Clinical trial NCT03048578
Conditions: Obesity
Keywords: Roux-en-Y gastric bypass (RYGB)
Sponsor: NYU Langone Health
Start date: 2017-05-22; Completion date: 2021-03-02
Enrollment: 132 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a randomized, double-blinded, placebo-controlled trial of liraglutide versus placebo over a follow-up period of 12 months in patients at least 18 months following Roux-en-Y gastric bypass (RYGB) who are experiencing weight regain. This study will assess the efficacy of liraglutide in improving cardiometabolic risk profile (as indicated by serum lipids, HbA1c, and waist circumference) and quality of life (as assessed by PHQ-9 (Patient Health Questionnaire), versus placebo in patients at least 18 months following RYGB who are experiencing weight regain as well as the safety of liraglutide in this patient population.

Detailed description:
The specific aims of this study are to:

* To evaluate the effects of liraglutide on body weight loss in patients who are experiencing weight regain following RYGB.
* To evaluate the effects of liraglutide on cardiometabolic risk and quality of life in patients who are experiencing weight regain following RYGB.
* To evaluate the safety of liraglutide in post-RYGB subjects.
* To evaluate the changes in obesity-related comorbid conditions in patients who are experiencing weight regain following RYGB.

Arms: arm 1: Week 1: 0.6mg/day Week 2: 1.2mg/day Week 3: 1.8mg/day Week 4: 2.4mg/day Week 5 and Onward: 3.0mg/day arm 2: Week 1: 0.6mg/day Week 2: 1.2mg/day Week 3: 1.8mg/day Week 4: 2.4mg/day Week 5 and Onward: 3.0mg/day
Interventions: intervention 1: Saxenda intervention 2: Placebo
Intervention descriptions: intervention 1: Week 1: 0.6mg/day Week 2: 1.2mg/day Week 3: 1.8mg/day Week 4: 2.4mg/day Week 5 and Onward: 3.0mg/day intervention 2: Subcutaneous Saline Solution

Protocol documents:
Prot_SAP_000.pdf: 
Universal Trial Number: U1111-1178-7319               Version 7: 10/11/2019                           Page   1 
 
 
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Protocol Title: Clinical Efficacy and Safety of Using 3.0mg Liraglutide to Treat Weight Regain After 
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Roux-en-Y Gastric Bypass Surgery 
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INVESTIGATOR-INITIATED STUDY PROTOCOL 
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Universal Trial Number: U1111-1178-7319 
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Regulatory Sponsor: 
Holly Lofton, M.D. 
Director, Medical Weight Management Program 
Assistant Professor, Department of Surgery 
Assistant Professor, Department of Medicine 
NYU School of Medicine 
530 First Avenue, Suite 10S 
New York, NY  10016-6497 
Tel: 212 263 2174 
Fax: 212 263 2139 
 
Funding: 
Novo Nordisk 
Study Product: 
Liraglutide (rDNA origin) injection, Saxenda® 
Protocol Number: 
NYULWMP-01, 16-01527 
NCT Number: 
NCT03048578 
 
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Initial Version: 11/10/2016 
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Version 2: 
06/01/2017 
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Version 3: 
10/25/2017 
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Version 4: 
12/11/2017 
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Version 5:  
04/12/2018 
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Version 6: 
02/13/2019 
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Version 7: 
10/11/2019 
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Clinical Research Protocol 


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Table of Contents 
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31 
STUDY SUMMARY ....................................................................................................................................... 6 
32 
1 
INTRODUCTION.................................................................................................................................. 7 
33 
1.1 
BACKGROUND AND SIGNIFICANCE ......................................................................................................... 7 
34 
1.2 
INVESTIGATIONAL AGENT..................................................................................................................... 7 
35 
1.2.1 
Name: Saxenda® (liraglutide (rDNA origin)) or matching placebo ................................................ 7 
36 
1.2.3 
Indications ................................................................................................................................. 8 
37 
1.2.4 
Adult dosage .............................................................................................................................. 8 
38 
1.2.5 
Administration ............................................................................................................................ 8 
39 
1.2.6 
Pharmacokinetics ....................................................................................................................... 8 
40 
1.2.7 
Mechanism of Action ................................................................................................................... 9 
41 
1.2.8 
Contraindications ....................................................................................................................... 9 
42 
1.2.9 
Limitations of Use ....................................................................................................................... 9 
43 
1.2.10 
Precautions ............................................................................................................................ 9 
44 
1.2.11 
Storage & Stability ............................................................................................................... 11 
45 
1.3 
PRECLINICAL DATA ............................................................................................................................ 12 
46 
1.4 
CLINICAL DATA TO DATE ................................................................................................................... 12 
47 
1.5 
DOSE RATIONALE .............................................................................................................................. 12 
48 
1.6 
RESEARCH RISKS & BENEFITS ............................................................................................................. 12 
49 
1.6.1 
Risk of Study Drug .................................................................................................................... 12 
50 
1.6.2 
Potential benefits ...................................................................................................................... 14 
51 
2 
STUDY OBJECTIVES ........................................................................................................................ 14 
52 
2.1 
PRIMARY OBJECTIVE .......................................................................................................................... 14 
53 
2.2 
SECONDARY OBJECTIVE ..................................................................................................................... 14 
54 
3 
STUDY DESIGN ................................................................................................................................. 14 
55 
3.1 
RESEARCH DESIGN AND METHODS ...................................................................................................... 14 
56 
3.2 
ENDPOINTS ........................................................................................................................................ 15 
57 
3.3 
STUDY TYPE ...................................................................................................................................... 15 
58 
3.4 
RATIONALE FOR STUDY DESIGN .......................................................................................................... 15 
59 
3.5 
PRIMARY STUDY ENDPOINTS .............................................................................................................. 15 
60 
3.6 
SECONDARY STUDY ENDPOINTS .......................................................................................................... 16 
61 
3.7 
PRIMARY SAFETY ENDPOINTS ............................................................................................................. 16 
62 
3.7.1 
Assessments for Safety ............................................................................................................... 16 
63 
4 
SUBJECT SELECTION AND WITHDRAWAL.................................................................................. 16 
64 
4.1 
NUMBER OF THE SUBJECTS: 132 ........................................................................................................... 16 
65 
4.2 
RATIONALE FOR STUDY POPULATION ................................................................................................... 16 
66 
4.3 
INCLUSION CRITERIA .......................................................................................................................... 16 
67 
4.4 
EXCLUSION CRITERIA ......................................................................................................................... 16 
68 
4.5 
SUBJECT RECRUITMENT AND SCREENING ............................................................................................. 17 
69 
4.5.1 
Recruitment and Screening ........................................................................................................ 17 
70 
4.5.2 
Informed Consent ..................................................................................................................... 18 
71 
4.6 
EARLY WITHDRAWAL OF SUBJECTS ..................................................................................................... 18 
72 
4.6.1 
When and How to Withdraw Subjects ......................................................................................... 18 
73 
4.6.2 
Data Collection and Follow-up for Withdrawn Subjects............................................................... 19 
74 
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STUDY DRUG ..................................................................................................................................... 19 
75 
5.1 
DESCRIPTION ..................................................................................................................................... 19 
76 
5.2 
TREATMENT REGIMEN ........................................................................................................................ 19 
77 
5.3 
SUBJECT COMPLIANCE MONITORING ................................................................................................... 20 
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5.4 
CONCOMITANT THERAPY .................................................................................................................... 20 
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5.5 
RECEIVING, STORAGE, DISPENSING AND RETURN .................................................................................. 20 
80 
5.5.1 
Receipt of Drug Supplies ........................................................................................................... 20 
81 
5.5.2 
Storage .................................................................................................................................... 20 
82 
5.6 
METHOD FOR ASSIGNING SUBJECTS TO TREATMENT GROUPS AND DISPENSING OF STUDY DRUG ............... 20 
83 
5.6.1 
Randomization Process ............................................................................................................. 20 
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5.6.2 
Dispensing of Study Drug .......................................................................................................... 21 
85 
5.6.3 
Return or Destruction of Study Drug .......................................................................................... 21 
86 
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STUDY PROCEDURES ...................................................................................................................... 21 
87 
1. 
FASTING IS REQUIRED ......................................................................................................................... 22 
88 
6.1 
VISIT 1 (BASELINE/PRE-TREATMENT) .................................................................................................. 22 
89 
6.1.1 
Screening and Enrollment ......................................................................................................... 22 
90 
6.1.2 
Medical History ........................................................................................................................ 22 
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6.1.3 
Demographics .......................................................................................................................... 22 
92 
6.1.4 
Physical Examination / Clinical Assessment................................................................................ 22 
93 
6.1.5 
Diet and Physical Activity Counseling ........................................................................................ 23 
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6.1.6 
Comorbidities Assessment ......................................................................................................... 23 
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6.1.7 
Blood work (total 25 ml blood collection) ................................................................................... 23 
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6.1.8 
Questionnaires ......................................................................................................................... 24 
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6.2 
VISIT 2, 3, 4 (POST-TREATMENT) ......................................................................................................... 24 
98 
6.2.1 
Physical Examination / Clinical Assessment................................................................................ 24 
99 
6.2.2 
Diet and Physical Activity Counseling ........................................................................................ 24 
100 
6.2.3 
Comorbidities Assessment ......................................................................................................... 24 
101 
6.2.4 
Blood work ............................................................................................................................... 24 
102 
6.2.5 
Questionnaires ......................................................................................................................... 25 
103 
6.2.6 
Adverse Events Assessment ........................................................................................................ 25 
104 
6.2.7 
Monthly phone call ................................................................................................................... 25 
105 
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STATISTICAL PLAN ......................................................................................................................... 25 
106 
7.1 
SAMPLE SIZE DETERMINATION ............................................................................................................ 25 
107 
7.2 
STATISTICAL METHODS ...................................................................................................................... 25 
108 
7.3 
SUBJECT POPULATION(S) FOR ANALYSIS .............................................................................................. 26 
109 
7.4 
INTERIM ANALYSIS ............................................................................................................................ 26 
110 
8 
SAFETY AND ADVERSE EVENTS .................................................................................................... 26 
111 
8.1 
DEFINITIONS ...................................................................................................................................... 26 
112 
8.1.1 
Unanticipated Problems Involving Risk to Subjects or Others ...................................................... 26 
113 
8.1.2 
Adverse Event ........................................................................................................................... 26 
114 
8.1.3 
Serious Adverse Event ............................................................................................................... 27 
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8.1.4 
Serious Adverse Drug Reaction (SADR) ..................................................................................... 27 
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8.1.5 
Severity Assessment Definitions ................................................................................................. 28 
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8.1.6 
Relationship to Study Drug Assessment Definitions ..................................................................... 28 
118 
8.1.7 
Outcome Categories and Definitions .......................................................................................... 28 
119 
8.2 
COLLECTION, RECORDING AND REPORTING OF ADVERSE EVENTS .......................................................... 28 
120 
8.2.1 
Collection and Recording of Adverse Events ............................................................................... 28 
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8.2.2 
Reporting of Serious Adverse Events and Unanticipated Problems ............................................... 30 
122 
8.2.3 
Follow-up of Adverse Events ..................................................................................................... 31 
123 
8.3 
LIABILITY ......................................................................................................................................... 32 
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8.4 
UNBLINDING PROCEDURES ................................................................................................................. 32 
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8.5 
STOPPING RULES................................................................................................................................ 32 
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8.6 
MEDICAL MONITORING ...................................................................................................................... 32 
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8.6.1 
Data Monitoring Committee ...................................................................................................... 32 
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DATA HANDLING AND RECORD KEEPING .................................................................................. 35 
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9.1 
CONFIDENTIALITY .............................................................................................................................. 35 
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9.2 
CONFIDENTIALITY AND HIPAA ........................................................................................................... 36 
131 
9.3 
SOURCE DOCUMENTS ......................................................................................................................... 36 
132 
9.4 
CASE REPORT FORMS ......................................................................................................................... 36 
133 
9.5 
RECORDS RETENTION ......................................................................................................................... 37 
134 
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STUDY MONITORING, AUDITING, AND INSPECTING ................................................................. 37 
135 
10.1 
STUDY MONITORING PLAN ............................................................................................................. 37 
136 
10.2 
AUDITING AND INSPECTING ............................................................................................................ 37 
137 
11 
ETHICAL CONSIDERATIONS .......................................................................................................... 37 
138 
12 
STUDY FINANCES ............................................................................................................................. 38 
139 
12.1 
FUNDING SOURCE .......................................................................................................................... 38 
140 
12.2 
CONFLICT OF INTEREST .................................................................................................................. 38 
141 
12.3 
COSTS TO THE SUBJECT .................................................................................................................. 38 
142 
12.4 
SUBJECT STIPENDS OR PAYMENTS ................................................................................................... 38 
143 
13 
PUBLICATION PLAN ........................................................................................................................ 38 
144 
14 
REFERENCES .................................................................................................................................... 39 
145 
15 
ATTACHMENTS ................................................................................................................................ 40 
146 
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List of Abbreviations/Formula 
148 
Term/Abbreviation 
Definition 
ADR 
Adverse Drug Reaction 
AE 
Adverse Event 
BMI 
Body Mass Index 
BMP 
Basic Metabolic Panel 
BMR 
Basal Metabolic Rate 
BP 
Blood pressure 
CPAP 
Continuous Positive Airway Pressure 
CRF 
Case Report Form 
GCP 
Good  Clinical Practice 
GI  
Gastrointestinal 
GLP-1 
Glucagon-Like Peptide-1 
HCG 
Human Chorionic Gonadotropin 
HIPAA 
Health Insurance Portability and Accountability Act 
HR 
Heart Rate 
IC 
Informed Consent 
ICH 
International Conference on Harmonisation 
IM 
Intramuscular 
IRB 
Institutional Review Board 
ITT 
Intention-To-Treat 
LAGB 
Laparoscopic Adjustable Gastric Banding 
MEN 
Multiple Endocrine Neoplasia 
MTC 
Medullary Thyroid Carcinoma 
NYULMC 
New York University Langone Medical Center 
OSA 
Obstructive Sleep Apnea 
PHQ 
Patient Health Questionnaire 
PI 
Principal Investigator 
PP 
Per-Protocol 
RD 
Registered Dietician 
RYGB 
Roux-en-Y Gastric Bypass 
SADR 
Serious Adverse Drug Reaction 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SC 
Subcutaneous 
SUSAR 
Suspected Unexpected Serious Adverse Reaction  
TBWL 
Total body weight loss 
UAE 
Unexpected Adverse Event 
WL 
Weight loss (Baseline weight – Follow-up visit weight) 
 
