Clinical trial NCT03523273
Conditions: Obesity
Sponsor: Michael Camilleri, MD
Start date: 2017-11-29; Completion date: 2021-08-31
Enrollment: 136 participants; Allocation: RANDOMIZED; Intervention model: FACTORIAL

Brief summary:
This study is being done to assess the stomach emptying effect of a maximum dose of 3 mg Liraglutide compared to placebo in subjects who are overweight or obese. Liraglutide is a medication approved by the Food and Drug Administration (FDA) for routine clinical use.

Detailed description:

Arms: arm 1: Liraglutide initiated at 0.6mg S.C. daily for 1 week; subjects will return to the Clinical Research Unit (CRU) each week until an increase by 0.6 mg/day in weekly intervals to a dose of 3.0 mg/day is achieved. Once maintenance dose of 3.0 mg is achieved, subjects will return approximately every 4 weeks to obtain new supply of study medication. arm 2: Placebo initiated at 0.6mg S.C. daily for 1 week; subjects will return to the Clinical Research Unit (CRU) each week until an increase by 0.6 mg/day in weekly intervals to a dose of 3.0 mg/day is achieved. Once maintenance dose of 3.0 mg is achieved, subjects will return approximately every 4 weeks to obtain new supply of study medication.
Interventions: intervention 1: Liraglutide intervention 2: Placebo
Intervention descriptions: intervention 1: Initiate at 0.6mg S.C. daily for 1 week; subjects will return to the Clinical Research Unit (CRU) each week until an increase by 0.6mg/day in weekly intervals to a dose of 3.0 mg/day is achieved (\~4 weeks). Once maintenance dose of 3.0 mg is achieved, subjects will return approximately every 4 weeks to obtain new supply of study medication. intervention 2: Placebo administration will match the study drug.

Protocol documents:
Prot_SAP_000.pdf: 
 
Effects of Liraglutide on Gastric 
Functions and their 
Relationship to Weight Loss in 
Obesity 
 
NCT# 03523273 
 
October 29, 2020 


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Title:  Effects of Liraglutide on Gastric Functions and their Relationship to Weight Loss in Obesity 
 
Principal Investigator:  Michael Camilleri, M.D. 
 
Co-Investigators:  Andres Acosta, M.D., Ph.D.; Alan R. Zinsmeister, Ph.D.; Matthew M. Clark, Ph.D. 
 
Technicians, Coordinators: Duane Burton, Deborah Eckert  
 
Collaborators: Adrian Vella, M.D. 
 
ABSTRACT  
 
    Obesity prevalence continues to increase worldwide; 69% of U.S. adults are overweight or obese. 
Despite advances in understanding obesity pathophysiology, weight loss with current non-surgical 
treatments (diet and medications) is highly variable, and predictors of weight loss with obesity 
pharmacotherapy are unknown. In studies funded by RO1-DK67071 in 509 participants, obesity was 
associated with greater fasting gastric volume, accelerated gastric emptying (solids and liquids), lower 
postprandial peak plasma PYY, and greater calories consumed to achieve satiation (volume to fullness) 
and to evoke satiety with an ad-libitum meal. We showed that a short-acting GLP-1 agonist, exenatide, 
5µg, SQ, BID for 30 days, delays gastric emptying and induces weight loss. Thus, quantitative 
gastrointestinal (GI) traits are associated with higher BMI, distinguish obesity phenotypes, and may predict 
efficacy of obesity drug therapy. In the R56-DK67071-funded pilot randomized, placebo-controlled trial of 
the longer-acting GLP-1 agonist, liraglutide, 3mg, SQ daily, we showed: (a) feasibility to recruit and 
randomize, over 8 months, 30 patients into a 4-month study (only 2 dropouts on treatment, to date); (b) 
safety data in all 30 randomized patients; (c) baseline quantitative traits of gastric emptying of solids and 
liquids, fasting and postprandial gastric volumes; satiation and satiety data; postprandial plasma incretins 
(GLP-1 and PYY) in all randomized patients; (d) gastric emptying data at fully escalated dose of liraglutide 
(weeks 5-6) in 30 patients; (e) repeat measurement (as in c) of quantitative traits at 16 weeks’ treatment in 
28 patients; (f) monthly weight data for duration on treatment in 28 patients.  
    Our overall hypothesis is that weight loss with pharmacological agents may be individualized, based on 
specific abnormalities in quantitative GI traits. We propose a randomized, controlled clinical and 
pharmacodynamics trial, using a 2-treatment stratified design, to assess the hypothesis that a quantitative 
trait (gastric emptying rate) can impact the weight loss response among overweight (BMI >27kg/m2 plus 
obesity co-morbidities) or obese (BMI >30kg/m2) patients to treatment with the FDA-approved GLP-1 
receptor agonist, liraglutide (dose escalated to maximum of 3mg, SQ, per day for 12 weeks) compared to 
placebo. Effects will be compared for those with baseline accelerated in comparison with normal gastric 
emptying.  
    Our aims are: first, to assess the effects of liraglutide, 3mg/day, on gastric motor functions, satiation, 
satiety, weight loss and incretins; and second, to appraise the association of baseline accelerated gastric 
emptying on weight loss in response to liraglutide treatment. By measuring quantitative Gl traits at 
baseline and after 12 weeks of liraglutide treatment, we shall further understand the mechanism of action 
of this GLP-1 agonist. As an exploratory assessment, we shall measure stiffness and fat content of liver at 
three different time points during the study: baseline, week 8, and week 16 of treatment in the 2 treatment 
groups. 
    Significance: Our study addresses the treatment of obesity, introducing an era of individualizing drug 
therapy for obesity based on quantitative biomarkers. Therefore, it addresses an important public health 
challenge.   
 
