model can be run for these variables. The other variables in this aim were 
782 
administered at each visit and can be included in the proposed models.  
783 
 
784 
Safety analysis. Given the modest sample size, we will not perform safety analysis. Instead, 
785 
safety labs will be reviewed on an individual basis with participants to assure that they are within 
786 
normal limits, and these will be available in summary for publications/presentations.  The details 
787 
for reporting SAEs to the IRB and procedures for taking action to safeguard participants are 
788 
described in the safety monitoring plan. 
789 
 
790 
Missing data and statistical models. Every effort will be made to obtain follow-up data on all 
791 
participants randomized. Based on prior studies that we have conducted, the dropout rate by 17 
792 
weeks could be as high as 15%. Our maximum likelihood approach assumes that any missing 
793 
outcome data are missing at random (i.e., missing data, including those due to drop-out, but not 
794 
dependent on any previously observed outcomes or treatment assignment). With this approach, 
795 
we will use all data that have been collected, without regard to whether data are missing for a 
796 
participant at another visit, including drop-out, and without explicit imputation of missing data.  
797 
We will conduct sensitivity analyses to examine the impact of missing data.  Details regarding 
798 
the sensitivity analyses will be pre-specified prior to unblinding.  Furthermore, we will assess 
799 
whether dropout status or level of compliance is associated with treatment condition as well as 
800 
baseline demographic variables using appropriate 2-sample tests, including Wilcoxon rank-sum 
801 
and t-tests for continuous variables, and Fisher's exact and Pearson Chi-square tests for 
802 
categorical variables, and all findings will be reported.  
803 
 
804 
Change in frequency of binge episodes per week also will be analyzed using a per protocol 
805 
analysis that, for liraglutide-treated participants, includes only those who were able to tolerate 
806 
and adhered to the full dose of liraglutide 3.0 mg. 
807 
 
808 
Interim Analysis 
809 
No interim analyses are planned (in order to maintain full power for the end-of-study 
810 
comparisons). 
811 
 
812 
Explorative Statistical Analysis for Pharmacogenetics and Biomarkers 
813 
No explorative statistical analysis for pharmacogenetics and biomarkers will be performed. 
814 
 
815 
5.20.19 Of note, due to unforeseen low response to advertising and the mis-allocation of 
816 
medication by our Investigational Drug Service, our number or participants with usable data is 
817 
low. We are unable to continue to staff and run the study at this point. 
818 


V 3 5.20.19 
23
Of the 21 participants enrolled in the first year, 5 participants were non-completers who 
819 
were not affected by the IDS mis-allocation, 1 was a completer and was not affected by the 
820 
misallocation, 9 received only one box of the same type of medication before being switched to 
821 
the opposite (e.g., liraglutide to placebo or vice versa) and were censored, 4 received two boxes 
822 
of the same medication or placebo consecutively and were retained, and 2 received three boxes 
823 
of the same medication or placebo consecutively and were retained. Thus, this first year yielded 
824 
1 completer and 11 censored or drop-out participants. In the current year we randomized 16 
825 
participants, but one was censored without usable data given she had concealed that she was 
826 
taking metformin, leaving 15 participants with usable data.  Of these, 1 was lost to follow-up, 4 
827 
have completed the trial, and 10 are currently still active in the trial.  In sum, we will include 36 
828 
participants in the proposed analyses.  
829 
 
830 
DATA HANDLING AND RECORD KEEPING: 
831 
Information about study subjects will be kept confidential and managed according to the 
832 
requirements of the Health Insurance Portability and Accountability Act of 1996 (HIPAA).  
833 
Those regulations require a signed subject authorization informing the subject of the following:  
834 
 Protected health information (PHI) collected from subjects in this study 
835 
 Who will have access to that information and why 
836 
 Who will use or disclose that information 
837 
 The rights of research subjects to revoke their authorization for use of their PHI 
838 
 View of PHI will be limited to individuals at the University of Pennsylvania directly 
839 
involved in the study. The company donating the study product will not have access to 
840 
PHI.  
841 
 
842 
All electronic PHI will be maintained by using an institutionally secured and managed network 
843 
drive, institutionally secured and managed devices, and institutionally approved third-party 
844 
computing environments.  Should PHI need to be transferred, it will be done so through the use 
845 
of a Penn-approved encrypted portable drive or a Penn-approved secure encrypted file transfer 
846 
solution. 
847 
 
848 
In the event that a subject revokes authorization to collect or use PHI, the investigator, by 
849 
regulation, retains the ability to use all information collected prior to the revocation of subject 
850 
authorization. For subjects who have revoked authorization to collect or use PHI, attempts will 
851 
be made to obtain permission to collect at least vital status (i.e. that the subject is alive) at the 
852 
end of their scheduled study period. 
853 
 
854 
Where possible, data will be entered directly into our password protected database, REDCap. All 
855 
data pertaining to the study will be saved on the Center for Weight and Eating Disorders’ 
856 
password-protected server.  Paper copies of informed consent, questionnaires, interviews, lab 
857 
results, and any correspondence will be kept in the case record in locked offices.   
858 
 
859 
ETHICS: 
860 
The principal investigator (PI) will initiate and enroll subjects only after receiving IRB approval 
861 
of the protocol and the informed consent documents. All recruiting materials used in the study 
862 


V 3 5.20.19 
24
will have IRB approval. Progress reports regarding the study will be submitted to the IRB in 
863 
accordance with institutional and regulatory guidelines.  
864 
 
865 
The study will be performed in compliance with the FDA Code of Federal Regulations for Good 
866 
Clinical Practice (GCP). These procedures ensure the protection of the rights and the integrity of 
867 
the subjects, adequate and correct conduct of all study procedures, adequate data collection, 
868 
adequate documentation, and adequate data verification.  
869 
 
870 
Before being enrolled, subjects will be provided informed consent. The nature, scope, and 
871 
possible consequences of the study will have been explained in a form understandable to them. A 
872 
copy of the consent document will be given to the subject. The PI will retain the original signed 
873 
consent document.   
874 
 
875 
Subject confidentiality will be maintained throughout the study according to applicable 
876 
guidelines, regulations and IRB requirements. All laboratory samples, study clinical data, and 
877 
reports of results will de-identify individual subjects. Subjects will be identified by initials, date 
878 
of birth, gender and subject number only for use in data collection. Published data will provide 
879 
subject numbers only if needed for clarity of presentation (e.g., in individual event listings).  
880 
 
881 
The study will be conducted in accordance with the Declaration of Helsinki. The study will be 
882 
conducted in accordance with the ICH GCP guidelines. The sponsor-investigator will comply 
883 
with all applicable regulatory and legal requirements, ICH GCP guidelines, and the Declaration 
884 
of Helsinki in obtaining and documenting the informed consent. 
885 
 