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Study Summary 
151 
Title 
Clinical Efficacy and Safety of Using 3.0mg Liraglutide to Treat Weight 
Regain After -Roux-en-Y Gastric Bypass Surgery 
Short Title 
Liraglutide after RYGB Weight Regain  
Protocol Number 
NYULWMP-01 
Phase 
Phase 4 
Methodology 
Randomized, double-blind, placebo controlled study 
Study Duration 
Mar. 2017 to Dec. 2020 
Study Center(s) 
Single-center 
Objectives 
The primary objective of this study is to assess the utility of 3.0mg liraglutide 
to reverse weight regain versus placebo in patients at least 18 months 
following RYGB who at the time of enrollment have regained of  ≥10% of 
maximum TBWL (total body weight loss) after surgery. 
Number of Subjects 
132 
Diagnosis and Main 
Inclusion Criteria 
• 
≥18 years who are deemed medically stable 
• 
≥18 months status-post RYGB 
• 
BMI 27 kg/m2 or greater in the presence of at least one weight-related 
comorbid condition 
• 
BMI 30 kg/m2 or greater   
• 
Regain of  ≥10% of maximum TBWL post-RYGB  
• 
Ability to provide informed consent before any trial-related activities 
• 
Express willingness to follow protocol requirements 
Study Product, Dose, 
Route, Regimen 
• 
Saxenda® (Liraglutide (rDNA origin)) injection, pre-dose pen  
• 
Solution for subcutaneous injection, pre-filled, multi-dose pen that 
delivers dose of 0.6mg,1.2mg, 1.8mg, 2.4mg or 3.0mg (6mg/mL, 3 mL) 
• 
The recommended dosage of Saxenda® is 3.0mg daily.   
• 
The dose escalation below will be used. 
Week 
Daily Dose 
1 
0.6 mg 
2 
1.2 mg 
3 
1.8 mg 
4 
2.4 mg 
5 and onward 
3.0 mg 
Duration of 
administration 
12 months 
Reference therapy 
A placebo 
Statistical Methodology 
Data will be analyzed on an intention-to-treat basis. Our primary outcome 
(proportion of subjects losing at least 5% enrollment body weight) will be 
assessed using Cochran-Mantel-Haenszel test after accounting for 
stratification variables.  The treatment groups will be further compared by 
secondary outcomes, using t-tests or Wilcoxon rank sum tests, (as 
appropriate) for continuous variables. 
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1 
Introduction 
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1.1 
Background and Significance 
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Nearly 90 million Americans are obese.  To combat obesity and its myriad comorbidities, annually almost 
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200,000 Americans undergo bariatric surgery, the most effective treatment for obesity.  Of contemporary 
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procedures, Roux-en-Y Gastric Bypass (RYGB) achieves the greatest weight loss - between one and two 
158 
years following RYGB, patients tend to have lost over 30% total body weight. However, the majority of 
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patients regain weight following a two-year nadir [1].  As time from surgery increases, so does the 
160 
amount of weight regained.  Some have reported that more than a third of patients no longer manifest loss 
161 
of more than 50% pre-surgical excess body weight by ten years after surgery [2].  Weight regain after 
162 
RYGB is associated with the return of obesity-related comorbidies initially resolved following surgery 
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[3]. Many patients opt for revisional bariatric surgery to address weight regain, but these procedures are 
164 
often the source of significant morbidity [4, 5].  There are currently few non-surgical therapies with which 
165 
to address inadequate weight loss and weight regain after bariatric surgery, and these are of limited 
166 
efficacy.    
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168 
The use of GLP-1 agonists holds great promise for this population, which likely numbers in the hundreds 
169 
of thousands in the United States alone.  GLP-1 agonist use has been associated with weight loss in 
170 
diabetic populations, with a meta-analysis finding an average loss of 3% total body weight with GLP-1 
171 
receptor agonists versus placebo [6].  Further, several recent randomized trials have demonstrated the 
172 
efficacy of a specific GLP-1 receptor agonist, liraglutide 3.0mg daily, for the purpose of weight loss.  In a 
173 
study of overweight and obese subjects who first completed a low calorie diet, Wadden and colleagues 
174 
reported 6.2% weight loss at 56 weeks versus 0.2% with placebo [7].  Another recent trial in over 3,500 
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overweight and obese patients randomized to liraglutide or placebo, in addition to lifestyle interventions, 
176 
demonstrated 8.0% weight loss in the liraglutide arm versus 2.6% in the placebo group [8].  Neither of the 
177 
above randomized trials included overweight or obese patients who had previously undergone bariatric 
178 
surgery.  Although the use of a GLP-1 receptor agonist as an adjuvant to bariatric surgery for weight loss 
179 
has shown promise in animal models, this therapy has yet to be tested in humans [9].    
180 
 
181 
The use of GLP-1 receptor agonists to augment weight loss and combat weight regain could provide a 
182 
sorely needed adjunctive therapy to prevent remission following bariatric surgery.  With nearly 200,000 
183 
bariatric surgical procedures performed annually in the United States, a sizable population of patients 
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experiencing post-surgical weight regain stands to potentially benefit from therapy with liraglutide.  The 
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safety and efficacy of the medication in this population must first be assessed, however.  The purpose of 
186 
the present study is to investigate the safety and efficacy of 3.0mg liraglutide to achieve weight loss in 
187 
patients at least 18 months status-post RYGB who are experiencing weight regain at the time of 
188 
enrollment. 
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1.2 
Investigational Agent 
190 
1.2.1 
Name: Saxenda® (liraglutide (rDNA origin)) or matching placebo 
191 
Saxenda® is a clear, colorless solution. Each 1 mL of Saxenda® solution contains 6 mg of liraglutide and 
192 
the following inactive ingredients: disodium phosphate dihydrate, 1.42 mg; propylene glycol, 14 mg; 
193 
phenol, 5.5 mg; and water for injection. Each pre-filled pen contains a 3 mL solution of Saxenda® 
194 
equivalent to 18 mg liraglutide (free-base, anhydrous). 
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Matching placebo will have the same ingredients without the active ingredient (6 mg of liraglutide). 
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1.2.2 
Class: Glucagon-like peptide-1 (GLP-1) receptor agonist 
199 
1.2.3 
Indications 
200 
Adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults 
201 
with an initial BMI of ≥30kg/m2 (obese), or ≥27kg/m2 (overweight) in the presence of at least 1 weight-
202 
related comorbid condition (eg, HTN, type 2 diabetes mellitus [DM], dyslipidemia) 
203 
1.2.4 
Adult dosage 
204 
Usual: 3.0mg daily; dose escalation should be used to reduce the likelihood of GI symptoms 
205 
 
206 
Dose Escalation: 
207 
Week 1: 0.6mg/day 
208 
Week 2: 1.2mg/day 
209 
Week 3: 1.8mg/day 
210 
Week 4: 2.4mg/day 
211 
Week 5 and Onward: 3.0mg/day 
212 
May delay dose escalation for 1 additional week if unable to tolerate increased dose 
213 
 
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215 
Missed Dose 
216 
If a dose is missed, resume once-daily regimen with next scheduled dose; do not take an extra 
217 
dose or increase dose to make up for missed dose 
218 
If >3 days have elapsed since last dose, reinitiate at 0.6mg/day and retitrate following dose 
219 
escalation schedule 
220 
1.2.5 
Administration 
221 
Subcutaneous route 
222 
Administer daily at any time of day, without regard to timing of meals 
223 
May inject in the abdomen, thigh, or upper arm; injection site/timing can be changed without 
224 
dose adjustment 
225 
1.2.6 
Pharmacokinetics 
226 
Absorption 
227 
• 
Bioavailability: subcutaneous: 55% 
228 
• 
Tmax, subcutaneous: 8 to 12 hours; 11 hours (Saxenda®)  
229 
 
230 
Distribution 
231 
• 
Vd, subcutaneous: 13 L; 20 to 25 L (patients weighing 100 kg)  
232 
• 
Vd, IV: 0.07 L/kg  
233 
• 
Protein binding: Greater than 98% 
234 
 
235 
Metabolism 
236 
• 
Metabolism: not significant 
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Excretion 
239 
• 
Fecal: 0% unchanged; 5% changed 
240 
• 
Renal excretion: 0% unchanged; 6% changed 
241 
• 
Total body clearance: 1.2 L/hr; 0.9 to 1.4 L/hr 
242 
Elimination Half Life 
243 
• 
13 hours 
244 
1.2.7 
Mechanism of Action 
245 
Liraglutide is an acylated human Glucagon-Like Peptide-1 (GLP-1) receptor agonist that acts to 
246 
increase insulin release in the presence of elevated glucose concentrations, decrease glucagon 
247 
secretion in a glucose-dependent manner, and delay gastric emptying, thereby reducing the rate at 
248 
which postprandial glucose appears in circulation. GLP-1 regulates appetite and calorie intake, 
249 
including via receptors that are present in the brain. The weight reduction effect of liraglutide is 
250 
due to decreased calorie intake 
251 
1.2.8 
Contraindications 
252 
• 
Hypersensitivity to liraglutide or any product component 
253 
• 
Personal or family history of medullary thyroid carcinoma 
254 
• 
Personal or family history of multiple endocrine neoplasia syndrome type 2 
255 
• 
Pregnancy 
256 
1.2.9 
Limitations of Use 
257 
• 
Saxenda® is not indicated for the treatment of type 2 diabetes mellitus 
258 
• 
Saxenda® and Victoza® both contain the same active ingredient, liraglutide, and therefore 
259 
should not be used together.  Saxenda® should not be used in combination with any other 
260 
GLP-1 receptor agonist. 
261 
• 
Saxenda® has not been studied in patients taking insulin.  Saxenda® and insulin should not 
262 
be used together. 
263 
• 
The effects of Saxenda® on cardiovascular morbidity and mortality have not established. 
264 
• 
The safety and effectiveness of Saxenda® in combination with other products intended for 
265 
weight loss, including prescription drugs, over-the-counter drugs, and herbal preparations, 
266 
have not been established. 
267 
• 
Saxenda® has not been studied in patients with a history of pancreatitis. 
268 
1.2.10 
Precautions 
269 
• 
Black Box Warning 
270 
• 
Risk of Thyroid C-cell Tumors 
271 
o Liraglutide causes dose -dependent and treatment-duration-dependent thyroid C-
272 
cell tumors at clinically relevant exposures in both genders of rats and mice.  It is 
273 
unknown whether Saxenda® causes thyroid C-cell tumors, including medullary 
274 
thyroid carcinoma (MTC), in humans, as the human relevance has not been 
275 
determined. 
276 
o Saxenda® is contraindicated in patients with a personal or family history of MTC 
277 
and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).  
278 
Counsel patients regarding the risk of MTC with use of Saxenda® and inform 
279 
them of symptoms of thyroid tumors (e.g. a mass in the neck, dysphagia, 
280 
dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using 
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thyroid ultrasound is of uncertain value for early detection of MTC in patients 
282 
treated with Saxenda®. 
283 
 
284 
• 
Warnings and Precautions 
285 
o Acute Pancreatitis: Discontinue promptly if pancreatitis is suspected since it may be 
286 
life-threatening.  Do not restart if pancreatitis is confirmed. 
287 
o Acute Gallbladder Disease: If cholelithiasis or cholecystitis are suspected, 
288 
gallbladder studies are indicated.  
289 
o Serious hypoglycemia: Can occur when Saxenda® is used with an insulin 
290 
secretagogue (eg, sulfonylureas).  Consider lowering the dose of anti-diabetic drugs 
291 
to reduce the risk of hypoglycemia. 
292 
o Heart rate increase: Monitor heart rate at regular intervals. Discontinue Saxenda® if 
293 
patients experience a sustained increase in resting heart rate. 
294 
o Renal impairment: Has been reported postmarketing, usually in association with 
295 
nausea, vomiting, diarrhea, or dehydration which may require hemodialysis.  Use 
296 
caution when initiating or escalating doses of Saxenda® in patients with renal 
297 
impairment.  
298 
o Hypersensitivity reactions: Postmarketing reports of serious hypersensitivity 
299 
reactions (e.g., anaphylactic reactions and angioedema).  Discontinue Saxenda® and 
300 
other suspect medications and promptly seek medical advice. 
301 
o Angioedema has been reported with other GLP-1 receptor agonists.  Use caution in a 
302 
patient with a history of angioedema with another GLP-1 receptor agonist because it 
303 
is unknown whether such patients will be predisposed to angioedema with Saxenda®. 
304 
o Suicidal behavior and Ideation: monitor for depression or suicidal thoughts.  
305 
Discontinue Saxenda® if symptoms develop. 
306 
 
307 
• 
Adverse Reaction 
308 
o Most common adverse reactions, reported in greater than or equal to 5% are: nausea, 
309 
hypoglycemia, diarrhea, constipation, vomiting, headache, decreased appetite, 
310 
dyspepsis, fatigue, dizziness, abdominal pain, and increased lipase. 
311 
 
312 
Pregnancy & Lactation 
313 
 
314 
U.S. Food and Drug Administration's Pregnancy Category: Category X (All 
315 
Trimesters) 
316 
 
317 
Crosses Placenta: Unknown 
318 
 
319 
Clinical Management 
320 
The brand name Saxenda®, which is indicated as an adjunct to diet and exercise for 
321 
chronic weight management in overweight or obese patients, has a pregnancy category of 
322 
X. Saxenda® is contraindicated in all pregnant women, including those who are already 
323 
overweight or obese, because weight loss may result in fetal harm. If a woman becomes 
324 
or wishes to become pregnant while on Saxenda®, discontinue treatment.  
325 
 
326 
Literature Reports 
327 
There are no adequate and well-controlled studies of liraglutide in pregnant women. In 
328 
animal studies, teratogenicity occurred when female rats were given SC doses of 0.1, 
329 
0.25, and 1 mg/kg/day (0.8, 3, and 11 times the human exposure at the maximum 
330 
recommended human dose (MRHD) based on plasma AUC) starting 2 weeks before 
331 
mating through gestation day 17. Fetal abnormalities, kidney and blood vessel variations, 
332 


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irregular skull ossification, and ossification were observed at all doses. In pregnant rats 
333 
given the same doses from gestation day 6 through weaning or termination of nursing on 
334 
lactation day 24, the majority had a slight delay in parturition. Group mean body weight 
335 
of neonatal rats from the liraglutide-treated group was lower compared with controls. 
336 
Male offspring had bloody scabs and agitated behavior following maternal exposure to 1 
337 
mg/kg/day. In pregnant rabbits, teratogenicity was seen following SC doses of 0.01, 
338 
0.025, and 0.05 mg/kg/day (less than the exposure at the MRHD at all doses) from 
339 
gestation day 6 through day 18. Reduced fetal weight and dose-dependent major fetal 
340 
abnormalities were reported at all doses. Malformations at the various doses included 
341 
kidney and scapula (0.01 mg/kg), the eyes and forelimbs (0.01 mg/kg or greater), the 
342 
brain, sacral vertebrae, major blood vessels, heart, and umbilicus (0.025 mg/kg), the 
343 
sternum (0.025 mg/kg and greater), and parietal bones and major blood vessels (0.05 
344 
mg/kg). Ossification, skeletal abnormalities, and dose-dependent minor skeletal 
345 
variations were observed. Visceral abnormalities and bilobed or bifurcated gallbladder 
346 
were seen in all dose groups. 
347 
 
348 
Breastfeeding 
349 
Micromedex Lactation Rating: Infant risk cannot be ruled out. 
350 
 
351 
Available evidence and/or expert consensus is inconclusive or is inadequate for 
352 
determining infant risk when used during breastfeeding. Weigh the potential benefits of 
353 
drug treatment against potential risks before prescribing this drug during breastfeeding. 
354 
 
355 
Clinical Management 
356 
It is not known whether liraglutide is excreted in human breast milk. In animal studies, 
357 
liraglutide was excreted unchanged in the milk of lactating rats at concentrations 
358 
approximately 50% of maternal plasma concentrations. Because data are limited and 
359 
because of the tumorigenicity potential evident in animal studies, either discontinue 
360 
nursing or discontinue liraglutide considering the importance of the drug to the mother. 
361 
1.2.11 
Storage & Stability 
362 
 
363 
Preparation for administration 
364 
• 
Inject liraglutide SC in the abdomen, thigh, or upper arm. Liraglutide may be 
365 
administered any time of the day, independent of meals. Do not share pens with other 
366 
patients. 
367 
• 
To reduce the risk of IM injections and for better tolerance, use 4, 5, or 6 mm needles in 
368 
all patients regardless of BMI or age. Injections should be given at a 90 degree angle to 
369 
the skin surface. When injecting into limbs or a slim abdomen, use a lifted skin fold (4 
370 
and 5 mm needles) or 45 degree angle (6 mm needle). 
371 
 
372 
Storage 
373 
• 
Store unopened prefilled pens refrigerated, between 2 and 8 degrees C (36 and 46 degrees 
374 
F).  
375 
• 
Store opened pens up to 30 days at controlled room temperature, between 15 and 30 
376 
degrees C (59 and 86 degrees F), or refrigerated, between 2 and 8 degrees C (36 and 46 
377 
degrees F).  
378 
• 
Protect from excessive heat and sunlight.  
379 
• 
Avoid storing directly adjacent to cooling compartment in refrigerator.  
380 
• 
Do not freeze or use a pen that has been frozen. 
381 


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1.3 
Preclinical Data 
382 
GLP-1 agonists such as liraglutide have been noted to induce satiety and weight loss in multiple 
383 
animal models. When given to both normal and obese rats, a significant reduction in food and 
384 
water intake was noted in both groups, leading to significant weight loss of up to 15% of initial 
385 
body weight [10]. A similar study in obese mini-pigs also noted substantial weight loss due to its 
386 
suppressive effect on food intake [11]. Candy-fed rats were also found to have normalized weight 
387 
and fat levels after administration of liraglutide, reversing the effects of their diets [12]. 
388 
1.4 
Clinical Data to Date 
389 
(Please see Background and Significance for additional relevant clinical data) 
390 
 