APPROACH: GENERAL METHODS 
Overall Design, Randomization and Allocation  


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     We shall perform a placebo-controlled, parallel-group trial of liraglutide for a treatment period of 3 
months after achieving the target dose (3mg QD) following dose escalation. All participants will undergo 
baseline measurements of GI, behavioral and psychological traits. These assessments are needed to 
evaluate potential confounders that may interact with the effects of liraglutide on the endpoints in these 
studies. Randomization will be stratified on gender, BMI, and GE of solids (accelerated or normal). 
Overweight or obese patients with delayed GE of solids will be excluded from the trial with liraglutide, 
given the theoretical risk of induction of symptomatic gastroparesis as a result of further delay in GE. All 
patients will be randomized to active drug or placebo. Once participants are randomized, the doses and 
dose escalation (on active drug) will be the same for all subjects, except for delayed dose escalation in 
patients who cannot tolerate the standard titration (0.6mg per week). A computer generated randomization 
schedule generated by the study statistician’s office will be submitted to the Mayo Clinic CCaTS Research 
Pharmacy.  
   Allocations will be concealed; studies will be blinded until data are transmitted to the statistician for data 
lock.  
Selection of Overweight and Obese Participants 
    We plan to study a cohort of 112 patients (using 2-treatment stratified design) with BMI >30kg/m2 or 
>27kg/m2 with an obesity-related co-morbidity [e.g. type 2 diabetes mellitus (T2DM) on metformin 
monotherapy or diet alone, hypertension, hyperlipidemia, obstructive sleep apnea]. We have already 
genotyped and obtained baseline quantitative trait measurements of interest [GE of solids, kcal intake at 
buffet meal, and glycemia indices in obese patients with hyperglycemia (T2DM receiving metformin)] in 
almost 500 patients residing within 75 miles of Mayo Clinic in Rochester, MN. Over 80% of these patients 
reside within 25 miles of Rochester, MN. Anticipating 20% drop out from the study (Lean et al. 2014), we 
will screen 160 patients to ensure 112 enter the 16 weeks’ trial of liraglutide, 3mg SQ daily versus 
placebo, analyzed using ITT principles.   
Inclusion criteria: 
a.  Overweight and obese adults (>30kg/m2 or >27kg/m2 with an obesity-related co-morbidity) residing 
within 125 miles of Mayo Clinic in Rochester, MN; these will be otherwise healthy individuals with no 
unstable psychiatric disease and not currently on treatment for cardiac, pulmonary, gastrointestinal, 
hepatic, renal, hematological, neurological, or endocrine (other than hyperglycemia or T2DM on 
metformin) disorders. 
b.  Age: 18-65 years.   
c.  Gender: Men or women. We shall recruit equal proportions of men and women. Women of childbearing 
potential will be using an effective form of contraception and have negative pregnancy tests within 48 
hours of enrollment and before each radiation exposure. In addition, since liraglutide is classified as 
Pregnancy Category X, monthly urine pregnancy testing will be performed in any female participant with 
childbearing potential. 
Exclusion criteria: 
a. Weight exceeding 137 kilograms (safety limit of camera for measuring gastric volumes)  
b. Abdominal surgery other than appendectomy, cholecystectomy, Caesarian section or tubal ligation  
c. Positive history of chronic GI diseases, systemic disease that could affect GI motility, or use of 
medications that may alter GI motility, appetite or absorption, e.g., Orlistat  
d. Patients with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia 
II 
e. Past or current history of pancreatitis, gallstones, history of alcoholism, blood triglyceride levels > 
500mg/dL  
f.  Significant untreated psychiatric dysfunction (Clark et al. 2007, Cunningham et al. 2012) based upon 
screening with the Hospital Anxiety and Depression Inventory [HAD (Zigmond & Snaith 1983)], a self-
administered alcoholism screening test [AUDIT-C (Bush et al. 1998)], and the Questionnaire on Eating 
and Weight Patterns-Revised [splurge eating disorders and bulimia (Yanovski et al. 2015)]. If such a 
dysfunction is identified by a HAD score >11 on either the Anxiety or Depression subscales or difficulties 


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with substance or eating disorders, the participant will be excluded and given a referral letter to his/her 
primary care doctor for further appraisal and follow-up treatment.   
g. Intake of any medication (except multivitamins) within 7 days of the study. Exceptions are birth control 
pill, estrogen and thyroxine replacement therapy, and any medication administered for co-morbidities as 
long as they do not alter GI motility including GE and gastric accommodation. For example, statins for 
hyperlipidemia, diuretics, β-adrenergic blockers, ACE inhibitors and angiotensin antagonists for 
hypertension, and metformin for T2DM or prediabetes are permissible. In contrast, resin sequestrants for 
hyperlipidemia (Psichas et al. 2012), α2-adrenerigc agonists for hypertension, or other GLP-1 agonists 
(exenatide) or amylin analogs (pramlintide) or DPP-IV inhibitors are not permissible since they significantly 
affect gastric functions or appetite.  
h. Delayed gastric emptying at 2 and 4 hours            
i. Hypersensitivity to liragutide  
j. Participate in highly intense physical activity program that could potentially interfere with study 
interpretation   
Baseline Primary Quantitative Trait Relevant to Effect of Liraglutide: Gastric Emptying 
    At baseline, GE of solids will be measured and participants characterized as having accelerated GE 
[T1/2 of solids <93min in females, <78min in males (Camilleri et al. 2012)] or normal GE (see 10th-90th 
percentile in Table 5). Patients with delayed GE of solids (>90th percentile according to gender) will be 
excluded, since it is unethical to potentially induce gastroparesis or significantly increase the delay in GE 
with a GLP-1 agonist in patients with baseline abnormal GE of solids. Note that gender, but not age or 
BMI, was associated with GE of solids (GE T1/2, and proportion emptied at 1h and 2h, all p<0.001) in 
healthy controls (Camilleri et al 2012).  
Table 5. GE in healthy controls using identical method to that in application (Camilleri et al 2012). 
Data show mean + SD 
All controls, n=319 
Male controls, n=104 
Female controls, n=215 
Age , y  
36.2 + 13.1 
34.6 + 13.3 
37.2 + 12.8 
BMI, kg/m2 
26.9 + 5.1 
27.8 + 4.5 
26.5 + 5.3 
Solid GE T1/2, 
121.7 + 29.8 
109.9 + 28.6 
127.7 + 28.7 
Baseline Characterization of Secondary Quantitative Traits Relevant to the Effects of Liraglutide 
     At baseline, we shall also measure gastric volume (fasting and post-300kcal Ensure® drink), satiation 
(volume to fullness and MTV by Ensure® drink test, that is, the kcal intake under constant nutrient liquid 
intake 30kcal/min), appetite/satiety (kcal intake at an ad libitum buffet meal, which will be summarized 
henceforth as “satiety”), and plasma GLP-1 and PYY during fasting and at 15, 30, 45, and 90 minutes after 
the start of ingestion during Ensure® drink test. Further details of these measurements are provided 
below.  
These measurements are essential to ensure that the study stratifies patients based on GE and 
appraises the effect of liraglutide on the quantitative traits that impact satiation and satiety. 
     Baseline and monthly measurements will be taken of hip-waist ratio, DEXA body composition (only at 
baseline and end of study), height, weight, blood pressure, pulse, and fasting blood glucose. The monthly 
measurements will also serve to enhance compliance and ongoing standardization of behavioral 
treatment. 
 