886 
STUDY SCHEDULE: 
887 
Table 3. Study Schedule (quarterly) 
888 
 
2017 
 
2018 
 
 
 
2019 
 
 
 
2020 
 
 
 
Study start, IRB approval  
6/1 
 
 
 
 
 
 
 
 
 
 
 
 
 
Recruitment 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
First subject screening visit 
 
7/1 
 
 
 
 
 
 
 
 
 
 
 
 
Enrollment/randomization 
 
4-5 subjects/month 
 
 
 
 
 
 
 
 
 
Last subject first visit 
 
 
 
 
 
 
 
 
 
 
12/1 
 
 
 
Data collection 
 
7/1 
 
 
 
 
 
 
 
 
 
 
4/1 
 
Data analysis/manuscripts 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Final study reports 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
889 
STUDY DRUGS AND MATERIALS: 
890 
Study medication(s) / devices(s) 
891 
Subjects assigned to liraglutide (Saxenda) or placebo will need 119 doses (5 pens). Subjects will 
892 
be provided with a 30-day supply of medication or placebo (1 pen) on 5 occasions (380 of each). 
893 
We will assign 76 subjects to liraglutide and 76 subjects to placebo.  
894 
Of note, we will complete the study with 36 participants total.  
895 
 
896 
Liraglutide (Saxenda) and placebo will be initiated at 0.6 mg subcutaneously, daily for 1 week, 
897 
and increase by 0.6 mg/day in weekly intervals until a dose of 3 mg/day is achieved. The pen 
898 
delivers doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg, or 3 mg (6 mg/mL, 3mL). 
899 


V 3 5.20.19 
25
 
900 
Packaging and Labelling of Study Medication(s) 
901 
Novo Nordisk’s Clinical Supplies (CS) will deliver study drugs (both Saxenda and placebo), as 
902 
ready-to-use, pre-filled, multi-dose pens.  Clinical Services will complete the labelling and 
903 
packaging of the pens, and ship the labelled study drugs to the Investigational Drug Service 
904 
(IDS) at the University of Pennsylvania (attention Dr. Ken Rockwell). The labels will have all 
905 
information required by US Health Authorities.  
906 
 
907 
CS will use a Dispensing Unit Number (DUN) on the label, which will be linked to the 
908 
randomization scheme (created at IDS at Penn). “Instructions for Use” will not be inside the 
909 
study drug box, but will be provided by CS as a print page that will be included in the first drug 
910 
shipment to site. 
911 
 
912 
Storage and Drug Accountability of Study Medication(s) 
913 
The medication will be refrigerated (36-46°F) (the temperature will be checked daily.) After first 
914 
use, the subject may store the medication at room temperature (59-86°F) or refrigerate (36-46°F). 
915 
The injection pen expires 30 days after first use. The sponsor-investigator will ensure the 
916 
availability of proper storage conditions and record and evaluate the temperature. No trial 
917 
medication(s) will be dispensed to any person not enrolled in the study. Unused medication(s) 
918 
will be stored separately from used trial medication(s). Subjects will be instructed to inspect the 
919 
medication visually for particulate matter and discoloration prior to administration.  
920 
 
921 
We will maintain adequate drug inventory and security at all times. Upon receipt of the study 
922 
drug, the Investigational Drug Service at Penn will perform an inventory of the shipment, 
923 
comparing the shipment inventory to actual study drug received, and complete and sign an 
924 
inventory log. The study investigators will immediately notify Novo Nordisk (or its designee) or 
925 
the drug distribution contractor of any damaged or unusable study drug that the center receives, 
926 
and document in the inventory log any damaged or unusable study drug. We will request that 
927 
additional study drug be shipped as needed.  
928 
 
929 
The drug supplies will be kept in a secured enclosure with limited access, both at the 
930 
Investigational Drug Service where the medication is received, and at the Center for Weight and 
931 
Eating Disorders, where it will be dispensed to subjects. The investigator will take appropriate 
932 
precautions to prevent theft or diversion of the study drug. 
933 
 
934 
At the conclusion of the study, a final inventory of study drug shipped to the Investigational 
935 
Drug Service, dispensed, and remaining at the Center for Weight and Eating Disorders will be 
936 
performed by the investigator. This reconciliation will be entered on the drug accountability log. 
937 
The investigator will return all unused drug to Novo Nordisk or its designee, unless alternative 
938 
arrangements for drug disposal are authorized. No study drug will be retained when the study is 
939 
completed; all study drugs will be returned to Novo Nordisk or its designee for destruction.  
940 
 
941 
Auxiliary Supply 
942 
No auxiliary supplies are planned. 
943 
 
944 
Randomization and Blinding 
945 


V 3 5.20.19 
26
Dr. Ken Rockwell from Penn’s Investigational Drug Service will generate the randomization 
946 
code. The randomization will be generated using a 1:1 randomization scheme of liraglutide or 
947 
placebo. The first subject to meet the treatment criteria will be assigned the first number in the 
948 
sequence; each subsequent subject to meet treatment criteria will be assigned the next number in 
949 
the sequence. This is a randomized, double-blind, placebo-controlled trial with a parallel groups 
950 
design.  
951 
 
952 
Breaking of Blinded Codes 
953 
Unblinding of the treatment codes will occur after all data have been verified and deemed clean 
954 
by the data managers and statistician, and right before analysis of the data occurs. 
955 
The code for a particular subject may be broken in a medical emergency if knowing the identity 
956 
of the treatment allocation would influence the treatment of the subject or if demanded by the 
957 
subject. Whenever a code is broken, the staff-member breaking the code will record the time, 
958 
date and reason as well as his/her initials in the source documents. All codes (whether broken or 
959 
not) will be kept throughout the trial period. Accountability of all broken or unbroken codes 
960 
(hard copy or electronic) will be performed at or after trial closure. 
961 
 
962 
CONCOMITANT ILLNESSES AND MEDICATIONS: 
963 
Definitions: 
964 
At trial entry (i.e., the screening visit), we will record details of any concomitant illness (i.e., any 
965 
illness that is present at the start of the trial) that is present and concomitant medication (i.e., any 
966 
medication other than the trial product(s) that is taken during the trial, including the screening 
967 
and run-in periods) in each subject’s record. The information collected for each concomitant 
968 
medication will include the start date, stop date or continuing, and indication. For each 
969 
concomitant illness, we will record the date of onset, date of resolution or continuing. Any 
970 
changes in concomitant medication use will be recorded at each visit. If the change influences 
971 
the subject’s eligibility to continue in the trial, the Sponsor will be informed. 
972 
 