391 
Initial clinical data regarding the use of liraglutide in the treatment of obesity is from the 
392 
NN8022-1807 study conducted by Astrup et al [13]. This was a double-blinded, placebo-
393 
controlled trial comparing liraglutide to Orlistat. Liraglutide was administered at 4 different doses 
394 
– 1.2 mg, 1.8 mg, 2.4 mg, and 3 mg daily. Patients taking liraglutide lost significantly more 
395 
weight than both the placebo and Orlistat groups.  Based on the success of this trial, participation 
396 
in the study was extended to two years. Subjects receiving the 2.4 mg/3.0 mg liraglutide doses for 
397 
two years lost on average 7.8 kg [14]. 67% of patients completed two year follow-up. The most 
398 
common reasons for discontinuing the study were poor results (placebo arm) and nausea/vomiting 
399 
(liraglutide arms). 
400 
 
401 
Further studies were then conducted in obese, non-diabetic subjects. Van Can et al. showed 
402 
increased satiety, fullness, and decreased gastric emptying using both liraglutide 1.8 mg and 3.0 
403 
mg dosing compared to placebo [15]. This suggested that liraglutide-induced weight loss was 
404 
secondary to reduced appetite and intake rather than increased energy expenditure. Pi-Sunyer et 
405 
al. conducted a recent trial in which over 3,500 overweight and obese patients were randomized 
406 
to liraglutide or placebo, in addition to lifestyle interventions. These authors demonstrated 8.0% 
407 
total body weight loss in the liraglutide arm, versus 2.6% in the placebo group [8]. 
408 
 
409 
None of the above randomized trials included overweight or obese patients who had previously 
410 
undergone bariatric surgery.  Although the use of a GLP-1 receptor agonist as an adjuvant to 
411 
bariatric surgery for weight loss has shown promise in animal models, this therapy has yet to be 
412 
rigorously tested in humans [9]. 
413 
1.5 
Dose Rationale 
414 
The dosage chosen for this study is 3 mg daily, injected subcutaneously. Dosages are steadily 
415 
escalated over a 5 week period, from 0.6 mg/day to 3.0 mg/day. Route of administration is 
416 
subcutaneous injection, as this is the only current formulation of the drug. The dosage chosen is 
417 
based on prior studies in obese patients. Astrup et al. demonstrated that the 3.0 mg daily dose 
418 
showed the greatest percentage of weight loss in patients, compared to doses of 1.2, 1.8, and 2.4 
419 
mg, without increased adverse events [13]. Subsequent studies have also used the 3.0 mg dosing 
420 
and shown comparable weight loss effects [7, 8]. The 3.0 mg dosing is currently approved by the 
421 
FDA for the indication of weight loss in overweight and obese individuals. The dosage regimen 
422 
and period in this study are also based on these prior studies. Liraglutide is a once-daily dosed 
423 
medicine, with a half-life of 11-12 hours [16].  
424 
1.6 
Research Risks & Benefits 
425 
1.6.1 
Risk of Study Drug 
426 
• 
Nausea (39.3%) 
427 


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• 
Diarrhea (20.9%) 
428 
• 
Hypoglycemia in Type 2 DM (23.0%) 
429 
• 
Constipation (19.4%) 
430 
• 
Vomiting (15.7%) 
431 
• 
Headache (13.6%) 
432 
• 
Decreased appetite (10.0%) 
433 
• 
Dyspepsia (9.6%) 
434 
• 
Fatigue (7.5%) 
435 
• 
Dizziness (6.9%) 
436 
• 
Abdominal pain (5.4%) 
437 
• 
Increased lipase (5.3%) 
438 
• 
Upper abdominal pain (5.1%) 
439 
• 
Gastroesophageal reflux disease (4.7%) 
440 
• 
Gastroenteritis (4.7%) 
441 
• 
Abdominal distension (4.5%) 
442 
• 
Eructation (4.5%) 
443 
• 
Urinary tract infection (4.3%) 
444 
• 
Flatulence (4.0%) 
445 
• 
Viral gastroenteritis (2.8%) 
446 
• 
Injection site erythema (2.5%) 
447 
• 
Injection site reaction (2.5%) 
448 
• 
Insomnia (2.4%) 
449 
• 
Dry mouth (2.3%) 
450 
• 
Asthenia (2.1%) 
451 
• 
Anxiety (1.6%)  
452 
• 
Cholelithiasis (1.5%) 
453 
• 
Hypotension (1.1%) 
454 
• 
Urticaria (0.7%) 
455 
• 
Breast cancer (0.6%) 
456 
• 
Cholecystitis (0.6%) 
457 
• 
Colorectal neoplasms (0.5%)  
458 
• 
Pancreatitis (0.3%) 
459 
• 
Cardiac conduction disorder (0.3%) 
460 
• 
Suicidal thoughts (0.2%) 
461 
• 
Papillary thyroid carcinoma (0.2%) 
462 
• 
Angioedema and anaphylactic reaction (reported, but percentage unknown) 
463 
• 
C-cell hyperplasia of thyroid (potential risk) 
464 
• 
Medullary thyroid carcinoma (potential risk) 
465 
 
466 
Measures to minimize the risks 
467 
• 
Dose escalation is used to reduce the likelihood of GI symptoms 
468 
• 
All contraindications included in exclusion criteria 
469 
• 
Lipase and Amylase included in study blood work 
470 
• 
Monitor heart rate during study visits  
471 
• 
Monitor depression during study visits 
472 
• 
Monitor fasting glucose at each study visit for hypoglycemia and lower the dose of 
473 
anti-diabetic drugs for patients taking an insulin secretagogue (eg, sulfonylureas) if 
474 
fasting glucose is ≤70 m/dL.  If hypoglycemia continues, the insulin secretagogue 
475 


Universal Trial Number: U1111-1178-7319               Version 7: 10/11/2019                           Page   14 
 
will be discontinued after consulting with the subject’s primary 
476 
physician/endocrinologist. 
477 
• 
Patients taking an insulin secretagogue (eg, sulfonylureas) will be informed of the 
478 
increased risk of hypoglycemia associated with co-administration of the study drug 
479 
and instructed to notify the investigators of any symptoms of hypoglycemia. 
480 
• 
If the subject is a female of childbearing potential (sexually active and not sterile nor 
481 
postmenopausal for at least 1 year), have a negative pregnancy test within 4 weeks 
482 
prior to study commencement, and then at 3, 6, and 9 months. 
483 
• 
Use of reliable contraception will be assessed during the study period. 
484 
• 
DSMB reviews all AEs including SAEs and provides the appropriate 
485 
recommendations 
486 
1.6.2 
Potential benefits 
487 
It is hypothesized that this study drug will help the subject lose weight and decrease the incidence 
488 
or severity of weight related co-morbidities.  In addition, the medical community and society 
489 
stand to benefit from a better understanding of the efficacy and safety of the study drug post-
490 
RYGB.  
491 
2 
Study Objectives 
492 
2.1 
Primary Objective 
493 
The primary objective of this study is to assess the utility of liraglutide to reverse weight regain versus 
494 
placebo in patients at least 18 months following RYGB who are experiencing weight regain. 
495 
2.2 
Secondary Objective 
496 
The secondary objectives of this study are to assess the efficacy of liraglutide in improving 
497 
cardiometabolic risk profile (as indicated by serum lipids, HbA1c, and waist circumference) and quality 
498 
of life (as assessed by PHQ-9 (Patient Health Questionnaire), versus placebo in patients at least 18 
499 
months following RYGB who are experiencing weight regain. as well as the safety of liraglutide in this 
500 
patient population. 
501 
3 
Study Design 
502 
3.1 
Research Design and Methods 
503 
The specific aims of this proposal are: 
504 
• 
To evaluate the effects of liraglutide on body weight loss in patients who are experiencing weight 
505 
regain following RYGB. 
506 
o We will perform a randomized, double-blinded, placebo-controlled trial of liraglutide 
507 
versus placebo over a follow-up period of 12 months.  
508 
▪ 
We hypothesize that the liraglutide group will contain a significantly greater 
509 
proportion of patients achieving at least 5% loss of pre-randomization body 
510 
weight at 12 months, than the placebo group.   
511 
• 
To evaluate the effects of liraglutide on cardiometabolic risk and quality of life in patients who 
512 
are experiencing weight regain following RYGB. 
513 
o We will perform a randomized, double-blinded, placebo-controlled trial of liraglutide 
514 
versus placebo over a follow-up period of 12 months.  
515 
▪ 
We hypothesize that the liraglutide group will demonstrate greater improvement 
516 
in cardiovascular risk profile (as assessed by serum lipids, HbA1c, and waist 
517 


Universal Trial Number: U1111-1178-7319               Version 7: 10/11/2019                           Page   15 
 
circumference) and quality of life (as assessed by the PHQ-9) at 12 months, than 
518 
the placebo group.   
519 
• 
To evaluate the safety of liraglutide in post-RYGB subjects. 
520 
o We will monitor adverse events, blood counts and serum chemistries in subjects 
521 
receiving liraglutide or placebo over a period of 12 months. 
522 
▪ 
We hypothesize that the liraglutide group will exhibit more frequent 
523 
hypoglycemia and elevations in lipase and amylase, but that these episodes will 
524 
be clinically insignificant. 
525 
• 
To evaluate the changes in obesity-related comorbid conditions in patients who are experiencing 
526 
weight regain following RYGB. 
527 
o We will monitor obesity-related comorbid conditions in subjects receiving liraglutide or 
528 
placebo over a period of 12 months.  
529 
▪ 
We hypothesize that the liraglutide group will exhibit improvements in obesity-
530 
related comorbid conditions (hyperglycemia, hyperlipidemia, blood pressure, and 
531 
obstructive sleep apnea) at 12 months, than the placebo group.   
532 
3.2 
Endpoints 
533 
• 
Primary Endpoint:  Proportion of subjects losing at least 5% of enrollment body weight at 12 months. 
534 
• 
Secondary Endpoints:  Fasting serum glucose, HbA1c, LDL-cholesterol, HDL-cholesterol, 
535 
triglycerides, waist circumference, blood pressure, STOP-BANG score, PHQ-9 
536 
• 
Primary and secondary endpoints will be assessed at clinic visits prior to randomization and at 3, 6, 9 
537 
and 12 months post-first study drug administration. 
538 
3.3 
Study Type 
539 
Randomized, single-center, double-blind, placebo-controlled study with two arms.  Randomization will 
540 
be 2:1 (drug:placebo) with stratification by gender and percent post-operative TBWL (25%, 25 – 49.9%).  
541 
3.4 
Rationale for study Design 
542 
A randomized, placebo-controlled study design was chosen as this is the methodology that will best 
543 
assess the efficacy of liraglutide for weight loss in the post-RYGB population.  2:1 randomization was 
544 
chosen with the intention of increasing potential participant interest given better than even odds of 
545 
randomization to liraglutide.   
546 
 
547 
A single-center study was chosen given that the NYU Langone weight management program has a pool 
548 
of 700 post-RYGB patients in our retrospective database, and that recent data from our program suggests 
549 
that 80 % of patients at least 18 months status-post RYGB exhibit regain of ≥10% of maximum post-
550 
surgical TBWL – our program has a potential subject pool of 560.  We estimate that at least 50% of 560 
551 
will be eligible for and agree to participate in the study, which will allow us to be able to enroll adequate 
552 
subjects from our program alone.  In addition, approximately five post-RYGB patients are referred to our 
553 
program monthly for evaluation of weight regain.   In the case that subject recruitment falls short of goals, 
554 
we would expand recruitment using advertisements.  
555 
3.5 
Primary Study Endpoints 
556 
Proportion of subjects losing at least 5% of enrollment body weight at 12 months. 
557 


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3.6 
Secondary Study Endpoints 
558 
Fasting serum glucose, HbA1c, LDL-cholesterol, HDL-cholesterol, triglycerides, waist circumference, 
559 
blood pressure, STOP-BANG score, PHQ-9, Obesity-related co-morbidities assessment 
560 
 
561 
Primary and secondary endpoints will be assessed prior to randomization and at clinic visits at 3, 6, 9 and 
562 
12 months post-first treatment administration. 
563 
3.7 
Primary Safety Endpoints 
564 
The primary safety endpoint is the percentage of patients who are experiencing AEs during 12 months of 
565 
the trial.   
566 
3.7.1 
Assessments for Safety 
567 
• 
BMP (Fasting glucose) 
568 
• 
Amylase 
569 
• 
Lipase 
570 
• 
Pregnancy Test (Only applicable for women of childbearing potential) 
571 
• 
Heart Rate 
572 
• 
PHQ-9 
573 
• 
Current medication list review  
574 
• 
Adverse event assessment including symptomatic hypoglycaemia for Type 2 DM patients 
575 
4 
Subject Selection and Withdrawal 
576 
4.1 
Number of the subjects: 132 
577 
Subjects will not be replaced if they withdraw or become ineligible. 
578 
4.2 
Rationale for study population 
579 
The Roux-en-Y gastric bypass (RYGB) is not only the most common bariatric procedure, but also the 
580 
gold standard to which all others are compared. The average weight loss after RYGB is approximately 
581 
35% total body weight.. However, the majority of patients who undergo this procedure experience weight 
582 
regain and thus are at risk of, or re-acquire co-morbid conditions, such as Type 2 diabetes mellitus or 
583 
hypertension. Revisional surgery, which is the most common treatment for weight regain after bariatric 
584 
surgery, is often thwarted by resistance from insurance companies, leaving patients with only diet and 
585 
behavioral change as an option. Due to the fact the GLP-1 agonism plays a significant role in weight loss 
586 
after RYGB, liraglutide is thought to be a promising adjunct to the long-term treatment plan in patients 
587 
who experience weight regain after RYGB.  
588 
4.3 
Inclusion Criteria 
589 
• 
>18 years who are deemed medically stable 
590 
• 
≥18 months status-post RYGB at time of enrollment 
591 
• 
BMI of ≥30 kg/m2 or ≥ 27 kg/m2 in the presence of at least one weight-related comorbid 
592 
condition 
593 
• 
Regain of ≥10% of maximum TBWL post-RYGB  
594 
• 
Ability to provide informed consent before any trial-related activities 
595 
• 
Express willingness to provide signed informed consent and follow protocol requirements 
596 
4.4 
Exclusion Criteria 
597 
• 
BMI of >45 kg/m2 
598 


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• 
Pregnancy at time of enrollment 
599 
• 
Intention of becoming pregnant or breast feeding in the next 12 months 
600 
• 
Females of childbearing potential who are not using adequate contraceptive methods  
601 
• 
Presence of acute psychiatric problems or immaturity which would compromise cooperation with 
602 
the study protocol 
603 
• 
Presence of biliary disease 
604 
• 
Known or suspected allergy to liraglutide or any product components 
605 
• 
Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia 
606 
syndrome type 2 
607 
• 
History of pancreatitis 
608 
• 
History of alcoholism 
609 
• 
History of Type 1 DM (Diabetes Mellitus) 
610 
• 
History of previous bariatric surgery other than RYGB except h/o LAGB and band removal. 
611 
• 
>10 years status-post RYGB 
612 
• 
< 25% TBWL at post-RYGB weight nadir 
613 
• 
>50% post-operative TBWL at time of screening 
614 
• 
Simultaneous use of any weight loss medications 
615 
• 
Use of insulin at the time of enrollment 
616 
• 
Current use of any GLP-1 agonist medication  
617 
• 
History of taking any GLP-1 agonist medication 
618 
• 
Participation in another ongoing clinical study  
619 
• 
Conditions that, in the opinion of the principal investigator, may jeopardize the patient’s well-
620 
being and/or the soundness of this clinical study 
621 
4.5 
Subject Recruitment and Screening 
622 
4.5.1 
Recruitment and Screening 
623 
Subject recruitment and screening will be conducted by members of the research team.   
624 
• 
Potentially eligible patients will be identified from the investigators’ confidential clinical registry 
625 
and referring physicians including self-referring patients 
626 
• 
If necessary, potential eligible patients will be recruited via online platform (i.e. Obesity Help, 
627 
Bariatric Pal, Facebook), newspaper advertisements, study fliers, or study brochures 
628 
• 
In addition to these methods, subjects may be recruited through MyChart (if indicated they are 
629 
willing to be contacted regarding research), DataCore, i2b2 or iConnect. 
630 
• 
DataCore may be used as a recruitment method to request reports from Epic, NYU’s electronic 
631 
medical record system.  The following data points will be requested: medical record number 
632 
(MRN), DOB (to assess current age), diagnosis, gender, and living status (alive). Patients will be 
633 
contacted either by phone or e-mail by members of the research team using an IRB approved 
634 
script. SendSafe Secure email will be used when sending these recruitment e-mails.  Once contact 
635 
is made, approved recruitment language will be used to communicate the reason they are being 
636 
contacted and subjects will be asked if they are interested in participating in this specific study. If 
637 
the potential subjects agree, the study team will provide the subjects with information regarding 
638 
the next steps for participation. If a subject is ineligible or chooses not to participate their 
639 
information will be deleted from the list immediately. PHI, including name, MRN, and DOB of 
640 
patients who schedule an appointment will be kept on secure NYU servers. This information will 
641 
be deleted if patients do not sign an informed consent form during their first visit. If a subject 
642 
requests information regarding opting out of further recruitment for all research, subjects will be 
643 
directed to contact study coordinator or have subjects contact research-contact-
644 
optout@nyumc.org or 1-855-777-7858. The amount of times EPIC will be searched over the 
645 