Standardization of Behavioral Treatment  
     Under the supervision of Matthew Clark, Ph.D., co-investigator and staff behavioral interventionist [as 
in our behavioral protocols in previous clinical trials (Vazquez-Roque et al. 2007, Grudell et al. 2008)] and 
in a weight regain intervention (Himes et al 2015), we will standardize for potential differences in 
behavioral aspects of weight reduction therapy. All participants will be given a standard text (“LEARN” 
Manual, 10th ed.) for guidance on healthy lifestyle changes (Brownell 2004) and will meet at baseline and 
approximately weeks 4, 8 and 12 with a behavioral intervenionist who has expertise in obesity treatment. 
Under the guidance of Matthew M. Clark, PhD, the behavioral interventionists (master’s or doctoral level 
psychologist, a registered nurse, and a bachelor’s level study coordinator) will provide brief behavioral 


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counseling for weight management to study participants.  Study team members will be trained in 
behavioral interventions through leading  or observed a 12 week clinical weight management group 
sessions provided by the Department of Psychiatry and Psychology.  Upon approval by Dr. M. Clark, 
these study team members will deliver behavioral interventions independently to active participants of this 
study.  Dr. Clark meets with the study interventionists monthly to provide ongoing feedback and guidance. 
The behavioral interventionists will follow a session outline to standardize session content. Study 
participants will be taught a range of behavioral skills for successful weight management. These will be 15 
to 20 minute, standardized counseling sessions that incorporate motivational interviewing strategies. To 
maintain treatment fidelity, the psychologists will then complete visit forms documenting the content of the 
completed counseling session. Additionally, study participants will have brief (10min) contact with a 
member of the study team approximately every 4 weeks to inquire about their adherence to study protocol, 
any difficulties they are experiencing, whether they are reading the LEARN Manual (Table 6), and to 
answer any additional questions arising from their reading and lifestyle change. At each study visit, 
adherence to medication intake will be assessed, and body weight and automated blood pressure will be 
recorded in the Mayo Clinical Research Unit. In previous studies (Levine et al. 2005), we have provided 
study participants with recognition to demonstrate our appreciation for their time and to reduce study 
attrition. At week 8, participants will receive a token of thanks (Mayo Clinic water bottle) and at week 16, a 
copy of the book, The Mayo Clinic Diet. 
Table 6. Content of counseling sessions and LEARN Manual assignments 
 
Discussion and Values 
Reading assigned 
1 
a. introduce the LEARN manual; b. discuss the concept of readiness for 
change; c. differences between lifestyle change and diet highlighted; d. 
value of keeping food records, identifying eating triggers, and e. importance 
of eating 3 scheduled meals per day 
chapters 1-4 of the 
LEARN manual prior to 
next visit 
2 
a. review chapters 1-4 of the LEARN manual; b. eating triggers, the 
benefits of physical activity, and problem solving strategies 
chapters 5-8 of the 
LEARN manual 
3 
a. review chapters 5-8 of the LEARN manual; b. role of social support for 
health behavior changes; c. strategies for goal setting and controlled eating 
chapters 9-12 of the 
LEARN manual 
4 
a.  review chapters 9-12 of the LEARN manual, b. review progress in physical activity and meal 
planning; c. strategies to challenge negative thinking and relapse prevention techniques 
After September  7, 2018, the MAYO CLINIC DIET BOOK will be used exclusively since the LEARN 
manual is no longer available. 
Session 
Discussion and Values 
Reading assigned 
1 
Introduce the Mayo Clinic Diet book: Chapter 1, Ready Set Go; Chapter 2, Add 
Five Habits; Chapter 5, What Have You Learned; Chapter 6, The Next Phase; 
Chapter 7, Know Your Goals; Chapter 11, Track Your Progress 
Chapters 1, 2, 5, 6, 7, 
11 
2 
Review chapters previously assigned: Chapter 3, Break Five Habits; Chapter 4, 
Adopt Five Bonus Habits; Chapter 10, Expand Your Activity Plan 
Chapters 3, 4, 10 
3 
Review chapters previously assigned:  Chapter 8, Set Your Targets; Chapter 9, 
Create Your Eating Plan; Chapter 12, Seek Support 
Chapters 8, 9, 12 
4 
Review chapters previously assigned:  Chapter 13, What’s Your Healthy Weight; 
Chapter 14, Energy Calories and Weight; Chapter 15, The Mayo Clinic Healthy 
Weight Pyramid; Chapter 16 Making Meals Easier; Chapter 17, Eating Out; 
Chapter 18, How to Change Behaviors; Chapter 19, Burning Even More 
Calories; Chapter 20, I Slipped Up-What Do I Do? 
Chapters 13-20 
 
Questionnaires to Assess GI Symptoms and Affective Disorders 
    Participants will complete a series of questionnaires (all included in the APPENDIX): GI symptoms with 
the validated Bowel Disease Questionnaire (Talley et al. 1989), the Psychosomatic Symptom Checklist to 
assess the level of somatization, and the Hospital Anxiety and Depression Inventory (Zigmond & Snaith 