973 
ADERSE EVENTS: 
974 
At each contact with subjects, study personnel will be responsive to reports of adverse events 
975 
with specific questioning and, as outlined in the procedures section, by physical examination.  
976 
The investigator will report all adverse events including serious adverse events (SAE), suspected 
977 
unexpected serious adverse reactions (SUSARs), serious adverse drug reactions (SADRs) (as 
978 
defined below) to the Data Safety and Monitoring Board established for the trial, and to the Penn 
979 
IRB. Information on all adverse events will be recorded immediately in the source document and 
980 
reported immediately, and also in the appropriate adverse event module of the case report form 
981 
(CRF). Information on study name, subject identification, event (i.e., diagnosis), drug, and 
982 
reporter identification (e.g., name) will be collected and recorded in the source document (as 
983 
detailed below). All serious adverse events will be reported to the IRB within 24 hours. The 
984 
investigator will report to Novo Nordisk all SAEs, SUSARs, and SADRs at the same time such 
985 
events are reported to regulatory authorities or within 15 days from the investigator becoming 
986 
aware of such adverse events, whichever comes first.  
987 
 
988 


V 3 5.20.19 
27
The PI and her investigative team acknowledge the definitions of the adverse events (AEs), 
989 
serious adverse events (SAEs), and other untoward occurrences as spelled out below. 
990 
 
991 
Definitions 
992 
 
993 
Adverse Event (AE): 
994 
An AE is any undesirable medical event occurring to a subject in a clinical trial, whether or not 
995 
related to the trial product(s). This includes events reported from the first trial-related activity 
996 
after the subject has signed the informed consent and until post-treatment follow-up period, as 
997 
defined in the protocol. 
998 
 
999 
Clinical Laboratory Adverse Event: 
1000 
A clinical laboratory AE is any clinical laboratory abnormality regarded as clinically significant 
1001 
i.e. an abnormality that suggests a disease and/or organ toxicity and is of a severity that requires 
1002 
active management, (i.e. change of dose, discontinuation of trial product, more frequent follow-
1003 
up or diagnostic investigation). 
1004 
 
1005 
Serious Adverse Event (SAE): 
1006 
A serious AE is an experience that at any dose results in any of the following: 
1007 
• Death 
1008 
• A life-threatening* experience 
1009 
• In-patient hospitalization or prolongation of existing hospitalization 
1010 
• A persistent or significant disability/incapacity 
1011 
• A congenital anomaly/birth defect 
1012 
• Important medical events that may not result in death, be life-threatening*, or require 
1013 
  hospitalization may be considered an SAE when, based upon appropriate medical judgement, 
1014 
they may jeopardise the subject and may require medical or surgical intervention to prevent 
1015 
one of the outcomes listed in this definition 
1016 
*The term life-threatening in the definition of SAE refers to an event in which the subject was at risk of death at the 
1017 
time of the event. It does not refer to an event which hypothetically might have caused death if it was more severe. 
1018 
 
1019 
Serious Adverse Drug Reaction (SADR):  
1020 
An adverse drug reaction (ADR) is an adverse event for which a causal relationship 
1021 
(Possible/Probable relation) between the study drug and the occurrence of the event is suspected. 
1022 
The ADR should be classified as serious if it meets one or more of the seriousness criteria.  
1023 
SUSAR (Suspected Unexpected Serious Adverse Reaction) 
1024 
An SAE which is unexpected and regarded as possibly or probably related to the trial/study 
1025 
product by the sponsor-investigator, Dr. Allison. 
1026 
 
1027 
Medical Events of Special Interest (MESI): A MESI is (1) a medication error (e.g. wrong drug 
1028 
administration or wrong route of administration) or (2) a suspected transmission of an infectious 
1029 
agent via the product 
1030 
 
1031 
Non-Serious Adverse Event: 
1032 
A non-serious AE is any AE which does not fulfil the definition of an SAE. 
1033 
 
1034 
Severity Assessment Definitions: 
1035 


V 3 5.20.19 
28
• Mild: Transient symptoms, no interference with the subject’s daily activities 
1036 
• Moderate: Marked symptoms, moderate interference with the subject’s daily activities 
1037 
• Severe: Considerable interference with the subject’s daily activities, unacceptable 
1038 
 
1039 
Relationship to study medication Assessment Definitions: 
1040 
• Probable: Good reasons and sufficient documentation to assume a causal relationship 
1041 
• Possible: A causal relationship is conceivable and cannot be dismissed 
1042 
• Unlikely: The event is most likely related to an etiology other than the trial product 
1043 
The PI (Dr. Allison) will evaluate all unexpected events and adverse reactions. 
1044 
 
1045 
Outcome Categories and Definitions: 
1046 
• Recovered: Fully recovered or by medical or surgical treatment the condition has returned to 
1047 
the level observed at the first trial related activity after the subject signed the informed consent 
1048 
• Recovering: The condition is improving and the subject is expected to recover from the event. 
1049 
This term should only be used when the subject has completed the trial 
1050 
• Recovered with sequelae: As a result of the AE, the subject suffered persistent and     
1051 
significant disability/incapacity (e.g. became blind, deaf, paralysed). Any AE recovered with 
1052 
sequelae should be rated as an SAE 
1053 
• Not recovered 
1054 
• Fatal 
1055 
• Unknown 
1056 
 
1057 
Collection, Recording and Reporting of Adverse Events 
1058 
All events meeting the definition of an adverse event will be collected and reported from the first 
1059 
trial related activity after the subject has signed the informed consent and until the end of the 
1060 
post-treatment follow-up period as stated in the protocol.  
1061 
At a minimum the following information will be reported: 
1062 
 Study name 
1063 
 Patient identification (e.g. subject number, initials, sex, age) 
1064 
 Event (Preferably diagnosis) 
1065 
 Trial drug 
1066 
 Reporter 
1067 
 Causality 
1068 
 Outcome 
1069 
 
1070 
Follow-up of Adverse Events 
1071 
During and following subjects’ participation in the study, the sponsor-investigator, Dr. Allison, 
1072 
and institution will provide adequate medical care to the study subject for any study-related 
1073 
adverse events, including clinically significant laboratory values related to the study. (Note: This 
1074 
section of the protocol will be written in consultation with Penn’s IRB, Office of Research 
1075 
Services, and Office of Legal Affairs. It will be addressed pending approval of the scientific 
1076 
aspects of the study.) 
1077 
 
1078 
Pregnancy 
1079 
Study subjects will be instructed to notify the sponsor-investigator, Dr. Allison, immediately if 
1080 
they become pregnant, discontinue the study drug, and consult an obstetrician or maternal-fetal 
1081 


V 3 5.20.19 
29
medicine specialist. The study physician or nurse practitioner will confirm via self-report that the 
1082 
participant is consulting with an obstetrician or maternal-fetal medicine specialist, record all 
1083 
complications, and obtain information regarding the overall health of the mother and baby once 
1084 
per trimester and post-delivery.  The investigator will report to Novo Nordisk any pregnancy 
1085 
occurring during the trial period. Reporting of pregnancy by the investigator will occur within 
1086 
the same timelines described above for reporting of Adverse Events. Pregnancy complications 
1087 
will be recorded as an adverse event(s). If the infant has a congenital anomaly/birth defect this 
1088 
will be reported and followed up as a serious adverse event. 
1089 
 