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course of the study will be dependent on the success of the results. We prefer to contact patients 
646 
who are open for recruitment (based on their choice listed in Epic) directly.  
647 
• 
Due to the time-sensitive inclusion criteria for this study (surgery between 18 months and 10 
648 
years), eligible participants may not have a treating physician on record in Epic as they may not 
649 
have continued their care at NYUMC during this time.  If they do have a primary care physician 
650 
listed, the study team will notify the provider through their NYUMC email address using an IRB 
651 
approved script stating that they are planning to contact this patient as indicated through a 
652 
DataCore search and provide the PI and study team contact information if there are any concerns.  
653 
If there is no primary care physician listed, this will be noted in the patient’s research record; 
654 
however they still may be contacted for research purposes.  
655 
• 
The following roles will have access to the EPIC search results: Principle Investigator, Research 
656 
Coordinator and Study Team Member. 
657 
• 
The research staff will contact the potential patients via email or telephone if the contact 
658 
information was sent to us via recruiting websites or the patients will contact the research staff 
659 
directly using the contact information on the online websites. 
660 
• 
Study eligibility will be determined by assessing evidence that the patient meets all inclusion and 
661 
exclusion criteria 
662 
• 
Patients will be offered the opportunity to participate in this study via telephone, email, mail 
663 
or/and in-person conversation in a private room to protect patient’s privacy.  More privacy will be 
664 
provided if required or demanded 
665 
• 
A verbal explanation of the study will be given followed by a written consent form 
666 
• 
For any patient who might be illiterate, consent forms will be read to him or her and witnessed by 
667 
an impartial third party Patients will be provided with ample time and opportunity to ask about 
668 
the details of the study, and decide whether or not they want to participate, and patient informed 
669 
consent will be obtained, prior to any study specific procedures 
670 
• 
No screening tests/procedures will be performed before a subject signs the consent form 
671 
4.5.2 
Informed Consent 
672 
The purpose, procedures, risks, benefits, and alternatives to study participation will be discussed with 
673 
each potential subject.  The subject must also give Authorization for Use and Release of Health and 
674 
Research Study Information and other written documentation in accordance with the relevant country and 
675 
local privacy requirements (where applicable) prior to any study-related procedures or change in 
676 
treatment.  
677 
 
678 
The Investigator or his/her authorized designee conducts the informed consent (IC) discussion and will 
679 
document in the subject’s medical records the acquisition of IC and the subject’s agreement.  The IC shall 
680 
include all aspects of the study that are relevant to the subject’s decision to participate throughout the 
681 
study.  The IC process should avoid any coercion or undue influence on, or inducement of, the subject to 
682 
participate.  The subject should personally sign and date the IC form.  The Investigator will retain the 
683 
original copy of the signed form, and the subject will receive a copy.  Upon signing the IC form, the 
684 
subject is considered to be enrolled in the study and receives a subject number that will be used on all 
685 
documentation for the subject throughout the study. The Investigator will ensure that important new 
686 
information is provided to new or existing subjects throughout the study. 
687 
4.6 
Early Withdrawal of Subjects 
688 
4.6.1 
When and How to Withdraw Subjects 
689 
• 
If a subject is not able to tolerate the study drug, the subject will be removed from the study. 
690 
• 
If a subject decides to withdraw from the study, the subject will be removed from the study. 
691 


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• 
If the PI believes that it is in a subject’s best interest to discontinue participation, the subject will 
692 
be removed from all remaining study requirements. 
693 
• 
A subject may be withdrawn from the study at the discretion of the PI due to a safety concern or 
694 
if judged non-compliant with trial procedures.  
695 
 
696 
If a subject fails to return for one scheduled study visits, the Investigator will attempt to contact the 
697 
subject to determine and document the reason the subject has failed to return and to encourage 
698 
compliance with the study visit schedule.  Before a subject can be considered lost to follow-up, a 
699 
minimum of 2 phone calls at different times of the day and a certified letter are required.  All of these 
700 
contact attempts will be documented in the source documents. 
701 
 
702 
In case of withdrawal from the study, the appropriate follow-up care will be provided for those cases, 
703 
including hospital and clinic follow-up when necessary.  
704 
4.6.2 
Data Collection and Follow-up for Withdrawn Subjects 
705 
Follow-up data will be collected at 12 months on the subjects who withdraw from the study after 
706 
obtaining the subject’s permission to record this information. 
707 
 
708 
Lost-to-follow-up 
709 
• 
A minimum of 2 phone calls and 1 certified letter contact attempts will be made before a patient 
710 
is considered as a lost-to-follow-up. 
711 
 
712 
5 
Study Drug  
713 
5.1 
Description 
714 
Saxenda® or matching placebo 
715 
• 
Subcutaneous Solution: 6 mg/ml 
716 
• 
Solution for subcutaneous injection, pre-filled, multi-dose pen that delivers doses of 0.6mg, 1.2 
717 
mg, 1.8 mg, 2.4 mg or 3.0 mg (6mg/mL, 3mL) 
718 
5.2 
Treatment Regimen 
719 
Dose: 
720 
• 
Recommended dose of Saxenda® or matching placebo is 3.0 mg daily 
721 
• 
Administer at any time of the day, without regard to the timing of meals 
722 
 
723 
Dose escalation should be used to reduce the likelihood of GI symptoms 
724 
• 
Week 1: 0.6mg/day 
725 
Week 2: 1.2mg/day 
726 
Week 3: 1.8mg/day 
727 
Week 4: 2.4mg/day 
728 
Week 5 and Onward: 3.0mg/day 
729 
• 
May delay dose escalation for 1 additional week if unable to tolerate increased dose 
730 
• 
Discontinue if patient is unable to tolerate the study drug for any reason 
731 
 
732 
Route: 
733 
• 
Inject subcutaneously in the abdomen, thigh or upper arm. 
734 
• 
The injection site and timing can be changed without dose adjustment. 
735 


Universal Trial Number: U1111-1178-7319               Version 7: 10/11/2019                           Page   20 
 
5.3 
Subject Compliance Monitoring 
736 
• 
The study drug will be dispensed to each subject at study visits (baseline, 3, 6, 9 months) and will 
737 
be recorded by the investigational pharmacy and study team.   
738 
• 
The subjects are required to return used pens when receiving new drug and the number of used 
739 
pens returned will be recorded by the investigational pharmacy. 
740 
• 
Subjects are required to bring a daily study drug administration log to 3, 6, 9, and 12 months 
741 
study visits. 
742 
• 
Subjects who are not compliant with administrating the study drug ≥ 30 days will be withdrawn 
743 
from the study. 
744 
5.4 
Concomitant Therapy 
745 
• 
Avoid use with insulin  
746 
• 
Avoid use with other glucagon-like peptide-1 receptor agonists 
747 
• 
Advise to take daily post RYGB supplements which include multivitamin with copper, calcium, 
748 
vitamin D, iron, and vitamin B12.   
749 
5.5 
Receiving, Storage, Dispensing and Return 
750 
5.5.1 
Receipt of Drug Supplies 
751 
• 
Upon receipt of the study treatment supplies, an inventory will be performed and a drug receipt 
752 
log filled out and signed by the person accepting the shipment.   
753 
• 
The designated study staff will counts and verifies that the shipment contains all the items noted 
754 
in the shipment inventory.   
755 
• 
Any damaged or unusable study drug in a given shipment (active drug or comparator) will be 
756 
documented in the study files.   
757 
• 
The investigator will notify Novo Nordisk of any damaged or unusable study drug that was 
758 
supplied to the investigator’s site. 
759 
5.5.2 
Storage 
760 
• 
All study drugs will be stored at the NYULMC investigational pharmacy and distributed by the 
761 
NYULMC investigational pharmacist.  
762 
• 
Store unopened prefilled pens refrigerated, between 2 and 8 degrees C (36 and 46 degrees F).  
763 
• 
Store opened pens up to 30 days at controlled room temperature, between 15 and 30 degrees C 
764 
(59 and 86 degrees F), or refrigerated, between 2 and 8 degrees C (36 and 46 degrees F) and 
765 
protect from excessive heat and sunlight.  
766 
• 
Avoid storing directly adjacent to cooling compartment in refrigerator.  
767 
• 
Do not freeze or use a pen that has been frozen. 
768 
5.6 
Method for Assigning Subjects to Treatment Groups and Dispensing 
769 
of Study Drug 
770 
5.6.1 
Randomization Process 
771 
Eligible subjects will be randomized to one of the two treatment groups in a 2:1 ratio to receive either 
772 
study drug (Liraglutide (rDNA origin) injection, 3 x Saxenda® pen, NDC 0169-2800-13) or matching 
773 
placebo, with stratification by gender and percent post-operative TBWL (<25%, 25 – 49.9%).  Stratified 
774 
block randomization will be employed. Randomization lists will be sent to the pharmacist who will then 
775 
be able to distribute the study drug/placebo as patients are enrolled, and the remainder of the study staff 
776 
will be blinded. 
777 


Universal Trial Number: U1111-1178-7319               Version 7: 10/11/2019                           Page   21 
 
5.6.2 
Dispensing of Study Drug 
778 
The study drug will be dispensed to each subject at study visits (baseline, 3, 6, 9 months) upon returning 
779 
the used pens and the compliance with study drug administration will be recorded by the investigational 
780 
pharmacy and study team.   
781 
 
782 
Study drug reconciliation will be performed to document drug assigned, drug consumed, and drug 
783 
remaining.  This reconciliation will be logged on the drug reconciliation form, and signed and dated by 
784 
the study team. 
785 
5.6.3 
Return or Destruction of Study Drug 
786 
At the completion of the study, there will be a final reconciliation of drug shipped, drug consumed, and 
787 
drug remaining.  This reconciliation will be logged on the drug reconciliation form, signed and dated.  
788 
Any discrepancies noted will be investigated, resolved, and documented prior to return or destruction of 
789 
unused study drug.  Drug destroyed on site will be documented in the study files. 
790 
6 
Study Procedures 
791 
 
792 
Visit Number 
1 
 
 
2 
 
 
3 
 
 
4 
 
 
5 
 
Baseline 
1M 
2M 
3 
months 
4M 
5M 
6 
months 
7M 
8M 
9 
months 
10M 
11M 
12 
months 
Visit window 
0-4 wks 
prior to 
the 
treatment 
 
 
± 4 wks 
 
 
± 4 wks 
 
 
± 4 wks 
 
 
± 4 wks 
Informed 
consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Screening 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Medical 
History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Weight, BP, 
HR, Waist & 
Neck 
Circumference 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Medications 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Blood 
Pregnancy 
Test (Beta 
Quantitative 
HCG) (Only 
applicable 
for women of 
childbearing 
potential) 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
1BMP, 
HbA1c, 1Lipid 
profile, 
Amylase, 
Lipase 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Additional 
plasma and 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 


Universal Trial Number: U1111-1178-7319               Version 7: 10/11/2019                           Page   22 
 
serum for 
future 
analyses 
PHQ-9, IPAQ, 
24 hr diet 
recall 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Diet and 
Physical 
Activity 
Counseling by 
RD  
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Body 
Composition 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Comorbidities: 
Diabetes, 
Hypertension, 
STOP-BANG 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
2AEs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Study 
Medication 
Compliance 
Phone call 
 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
 
1. 
Fasting is required 
793 
2. 
Ask about hypoglycemia symptoms for patients with Type 2 DM 
794 
6.1 
Visit 1 (Baseline/Pre-Treatment) 
795 
6.1.1 
Screening and Enrollment 
796 
Patients meeting all inclusion and no exclusion criteria will be offered the opportunity to participate in 
797 
this study. Patient informed consent will be obtained prior to any study specific procedures and patients 
798 
will be provided with ample time and opportunity to ask about the details of the study, and decide 
799 
whether or not to participate.  
800 
6.1.2 
Medical History 
801 
A full medical history will be taken during the baseline visit. Medical history includes previous bariatric 
802 
and non-bariatric surgeries, and recent & lifetime health history.   
803 
6.1.3 
Demographics  
804 
At baseline, the following demographic data will be collected and recorded: gender, date of birth, and 
805 
race/ethnicity. 
806 
6.1.4 
Physical Examination / Clinical Assessment  
807 
During the baseline and all in-office follow-up visits, a physical examination will be performed and the 
808 
following data will be collected and recorded:  
809 
• 
Blood pressure 
810 
• 
Heart rate 
811 
• 
Height (only at baseline) 
812 
• 
Weight 
813 
• 
Waist and neck circumference 
814 
• 
Medications 
815 


Universal Trial Number: U1111-1178-7319               Version 7: 10/11/2019                           Page   23 
 
6.1.5 
Diet and Physical Activity Counseling 
816 
• 
Initial nutritional assessment by RD (Registered Dietician) 
817 
• 
24 hr diet recall (see attachment) 
818 
• 
Body composition (Basic metabolic rate, % total body fat, % body water weight, muscle mass 
819 
weight) 
820 
6.1.6 
Comorbidities Assessment 
821 
Comorbidity status will be assessed at baseline.  The following co-morbid conditions will be assessed:  
822 
diabetes, hypertension, and STOP-BANG score.  
823 
 
824 
Diabetes Scale 
825 
Score 
Description 
0 
Fasting blood glucose (<100 mg/dL) 
1 
Fasting blood glucose ≥100-125 mg/dL or diabetes, no medications 
2 
Fasting blood glucose ≥126 mg/dL or diabetes treated with medication (oral and/or 
injectable) 
Number of medications: ______ 
826 
Hypertension Scale 
827 
 
Description 
0 
Normal BP, no indication of hypertension (BP below 120/80 mmHg), no medication 
1 
Prehypertension (systolic BP 120-139 or diastolic BP 80-89 mmHg), no medication 
2 
Stage 1 hypertension (systolic BP 140-159 or diastolic BP 90-99 mmHg) or 
hypertension controlled with single medication 
3 
Stage 2 hypertension (systolic BP ≥160 mmHg or diastolic BP ≥ 100 mmHg) or 
hypertension controlled with multiple medications 
4 
Hypertension poorly controlled despite multiple medications 
 
828 
 
STOP-BANG score: _____ 
829 
1. Do you snore loudly (louder than talking or loud enough to be heard 
through closed doors)? 
Yes 
No 
2. Do you often feel tired, fatigued, or sleepy during daytime?  
Yes 
No 
3. Has anyone observed you stop breathing during your sleep?  
Yes 
No 
4. Do you have or are you being treated for high blood pressure?  
Yes 
No 
5. BMI >30kg/m2 
Yes 
No 
6. Age >50 
Yes 
No 
7. Neck circumference >16 inches 
Yes 
No 
8. Male 
Yes 
No 
 