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1983) to appraise the contribution of affective disorder, which may confound assessment of weight effects 
of liraglutide. 
Questionnaires to Exclude Addiction and Psychiatric Eating Disorders (potential confounders of 
weight effects of liraglutide) 
a. AUDIT-C Alcoholism Screening Test (Bush et al. 1998) - The AUDIT-C is a 3-item alcohol screening 
questionnaire that reliably identifies participants who are hazardous alcohol drinkers or have active alcohol 
use disorders. This score will be used in screening by the study physician/nurse coordinator. The AUDIT-
C is scored on a scale of 0-12. Each AUDIT-C question has 5 answer choices. Points allotted are: a=0 
points; b=1 point; c=2 points; d=3 points; e=4 points. In men, a score of 4 or more will be reviewed by 
study personnel, and in women, a score of 3 or more will be reviewed by study personnel. However, when 
the points are above recommended limits, the provider will review patient’s alcohol intake over past few 
months to confirm accuracy.    
b. Eating Disorders Questionnaire - The Questionnaire on Eating and Weight Patterns-5 (QEWP-5, 
Appendix 7) (Yanovski et al. 2015) is a valid measure of screening for eating disorders which has been 
used in its different iterations since 1993 (Yanovski 1993) in several national multi-site field trials. 
Respondents are classified as binge eating disorder or bulimia nervosa. We have used this instrument to 
screen for eating disorders in obese populations (Vazquez-Roque et al. 2007). Since the QEWP-5 may 
not be sufficiently sensitive and specific to rule out binge eating disorder, based on a gold-standard 
diagnostic interview (de Zwaan et al. 1993), we shall be most careful to rule out binge eating disorder via 
clinical interview (with the expertise of Dr. Matthew Clark), since this important phenotype has been 
shown to have an impact on energy intake in laboratory studies (Walsh et al. 2003) and on gastric size 
(Geliebter et al. 2004). In a community sample, we found an association with binge eating patterns and GI 
symptoms (Cremonini et al. 2009). We will also administer the QEWP-5 for DSM-5 criteria assessment.    
c.   Body Image Satisfaction - The Multidimensional Body-Self Relations Questionnaire (Brown et al. 
1990) provides a standardized attitudinal assessment of body image, normed from a national body-image 
survey (Cash et al. 1986). Items are rated on a 5-point scale, ranging from 1=Definitely Disagree to 
5=Definitely Agree. In this study, we will use one of the sub-scales, the Body Areas Satisfaction Scale, 
which measures feelings of satisfaction with discrete aspects of physical appearance (e.g., face, weight, 
hair). Cronbach’s α values range from .70 to .89 (Cash 1994).    
d.   Eating Behaviors - The Weight Efficacy Life-Style Questionnaire [WEL (Clark et al. 1991; Batsis et 
al. 2009; Ames et al. 2015)] is a 20-item eating self-efficacy scale consisting of a total score and five 
situational factors: negative emotions, availability, social pressure, physical discomfort, and positive 
activities. Subjects are asked to rate their confidence about being able to successfully resist the urge to 
eat using a 10-point scale ranging from 0=not confident to 9=very confident.  
e.   Physical Activity Level - The four-item Physical Activity Stages of Change Questionnaire (Marcus 
et al. 1982) will be utilized to assess the physical activity level of participants. Mayo Clinic investigators, 
led by co-investigator Dr. Matt Clark, have used these items to explore the relationship between quality of 
life and physical activity in long-term lung cancer survivors (Clark et al. 2008, Solberg Nes et al. 2012). 
 
Study Medication: Liraglutide, a Longer-Acting GLP-1 Receptor Agonist 
Introduction: Whereas, liraglutide is approved for the treatment of obesity (or overweight with co-
morbidities), these data are based on large multicenter studies in which the average weight loss was only 
about 5.6kg over placebo (mean weight loss from baseline 8.4kg) with 12-56 weeks of treatment (Pi-
Sunyer et al. 2015).  
 


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Figure 6. Effect of liraglutide vs. placebo on weight 
loss in multicenter study of Pi-Sunyer et al. 2015    
  Almost 20% of patients treated with liraglutide 
developed adverse events including acute, severe 
abdominal pain or acute pancreatitis and, more 
commonly, nausea and vomiting that led to either 
discontinuation or failure to reach the full dose of 3mg 
daily after the first 4 weeks of dose escalation required 
in the trial. Moreover, another multicenter study 
showed that liraglutide produced small but statistically 
significant improvements in several cardiometabolic 
risk factors compared with placebo (Wadden et al. 
2013). Given the fact that the multicenter studies may include nonuniform cohorts (e.g. the Pi-Sunyer 
study included 191 sites in 27 countries in Europe, North America, South America, Asia, Africa, and 
Australia), studies that explore MECHANISMS of action of the medication require standardized, validated 
methods. We propose a single-center study in our lab at Mayo Clinic because of the extensive experience 
and validation of all the quantitative traits [including one study of 509 participants (Acosta et al. 2015)], 
ensuring eligibility of participants and characterization of behavioral traits (which are potential 
confounders. The feasibility of the proposed, unique studies are demonstrated in our preliminary data 
with liraglutide 3mg. 
 
Prior Reports of Effects of Liraglutide on Gastric Functions Are Inconclusive   
(i). Horowitz et al. (2012) showed in patients with T2DM that liraglutide, up to 1.8mg dose, resulted in 
retardation of liquid GE, since it was measured by plasma acetaminophen method.  
(ii). Rotondo et al. (2013) showed that 0.6mg liraglutide had no effects on gastric perception, compliance 
or satiation, but it inhibited gastric accommodation measured by balloon in 10 healthy controls with normal 
BMI.  
(iii) Van Can et al. (2014) studied effects of once daily liraglutide, 1.8mg, 3.0mg, or placebo, in a double-
blind, incomplete crossover, 5-week trial on GE, glycemic parameters, appetite and energy metabolism in 
obese, non-diabetic adults. They showed reductions in 1-hour GE of 23% with liraglutide, 3.0 mg, and 13% 
with 1.8mg compared to placebo. Given the method used to measure GE (plasma acetaminophen), the 
study could only appraise GE of liquids, and the effect of the GLP-1 agonist was only demonstrable in the 
first hour. It is not surprising that the 5-hour AUC was not different between liraglutide and placebo, since, 
over that period, all the acetaminophen should be emptied from the stomach and absorbed in the normal 
small bowel.  
Thus, prior PUBLISHED studies are inconclusive, and effects of 3mg liraglutide on GE solids in 
short term (5 wk) and at 16 wks were unknown, other than the preliminary data from our pilot 
study.  
 
Approval status by FDA (December 23, 2014): Liraglutide is indicated as an adjunct to a reduced-calorie 
diet and increased physical activity for chronic weight management in adults with BMI of ≥30 kg/m2 
(obesity) or a BMI of ≥27 kg/m2 (overweight) with >1 weight-related condition (e.g., hypertension, T2DM, 
dyslipidemia). 
Dosing recommendations: Initiate at 0.6mg S.C. daily for 1 week; increase by 0.6mg/day in weekly 
intervals until a dose of 3mg/day is achieved.  
Supply: Liraglutide (3mg SQ injection) and placebo will be dispensed by Mayo Clinic Research Pharmacy. 
As in the pilot study, all supplies will be dispensed by the pharmacy staff at a site away from the Clinical 
Research Unit and the study staff. 
Randomization: The randomization schedule will be generated before the start of the study in the Section 
of Biostatistics, Mayo Clinic, and will be given to the research pharmacist. Medications will be stored in a 