1090 
Precautions/Over-dosage 
1091 
In case of suspected overdose, subjects will be instructed to call their healthcare provider 
1092 
immediately, as excessive intake of Saxenda may cause severe nausea and vomiting.  
1093 
 
1094 
LIABILITY AND SUBJECT INSURANCE: 
1095 
During and following a subject’s participation in trial, Dr. Allison and Penn Medicine will 
1096 
provide adequate medical care to the study subject for any study-related adverse events, 
1097 
including clinically significant laboratory values related to the study. This medical care for study 
1098 
subjects will be provided regardless of their insurance status. 
1099 
 
1100 
Dr. Allison will be responsible for the conduct of the study and agrees to defend, indemnify, and 
1101 
hold harmless Novo Nordisk, any of its parent companies, affiliates, or subsidiaries, and their 
1102 
respective officers, directors, employees, agents, representatives, distributors, salespersons, 
1103 
customers, licensees, and end-users from and against any claim, suit, demand, loss, damage, 
1104 
expense or liability imposed by any third party arising from or related to: (a) any breach of 
1105 
sponsor-investigator's obligations or representations; or (b) sponsor-investigator’s negligent or 
1106 
grossly negligent use or willful misuse of the study drug, the results, or services derived 
1107 
therefrom.  This indemnification shall not apply in the event and to the extent that a court of 
1108 
competent jurisdiction or a duly appointed arbiter determines that such losses or liability arose as 
1109 
a result of Novo Nordisk’s gross negligence, intentional misconduct, or material breach of its 
1110 
responsibilities. 
1111 
 
1112 
EVALUABILITY OF SUBJECTS: 
1113 
Subjects will be excluded from data analysis in the event of pregnancy, amputation, bariatric 
1114 
surgery, or death.  Additional criteria associated with subject censorship will be considered prior 
1115 
to initiating recruitment.  Any censorship will be documented in case records and appropriately 
1116 
reported. 
1117 
 
1118 
PK and/or PD Modelling 
1119 
No PK/PD modelling is planned in this trial. 
1120 
 
1121 
PREMATURE TERMINATION OF STUDY: 
1122 
We believe that it is highly unlikely that the study will be terminated prematurely, given the 
1123 
safety of the intervention and its expected effects. Termination would be considered, however, in 
1124 
view of: 
1125 


V 3 5.20.19 
30
 Unacceptable safety concerns of the study medication 
1126 
 The benefits observed do not ethically permit the trial to continue 
1127 
 
1128 
Of note, we have stopped recruitment and will terminate the study after the last enrolled 
1129 
participants completes study visits (anticipated at the beginning of September, 2019). This was 
1130 
due to low yield from recruitment efforts as well as the misallocation of drug and placebo by IDS 
1131 
affected the number of participants with usable data.  
1132 
 
1133 
PUBLICATION PLAN: 
1134 
We will register the study with a publicly assessable database, e.g., clinicaltrials.gov.  
1135 
An initial report of the findings will be presented at an annual scientific meeting (e.g., The 
1136 
Obesity Society’s Obesity Week and/or The Academy for Eating Disorders’ International 
1137 
Conference on Eating Disorders). We plan to publish the study results approximately 6 months 
1138 
after study completion.  
1139 
 
1140 
The report of the primary outcome will be submitted to International Journal of Eating Disorders.  
1141 
If not accepted, we would submit it next to the Journal of Eating and Weight Disorders. A 
1142 
secondary paper likely will be submitted regarding the clinical significance of the size of binge 
1143 
eating as compared to the degree of loss of control in relation to the current diagnostic criteria for 
1144 
BED to the International Journal of Eating Disorders or Frontiers in Eating Behavior.  
1145 
 
1146 
REFERENCES: 
1147 
1. Stunkard AJ.  Eating patterns and obesity.  Psychiatr Q. 1959; 33:284-94. 
1148 
2. Spitzer RL, Yanovski S, Wadden T, Wing R, Marcus MD, Stunkard A, Devlin M, Mitchell J, 
1149 
Hasin D, Horne RL. Binge eating disorder: its further validation in a multisite study. Int J Eat 
1150 
Disord. 1993;13:137-53. 
1151 
3. Javaras KN, Pope HG, Lalonde JK et al. Co-occurrence of binge eating disorder with 
1152 
psychiatric and medical disorders. J Clin Psychiatry 2008;69:266-73. 
1153 
4. Grilo, C. M., White, M. A., Masheb, R. M. DSM-IV psychiatric disorder comorbidity and its 
1154 
correlates in binge eating disorder. Int J Eat Disord. 2009;42:228-234. 
1155 
5. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 
1156 
Fifth Edition. American Psychiatric Association, 2013. 
1157 
6. Hudson JI, Hiripi E, Pope HG Jr, Kessler RC.  The prevalence and correlates of eating 
1158 
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ICF_001.pdf: 
Current/Last Informed Consent Form 4.9.2019 
 
Protocol Title: A Randomized Controlled Trial of Liraglutide 3.0 mg/d for Binge Eating 
Disorder 
 
Principal Investigator: 
Kelly C. Allison, Ph.D.


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University of Pennsylvania 
Research Subject Informed Consent and HIPAA Authorization Form 
 
Protocol Title: A Randomized Controlled Trial of Liraglutide 3.0 mg/d for Binge Eating 
Disorder 
 
Principal Investigator: 
Kelly C. Allison, Ph.D. 
 
Co-investigators: 
Robert Berkowitz, M.D. 
Thomas A. Wadden, Ph.D. 
 
University of Pennsylvania School of Medicine 
Center for Weight and Eating Disorders 
3535 Market Street, 3rd Floor 
Philadelphia, PA 19104 
215-898-7314 
 
Principal Investigator Contact Information: 
 
Kelly C. Allison, Ph.D. 
215-898-2823 
24-Hour Emergency #: 
215-662-6059 
Ask for the Psychiatric Resident on call 
Why am I being asked to volunteer? 
You are being invited to participate in the 20-week research study because you have indicated 
that you are interested in reducing your binge episodes and potentially are agreeable to using a 
medication. The medication is currently FDA-approved for weight loss, but not BED, which is 
why we are testing it in this study. You may choose not to participate in the study at any time. 
All participants will be provided with one of the two interventions which will be administered in 
the form of an injection, either liraglutide 3.0mg/day (Saxenda®) or a placebo. A placebo is an 
inactive substance (has no medical effect) that looks like the study drug, but contains no 
medication. This consent form discusses the two interventions in detail. Your participation is 
voluntary, which means you can choose whether or not you want to participate. If you choose not 
to participate, there will be no loss of benefits to which you are otherwise entitled. Before you 
can make your decision, you will need to know what the study is about, the possible risks and 
benefits of participating in the study, and what will be required of you during the study. The 
research team is going to talk with you about the study, and a staff member will give you this 
consent form to read. You may wish to discuss it with your family, friends, or primary care 
provider. You may find some of the medical language difficult to understand. Please ask the 
study staff if you have any questions. If you decide to participate, you will be asked to sign this 
form. 