830 
6.1.7 
Blood work (total 25 ml blood collection) 
831 
• 
Blood Pregnancy (Total Beta Quantitative HCG) (Only applicable for women of childbearing 
832 
potential) 
833 
• 
Fasting BMP 
834 
• 
HbA1c 
835 
• 
Lipid profile 
836 
• 
Amylase 
837 
• 
Lipase 
838 


Universal Trial Number: U1111-1178-7319               Version 7: 10/11/2019                           Page   24 
 
• 
Additional 15 ml blood for future analyses - Banking of additional plasma and serum for future 
839 
markers of caridometabolic risk in post-RYGB patients. 
840 
o 
Collecting additional blood for future analysis is mandatory because it is imperative that the stored 
841 
sample be used for continued analyses as new scientific discoveries are available and for retesting 
842 
during the course of the study if necessary. 
843 
o 
Samples will be stored in the Bell Vascular Biology Research Program (NYU Smilow 7th floor) 
844 
and accessed only by the study team members. The unique code number that is used to label the 
845 
samples will not be based on any subject’s identifiers. The master list linking names to code 
846 
numbers will be kept into the password-protected REDCap data management system. 
847 
o 
Results from these analyses will be preliminary, and the clinical implications of any findings may 
848 
not be understood for years. Therefore, individual study results will not be shared with the 
849 
subjects. 
850 
o 
No genetic testing will be done on the stored samples. 
851 
o 
Some of the stored de-identified samples may be sent to other places to study the related diseases 
852 
and conditions.  
853 
o 
All samples will be destroyed no more than twenty years from the end of the study.  However, if 
854 
the subject requests to destroy the stored samples, the study team will destroy the samples upon 
855 
receiving your written request. 
856 
 
857 
6.1.8 
Questionnaires 
858 
• 
PHQ-9 (see attachment) 
859 
• 
IPAQ (see attachment) 
860 
 
861 
6.2 
Visit 2, 3, 4 (Post-treatment) 
862 
6.2.1 
Physical Examination / Clinical Assessment  
863 
During the baseline and all in-office follow-up visits, a physical examination will be performed and the 
864 
following data will be collected and recorded:  
865 
• 
Blood pressure 
866 
• 
Heart Rate 
867 
• 
Weight 
868 
• 
Waist and neck circumference 
869 
• 
Medications 
870 
6.2.2 
Diet and Physical Activity Counseling 
871 
• 
Follow up diet and physical activity counseling by RD 
872 
• 
Collection of diet and exercise diaries (see attachment) 
873 
• 
Body composition (Basic metabolic rate, % total body fat, % body water weight, muscle mass 
874 
weight) 
875 
6.2.3 
Comorbidities Assessment 
876 
The following co-morbid conditions will be assessed: diabetes, hypertension, and STOP-BANG score at 
877 
the 3, 6, 9 and 12 month visits. 
878 
6.2.4 
Blood work  
879 
Total 10 ml blood collection for visit 2 and 4 
880 
Total 25 ml blood collection for visit 3 and 5 
881 
• 
Blood Pregnancy (Total Beta Quantitative HCG) (Only applicable for women of childbearing 
882 
potential) 
883 


Universal Trial Number: U1111-1178-7319               Version 7: 10/11/2019                           Page   25 
 
• 
BMP 
884 
• 
HbA1c 
885 
• 
Lipid profile 
886 
• 
Amylase 
887 
• 
Lipase 
888 
• 
Additional 15 ml blood for future analyses - Banking of additional plasma and serum for future 
889 
markers of caridometabolic risk in post-RYGB patients (6 and 12 months only). 
890 
6.2.5 
Questionnaires 
891 
• 
PHQ-9  
892 
• 
IPAQ  
893 
6.2.6 
Adverse Events Assessment 
894 
Through-out the study the occurrence of drug-related AEs and pregnancies will be monitored, recorded, 
895 
and reported to IRB and Novo Nordisk. 
896 
6.2.7 
Monthly Contact 
897 
Study staff will call or email each subject at 1, 2, 4, 5, 7, 8, 10, and 11 months to review medication compliance and 
898 
adverse events.  
899 
7 
Statistical Plan 
900 
7.1 
Sample Size Determination 
901 
We intend to recruit 132 subjects.  A recent study of liraglutide versus placebo in subjects weighing 106.2 
902 
+/- 21.1 kg (BMI 38.2 ± 6.4) at baseline demonstrated that nearly 2/3 of subjects treated with liraglutide 
903 
for 56 weeks lost at least 5% of enrollment body weight, vs. approximately 1/4 with placebo.  We expect 
904 
to see similar results in our subjects.  In order to detect an absolute difference of 36.1% in the proportion 
905 
of subjects losing at least 5% of enrollment body weight in the liraglutide (expected proportion 63.2%) 
906 
and placebo arms (expected proportion 27.1%), with an alpha of 0.05 and beta of 0.1, we will require a 
907 
sample size of 99 (2x liraglutide:1x placebo).  In order to account for an estimated loss-to-follow-up of 
908 
25%, we increase the sample size to 132. 
909 
7.2 
Statistical Methods 
910 
Data will be analysed on an intention-to-treat basis. Missing values will be assessed for patterns and 
911 
imputed using a multiple imputation method for measurements made after baseline. Patient demographics 
912 
will be summarized by treatment group.  Categorical variables will be presented as proportions, normally 
913 
distributed continuous variables will be presented as mean ± standard deviation, and skewed continuous 
914 
variables will be presented as median [interquartile range]. Our primary outcome (proportion of subjects 
915 
losing at least 5% enrollment body weight) will be assessed using Cochran-Mantel-Haenszel test after 
916 
accounting for stratification variables.  The treatment groups will be further compared by secondary 
917 
outcomes, using t-tests or Wilcoxon rank sum tests, (as appropriate) for continuous variables. Prior to 
918 
analysis, non-normally distributed continuous data will be categorized using quartiles or using an 
919 
appropriate transformation method (e.g. log-transformed).   
920 
 
921 
Paired sample t-tests assessing change at 6 months and 12 months will be used to test, separately for each 
922 
treatment group, whether each of the post-intervention measurements differs from the baseline 
923 
measurement. Change in continuous secondary outcome variables will be compared between treatment 
924 
groups using independent samples t-tests.  An ANCOVA model including stratification variables (gender, 
925 
percent post-operative weight loss) will be used to assess changes in these secondary outcomes.  These 
926 


Universal Trial Number: U1111-1178-7319               Version 7: 10/11/2019                           Page   26 
 
results will provide information to inform further studies, but will remain descriptive given our limited 
927 
power. 
928 
7.3 
Subject Population(s) for Analysis 
929 
Primary and secondary analyses will be performed in the all-treated population. 
930 
7.4 
Interim Analysis 
931 
Given the limited duration of the study, we do not plan interim analyses of efficacy parameters.   
932 
8 
Safety and Adverse Events 
933 
8.1 
Definitions 
934 
8.1.1 
Unanticipated Problems Involving Risk to Subjects or Others 
935 
Any incident, experience, or outcome that meets all of the following criteria:  
936 
• Unexpected in nature, severity, or frequency   
937 
• Related or possibly related to participation in the research (i.e. possibly related means there is a 
938 
reasonable possibility that the incident experience, or outcome may have been caused by the 
939 
procedures involved in the research) 
940 
• Suggests that the research places subjects or others at greater risk of harm (including physical, 
941 
psychological, economic, or social harm). 
942 
8.1.2 
Adverse Event 
943 
An adverse event (AE) is any symptom, sign, illness or experience that develops or worsens in severity 
944 
during the course of the study.  Intercurrent illnesses or injuries should be regarded as adverse events.  
945 
Abnormal results of diagnostic procedures are considered to be adverse events if the abnormality: 
946 
• results in study withdrawal 
947 
• is associated with a serious adverse event 
948 
• is associated with clinical signs or symptoms 
949 
• leads to additional treatment or to further diagnostic tests 
950 
• is considered by the investigator to be of clinical significance 
951 
8.1.2.1 
Expected Adverse Events related to study drug 
952 
• 
Nausea (39.3%) 
953 
• 
Diarrhea (20.9%) 
954 
• 
Hypoglycemia in Type 2 DM (23.0%) 
955 
• 
Constipation (19.4%) 
956 
• 
Vomiting (15.7%) 
957 
• 
Headache (13.6%) 
958 
• 
Decreased appetite (10.0%) 
959 
• 
Dyspepsia (9.6%) 
960 
• 
Fatigue (7.5%) 
961 
• 
Dizziness (6.9%) 
962 
• 
Abdominal pain (5.4%) 
963 
• 
Increased lipase (5.3%) 
964 
• 
Upper abdominal pain (5.1%) 
965 
• 
Gastroesophageal reflux disease (4.7%) 
966 
• 
Gastroenteritis (4.7%) 
967 


Universal Trial Number: U1111-1178-7319               Version 7: 10/11/2019                           Page   27 
 
• 
Abdominal distension (4.5%) 
968 
• 
Eructation (4.5%) 
969 
• 
Urinary tract infection (4.3%) 
970 
• 
Flatulence (4.0%) 
971 
• 
Viral gastroenteritis (2.8%) 
972 
• 
Injection site erythema (2.5%) 
973 
• 
Injection site reaction (2.5%) 
974 
• 
Insomnia (2.4%) 
975 
• 
Dry mouth (2.3%) 
976 
• 
Asthenia (2.1%) 
977 
• 
Anxiety (1.6%)  
978 
• 
Cholelithiasis (1.5%) 
979 
• 
Hypotension (1.1%) 
980 
• 
Urticaria (0.7%) 
981 
• 
Breast cancer (0.6%) 
982 
• 
Cholecystitis (0.6%) 
983 
• 
Colorectal neoplasms (0.5%)  
984 
• 
Pancreatitis (0.3%) 
985 
• 
Cardiac conduction disorder (0.3%) 
986 
• 
Suicidal thoughts (0.2%) 
987 
• 
Papillary thyroid carcinoma (0.2%) 
988 
• 
Angioedema and anaphylactic reaction (reported, but percentage unknown) 
989 
• 
C-cell hyperplasia of thyroid (potential risk) 
990 
• 
Medullary thyroid carcinoma (potential risk) 
991 
8.1.3 
Serious Adverse Event 
992 
Adverse events are classified as serious or non-serious.  A serious adverse event is any AE that is:  
993 
• fatal 
994 
• life-threatening 
995 
• requires or prolongs hospital stay 
996 
• results in persistent or significant disability or incapacity 
997 
• a congenital anomaly or birth defect 
998 
• suspicion of transmission of infectious agents 
999 
• an important medical event 
1000 
 
1001 
Important medical events are those that may not be immediately life threatening, but are clearly of major 
1002 
clinical significance.   They may jeopardize the subject, and may require intervention to prevent one of 
1003 
the other serious outcomes noted above.  For example, drug overdose or abuse, a seizure that did not 
1004 
result in in-patient hospitalization, or intensive treatment of bronchospasm in an emergency department 
1005 
would typically be considered serious.  
1006 
 
1007 
All adverse events that do not meet any of the criteria for serious should be regarded as non-serious 
1008 
adverse events.  
1009 
8.1.4 
Serious Adverse Drug Reaction (SADR) 
1010 
An adverse drug reaction (ADR) is an adverse event for which a causal relationship (Possible/Probable 
1011 
relation) between the study drug and the occurrence of the event is suspected. The ADR should be 
1012 
classified as serious if it meets one or more of the seriousness criteria.  
1013 


Universal Trial Number: U1111-1178-7319               Version 7: 10/11/2019                           Page   28 
 
8.1.4.1 
Reported serious adverse events/reactions related to study drug 
1014 
• 
Potential Risk of Thyroid C-Cell Tumors  
1015 
• 
Acute Pancreatitis  
1016 
• 
Acute Gallbladder Disease  
1017 
• 
Risk for Hypoglycemia with Concomitant Use of Anti-Diabetic Therapy  
1018 
• 
Heart Rate Increase  
1019 
• 
Renal Impairment  
1020 
• 
Hypersensitivity Reactions  
1021 
• 
Suicidal Behavior and Ideation  
1022 
8.1.5 
Severity Assessment Definitions 
1023 
• 
Mild: Transient symptoms, no interference with the subject’s daily activities 
1024 
• 
Moderate: Marked symptoms, moderate interference with the subject’s daily activities 
1025 
• 
Severe: Considerable interference with the subject’s daily activities, unacceptable 
1026 
8.1.6 
Relationship to Study Drug Assessment Definitions 
1027 
• 
Probable: Good reasons and sufficient documentation to assume a causal relationship 
1028 
• 
Possible: A causal relationship is conceivable and cannot be dismissed 
1029 
• 
Unlikely: The event is most likely related to an etiology other than the trial product 
1030 
8.1.7 
Outcome Categories and Definitions 
1031 
• 
Recovered: Fully recovered or by medical or surgical treatment the condition has returned to 
1032 
the level observed at the first trial related activity after the subject signed the informed 
1033 
consent 
1034 
• 
Recovering: The condition is improving and the subject is expected to recover from the event. 
1035 
This term should only be used when the subject has completed the trial 
1036 
• 
Recovered with sequelae: As a result of the AE, the subject suffered persistent and significant 
1037 
disability/incapacity (e.g. became blind, deaf, paralysed). Any AE recovered with sequelae 
1038 
should be rated as an SAE 
1039 
• 
Not recovered 
1040 
• 
Fatal 
1041 
• 
Unknown 
1042 
8.2 
Collection, Recording and Reporting of Adverse Events 
1043 
8.2.1 
Collection and Recording of Adverse Events 
1044 
All events meeting the definition of an adverse event must be collected and reported from the first trial 
1045 
related activity after the subject has signed the informed consent and until the end of the post-treatment 
1046 
follow-up period as stated in the protocol.  
1047 
 
1048 
At each contact with the subject, the investigator must seek information on adverse events by specific 
1049 
questioning and, as appropriate, by examination.  Information on all adverse events should be recorded 
1050 
immediately in the source document, and also in the appropriate adverse event module of the case report 
1051 
form (CRF).  All clearly related signs, symptoms, and abnormal diagnostic procedures results should 
1052 
recorded in the source document, though should be grouped under one diagnosis. 
1053 
 
1054 
The study period during which adverse events must be reported is normally defined as the period from the 
1055 
initiation of any study procedures to the end of the study treatment follow-up.  For this study, the study 
1056 
treatment follow-up is defined as 30 days following the last administration of study treatment.  
1057 


Universal Trial Number: U1111-1178-7319               Version 7: 10/11/2019                           Page   29 
 
 
1058 
All adverse events occurring during the study period must be recorded.  The clinical course of each event 
1059 
should be followed until resolution, stabilization, or until it has been determined that the study treatment 
1060 
or participation is not the cause.  Serious adverse events that are still ongoing at the end of the study 
1061 
period must be followed up to determine the final outcome.  Any serious adverse event that occurs after 
1062 
the study period and is considered to be possibly related to the study treatment or study participation 
1063 
should be recorded and reported immediately. 
1064 
8.2.1.1 
Preexisting Condition 
1065 
A preexisting condition is one that is present at the screening of the study.  A preexisting condition should 
1066 
be recorded as an adverse event if the frequency, intensity, or the character of the condition worsens 
1067 
during the study period. 
1068 
8.2.1.2 
General Physical Examination Findings 
1069 
At screening, any clinically significant abnormality should be recorded as a preexisting condition.  At the 
1070 
end of the study, any new clinically significant findings/abnormalities that meet the definition of an 
1071 
adverse event must also be recorded and documented as an adverse event.  
1072 
8.2.1.3 
Abnormal Laboratory Values 
1073 
A clinical laboratory abnormality should be documented as an adverse event if any one of the following 
1074 
conditions is met:  
1075 
• The laboratory abnormality is not otherwise refuted by a repeat test to confirm the abnormality 
1076 
• The abnormality suggests a disease and/or organ toxicity 
1077 
• The abnormality is of a degree that requires active management; e.g. change of dose, 
1078 
discontinuation of the drug, more frequent follow-up assessments, further diagnostic investigation, 
1079 
etc. 
1080 
8.2.1.4 
Hospitalization, Prolonged Hospitalization or Surgery 
1081 
Any adverse event that results in hospitalization or prolonged hospitalization should be documented and 
1082 
reported as a serious adverse event unless specifically instructed otherwise in this protocol.  Any 
1083 
condition responsible for surgery should be documented as an adverse event if the condition meets the 
1084 
criteria for any adverse event.  
1085 
 