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monitored, climate-controlled environment according to manufacturer’s directions. Monitoring records will 
be available for review to ensure quality control.  
Medication dispensing and delivery: Medications will be dispensed and delivered in such a manner that (a) 
all study personnel, nurses and technicians in the Clinical Research Unit, (b) the study staff and 
investigators directly involved in this research, and (c) the participants will be blinded to the nature of the 
study medication. The nursing personnel of the Clinical Research Unit will dispense the medication guide 
instructions and will provide the subject education on the proper administration of the study medication 
prior to start of dosing. A “Direction for Use” pamphlet will be given to subjects, who will be instructed how 
to use liraglutide and placebo. 
Quantitative Traits  
     On different days, participants will attend the Mayo Clinic Clinical Research Trials Unit (CRTU) at 
scheduled time after an 8-hour fasting period, and the following validated quantitative traits will be 
measured:  
1.  GE of solids by scintigraphy: The primary endpoint is gastric half-emptying time (GE T1/2), and the 
secondary endpoints are proportions emptied at 2 and 4 hours (Vazquez-Roque et al. 2006). The normal 
range for GE T1/2 is based on 10th and 90 th percentiles in healthy volunteers, based on gender (see Table 
5, Camilleri et al. 2012). In general, GE of liquids is non-contributory in the context of postprandial 
symptoms (Sachdeva et al. 2011); in order to reduce radiation burden (needing two isotopes to assess 
both liquid and solid emptying), we will study exclusively GE of solids.   
2.  Fasting and postprandial Gastric Volume (GV) by single photon emission computed tomography 
(SPECT), developed and validated (including performance characteristics) in our lab (Bouras et al. 2002; 
Delgado-Aros et al. 2005; Breen et al. 2011).  
3.  Satiation by Ensure® nutrient drink test (1kcal/mL, 11% fat, 73% carbohydrate, and 16% protein) 
ingested at a constant rate of 30ml/min to measure volume to fullness (VTF) and maximal tolerated 
volume, MTV (Chial et al. 2002). Briefly, participants record their sensations every 5 minutes using a 
numerical scale from 0 to 5, with level 0 being no symptoms, level 3 corresponding to fullness sensation 
after a typical meal (VTF) and level 5 corresponding to the MTV (maximum or unbearable 
fullness/satiation).  Nutrient intake is stopped when subjects reach the score of 5. Postprandial symptoms 
of fullness, nausea, bloating, 
and pain are measured 30 minutes after the meal using 100 mm horizontal visual analog scales, with the 
words “none” and “worst ever” anchored at each end. 
4.  Satiety (for assessment of kcal intake as a measure of appetite) by ad-libitum buffet meal to 
measure total caloric intake and macronutrient distribution in the chosen food (Vazquez-Roque et al. 
2006). Five hours after ingesting 300 mL liquid nutrient (Ensure®) as part of the SPECT gastric volume 
study, participants will be invited to eat, during a 30-minute period, a standard ad libitum meal that 
includes: 
a.  standardized lasagna meal (Stouffers, Nestle USA, Inc, Solon, OH; nutritional analysis of each 326-g 
box: 420 kcal, 17 g protein [16% of energy], 38 g carbohydrate [37% of energy], and 22 g fat [47% of 
energy]; vanilla pudding (Hunts, Kraft Foods North America, Tarrytown, NY; nutritional analysis of each 
99-g carton: 130 kcal, 1 g protein [3% of energy], 21 g carbohydrate [65% of energy], and 4.5 g fat [32% of 
energy]); and  
b. skim milk (nutritional analysis of each 236-mL carton: 90 kcal, 8 g protein [36% of energy], 13 g 
carbohydrate [64% of energy], and 0 g fat).  
The total amount (grams and kilocalories) of food consumed and the kilocalories of each macronutrient at 
the ad libitum meal were analyzed by using validated software (ProNutra 3.0; Viocare Tech. Inc., 
Princeton, NJ). 
Overweight or obese participants will be subdivided into “excessive eaters” [the top tertile (1176 kcal) as 
defined in a prior study of 264 participants] and the bottom 2 tertiles, defining non-excessive intake.  
5. Ratings of appetite will be measured every 30 minutes between the time of ingestion of standard liquid 
breakfast and the start of the ad libitum meal, ratings for appetite (satiety, fullness, hunger and prospective 
food consumption), thirst, well-being and nausea will be recorded using visual analog scales, as described 


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by Flint et al. (2000). VAS, 100mm in length with words anchored at each end expressing the most 
positive and the most negative rating, will be used to assess hunger, satiety, fullness, prospective food 
consumption, desire to eat something fatty, salty, sweet or savory, and the palatability (5 questions) of the 
test meal. Overall appetite score will be calculated as average of the 4 individual scores (satiety + fullness 
+ (100-prospective food consumption) + (100-hunger))/4 
6.  Plasma gastrointestinal hormones (GLP-1 and PYY) by radioimmunoassay, measured fasting, and 
15, 45, and 90 minutes postprandially, with the primary endpoint being the peak postprandial level.  
Ghrelin and CCK levels will not be measured in proposal, since they were non-informative in our prior 
study.  
GLP-1 will be measured as the biologically active GLP-1 (active and total) using a 2-site non-competitive 
immunoassay based on enzyme-labeled quantification of GLP-1 detected by a fluorogenic substrate.  
PYY will be measured by radioimmunoassay (Linco Research, Inc., St. Charles, MO). PYY exists in at 
least 2 molecular forms, 1-36 and 3-36, both of which are physiologically active and are detected by the 
assay.    
7.  Self-administered questionnaires assessing affect, exercise performance, attitudes, satisfaction with 
body image, and eating behavior (Bush et al. 1998; Clark & King 2000; Clark et al. 2008; Lloyd-
Richardson et al. 2000; Yanovski 1993; Zigmond & Snaith 1983); details of each questionnaire are 
provided above. 
8. Storage of biological samples:  
   a. Blood Samples (fasting and postprandial) will be stored in a -70°C freezer in our lab for future assays. 
   b. Genomic DNA will be isolated from peripheral blood leukocytes as in previous studies (Qiagen Kit) for 
possible future studies. 
9. DEXA body composition: Total body fat, leg fat, fat percentage, and fat free mass will be measured by 
DEXA scanning (QDR-2000) (Jensen et al. 1995).  
10. Liver Stiffness and fat content: We will measure the stiffness and fat content of liver non-invasively 
using different ultrasound equipment at baseline, 8 weeks and 16 weeks in participants who provide 
informed consent.  The GE Logiq E9 and/or the Verasonics scanner will be used to for ultrasound 
measurements. It is beneficial to test the measurements on different ultrasound scanners to evaluate 
performance. We will analyze results as we study the patients. Based on the results, we may pick one 
scanner (either GE or Verasonics scanner) to continue the study. Regardless whether one or two 
scanners are used, we will keep the ultrasound study time within 30 minutes as stated in the consent form. 
 
General Approach for Statistical Analyses   
     
The analyses will be based on a 2-treatment stratified design to compare the effects of 
liraglutide and placebo on post-treatment gastric functions, satiation, satiety, incretins, body composition 
and weight loss; in addition, the effects of liraglutide will be compared between patients with (vs. without) 
the trait of interest (i.e., the strata being accelerated vs. normal GE of solids using the 10th percentile for 
GE of solids in health). The analyses will use a 2-way analysis of covariance (ANCOVA) model with 
treatment, the quantitative trait, and a treatment by quantitative trait interaction term.  
The sample size is based on the feasibility to perform a 16-week therapeutic trial over 4 years, 
during which approximately 40 participants completed/ year.  Year 5 of the proposed application will be 
necessary for completion of all trait analyses, and writing manuscripts.  
Interim Analysis: As part of an on-going method to compare the effects of medication tested (liraglutide) 
and placebo, an interim analysis will be conducted when >66% of aim 1 has been reached.   
 