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What is liraglutide? 
Liraglutide 3.0 mg (Saxenda®) belongs to a class of medications called glucagon-like peptide-1 
(GLP-1) receptor agonists. When activated by liraglutide, the GLP-1 receptor stimulates the 
release of insulin into the bloodstream. Liraglutide is a once-daily self-administered, 
subcutaneous (beneath the skin) injection that evidence shows may reduce appetite and reduce 
the urge to engage in binge eating. Liraglutide is approved by the U.S. Food and Drug 
Administration (FDA) for chronic weight management and diabetes management when 
combined with a reduced-calorie diet and increased physical activity. The present study aims to 
examine the effectiveness of the drug in treating BED as compared to placebo. The placebo, as 
mentioned previously, is an inactive substance and is designed to look like the study drug, but 
contains no medication. The placebo’s ingredients include: disodium phosphate dihydrate, 1.42 
mg; propylene glycol, 14 mg; phenol, 5.5 mg; and water for injection. Please see below for more 
specific goals of the present study. 
 
What is the purpose of this research study? 
 
This study has several goals. They include examining the effectiveness of liraglutide 3.0mg/day 
as compared to placebo in reducing the number of binge episodes per week during a 17-week, 
randomized, placebo-controlled trial. The study will also examine the proportion of participants 
on liraglutide 3.0 mg/day as compared to placebo who achieve a change in binge episodes from 
the start of the study compared to week 17. Additionally, the study will compare differences 
between the liraglutide 3.0 mg/day and placebo groups in changes in body weight, global BED 
symptom improvement, and other eating and mood related measures at treatment end. 
Approximately one half of the participants will be randomly assigned to receive liraglutide and 
one half will be randomly assigned to receive the placebo. Researchers at the University of 
Pennsylvania do not know whether the use of liraglutide 3.0 mg/day will lead to fewer binge 
episodes per week. This study is designed to answer this question. 
 
How long will I be in the study? How many other people will be in the study? 
 
A total of 152 participants will be enrolled in this study, and the total duration of the study for 
each participant will be about 20 weeks (from initial assessment through the end of treatment). 
The entire study, with all participants, will be completed in about 3 years. 
 
What am I being asked to do? 
 
You are being asked to participate in this study because you have indicated that you are 
interested in reducing your binge episodes and potentially are agreeable to using liraglutide 3.0 
mg/day, which is an FDA-approved drug for weight loss, for the treatment of BED. 
 
Procedures 


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Screening Evaluation 
 
Behavioral screening visit. Persons who are interested in the study first will attend a behavioral 
screening visit. You will meet with a psychologist (or other qualified staff member) who will 
inform you about the study, review this consent form with you, and obtain your written informed 
consent. The study staff will assess your behavioral eligibility for the study, which includes 
evaluating your willingness to participate in the research procedures, as well as determining 
whether you meet the study criteria. The study staff will assess your BED symptoms, your 
mood, and possible psychiatric illness. With your permission, you may be asked to be audio 
recorded the administration of one of the interviews that assesses eating behaviors. The purpose 
of recording this section is to confirm reliability across interviewers and ensuring accurate 
diagnosis of binge episodes, when necessary. The recordings will be taken using recording 
devices and stored in a locked office. The recordings will be downloaded to a password 
protected and institutionally secured and managed network drive on University of Pennsylvania 
secured and managed computers. The recordings will be deleted from both the recorder and the 
network drive once study analysis has concluded. 
 
Medical screening visit. Following successful completion of the behavioral assessment, you 
will: 
 Undergo a complete medical history and physical examination. 
 Your height, weight, blood pressure, pulse, and waist circumference will be measured. 
 You will have an electrocardiogram (EKG) to assess your heart functioning. 
 Several blood tests will be performed and approximately 1 tablespoon of blood will be 
collected. 
 For women of childbearing potential, a urine pregnancy test also will be performed. 
 
These labs will also be repeated at week 17 (treatment end). Results of these tests and 
evaluations will be reviewed by the study’s physician to determine whether you have any 
contraindications to the treatment or to the use of liraglutide. Those who have recently 
used any other investigational drug and those who have previously participated in this 
trial will be ineligible to participate in the study. You will be referred to seek medical 
attention if the tests reveal any health concerns that require attention. 
 
In order to participate in this study, you must have a primary care provider (PCP) who is 
responsible for providing routine medical care. If you do not have a PCP, you may ask the study 
team to provide you with a referral. You will not, however, be eligible to participate in the study 
until you have met with your new PCP. 
 
Run-In Period 
Upon successful completion of the screening visit, you will be asked to not change anything and 
eat normally for 2 weeks. Once per week over the next two weeks you will receive a brief 
survey to assess your binge eating episodes over the past week. If you do not have internet 
access, study staff will ask you these questions over the phone. You will be trained at the 
screening visit on general guidelines for the definition of a binge episode. 


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Randomization Visit 
 
After the 2 week run-in period, the principal investigator will review all materials and further 
assess eligibility criteria based on the information gathered up to this point. If you meet all 
eligibility criteria assessed at the screening visit and during the 2 week run-in period, you will be 
scheduled for a randomization screening visit. If the criteria are not met, your participation 
would end at this point. 
 
At the randomization visit, your weight, blood pressure, and pulse will be measured. You will 
then be randomly assigned by chance to one of the two intervention groups (i.e., liraglutide 3.0 
mg/day or placebo). You will not be able to choose the group that you prefer (if you have a 
preference), and you must be willing to participate in either of the two groups to which you are 
randomly assigned. If you are not willing to participate in either of the two groups, then this 
research study is not appropriate for you, and you should not proceed to give your informed 
consent. The study team will provide other recommendations for treating BED. 
 
Because the study is double-blind, this means that neither you, Dr. Allison, the study physician, 
or the study staff are aware of what condition you will have been randomized to. A 
randomization code will be created by Penn’s Investigational Drug Service (IDS). At the 
conclusion of the study, the randomization code will be opened and the conditions of each 
participant will be revealed. In the case of a medical emergency, the code may be broken if the 
identity of the treatment would influence your treatment. You are not permitted to participate in 
any other treatments for BED, including medications or psychotherapy, while you are 
participating in this study. 
 
 
During this first treatment visit, you will have a medical visit with the study physician who will 
instruct you in the use of the medication. You will be provided with the first month’s supply of 
medication or placebo, which will be provided as pre-filled, disposable, personal injectors. 
 