1086 
Neither the condition, hospitalization, prolonged hospitalization, nor surgery are reported as an adverse 
1087 
event in the following circumstances: 
1088 
• Hospitalization or prolonged hospitalization for diagnostic or elective surgical procedures for a 
1089 
preexisting condition.  Surgery should not be reported as an outcome of an adverse event if the 
1090 
purpose of the surgery was elective or diagnostic and the outcome was uneventful. 
1091 
• Hospitalization or prolonged hospitalization required to allow efficacy measurement for the study. 
1092 
• Hospitalization or prolonged hospitalization for therapy of the target disease of the study, unless it 
1093 
is a worsening or increase in frequency of hospital admissions as judged by the clinical 
1094 
investigator. 
1095 
8.2.1.5 
Pregnancy 
1096 
If a female becomes pregnant during the study, the Investigator should stop the study drug.  The 
1097 
Investigator shall instruct the subject to notify her physician of the study drug.  Best practices should be 
1098 
followed in order to ensure the welfare of the subject and the fetus.  The subject will continue to be 
1099 
followed as part of the ITT population, but the pregnancy will be documented as a protocol deviation.  
1100 
The subject will not be evaluated as part of the PP population for timepoints after the pregnancy is 
1101 
confirmed.  
1102 


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1103 
Pregnancy by itself will not be considered an AE or serious adverse event (SAE).  Hospitalization for a 
1104 
normal delivery does not constitute an SAE.  However, the occurrence of an adverse pregnancy outcome 
1105 
for the mother or child may constitute an AE or SAE, and these should be reported as AE.  Reporting of 
1106 
all pregnancies to Novo Nordisk should occur within 5 working days from the time the investigator 
1107 
becomes aware of the event. 
1108 
8.2.2 
Reporting of Serious Adverse Events and Unanticipated Problems 
1109 
Investigators must conform to the adverse event reporting timelines, formats and requirements of the 
1110 
various entities including Novo Nordisk, but at a minimum those events that must be reported are those 
1111 
that are: 
1112 
• related to study participation, 
1113 
• unexpected,  
1114 
• serious or involve risks to subjects or others, and 
1115 
• serious adverse events  
1116 
 
1117 
For Narrative Reports of Safety Events 
1118 
If the report is supplied as a narrative, the minimum necessary information to be provided at the time of 
1119 
the initial report includes: 
1120 
• 
Study identifier 
• 
Study Center 
• 
Subject number 
• 
A description of the event 
• 
Date of onset 
• 
Current status 
• 
Whether study treatment was discontinued 
• 
The reason why the event is classified as serious 
• 
Investigator assessment of the association between 
the event and study treatment 
8.2.2.1 
Investigator reporting: notifying the IRB 
1121 
Report Promptly, but no later than 5 working days: 
1122 
Researchers are required to submit reports of the following problems promptly but no later than 5 
1123 
working days from the time the investigator becomes aware of the event: 
1124 
Unanticipated problems including adverse events that are unexpected and related 
1125 
• 
Unexpected: An event is “unexpected” when its specificity and severity are not accurately 
1126 
reflected in the protocol-related documents, such as the IRB-approved research protocol, any 
1127 
applicable investigator brochure, and the current IRB-approved informed consent document and 
1128 
other relevant sources of information, such as product labeling and package inserts.  
1129 
• 
Related to the research procedures: An event is related to the research procedures if in the opinion 
1130 
of the principal investigator, the event was more likely than not to be caused by the research 
1131 
procedures.  
1132 
• 
Harmful: either caused harm to subjects or others, or placed them at increased risk 
1133 
 
1134 
Other Reportable events: 
1135 
The following events also require prompt reporting to the IRB, though no later than 5 working days: 
1136 
• 
Complaint of a research subject when the complaint indicates unexpected risks or the 
1137 
complaint cannot be resolved by the research team. 
1138 
• 
Protocol deviations or violations (includes intentional and accidental/unintentional deviations 
1139 
from the IRB approved protocol) for any of the following situations:  
1140 
o one or more participants were placed at increased risk of harm  
1141 
o the event has the potential to occur again 
1142 


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o the deviation was necessary to protect a subject from immediate harm 
1143 
• 
Breach of confidentiality 
1144 
• 
Incarceration of a participant when the research was not previously approved under Subpart C 
1145 
and the investigator believes it is in the best interest of the subject to remain on the study. 
1146 
• 
New Information indicating a change to the risks or potential benefits of the research, in 
1147 
terms of severity or frequency. (e.g. analysis indicates lower-than-expected response rate or a 
1148 
more severe or frequent side effect; Other research finds arm of study has no therapeutic value; 
1149 
FDA labeling change or withdrawal from market) 
1150 
 
1151 
Reporting Process 
1152 
The reportable events noted above will be reported to the IRB using the form: “Reportable Event Form” 
1153 
or as a written report of the event (including a description of the event with information regarding its 
1154 
fulfillment of the above criteria, follow-up/resolution and need for revision to consent form and/or other 
1155 
study documentation). 
1156 
 
1157 
Copies of each report and documentation of IRB notification and receipt will be kept in the Clinical 
1158 
Investigator’s study file. 
1159 
8.2.2.2 
AE Reporting to Novo Nordisk 
1160 
The investigator will report to Novo Nordisk all SAEs, SUSARs, and SADRs at the same time such 
1161 
events are reported to regulatory authorities or within 15 days from the investigator becoming aware of 
1162 
such adverse events, whichever comes first. 
1163 
 
1164 
The investigator will collect the following information at minimum for each of these events: 
1165 
• 
Study name 
1166 
• 
Patient identification (e.g. initials, sex, age) 
1167 
• 
Event (preferably a diagnosis) 
1168 
• 
Drug  
1169 
• 
Reporter identification (e.g. Name, or initials) 
1170 
• 
Causality 
1171 
• 
Outcome 
1172 
8.2.3 
Follow-up of Adverse Events 
1173 
During and following a subject’s participation in a clinical trial, the investigator and institution will 
1174 
provide adequate medical care to the study subject for any study-related adverse events, including 
1175 
clinically significant laboratory values related to the study. State that this medical care for study subjects 
1176 
will be provided regardless of their insurance status.  
1177 
 
1178 
All adverse events classified as serious or severe or possibly/probably related to the trial product must be 
1179 
followed until the subject has recovered and all queries have been resolved. For cases of chronic 
1180 
conditions follow-up until the outcome category is “recovered” is not required, as these cases can be 
1181 
closed with an outcome of “recovering” or “not recovered”. 
1182 
 
1183 
All other adverse events must be followed until the outcome of the event is “recovering” (for chronic 
1184 
conditions), or “recovered” or until the end of the post-treatment follow-up stated in the protocol, 
1185 
whichever comes first, and until all queries related to these AEs have been resolved. 
1186 


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8.3 
Liability 
1187 
The sponsor-investigator will be responsible for the conduct of the study and agrees to defend, indemnify, 
1188 
and hold harmless Novo Nordisk, any of its parent companies, affiliates, or subsidiaries, and their 
1189 
respective officers, directors, employees, agents, representatives, distributors, salespersons, customers, 
1190 
licensees, and end-users from and against any claim, suit, demand, loss, damage, expense or liability 
1191 
imposed by any third party arising from or related to: (a) any breach of sponsor-investigator's obligations 
1192 
or representations; or (b) sponsor-investigator’s negligent or grossly negligent use or willful misuse of the 
1193 
study drug, the results, or services derived therefrom.  This indemnification shall not apply in the event 
1194 
and to the extent that a court of competent jurisdiction or a duly appointed arbiter determines that such 
1195 
losses or liability arose as a result of Novo Nordisk’s gross negligence, intentional misconduct, or 
1196 
material breach of its responsibilities 
1197 
8.4 
Unblinding Procedures 
1198 
The randomization information will be revealed to the investigator only in a medical emergency, i.e. 
1199 
when this appears necessary to ensure the subject’s safety and would be instrumental in further treatment 
1200 
decisions. 
1201 
 
1202 
If a subject’s treatment is unblinded, details of the time and reason for revealing must be documented in 
1203 
the subject’s medical records and in the CRF and should be reported to DSMB in 48 hours. 
1204 
8.5 
Stopping Rules  
1205 
• 
The trial will be terminated if two or more patients die within the 30 days of study drug 
1206 
administration.  
1207 
• 
The trial will be terminated if during the follow-up period five or more of the first 50 patients 
1208 
developed gastrointestinal or endocrine disorder leading to inpatient admission.  
1209 
• 
The trial will be terminated if the DSMB determine that the study should be terminated.   
1210 
8.6 
Medical Monitoring 
1211 
It is the responsibility of the Principal Investigator to oversee the safety of the study.  This safety 
1212 
monitoring will include careful assessment and appropriate reporting of adverse events as noted above, as 
1213 
well as the construction and implementation of a site data and safety-monitoring plan.   
1214 
8.6.1 
Data Monitoring Committee 
1215 
 
1216 
Data Safety and Monitoring Board (DSMB) 
1217 
8.6.1.1 
DSMB Responsibilities 
1218 
• 
Review the research protocol, informed consent documents, and plans for data safety; 
1219 
• 
Review the following blinded data; 
1220 
o baseline data 
1221 
o safety data (mortality and morbidity) 
1222 
o efficacy data 
1223 
o study withdrawal due to non-compliance and AEs 
1224 
o major protocol violation 
1225 
• 
Review external data to the study when relevant information that may have an impact on 
1226 
subject safety becomes available; 
1227 
• 
Review and evaluate ad hoc safety issues concerning the study at the request by study team; 
1228 
and  
1229 


Universal Trial Number: U1111-1178-7319               Version 7: 10/11/2019                           Page   33 
 
• 
Make recommendations to the investigators concerning continuation, termination, or other 
1230 
modifications of the study based on the observed beneficial or adverse effects of the study. 
1231 
 
1232 
All DSMB members will disclose their conflicts of interests before the study initiation and any updates 
1233 
during the study period. 
1234 
8.6.1.2 
DSMB membership 
1235 
The data safety monitoring board will be composed of several physicians at least one independent 
1236 
physician whose expertise is in the treatment of obesity, clinical trials, and statistical knowledge.  One 
1237 
DSMB member will serve as chair.  The DSMB chair must have served as a member and chair of this 
1238 
study and be willing to make firm commitment to participate as chair for the duration of the study. 
1239 
 
1240 
Members 
1241 
Medical monitor (Chair): an independent endocrinologist or gastroenterologist whose expertise 
1242 
is in the treatment of obesity, clinical trials, and statistical knowledge 
1243 
Jose O Aleman, M.D. 
1244 
Department of Medicine, NYUSOM, 212-501-0585, jose.aleman@nyumc.org 
1245 
 
1246 
Physicians: an independent endocrinologist or gastroenterologist 
1247 
 
Elizabeth Weinshel, M.D.  
1248 
Department of Medicine, NYUSOM, 212-686-7500, elizabeth.weinshel@nyumc.org 
1249 
 
1250 
Holly Lofton, M.D.  
1251 
Department of Surgery, Medical Weight Loss Physician, NYUSOM, 212-263-0883, 
1252 
holly.lofton@nyumc.org 
1253 
 
1254 
Christine Ren-Fielding, M.D. 
1255 
Department of Surgery, Bariatric Surgeon, 212-263-2174, christine.ren-fielding@nyumc.org 
1256 
 
1257 
Sean Heffron, M.D., M.S., M.Sc. 
1258 
Department of Medicine, Leon H. Charney Division of Cardiology, 212-263-0855, 
1259 
sean.heffron@nyumc.org 
1260 
8.6.1.3 
Projected Schedule of Meetings 
1261 
Initial Meeting: An initial meeting of the DSMB will be held prior to any subject enrollment in order to 
1262 
review the protocol, establish a distribution and meeting schedules, the study modification, termination 
1263 
guidelines, and reports formats.  This meeting will be done via e-mail or telephone conference. 
1264 
 
1265 
Regular DSMB Meetings: Subsequent DSMB meetings will be held to review and discuss study data 
1266 
according to the schedule as described in the table below. This meeting will be done via telephone 
1267 
conference or in-person meeting after distributing the data/reports via e-mail. 
1268 
 
1269 
Timeline 
Data Review by 
Type of Data 
When the first 25 patients were 
enrolled. 
Entire DSMB 
baseline data 
safety data (mortality and morbidity) 
efficacy data 
study withdrawal due to non-compliance and 
AEs 
accrual and withdrawal rates 
major protocol violation 


Universal Trial Number: U1111-1178-7319               Version 7: 10/11/2019                           Page   34 
 
external data to the study if available  
When the first 50 patients were 
completed. 
Entire DSMB 
baseline data 
safety data (mortality and morbidity) 
efficacy data 
study withdrawal due to non-compliance and 
AEs 
accrual and withdrawal rates 
major protocol violation 
external data to the study if available  
When the first 100 patients were 
completed. 
Entire DSMB 
safety data (mortality and morbidity) 
efficacy data 
study withdrawal due to non-compliance and 
AEs 
accrual and withdrawal rates 
major protocol violation 
study conduct issues 
external data to the study if available 
Upon completion (132 patients) or 
termination of study 
Entire DSMB 
safety data (mortality and morbidity) 
efficacy data 
study withdrawal due to non-compliance and 
AEs 
accrual and withdrawal rates 
major protocol violation 
study conduct issues 
external data to the study if available 
 
1270 
Ad Hoc meetings: An ad hoc meeting will be called at any time by the investigator and DSMB member 
1271 
if immanent study subject safety issues arise.  If a significant safety concern arises during the study, the 
1272 
DSMB chair or PI may convene a meeting to review safety and any other aspects of the study.  
1273 
 
1274 
Significant safety events may include, but are not limited to the followings: 
1275 
• 
A death or life-threatening condition sustained by a study subject, regardless of causality 
1276 
• 
An unexpected serious safety issue newly identified that could expose participants to 
1277 
unnecessary risks. 
1278 
 
1279 
The above case may require suspension or termination of study if DSMB review confirms that the risks 
1280 
are too high to continue the study enrollment 
1281 
 
1282 
Proposed study amendments that significantly alter the treatment plan and /or deal with subject safety 
1283 
concerns will prompt an ad hoc meeting for review prior to implementation of changes.  This may require 
1284 
suspension of enrollment pending DSMB review. 
1285 
8.6.1.4 
Meeting Format 
1286 
DSMB meetings will generally be conducted by face to face or teleconference and facilitated by the 
1287 
DSMB chair. The investigator and study coordinator will attend the meeting with DSMB members to 
1288 
provide additional information requested or answer the questions raised during the review of the data. 
1289 
 
1290 
All Adverse Events Report including expected and unexpected will be recorded and reported to DSMB 
1291 
using Excel and SPSS program. The AE reports will not contain any information that can potentially 
1292 
disclose any subject’s treatment group. AE reports will include the followings.  
1293 


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• 
Name of event 
1294 
• 
Onset and end date 
1295 
• 
UAE 
1296 
• 
Severity (mild, moderate, severe) 
1297 
• 
Seriousness 
1298 
• 
Relationship to the study drug/procedure 
1299 
• 
Action taken 
1300 
• 
Outcomes  
1301 
 
1302 
All reports will be submitted by the study coordinator. 
1303 
 
1304 
Meeting Minutes: Minutes of DSMB meetings will be distributed to members, all investigators, and 
1305 
study personnel within 4 weeks and also to IRB annually if available.  
1306 
Minutes include at a minimum: 
1307 
• 
Protocol number and study title 
1308 
• 
DSMB meeting date 
1309 
• 
Copy of agenda 
1310 
• 
A list of attendances, including DSMB members and any other people present, listing their 
1311 
professional title and role at the meeting 
1312 
• 
Information reviewed and related discussion during the meeting 
1313 
• 
DSMB recommendations including clear and concise rationale 
1314 
 