 
Rationale for Interim Analysis:  
a. To asses power of the study based on the actual coefficient of variation as measured in the actual study 
with >66% completed; this is because the coefficient of variation could be different from the COV used in 
the a priori power calculation used  in development of the protocol.  


U1111-1165-6027 Camilleri                        October 29 , 2020  vers     7                                            Page 9 
 
b. As part of the analysis, the statisticians will also provide a comparison of the results on the primary and 
secondary endpoints; this assessment will be communicated to the investigators as average data (e.g. 
median and IQR) for the treatment GROUPS rather than individual patient data. These group data could 
be used for preparation of preliminary reports in the form of abstract for national meetings specifically 
digestive disease week to be held in May 2021 for which the deadline for abstract submission is 
December 1, 2020. 
c. As a result of the power analysis, it is possible that the sample size may be either reduced or increased 
or the study could be stopped because of “futility” if there is no evidence of a trend to suggest efficacy of 
treatment 
    
 
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ICF_001.pdf: 
 
 
Approval Date:  
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IRB#: 15-001783 01  
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Name and Clinic Number 
 
 
RESEARCH PARTICIPANT CONSENT AND PRIVACY 
AUTHORIZATION FORM 
 
 
Study Title: Pilot Study of the Effect of Liraglutide on Weight Loss and Gastric Functions in 
Obesity   
 
IRB#:  
15-001783  
 
Principal Investigator: Dr. Camilleri and Colleagues 
 
Please read this information carefully. It tells you important things about this research study. A 
member of our research team will talk to you about taking part in this research study.  If you 
have questions at any time, please ask us. 
 
Take your time to decide.  Feel free to discuss the study with your family, friends, and healthcare 
provider before you make your decision.   
 
To help you decide if you want to take part in this study, you should know: 
• Taking part in this study is completely voluntary.  
• You can choose not to participate.  
• You are free to change your mind at any time if you choose to participate.   
• Your decision won’t cause any penalties or loss of benefits to which you’re otherwise 
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• Your decision won’t change the access to medical care you get at Mayo Clinic now or in 
the future if you choose not to participate or discontinue your participation.   
 
For purposes of this form, Mayo Clinic refers to Mayo Clinic in Arizona, Florida and Rochester, 
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entities. 
 
If you decide to take part in this research study, you will sign this consent form to show that you 
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CONTACT INFORMATION 
 
 
You can contact … 
At … 
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Principal 
Investigator(s): 
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Study Team Contact: 
Deb Eckert 
Ann Taylor  
Irene Busciglio 
 
 
 
Phone: 
(507) 776-2305 
 
 
Phone: 
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(507) 266-3421 
(507) 266-6615 
Address: 
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Rochester, MN  55905 
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1. 
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You are being asked to take part in this research study because you have been identified as 
someone who is healthy and overweight or obese. 
 
 
2. 
Why is this research study being done? 
 
 
This study is being done to assess the stomach emptying effect of a maximum dose of 3 mg 
Liraglutide compared to placebo in subjects who are overweight or obese. Liraglutide is a 
medication approved by the Food and Drug Administration (FDA) for routine clinical use.   
 
The plan is to have about 200 people aged 18 to 65 complete this study at Mayo Clinic.  
 
 
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Information you should know 
 
 
Who is Funding the Study? 
 
The National Institutes of Health is funding the study. The National Institutes of Health will pay 
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participants in this research project or to the integrity of the research. 
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details of this Financial Conflict of Interest and how it is being managed by contacting 
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• One or more of the investigators associated with this project and Mayo Clinic have a 
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investigator(s) and Mayo Clinic may stand to gain financially from the successful 
outcome of the research. 
 
 
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You will be in this study for about 18 weeks from the date of the first visit to the end of the 
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Screening:  
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Study Physician will review the results. If you aren’t eligible, we will tell you why.   
At this visit we will: 
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(blood pressure, temperature, heart and breathing rates) 
• Females of child-bearing potential will be asked to have a urine pregnancy test (which 
must be negative) within 48 hours prior to this test 
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• Ask  you to complete 8 questionnaires about your general health and well-being and any 
bowel issues you have experienced during the past year 
• The study physician will decide if you need any additional blood/urine tests  to determine 
your eligibility 
 
This visit will last approximately 1 to 1.5 hours. 
 


 
 
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Page 5 of 19 
IRB Template Ver 4/10/2013 
 
 
 
 
 
 
 
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Baseline Period:  
You will have the following tests and procedures. Note: There must be one day between the 
Gastric Emptying test and the Gastric Volume Test. 
 
Baseline Gastric Emptying Test and DEXA body composition scan: You will come to the 
CRTU after an 8 hour fast (nothing to eat or drink prior to your visit).  Refrain from alcohol use 
for 48 hours prior to testing.  Refrain from caffeine (e.g. tea, coffee, energy drinks, caffeine-
containing sweets) for 24 hours before and until the end of testing.  Notify the study team in 
advance if you have any food allergies or intolerances. 
 
At this visit we will: 
• Females of child-bearing potential will be asked to have a urine pregnancy test (which 
must be negative) within 48 hours prior to this test.   
• Measure  your “vital signs” (blood pressure, temperature, heart and breathing rates) 
• Measure your height and weight 
• Measure your hip and waist circumference and upper arm skin fold thickness 
• Test your fasting blood glucose by sticking your finger for a drop of blood 
• Administer the Gastric Emptying Test: The test involves eating a meal of scrambled eggs, 
1 slice of bran bread toast and 1 cup of skim milk within 10 minutes. The eggs in this 
meal contain a small amount of radioactive material (Notify the study team in advance if 
you have any allergies or intolerances to these foods).  This allows us to time the 
movement of food through your stomach by taking pictures (scans) through the use of an 
external camera.   
• At the completion of the breakfast test meal, you will be instructed to stand in front of a 
special camera and pictures will be taken at specific intervals. Each of these scans will 
take approximately 5 minutes. This entire test takes about 5 hours to be completed.  
Please do not eat or drink anything (except water) until after the 4 hour scan. 
• Administer the DEXA body composition scan: You will have your total body fat 
measured using an external machine (called DEXA) that uses a very small dose of x-ray. 
This involves lying (face up) on an x-ray bed for about 15 minutes. 
 