Ongoing Medical and Safety Measures 
 
After randomization, you will return at week 1 to assess your eating and any other effects of the 
medication. You will return for study visits every two weeks thereafter, at weeks 3, 5, 7, 9, 11, 
13, 15, and 17. At these visits, there will be brief (5-10 minutes) medical visits with a physician 
or nurse practitioner (total of 9 visits). Weight and vital signs (blood pressure and pulse) will be 
measured at each of the visits. At each medical visit, your response to the treatment will be 
assessed. You will be asked whether there has been any change in your health or medications. 
 
At these visits, you will also meet with the study staff to assess binge eating episodes and will be 
asked about your mood or any thoughts of harming yourself, as assessed by clinical interviews 
and questionnaires. You will be referred to your PCP if your mood significantly disrupts your 
normal function (as reflected by symptoms that include feeling blue, not enjoying usual 
activities, trouble sleeping or concentrating, or having thoughts of dying or harming oneself). In 
the event of reports of suicidal ideation or disturbances in mood, you will be referred to the 
study’s psychologist or psychiatrist for further evaluation, as appropriate. You will be referred to 


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your own PCP for all non-study-related medical events and asked to follow up with the study 
team with any medical events. You will be asked to report all study-related medical events to the 
study staff who will closely monitor them. 
 
Outcome Assessment Measures 
 
Study visits will assess the primary and secondary outcome measures used to judge the 
effectiveness of the treatments for BED. 
 
Binge episodes. Reported binge episodes will be assessed by an interviewer-based 
questionnaire to measure the change in binge episodes per week from week 0 (randomization) to 
week 17. With your consent, you may be audio recorded during this portion of the study for the 
purpose of confirming reliability across interviewers and ensuring accurate diagnosis of binge 
episodes, when necessary 
 
Questionnaires. You will be asked to complete several questionnaires at each of the 
assessment visits. These questionnaires are designed to assess your mood, quality of life, hunger, 
and attitudes towards food. You will have the opportunity to examine the questionnaires before 
you complete them. Your answers to these questionnaires will provide data for the secondary 
outcomes. 
 
Blood tests. You will undergo fasting blood tests at your screening visit and week 17, as 
described previously. Approximately 1 tablespoon (i.e., 15 ml) of blood will be needed at these 
two visits. The results of these assessments will be used by the study physician to monitor your 
health, in addition to providing research data. 
 
Vital signs and weight measurement. Vital signs, such as blood pressure and pulse, and 
weight will be measured at each of the study visits to monitor your health, in addition to 
providing research data. 
 
What are the possible risks or discomforts? 
 
Risks of the 17-Week Treatment – Liraglutide 3.0mg/d or Placebo 
 
Blood draw. Risks of drawing blood include pain or discomfort, bruising at the puncture 
site, swelling, feeling faint or lightheaded, and rarely infection. 
 
Subcutaneous Injection. Risks of subcutaneous injection of the study medication 
include pain or discomfort, bruising at the puncture site, swelling, feeling faint or lightheaded, 
and rarely infection. 
 
 
Risks of Liraglutide 
 
All drugs carry some risk of side effects. In order to prevent harm, you must inform the study 
team if you experience any side effects from the study medication. 


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In several clinical trials of at least 1-year duration, the following side effects were reported in 
greater than 5% of persons taking liraglutide and more frequently than in placebo-treated 
patients: 
 
 Nausea 
 Low blood sugar 
 diarrhea 
 constipation 
 vomiting 
 increased lipase (an indicator of liver and pancreas abnormalities) 
 abdominal pain 
 indigestion 
 headache 
 dizziness 
 decreased appetite 
 fatigue 
 
 
Adverse reactions reported in greater than or equal to 2% of liraglutide-treated patients and more 
frequently than in placebo-treated patients included: 
 
 
 
 gastroesophageal reflux disease 
 bloating 
 belching 
 flatulence 
 hypoglycemia 
 dry mouth 

 injection site erythema (redness) 
 injection site reaction 
 asthenia (weakness) 
 gastroenteritis (stomach flu) 
 urinary tract infection 
 insomnia 
 anxiety 
 
 
 
 
Liver enzyme elevation. Blood test abnormalities that have been reported with the use of 
liraglutide include increases in alanine amino transferase (ALT), a liver enzyme. During this 
study, you will have your blood tested regularly to monitor for any changes. 
 
Thyroid C-Cell Tumors. Liraglutide causes both cancerous and non-cancerous thyroid C- 
cell tumors in mice and rats; the relevance of this finding to humans has not been determined. 
Persons with a personal or family history of thyroid tumors are not eligible for this study. If you 
experience any signs or symptoms of thyroid tumors (e.g., a lump in the neck, hoarseness, 
difficulty swallowing, or shortness of breath) you should contact your primary care provider 
(PCP) or the study staff. 


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Acute pancreatitis. Acute pancreatitis (inflammation of the pancreas) has been observed in 
patients treated with liraglutide. Contact your PCP or the study staff if you experience severe 
pain in your stomach area (abdomen) that is persistent. 
 
Acute gallbladder disease. Gallbladder problems, including gallstones, have been reported 
in patients taking liraglutide. Contact your PCP or the study staff if you experience pain in your 
stomach area (abdomen), fever, yellowing of your skin and eyes (jaundice), or clay-colored 
stools. 
 
Increased heart rate. Liraglutide may increase heart rate. During this study, you will have 
your heart rate measured regularly to monitor for any changes. 
 
Kidney impairment. In patients treated with GLP-1 receptor agonists, including liraglutide, 
there have been reports of acute kidney failure and worsening chronic kidney (renal) failure, 
sometimes requiring dialysis. Persons with clinically significant kidney disease are not eligible 
for this study. During this study, you will have your blood tested regularly to monitor for any 
changes in kidney function. 
 
Suicidal behavior and ideation. Suicidal behavior and thoughts were reported in liraglutide- 
treated patients. Persons who are at risk for suicide attempts or those with active suicidal 
thoughts should not take liraglutide. (That is why study staff will ask you questions about these 
issues at your screening visit.) Your mood will be assessed throughout the program. If you 
experience a change in mood, or have thoughts of harming yourself, you should contact your 
primary care provider and the study staff. 
 
Unforeseen risks. People may have allergic reactions to medications. A severe allergic 
reaction could be life-threatening. Examples of an allergic reaction include rash, difficulty 
breathing, wheezing, sudden drop in blood pressure, fast pulse, sweating, and swelling around 
the mouth, throat, or eyes. There may be other risks associated with liraglutide that have not been 
identified. If additional risks are identified during the study, you will be informed of them by the 
study team. 
 