1315 
Communications 
1316 
The DSMB chair communicates directly with the investigators to allow them the opportunity to ask 
1317 
questions and discuss any recommendations.  If the investigator(s) accepts the recommendations of the 
1318 
DSMB, the investigator(s) will be responsible for implementing the actions in response.  In the event the 
1319 
study must be amended, the investigator will prepare and submit the amendment to the DSMB for 
1320 
approval prior to implementing amendment changes. 
1321 
8.6.1.5 
Reportable Adverse Events 
1322 
All SAEs will be reported to all DSMB member and all investigators via e-mail within one or two 
1323 
working day of learning of the event.   A summary of all adverse events, (previously reported or not, 
1324 
serious or not) will be submitted to the DSMB as described in this plan. 
1325 
 
1326 
All unexpected serious adverse events will be reported to IRB, DSMB, and Novo Nordisk regardless the 
1327 
relationship to the study drug. 
1328 
8.6.1.6 
DSMB Considerations and Policies 
1329 
Stopping Rules: After reviewing/considering the information, the DSMB will determine whether the 
1330 
study should continue as planned, proceed with modifications, or be terminated.  The justification to 
1331 
terminate the study may be due to the DSMB’s analysis that there is overwhelming safety issue.   
1332 
9 
Data Handling and Record Keeping 
1333 
9.1 
Confidentiality 
1334 
To safeguard against the loss of confidentiality, all study information will be stored using REDCap 
1335 
(Research Electronic Date Capture) database, which is a commonly used, secure, web-based system that 
1336 
is compliant with HIPAA standards.  Access to the database will be restricted to the members of the 
1337 
research staff for this project.  The unique study ID will be used to link the subject’s identifiers.  No 
1338 


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names or other identifying information will be used in publications which stem from this research. Only 
1339 
research staff will have the linking key.  Subjects will be informed of these exceptions in the informed 
1340 
consent document.   
1341 
 
1342 
Only consent forms signed by study subjects will be stored in a locked cabinet inside a locked office on 
1343 
NYULMC property.  
1344 
9.2 
Confidentiality and HIPAA 
1345 
Information about study subjects will be kept confidential and managed according to the requirements of 
1346 
the Health Insurance Portability and Accountability Act of 1996 (HIPAA).  Those regulations require a 
1347 
signed subject authorization informing the subject of the following:  
1348 
• What protected health information (PHI) will be collected from subjects in this study 
1349 
• Who will have access to that information and why 
1350 
• Who will use or disclose that information  
1351 
• The rights of a research subject to revoke their authorization for use of their PHI.  
1352 
In the event that a subject revokes authorization to collect or use PHI, the investigator, by regulation, 
1353 
retains the ability to use all information collected prior to the revocation of subject authorization.  For 
1354 
subjects that have revoked authorization to collect or use PHI, attempts should be made to obtain 
1355 
permission to collect at least vital status (i.e. that the subject is alive) at the end of their scheduled study 
1356 
period. 
1357 
9.3 
Source Documents 
1358 
Source data is all information, original records of clinical findings, observations, or other activities in a 
1359 
clinical trial necessary for the reconstruction and evaluation of the trial.  Source data are contained in 
1360 
source documents.  Examples of these original documents, and data records include: hospital records, 
1361 
clinical and office charts, laboratory notes, memoranda, subjects’ diaries or evaluation checklists, 
1362 
pharmacy dispensing records, recorded data from automated instruments, copies or transcriptions certified 
1363 
after verification as being accurate and complete, microfiches, photographic negatives, microfilm or 
1364 
magnetic media, x-rays, subject files, and records kept at the pharmacy, at the laboratories, and at medico-
1365 
technical departments involved in the clinical trial. 
1366 
9.4 
Case Report Forms 
1367 
The study case report form (CRF) is the primary data collection instrument for the study.  All data 
1368 
requested on the CRF must be recorded.  All missing data must be explained.  If a space on the CRF is 
1369 
left blank because the procedure was not done or the question was not asked, write “N/D”.  If the item is 
1370 
not applicable to the individual case, write “N/A”.  All entries should be printed legibly in black ink.  If 
1371 
any entry error has been made, to correct such an error, draw a single straight line through the incorrect 
1372 
entry and enter the correct data above it.  All such changes must be initialed and dated.  DO NOT ERASE 
1373 
OR WHITE OUT ERRORS.  For clarification of illegible or uncertain entries, print the clarification 
1374 
above the item, then initial and date it. 
1375 
 
1376 
All research data will be collected in Case Report Forms (CRFs). Clinical safety data, labs, screening 
1377 
information, questionnaires, informed consent, and progress notes will also be collected in Source 
1378 
Documents.  
1379 
 
1380 
CRFs of all research data will be entered into a password protected electronic database using a secure 
1381 
server at NYU Langone School of Medicine. The computer used for this study will be password protected 
1382 
and kept locked in a locked office at NYU Langone Weight Management Program. Only designated study 
1383 
staff will have access to patient data and these include: the PI of the study, sub-investigators, the research 
1384 


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coordinator and the research assistant.  Though the information collected in this study may be published, 
1385 
no patient will be identified by name or other personal information. 
1386 
9.5 
Records Retention 
1387 
It is the investigator’s responsibility to retain study essential documents for at least 2 years after 
1388 
completion of the study. These documents will be retained for a longer period if required by an agreement 
1389 
with Novo Nordisk.  In such an instance, it is the responsibility of Novo Nordisk to inform the 
1390 
investigator/institution as to when these documents no longer need to be retained.  
1391 
10 Study Monitoring, Auditing, and Inspecting 
1392 
10.1 Study Monitoring Plan 
1393 
A contracted CRA will conduct monitoring visit after the first 10 enrollments and every 30 enrollments 
1394 
after the initial monitoring to review subject and drug accountability records for compliance with the 
1395 
protocol.  Any protocol deviations will be discussed with the Investigator upon identification.  All 
1396 
protocol deviations will be reported to the Institutional Review Board (IRB) according to the IRB’s 
1397 
reporting requirements. The investigator will allocate adequate time for such monitoring activities.  The 
1398 
Investigator will also ensure that the monitor or other compliance or quality assurance reviewer is given 
1399 
access to all the above noted study-related documents and study related facilities (e.g. pharmacy, 
1400 
diagnostic laboratory, etc.), and has adequate space to conduct the monitoring visit. 
1401 
10.2 Auditing and Inspecting 
1402 
The investigator will permit study-related monitoring, audits, and inspections by the IRB/EC, Novo 
1403 
Nordisk, government regulatory bodies, and University compliance and quality assurance groups of all 
1404 
study related documents (e.g. source documents, regulatory documents, data collection instruments, study 
1405 
data etc.).  The investigator will ensure the capability for inspections of applicable study-related facilities 
1406 
(e.g. pharmacy, diagnostic laboratory, etc.). 
1407 
 
1408 
Participation as an investigator in this study implies acceptance of potential inspection by government 
1409 
regulatory authorities and applicable University compliance and quality assurance offices. 
1410 
11 Ethical Considerations 
1411 
This study is to be conducted accordance with applicable US government regulations, Internaltional 
1412 
Conference on Harmonisation Good Clinical Practice guidelines, and applicable institutional research 
1413 
policies and procedures. 
1414 
 
1415 
This protocol and any amendments will be submitted to a properly constituted Institutional Review Board 
1416 
(IRB) or independent Ethics Committee (EC) in agreement with local legal prescriptions, for formal 
1417 
approval of the study conduct.  The decision of the IRB/EC concerning the conduct of the study will be 
1418 
made in writing to the investigator and a copy of this decision will be provided to before commencement 
1419 
of this study.   
1420 
 
1421 
The study team will comply with all applicable regulatory and legal requirements, ICH GCP guidelines, 
1422 
and the Declaration of Helsinki in obtaining and documenting the informed consent.  All subjects for this 
1423 
study will be provided a consent form describing this study and providing sufficient information for 
1424 
subjects to make an informed decision about their participation in this study.  The formal consent of a 
1425 
subject, using the IRB/EC-approved consent form, must be obtained before that subject undergoes any 
1426 
study procedure.  The consent form must be signed by the subject or legally acceptable surrogate, and the 
1427 
investigator-designated research professional obtaining the consent.  
1428 


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12 Study Finances 
1429 
12.1 Funding Source 
1430 
This study will be financed by Novo Nordisk. 
1431 
12.2 Conflict of Interest 
1432 
Any investigator who has a conflict of interest with this study (patent ownership, royalties, or financial 
1433 
gain greater than the minimum allowable by their institution, etc.) must have the conflict reviewed by a 
1434 
properly constituted Conflict of Interest Committee with a Committee-sanctioned conflict management 
1435 
plan prior to participation in this study.  All NYULMC investigators will follow the applicable University 
1436 
conflict of interest policies. 
1437 
12.3 Costs to the Subject 
1438 
There is no cost for the research related components (study drugs, visits, tests, procedures). 
1439 
12.4 Subject Stipends or Payments 
1440 
For their participation in each aspect of the study, patients will be paid in gift cards up to $500 for their 
1441 
time and travel expenses.  The subjects will receive a gift card for each completed visit according to the 
1442 
below schedule.  The subjects will receive a matching gift card if the visit is completed within the time 
1443 
below.  
1444 
• 
$50 - Visit 2 (3 month +/- 4 weeks from the first day of study drug) 
1445 
• 
$50 - Visit 3 (6 months +/- 4 weeks from the first day of study drug) 
1446 
• 
$50 - Visit 4 (9 months +/-  4 weeks from the first day of study drug) 
1447 
• 
$100 - Visit 5 (12 months +/- 4 weeks from the first day of study drug) 
1448 
13 Publication Plan 
1449 
Once the data analysis is complete the data will then be prepared for publication in a peer reviewed 
1450 
journal deemed appropriate by Novo Nordisk and PI or otherwise disclose publicly the data or results of 
1451 
this study.  The study information will be registered at clinicaltrials.gov. 
1452 
 
1453 
Neither the complete nor any part of the results of the study carried out under this protocol, nor any of the 
1454 
information provided by Novo Nordisk for the purposes of performing the study, will be published or 
1455 
passed on to any third party without the consent of Novo Nordisk.  Any investigator involved with this 
1456 
study is obligated to provide Novo Nordisk with complete test results and all data derived from the study. 
1457 
 
1458 
PI will provide Novo Nordisk with a manuscript of submission(s) for review and comment.  PI will not 
1459 
publish any manuscript without Novo Nordisk’s prior approval. 
1460 
1461 


Universal Trial Number: U1111-1178-7319               Version 7: 10/11/2019                           Page   39 
 
 
1462 
14 References 
1463 
 
1464 
1. 
Courcoulas, A.P., et al., Weight change and health outcomes at 3 years after bariatric surgery 
1465 
among individuals with severe obesity. JAMA, 2013. 310(22): p. 2416-25. 
1466 
2. 
Christou, N.V., D. Look, and L.D. Maclean, Weight gain after short- and long-limb gastric 
1467 
bypass in patients followed for longer than 10 years. Ann Surg, 2006. 244(5): p. 734-40. 
1468 
3. 
Sjostrom, L., et al., Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric 
1469 
surgery. N Engl J Med, 2004. 351(26): p. 2683-93. 
1470 
4. 
Himpens, J., et al., Outcomes of revisional procedures for insufficient weight loss or weight 
1471 
regain after Roux-en-Y gastric bypass. Obes Surg, 2012. 22(11): p. 1746-54. 
1472 
5. 
Hallowell, P.T., et al., Should bariatric revisional surgery be avoided secondary to increased 
1473 
morbidity and mortality? Am J Surg, 2009. 197(3): p. 391-6. 
1474 
6. 
Vilsboll, T., et al., Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic 
1475 
review and meta-analyses of randomised controlled trials. BMJ, 2012. 344: p. d7771. 
1476 
7. 
Wadden, T.A., et al., Weight maintenance and additional weight loss with liraglutide after low-
1477 
calorie-diet-induced weight loss: the SCALE Maintenance randomized study. Int J Obes (Lond), 
1478 
2013. 37(11): p. 1443-51. 
1479 
8. 
Pi-Sunyer, X., et al., A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight 
1480 
Management. N Engl J Med, 2015. 373(1): p. 11-22. 
1481 
9. 
Habegger, K.M., et al., GLP-1R agonism enhances adjustable gastric banding in diet-induced 
1482 
obese rats. Diabetes, 2013. 62(9): p. 3261-7. 
1483 
10. 
Larsen, P.J., et al., Systemic administration of the long-acting GLP-1 derivative NN2211 induces 
1484 
lasting and reversible weight loss in both normal and obese rats. Diabetes, 2001. 50(11): p. 2530-
1485 
9. 
1486 
11. 
Raun, K., P. von Voss, and L.B. Knudsen, Liraglutide, a once-daily human glucagon-like 
1487 
peptide-1 analog, minimizes food intake in severely obese minipigs. Obesity (Silver Spring), 
1488 
2007. 15(7): p. 1710-6. 
1489 
12. 
Raun, K., et al., Liraglutide, a long-acting glucagon-like peptide-1 analog, reduces body weight 
1490 
and food intake in obese candy-fed rats, whereas a dipeptidyl peptidase-IV inhibitor, vildagliptin, 
1491 
does not. Diabetes, 2007. 56(1): p. 8-15. 
1492 
13. 
Astrup, A., et al., Effects of liraglutide in the treatment of obesity: a randomised, double-blind, 
1493 
placebo-controlled study. Lancet, 2009. 374(9701): p. 1606-16. 
1494 
14. 
Astrup, A., et al., Safety, tolerability and sustained weight loss over 2 years with the once-daily 
1495 
human GLP-1 analog, liraglutide. Int J Obes (Lond), 2012. 36(6): p. 843-54. 
1496 
15. 
van Can, J., et al., Effects of the once-daily GLP-1 analog liraglutide on gastric emptying, 
1497 
glycemic parameters, appetite and energy metabolism in obese, non-diabetic adults. Int J Obes 
1498 
(Lond), 2014. 38(6): p. 784-93. 
1499 
16. 
Peterson, G.E. and R.D. Pollom, Liraglutide in clinical practice: dosing, safety and efficacy. Int J 
1500 
Clin Pract Suppl, 2010(167): p. 35-43. 
1501 
 
1502 
1503 


Universal Trial Number: U1111-1178-7319               Version 7: 10/11/2019                           Page   40 
 
 
1504 
15 Attachments 
1505 
15.1 Attachment 1- Study Procedures 
1506 
15.2 Attachment 2- PHQ (Patient Health Questionnaire) 
1507 
15.3 Attachment 3- International Physical Activity Questionnaire (IPAQ) 
1508 
15.4 Attachment 4- 24 hours Food Recall 
1509 
15.5 Attachment 5- Diet and Exercise Diary with Preferred Starches List 
1510 
 
1511 
 
1512 
 
1513 
1514 


Universal Trial Number: U1111-1178-7319               Version 7: 10/11/2019                           Page   41 
 
 
1515 
ATTACHMENT 1 
1516 
Visit Number 
1 
 
 
2 
 
 
3 
 
 
4 
 
 
5 
 
Baseline 
1M 
2M 
3 
months 
4M 
5M 
6 
months 
7M 
8M 
9 
months 
10M 
11M 
12 
months 
Visit window 
0-4 wks 
prior to 
the 
treatment 
 
 
± 4 wks 
 
 
± 4 wks 
 
 
± 4 wks 
 
 
± 4 wks 
Informed 
consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Screening 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Medical 
History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Weight, BP, 
HR, Waist & 
Neck 
Circumference 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Medications 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Blood 
Pregnancy 
Test (Beta 
Quantitative 
HCG) (Only 
applicable 
for women of 
childbearing 
potential) 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
1BMP, 
HbA1c, 1Lipid 
profile, 
Amylase, 
Lipase 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Additional 
plasma and 
serum for 
future 
analyses 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
PHQ-9, IPAQ, 
24 hr diet 
recall 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Diet and 
Physical 
Activity 
Counseling by 
RD  
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Body 
Composition 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Comorbidities: 
Diabetes, 
Hypertension, 
STOP-BANG 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 


Universal Trial Number: U1111-1178-7319               Version 7: 10/11/2019                           Page   42 
 