Baseline Nutrient Drink Test: 
You will come to the CRTU after an 8 hour fast (nothing to eat or drink prior to your visit).  
Refrain from alcohol use for 48 hours prior to testing.  Refrain from caffeine (e.g. tea, coffee, 
energy drinks, and caffeine-containing sweets) for 24 hours before and until the end of testing.  
 


 
 
Approval Date:  
June 3, 2020 
Not to be used after: June 2, 2021 
 
 
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At this visit we will:  
• Place an IV catheter in your forearm for repeated blood draws at fasting, 15, 45 and 90 
minutes. 
• Draw a blood sample for DNA (baseline test only) 
• Administer the Nutrient Drink Test: This test involves drinking Ensure at a rate of one 
ounce per minute until you cannot tolerate any more. At the same time, you will record 
your symptoms while you drink the Ensure and 30 minutes after you have reached the 
maximum volume you could bear.  
 
This visit will last approximately 2 hours. 
 
Baseline Gastric Volume Test: 
You will come to the CRTU after an 8 hour fast (nothing to eat or drink prior to your visit). 
Refrain from alcohol use for 48 hours prior to testing.  Refrain from caffeine (e.g. tea, coffee, 
energy drinks, and caffeine-containing sweets) for 24 hours before and until the end of testing.  
Note this test and the baseline buffet meal must occur on the same day.   
 
At this visit we will:  
• Females of child-bearing potential will be asked to have a urine pregnancy test (which 
must prove negative) within 48 hours prior to this test.   
• Administer the Gastric Volume Test: This test involves SPECT imaging to measure the 
volume of your stomach with an external camera that revolves around the abdomen, 
while you are lying on a mattress and table. Stomach volume will be checked during 
fasting, starting 10 minutes after an intravenous injection of a radioactive material.  
• You will ingest 300 mL of a liquid nutrient drink (flavored Ensure) and one more image 
of the stomach will be obtained over the next 30 minutes.   
 
This visit will last approximately 1 hour. Buffet meal to follow approximately 5 hours later. 
 
Baseline Buffet Meal: 
You will report to the CRTU about 5 hours after your Gastric Volume test.  Notify the study 
team in advance if you have any food allergies or intolerances.   
 
At this visit: 
• You will be given a meal of lasagna, pudding and milk and allowed to eat as much of 
each item as you wish until you are full. 
 
This visit will last approximately 30-45 minutes.   
 


 
 
Approval Date:  
June 3, 2020 
Not to be used after: June 2, 2021 
 
 
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Randomization and study medication dispensed: 
You will report to the CRTU fasting. 
 
At this visit we will: 
• Measure  your “vital signs” (blood pressure, temperature, heart and breathing rates) 
• Females of child-bearing potential will be asked to have a urine pregnancy test (which 
must be negative) within 48 hours prior to study medication being dispensed.   
• Measure  your height and weight 
• Measure your hip and waist circumference and upper arm skin fold thickness 
• Measure your fasting blood glucose by sticking your finger for a drop of blood  
• Give you the Mayo Clinic Diet book, which is a commercially available education 
manual for weight loss, and have you meet with a Behavioral Interventionist to discuss 
the Mayo Clinic Diet and receive guidance in healthy lifestyle changes 
• Instruct you how to self-inject the study medication 
• Dispense a four-week supply of your study medication with instructions. You will be 
randomized to the 3 mg of Liraglutide treatment group or the placebo group (inactive). A 
placebo contains no active ingredient. We will supply all needles and supplies needed for 
you to self-administer your study medication. You will also receive instructions how to 
store the study medication. 
• You will be asked to record the date and time that you take your injections on a daily 
medication diary for the remainder of the study. 
 
This visit will last approximately 1 to 1.5 hours.   
 
Dose Escalation Period 
 
Your self-injection of the study medication will begin on the date scheduled for you and continue 
daily as instructed.  The first weeks of dosing will involve an escalation of the dose.   
 
Study medication dose escalation visits: 
 
You will come to the CRTU weekly at an agreed upon time for a minimum of four visits to 
receive your dose escalations of study medication. Bring your study medication and supplies to 
these visits.  You will continue to self-inject your study medication.  These visits will last 
approximately 15 minutes. 
 
 
 
 


 
 
Approval Date:  
June 3, 2020 
Not to be used after: June 2, 2021 
 
 
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Name and Clinic Number 
Treatment Period 
 
Month 1 Study medication dispensed: 
You will report to the CRTU fasting.  Bring your study medication and supplies to this visit. 
 
At this visit we will: 
• Females of child-bearing potential will be asked to have a urine pregnancy test (which 
must be negative) within 48 hours prior to study medication being dispensed.   
• Measure  your “vital signs” (blood pressure, temperature, heart and breathing rates) 
• Measure your height and weight 
• Measure your hip and waist circumference and upper arm skin fold thickness 
• Measure  your fasting blood glucose by sticking your finger for a drop of blood  
• Have you meet with a Behavioral Interventionist to discuss the Mayo Clinic Diet and 
receive guidance in healthy lifestyle changes.  
• Dispense your four-week supply of study medication and you will self-inject your study 
medication for 4 more consecutive weeks.  
 
This visit will last approximately 1 hour. 
 
Interim Gastric Emptying Test: 
After receiving approximately 5 weeks of study medication, you will come to the CRTU at the 
prescheduled time after an overnight fast (nothing to eat or drink except water for 8 hours prior 
to your visit). Refrain from alcohol use for 48 hours prior to testing.  Refrain from caffeine (e.g. 
tea, coffee, energy drinks, caffeine-containing sweets) for 24 hours before and until the end of 
testing.    
• Self-inject your study medication before you come in for the testing.  
• Note this time and provide this time to the nurse/study staff so they can document the 
time of your dosing that day.   
 
At this visit we will: 
• Females of child-bearing potential will be asked to have a urine pregnancy test (which 
must be negative) within 48 hours prior to this test.   
• Measure your “vital signs” (blood pressure, temperature, heart and breathing rates) 
• Measure  your height and weight 
• Measure your hip and waist circumference and upper arm skin fold thickness 
• Test your fasting blood glucose by sticking your finger for a drop of blood 


 
 
Approval Date:  
June 3, 2020 
Not to be used after: June 2, 2021 
 
 
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• Administer the Gastric Emptying Test: The test involves eating a meal of scrambled eggs, 
1 slice of bran bread toast and 1 cup of skim milk within 10 minutes. The eggs in this 
meal contain a small amount of radioactive material. This allows us to time the 
movement of food through your stomach by taking pictures (scans) through the use of an 
external camera.   
• At the completion of the breakfast test meal, you will be instructed to stand in front of a 
special camera and pictures will be taken at specific intervals.  
• Each of these scans will take approximately 5 minutes. This test takes about 5 hours to be 
completed. Please do not eat or drink anything (except water) until after the 4 hour scan. 
 