Reproductive risks. The use of liraglutide may pose risks to pregnancy and/or an unborn 
baby. Therefore, you should not become pregnant while you are in the study. If you are able to 
become pregnant, you will be required to follow a study-approved method of birth control while 
participating in the study. Adequate birth control in this study is the use of double barrier 
methods (condom with spermicide or diaphragm with spermicide), stable hormonal 
contraception, intrauterine device, abstinence, or tubal ligation. 
 
Liraglutide also may have unknown risks to breast-fed babies. Therefore, you should not 
breastfeed while you are taking this drug. 
 
If you are a male, there is no documented risk for males who reproduce while taking the study 
drug. Therefore, using birth control is not a requirement for participation in the study. 


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Although pregnancy testing will be performed, it is possible that the results could be wrong. If 
you do become pregnant during the study, you will be asked to immediately notify the study 
team, to discontinue the drug, and to consult an obstetrician or maternal-fetal specialist. You will 
be withdrawn from the study but the study physician or nurse practitioner will remain in contact 
with you to learn the outcome of your pregnancy. The study physician or nurse practitioner will 
confirm that you are consulting with an obstetrician or maternal-fetal medicine specialist, record 
any complications, and obtain information regarding the overall health of you and the baby via 
self-report measures each trimester and post-delivery. The study physician will share this 
information with the University of Pennsylvania Institutional Review Board and with Novo- 
Nordisk, who manufactures the medication. 
 
Risks of Placebo 
 
Because the placebo does not contain any active ingredients and is not intended to treat your 
symptoms, there is a risk that your binge-eating may get worse. 
 
What if new information becomes available about the study? 
 
During the course of the study, we may discover new information that could be important to you. 
This includes information that, once learned, might cause you to change your mind about being 
in the study. We will notify you as soon as possible if such information becomes available. 
 
What are the possible benefits of the study? 
 
It is not known if the study drug will cause any reduction in binge episodes or any medical 
benefit. This study may benefit society at large by providing information about the effectiveness 
of liraglutide 3.0 mg/day. 
 
What other choices do I have if I do not participate? 
 
Your alternative is not to participate in this study. Should you choose not to participate in this 
research study, there are several ways to reduce binge episodes that do not require the methods 
used in this program. These include psychotherapies, specifically cognitive behavioral therapy. 
Additionally, other pharmacological treatments are sometimes used to treat BED including 
antidepressant medications, antiepileptic medications, weight loss medications, and stimulant 
(ADHD) medications. Lisdexamfetamine is the only currently approved drug by the U.S. Food 
and Drug Administration (FDA) for treating BED, which has been shown to reduce binge eating 
episodes, increase cessation of binge episodes, and increase weight loss compared to placebo. 
We do not know how lisdexamfetamine or other treatments compare in safety and effectiveness 
to liraglutide 3.0 mg (Saxenda®) as there have been no previous randomized controlled trials 
examining the effectiveness of liraglutide 3.0 mg in treating BED (or comparing liraglutide 3.0 
mg to lisdexamfetamine or other treatments, for that matter). This present study is designed to 
collect data on efficacy and safety of use of liraglutide compared with placebo. We may then 
compare the results of the present study to studies published using lisdexamfetamine to examine 
effects on BED and on frequency of adverse events for the two different medications. 


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Will I be paid for being in this study? 
 
You will receive travel funds of $10 at the randomization visit and each of the study visits 
(weeks 1, 3, 5, 7, 9, 11, 13, and 15). You also will also receive $30 for the first screening visit 
and week 17 visit. Additionally, you will receive a $100 bonus for completing the study. This is 
a total of $250.00. You will only receive payment for the visits you complete. Please note: In 
order to be compensated for your participation in this study, you must provide your Social 
Security Number. Additionally, please note that the University of Pennsylvania is required to 
report to the IRS any cumulative payments for participation in research studies that exceed a 
total of $600 in a calendar year. 
 
Will I have to pay for anything? 
 
There is no cost or financial risk for participating in this study. All study medication and 
assessment measures will be provided free of charge. 
 
This research is being sponsored by an Investigator Initiated Study grant (to Kelly Allison, 
Ph.D.) from Novo Nordisk, the pharmaceutical company that manufacturers and markets 
liraglutide 3.0 mg (Saxenda). Dr. Allison, with assistance from colleagues, designed the present 
research trial and is the principal investigator of the study at the University of Pennsylvania 
(which is the only site at which the study is being conducted). Novo Nordisk will not be involved 
in conducting this research trial but will receive periodic reports on the study’s progress. 
 
What happens if I am injured or hurt during the study? 
 
If you have a medical emergency during the study you should go to the nearest emergency room. 
You may contact the Principal Investigator, Kelly Allison, Ph.D. (215-898-2823) or emergency 
contact (215-662-2121). You may also contact your own doctor, or seek treatment outside of the 
University of Pennsylvania. Be sure to tell the doctor or his/her staff that you are in a research 
study being conducted at the University of Pennsylvania. Ask them to call the telephone 
numbers on the first page of this consent form for further instructions or information about your 
care. 
 
We will offer you the care needed to treat injuries directly resulting from taking part in this 
research study. We may bill your insurance company or other third parties, if appropriate, for 
the costs of the care you get for the injury, but you may also be responsible for some of them. 
 
There are no plans for the University of Pennsylvania to pay you or give you other compensation 
for an injury. You do not give up your legal rights by signing this form. 
 
If you think you have been injured as a result of taking part in this research study, you should 
contact the Principal Investigator listed on page 1 of this form. 
 
When is the study over? Can I leave the study before it ends? 


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The study will end after all participants have completed all visits and all research information has 
been collected. The study may be stopped without your consent for the following reasons: 
 
 The Principal Investigator or your physician believes it is necessary for your health or 
safety. You will be informed if such a decision is made and the reasons for the decision. 
 You have not followed study instructions. 
 The Principal Investigator or the Office of Regulatory Affairs at the University of 
Pennsylvania has decided to stop the study. 
 
Your participation in this study is voluntary. You may withdraw from the study at any time 
without penalty or loss of any benefits to which you are otherwise entitled. Withdrawal will not 
affect your future care at the University of Pennsylvania Health System. If you wish to withdraw, 
you should contact the Principal Investigator listed on page 1 of this form. 
 
How will confidentiality be maintained and my privacy be protected? 
 
Personal information is anything that can be used to identify who you are. Examples include 
your name, address, telephone number, medical record number, social security number, or 
electronic mail address. We will do our best to make sure that the personal information obtained 
during the course of this research study will be kept confidential. However, we cannot guarantee 
total privacy. Your personal information may be given out if required by law. If information 
from this study is published or presented at scientific meetings, your name and other personal 
information will not be used. 
 
Where will study records and data collected at this site be stored? 
 
 In a locked office 
 In password protected and institutionally secured and managed computers 
 In password protected and institutionally secured and managed network storage 
 
What information about me may be collected, used, or shared with others? 
 