2AEs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Study 
Medication 
Compliance 
Phone call 
 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
 
1. 
Fasting is required 
1517 
2. 
Ask about hypoglycemia symptoms for patients with Type 2 DM 
1518 
 
1519 
 
1520 
 
1521 
 
1522 
 
1523 
 
1524 
 
1525 
 
1526 
 
1527 
 
1528 
1529 


Universal Trial Number: U1111-1178-7319               Version 7: 10/11/2019                           Page   43 
 
 
1530 
ATTACHMENT 2:  
1531 
15.4.1.1 PHQ-9 (Patient Health Questionnaire Nine Symptom Checklist) 
1532 
 
1533 
Name ______________________ Date _________ 
Over the last 2 weeks, how often 
have you been bothered by any of 
the following problems? 
Not at all 
Several days More than half 
the days 
Nearly every day 
1. Little interest or pleasure in 
doing things 
0 
1 
2 
3 
2. Feeling down, depressed, or 
hopeless 
0 
1 
2 
3 
3. Trouble falling or staying 
asleep, or sleeping too much 
0 
1 
2 
3 
4. Feeling tired or having little 
energy 
0 
1 
2 
3 
5. Poor appetite or overeating 
0 
1 
2 
3 
6. Feeling bad about yourself—or 
that you are a failure or have let 
yourself or your family down 
0 
1 
2 
3 
7. Trouble concentrating on 
things, such as reading the 
newspaper or watching television 
0 
1 
2 
3 
8. Moving or speaking so slowly 
that other people could have 
noticed? Or the opposite—being 
so fidgety or restless that you have 
been moving around a lot more 
than usual 
0 
1 
2 
3 
9. Thoughts that you would be 
better off dead or of hurting 
yourself in some way 
0 
1 
2 
3 
(For office coding: Total Score ____ = ____ + ____ + ____) 
If you checked off any problems, how difficult have these problems made it for you to do your 
1534 
work, take care of things at home, or get along with other people? 
1535 
Not difficult at all 
Somewhat difficult 
Very difficult 
Extremely difficult 
□ 
□ 
□ 
□ 
 
1536 
 
1537 


Universal Trial Number: U1111-1178-7319               Version 7: 10/11/2019                           Page   44 
 
ATTACHMENT 3 
1538 
INTERNATIONAL PHYSICAL ACTIVITY QUESTIONNAIRE 
1539 
(AUGUST 2002) 
1540 
SHORT LAST 7 DAYS SELF-ADMINISTERED FORMAT 
1541 
FOR USE WITH YOUNG AND MIDDLE-AGED ADULTS (15-69 years) 
1542 
 
1543 
THE INTERNATIONAL PHYSICAL ACTIVITY QUESTIONNAIRES (IPAQ) COMPRISES A 
1544 
SET OF 4 QUESTIONNAIRES. LONG (5 ACTIVITY DOMAINS ASKED INDEPENDENTLY) 
1545 
AND SHORT (4 GENERIC ITEMS) VERSIONS FOR USE BY EITHER TELEPHONE OR 
1546 
SELF-ADMINISTERED METHODS ARE AVAILABLE. THE PURPOSE OF THE 
1547 
QUESTIONNAIRES IS TO PROVIDE COMMON INSTRUMENTS THAT CAN BE USED TO 
1548 
OBTAIN INTERNATIONALLY COMPARABLE DATA ON HEALTH–RELATED PHYSICAL 
1549 
ACTIVITY. 
1550 
 
1551 
BACKGROUND ON IPAQ 
1552 
THE DEVELOPMENT OF AN INTERNATIONAL MEASURE FOR PHYSICAL ACTIVITY 
1553 
COMMENCED IN GENEVA IN 1998 AND WAS FOLLOWED BY EXTENSIVE RELIABILITY 
1554 
AND VALIDITY TESTING UNDERTAKEN ACROSS 12 COUNTRIES (14 SITES) DURING 
1555 
2000.  THE FINAL RESULTS SUGGEST THAT THESE MEASURES HAVE ACCEPTABLE 
1556 
MEASUREMENT PROPERTIES FOR USE IN MANY SETTINGS AND IN DIFFERENT 
1557 
LANGUAGES, AND ARE SUITABLE FOR NATIONAL POPULATION-BASED PREVALENCE 
1558 
STUDIES OF PARTICIPATION IN PHYSICAL ACTIVITY. 
1559 
Using IPAQ  
1560 
Use of the IPAQ instruments for monitoring and research purposes is encouraged. It is recommended that 
1561 
no changes be made to the order or wording of the questions as this will affect the psychometric 
1562 
properties of the instruments.  
1563 
Translation from English and Cultural Adaptation 
1564 
Translation from English is supported to facilitate worldwide use of IPAQ. Information on the availability 
1565 
of IPAQ in different languages can be obtained at  www.ipaq.ki.se. If a new translation is undertaken we 
1566 
highly recommend using the prescribed back translation methods available on the IPAQ website. If 
1567 
possible please consider making your translated version of IPAQ available to others by contributing it to 
1568 
the IPAQ website. Further details on translation and cultural adaptation can be downloaded from the 
1569 
website. 
1570 
16 Further Developments of IPAQ  
1571 
International collaboration on IPAQ is on-going and an International Physical Activity Prevalence Study 
1572 
is in progress. For further information see the IPAQ website.  
1573 
More Information 
1574 
More detailed information on the IPAQ process and the research methods used in the development of 
1575 
IPAQ instruments is available at www.ipaq.ki.se and Booth, M.L. (2000).  Assessment of Physical 
1576 
Activity: An International Perspective.  Research Quarterly for Exercise and Sport, 71 (2): s114-20.  
1577 
Other scientific publications and presentations on the use of IPAQ are summarized on the website. 
1578 
INTERNATIONAL PHYSICAL ACTIVITY QUESTIONNAIRE 
1579 
We are interested in finding out about the kinds of physical activities that people do as part of their 
1580 
everyday lives.  The questions will ask you about the time you spent being physically active in the last 7 
1581 


Universal Trial Number: U1111-1178-7319               Version 7: 10/11/2019                           Page   45 
 
days.  Please answer each question even if you do not consider yourself to be an active person.  Please 
1582 
think about the activities you do at work, as part of your house and yard work, to get from place to place, 
1583 
and in your spare time for recreation, exercise or sport. 
1584 
 
1585 
Think about all the vigorous activities that you did in the last 7 days.  Vigorous physical activities refer 
1586 
to activities that take hard physical effort and make you breathe much harder than normal.  Think only 
1587 
about those physical activities that you did for at least 10 minutes at a time. 
1588 
 
1589 
1. 
During the last 7 days, on how many days did you do vigorous physical activities like heavy 
1590 
lifting, digging, aerobics, or fast bicycling?  
1591 
_____ days per week  
1592 
 
1593 
 
  
No vigorous physical activities  
Skip to question 3 
1594 
 
1595 
2. 
How much time did you usually spend doing vigorous physical activities on one of those days? 
1596 
_____ hours per day  
1597 
_____ minutes per day 
 
1598 
 
Don’t know/Not sure  
1599 
Think about all the moderate activities that you did in the last 7 days.  Moderate activities refer to 
1600 
activities that take moderate physical effort and make you breathe somewhat harder than normal.  Think 
1601 
only about those physical activities that you did for at least 10 minutes at a time. 
1602 
 
1603 
3. 
During the last 7 days, on how many days did you do moderate physical activities like carrying 
1604 
light loads, bicycling at a regular pace, or doubles tennis?  Do not include walking. 
1605 
_____ days per week 
1606 
 
1607 
 
  
No moderate physical activities  
Skip to question 5 
1608 
 
1609 
4. 
How much time did you usually spend doing moderate physical activities on one of those days? 
1610 
_____ hours per day 
1611 
_____ minutes per day 
1612 
 
Don’t know/Not sure  
1613 
 
1614 
Think about the time you spent walking in the last 7 days.  This includes at work and at home, walking 
1615 
to travel from place to place, and any other walking that you have done solely for recreation, sport, 
1616 
exercise, or leisure. 
1617 
 
1618 
5. 
During the last 7 days, on how many days did you walk for at least 10 minutes at a time?   
1619 
_____ days per week 
1620 
 
 
1621 
 
  
No walking  
 
  Skip to question 7 
1622 
 
1623 
6. 
How much time did you usually spend walking on one of those days? 
1624 
_____ hours per day 
1625 
_____ minutes per day 
 
1626 


Universal Trial Number: U1111-1178-7319               Version 7: 10/11/2019                           Page   46 
 
 
Don’t know/Not sure  
1627 
The last question is about the time you spent sitting on weekdays during the last 7 days.  Include time 
1628 
spent at work, at home, while doing course work and during leisure time.  This may include time spent 
1629 
sitting at a desk, visiting friends, reading, or sitting or lying down to watch television. 
1630 
7. During the last 7 days, how much time did you spend sitting on a week day? 
1631 
_____ hours per day  
1632 
_____ minutes per day 
 
1633 
 
 
Don’t know/Not sure  
1634 
This is the end of the questionnaire, thank you for participating. 
1635 
1636 


Universal Trial Number: U1111-1178-7319               Version 7: 10/11/2019                           Page   47 
 
Attachment 4 
1637 
24 Hour Food/Drink Recall 
Breakfast 
Food/Drinks Item 
Amount 
consumed 
Serving unit (i.e. slice, cup, 
tablespoon, ounce) 
  
  
  
  
  
  
  
  
  
  
  
  
Lunch 
Food/Drinks Item 
Amount 
consumed 
Serving unit (i.e. slice, cup, 
tablespoon, ounce) 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Dinner 
Food/Drinks Item 
Amount 
consumed 
Serving unit (i.e. slice, cup, 
tablespoon, ounce) 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Snacks 
Food/Drinks Item 
Amount 
consumed 
Serving unit (i.e. slice, cup, 
tablespoon, ounce) 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Desserts 
Food/Drinks Item 
Amount 
consumed 
Serving unit (i.e. slice, cup, 
tablespoon, ounce) 
  
  
  
  
  
  
  
  
  
  
  
  
 
1638 
ATTACHMENT 5 
1639 


Universal Trial Number: U1111-1178-7319               Version 7: 10/11/2019                           Page   48 
 
Diet and Exercise Diary with Preferred Starches List 
1640 


Universal Trial Number: U1111-1178-7319               Version 7: 10/11/2019                           Page   49 
 
Name: 
Date: 
Goal of this diet is to eat protein with every meal and snack and decrease carbohydrate intake as the day progresses- No fried food 
 
Portion mate 
cylinder color 
Red 
Orange 
Green 
Yellow 
Purple 
Water 
 
Meal Type 
Recommendations 
All meats, poultry, 
fish, seafood, tofu, 
eggs, egg whites 
All carbohydrate 
Non-preferred fruits 
All vegetables 
Preferred fruits List 
(Apple, pear, raspberry, 
blackberry, blueberry) 
Fat, cheese, 
oils, nuts, 
seeds 
Drink 48- 
64 oz. (1.5 
to 2 liters) 
Refer to starch list 
(avoid after 6 pm) 
Not including veggies in 
the starch list 
Up to 1 serving each day 
(avoid after 6 pm) 
Up to 2 serving 
each day 
Avoid soda 
and juice 
 
Write down number of 
portions you ate (i.e. 1, 
2,3) 
Write down number of 
portions you ate (i.e. 1, 
2,3) 
Write down number of 
portions you ate (i.e. 1, 
2,3) 
Write down number of 
portions you ate (i.e. 1, 2,3) 
Write down 
number of portion 
you ate (i.e. 1, 
2 3)
Write down 
number of oz. 
you drank 
Breakfast 
Eat calories 
within 1-2 
hours of 
waking up 
Up to 1 Red 
Up to 1 Orange 
Up to 1 Green 
 
Lunch 
Up to 1 Red 
Up to 1 Orange 
Up to 1 Green 
Dinner 
Eat veggies 
first, then 
protein 
Up to 1 Red 
Up to 1 Green 
(No Orange) 
Snack 1 
Snack 2 
Other food 
Exercise 
Number of Steps:   
 
Other exercise: 
minutes 
IDEAL SNACKS - 6 OZ NONFAT OR LOW FAT GREEK YOGURT (MUST HAVE MORE PROTEIN GRAMS THAN CARB GRAMS) , 1-2 LOW FAT MOZZARELLA 
STRING CHEESE STICKS OR MINI BABYBEL LIGHT CHEESE ROUNDS, 4 OZ SLICED DELI TURKEY, HAM, LEAN ROAST BEEF (NO MARBLED MEATS: 
PEPPERONI, SALAMI, ETC.), 1/2 CUP LOW FAT COTTAGE CHEESE, OTHER FOODS FROM THE PROTEIN LIST ABOVE 
Activity 
• 
Goal of 150 minutes of exercise weekly - You can split this up however you would like 
• 
You may want to use a Pedometer – Ultimate goal of at least 10,000 steps daily 
Behavioral - Chew each bite at least 20 times before swallowing 


Universal Trial Number: U1111-1178-7319               Version 7: 10/11/2019                           Page   1 
 
PREFERRED STARCHES 
NON-PREFERRED STARCHES 
BREAD 
BREAD 
Bread, pumpernickel 
Bagel 
Bread, rye 
Biscuit 
Bread, whole wheat 
Bread, white 
Bread, reduced calorie 
English Muffin 
English muffin, whole wheat 
Hot dog bun or Hamburger bun 
Pancake, whole wheat 
Naan 
Pita, whole wheat 
Pancake 
Tortilla, wheat 
Pita 
Roll 
Raisin bread 
Stuffing 
Taco shell 
Tortilla, corn or flour 
Waffle 
CEREAL AND GRAINS 
CEREAL AND GRAINS 
Bran cereals 
Cornmeal 
Bulgar 
Granola 
Cereals, cooked 
Grits 
Cereals, unsweetened 
Pasta, white 
Couscous 
Puffed cereal 
Kasha 
Rice, white 
Millet 
Sugar-frosted cereal 
Muesli 
Oats 
Pasta, whole wheat 
Rice, brown 
Shredded wheat 
Wheat germ 
STARCHY VEGETABLES 
STARCHY VEGETABLES 
Corn 
Baked beans 
Corn on the cob 
French-fried potatoes 
Mixed vegetables with corn and peas 
Potato, boiled 
Peas, green 
Potato, mashed 
Plantain 
Potato, baked with skin 
Squash, winter (acorn, butternut, pumpkin) 
Yam, sweet potato, plain with skin 
CRACKERS AND SNACKS 
CRACKERS AND SNACKS 
Popcorn (no fat or low-fat microwave) 
Animal crackers 
Rice cakes 
Chow mein noodles 
Snack chips, fat free or baked (tortilla, potato) 
Crackers, round butter type 


Universal Trial Number: U1111-1178-7319               Version 7: 10/11/2019                           Page   2 
 
PREFERRED STARCHES 
NON-PREFERRED STARCHES 
Whole wheat crackers, no fat added 
Graham cracker 
 
Matzoh 
 
Oyster crackers 
 
Pretzels 
 
Saltine-type crackers 
 
Sandwich crackers, cheese or peanut filling 
 
 
BEANS, PEAS AND LENTILS 
BEANS, PEAS AND LENTILS 
Beans/peas (garbanzo, pinto, kidney, white) 
 
Hummus 
 
Lima beans 
 
Lentils 
 
Miso 
 
 
 
FRUIT 
FRUIT 
Apple, unpeeled, small 
Apples, dried 
Applesauce, unsweetened 
Apricots, fresh 
Blackberries 
Apricots, dried 
Blueberries 
Banana 
Pear, fresh 
Cantaloupe 
Raspberries 
Cherries, fresh 
 
Cherries, sweet, canned 
 
Dates 
 
Figs, dried 
 
Fruit cocktail 
 
Grapefruit 
 
Grapes 
 
Honeydew melon 
 
Kiwi 
 
Mandarin oranges, canned 
 
Mango 
 
Nectarine 
 
Orange 
 
Papaya 
 
Peach, fresh 
 
Peaches, canned 
 
Pears, canned 
 
Pineapple, fresh 
 
Pineapple, canned 
 
Plums 
 
Raisins 
 
Tangerines 
 
Strawberries 
 
Watermelon