The following personal health information will be collected, used for research, and may be 
disclosed during your involvement with this study: 
 
 Name, address, telephone number, and date of birth 
 Social security number 
 Personal and family medical history 
 Electronic mail address 
 Medical record number 
 Current and past medications or therapies 
 Information from a physical examination that generally also includes blood pressure 
reading, heart rate, weight, height, and waist measurements 
 Results of tests and procedures you will undergo during this research study as described 
in the informed consent form 


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What Is an Electronic Medical Record and/or a Clinical Trial Management System? 
An Electronic Medical Record (EMR) is an electronic version of the record of your care within a 
health system. An EMR is simply a computerized version of a paper medical record. 
 
A clinical trial management system (CTMS) is used to register your information as a participant 
in a study and to allow for your research data to be entered/stored for the purposes of data 
analysis and any other required activity for the purpose of the conduct of the research. 
 
If you are receiving care or have received care within the University of Pennsylvania Health 
System (UPHS) (outpatient or inpatient) and are participating in a University of Pennsylvania 
research study, information related to your participation in the research (i.e. laboratory tests, 
imaging studies and clinical procedures) may be placed in your existing EMR maintained by 
UPHS. Information related to your participation in clinical research will also be contained in the 
CTMS. 
 
If you have never received care within UPHS and are participating in a University of 
Pennsylvania research study that uses UPHS services, an EMR will be created for you for the 
purpose of maintaining any information produced from your participation in this research study. 
The creation of this EMR is required for your participation in this study. In order to create your 
EMR, the study team will need to obtain basic information about you that would be similar to the 
information you would provide the first time you visit a hospital or medical facility (i.e. your 
name, the name of your primary doctor, the type of insurance you have). Information related to 
your participation in the study (i.e. laboratory tests, imaging studies and clinical procedures) may 
be placed in this EMR. 
 
Once placed in your EMR or in the CTMS, your information may be accessible to appropriate 
UPHS workforce members that are not part of the research team. Information within your EMR 
may also be shared with others who are determined by UPHS to be appropriate to have access to 
your EMR (e.g. health insurance company, disability provider, etc.). 
 
Why is my personal health information being collected? 
 
Your personal health information and results of tests and procedures are being collected as part 
of this research study and for the advancement of medicine and clinical care. 
 
How is my information being used? 
 
Your information is used by the research team to contact you during the study via telephone or 
email. Your social security number is used to process any reimbursement payments. Your 
information and results of tests and procedures are used to: 
 
 Conduct the research 
 Oversee the research 
 Determine if the research was executed properly 
 
Who may use and share information about me? 


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The following individuals and organizations may use or disclose your personal health 
information for this research study: 
 
 The Principal Investigator and the research team associated with the study 
 The University of Pennsylvania Institutional Review Board (the committee responsible 
for overseeing research on human participants) and the University of Pennsylvania Office 
of Regulatory Affairs 
 The University of Pennsylvania Office of Human Research (the office which monitors 
research studies) 
 Authorized members of the University of Pennsylvania Health System and School of 
Medicine workforce who may need to access your information in the performance of 
their duties (for example: to provide treatment, to ensure integrity of the research, 
accounting or billing matters, etc.) 
 Other research personnel with access to the databases for research and/or study 
coordination and as otherwise approved by the IRB 
 
We will do our best to make sure that the personal information obtained during the course of this 
research study will be kept private. However, we cannot guarantee total privacy. Your personal 
information may be given out if required by law. If information from this study is published or 
presented at scientific meetings, your name and other personal information will not be used. 
 
Who, outside of the School of Medicine, might receive my personal health information? 
 
 The Food and Drug Administration 
 The OHR Protections 
 Medical personnel from Novo Nordisk Inc. which manufactures, markets, and distributes 
liraglutide. 
 Quest diagnostics 
 
Once your personal health information is disclosed to others outside the School of Medicine, it 
may no longer be covered by federal privacy protection regulations. The study team will inform 
you if there are any additions to the list above during your participation in the study. Any 
additions will be subject to University of Pennsylvania procedures developed to protect your 
privacy. 
 
How long may the School of Medicine use or disclose my personal health information? 
 
Your authorization for use of your personal health information for this specific study does not 
expire. Your information may be held in a research database. However, the School of Medicine 
may not re-use or re-disclose information collected in this study for a purpose other than the 
study unless: 
 
 You have given written authorization 
 The University of Pennsylvania Institutional Review Board grants permission 
 As permitted by law 


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Can I change my mind about giving permission for use of my personal health information? 
 
You may withdraw your permission to use and disclose your health information at any time. You 
do this by sending written notice to the Principal Investigator of the study. Even if you withdraw 
your permission, the Principal Investigator may still use your personal information that was 
collected prior to your written withdrawal request. If you withdraw your permission to use your 
personal health information, you will not be able to remain in the study. 
 
Who can I call with questions or complaints, or if I’m concerned about my rights as a 
research participant? 
 
If you have questions, complaints, or concerns regarding your participation in this study or your 
rights as a research participant, you should speak with the Principal Investigator listed on page 1 
of this form. If a member of the study team cannot be reached or you want to talk with someone 
other than those working on the study, you may call the Office of Regulatory Affairs at the 
University of Pennsylvania at (215) 898-2614. 
 
What if I decide not to give permission to use my personal health information? 
 
You will not be able to participate in this study if you do not give permission to use your 
personal health information. 


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By signing this document, you are permitting the School of Medicine to use and disclose 
personal health information collected about you for research purposes, as described above. 
 
 
 
 
You will be given a copy of this consent form. 
 
 
 
Name of Participant (Please Print) 
Signature of Participant 
Date 
 
 
 
Name of Person Obtaining 
Signature 
Date 
Consent (Please Print) 
 
Please indicate whether you agree to be audiotaped during an assessment of eating behavior: 
 
□ Yes □ No 
Initials:  
 
When you sign this form, you are agreeing to take part in this research study. This means 
that you have read the consent form, your questions have been answered, and you have 
decided to volunteer. Your signature also means that you are permitting the University of 
Pennsylvania to use your personal health information collected about you for research 
purposes within our institution. You are also allowing the University of Pennsylvania to 
disclose that personal health information to outside organizations or people involved with 
the operations of this study. 


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Schedule of Visits and Assessments 
 
 
 
 
Screening 
RCT 
Weeks 
 
Screen 
2-week 
run-in 
Randomization/ 
Week 0 
1 
3 
5 
7 
9 
11 
13 
15 
17 
Procedures 
Informed consent 
x 
Adverse events actively collected 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Behavioral evaluation 
x 
History and physical 
x 
EKG 
x 
Blood draw 
x 
x 
Labs 
x 
x 
Log of BED behaviors 
x 
Self-reported outcomes 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Medical visit 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Psychological assessment of BED 
symptoms 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Vital signs 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x