Month 2 Study medication dispensed: 
You will report to the CRTU fasting.  Bring your study medication and supplies to this visit. 
 
At this visit we will: 
• Females of child-bearing potential will be asked to have a urine pregnancy test (which 
must negative) within 48 hours prior to study medication being dispensed.   
• Measure your “vital signs” (blood pressure, temperature, heart and breathing rates) 
• Measure your height and weight 
• Measure your hip and waist circumference and upper arm skin fold thickness 
• Measure your fasting blood glucose by sticking your finger for a drop of blood  
• Have you meet with a Behavioral Interventionist to discuss the Mayo Clinic Diet and 
receive guidance in healthy lifestyle changes.  
Dispense your four-week supply of study medication and then you will self-inject for 4 
consecutive weeks.  
 
This visit will last approximately 1.5 hours. 
 
Month 3 Study medication dispensed: 
You will report to the CRTU fasting.  Bring your study medication and supplies to this visit. 
 
At this visit we will: 
• Females of child-bearing potential will be asked to have a urine pregnancy test (which 
must negative) within 48 hours prior to study medication being dispensed.   
• Measure your “vital signs” (blood pressure, temperature, heart and breathing rates) 
• Measure your height and weight 
• Measure your hip and waist circumference and upper arm skin fold thickness 
• Measure your fasting blood glucose by sticking your finger for a drop of blood  


 
 
Approval Date:  
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• Have you meet with a Behavioral Interventionist to discuss the Mayo Clinic Diet and 
receive guidance in healthy lifestyle changes.  
• Dispense your four-week supply of study medication and then you will self-inject for 4 
consecutive weeks.  
 
This visit will last approximately 1 hour. 
 
End of Treatment Testing:  
You will have the following tests and procedures. Note: There must be one day between the 
Gastric Emptying test and the Gastric Volume Test. 
• Self-inject your study medication in the morning before you come in for the testing.  
• Note this time and provide this time to the nurse/study staff so they can document the 
time of your dosing that day.   
 
Gastric Emptying Test 
Same as Baseline Gastric Emptying Test, at the completion of the breakfast test meal, you will be 
instructed to stand in front of a special camera and pictures will be taken at specific intervals. Each of 
these scans will take approximately 5 minutes. This test takes about 5 hours to be completed 
 
Nutrient Drink Test 
Same as Baseline Nutrient Drink Test, this visit will take approximately 2 hours. 
 
Gastric Volume Test 
Same as Baseline Gastric Volume Test, this visit will take approximately 1 hour.   
 
Buffet Meal 
Same as Baseline Buffet Meal, this visit will take approximately 30-45 minutes.   
 
DEXA Body Composition Scan 
Same as Baseline DEXA Body Composition Scan, this visit will take approximately 30 minutes.  
  


 
 
Approval Date:  
June 3, 2020 
Not to be used after: June 2, 2021 
 
 
IRB#: 15-001783 01  
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6. 
What are the possible risks or discomforts from being in this  
research study? 
 
 
Most common side effects of Liraglutide are as follows:  
• bladder pain 
• bloody or cloudy urine 
• cough or hoarseness 
• diarrhea 
• difficult, burning, or painful urination 
• fever or chills 
• frequent urge to urinate 
• general feeling of discomfort or illness 
• headache 
• joint pain 
• loss of appetite 
• lower back or side pain 
• muscle aches and pains 
• nausea 
• runny nose 
• shivering 
• sore throat 
• sweating 
• trouble sleeping 
• unusual tiredness or weakness 
• vomiting
 
Liraglutide may cause serious side effects, including: 
• Inflammation of your pancreas (pancreatitis). Stop using Saxenda® and call your 
health care provider right away if you have severe pain in your stomach area (abdomen) 
that will not go away, with or without vomiting. You may feel the pain from your 
abdomen to your back 
• Low blood sugar (hypoglycemia). Your risk for getting low blood sugar may be higher 
if you use liraglutide with another medicine that can cause low blood sugar, such as a 
sulfonylurea or insulin  
Signs and symptoms of low blood sugar may include: 
o dizziness or light-headedness 
o blurred vision 
o anxiety, irritability, or mood changes 
o sweating 
o slurred speech 
o hunger 
o confusion or drowsiness 
o shakiness 
o weakness 
o headache 
o fast heartbeat 
o feeling jittery 


 
 
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• Kidney problems (kidney failure). In people who have kidney problems, diarrhea, 
nausea, and vomiting may cause a loss of fluids (dehydration) which may cause kidney 
problems to get worse. 
• Gallbladder problems. Saxenda® may cause gallbladder problems including gallstones. 
Some gallbladder problems need surgery. Call your healthcare provider if you have any 
of the following symptoms: 
• Pain in your upper stomach (abdomen) 
• Fever 
• Yellowing of your skin or eyes (jaundice) 
• Clay-colored stools 
 
As with any medication, allergic reactions are a possibility, including itching, rash, or difficulty 
breathing.  
 
Blood draw: The risks of drawing blood include pain, bruising, lightheadedness, and/or fainting, 
or rarely, infection at the site of the needle stick.   
 
Radiation: You will be exposed to radiation during the Gastric Emptying tests, the Gastric 
Volume tests and the DEXA Body Composition Scan in this research study. The amount of 
radiation you will receive has a low risk of harmful effects.  
 
Test Meals:  Participation in this study requires the consumption of standardized test meals.  
You should inform the study team if you have any food allergies or intolerances. 
 
Questionnaires: Some questions you will be asked to answer in the study questionnaires may 
make you feel uncomfortable.  You may choose not to answer any questions that make you feel 
uncomfortable. 
 
Electrocardiogram (ECG):  Is a harmless procedure that records the electrical activity of your 
heart. No electricity is sent through your body. 
 
Pregnancy and Birth Control:  
Women of child-bearing-potential will be able to participate in this study if they have a negative 
pregnancy test and agree to use acceptable birth control (see below) since the risks to an unborn 
child are either unknown or potentially serious.   
• Surgical sterilization 
• Approved hormonal methods, such as birth control pills, patches, injections, vaginal ring, 
or implants 


 
 
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• Barrier methods (such as a condom or diaphragm) used with a spermicide (a foam, 
cream, or gel that kills sperm) 
• Intrauterine device (IUD) 
• Abstinence (no sex) 
 
There is not enough medical information to know what the risks might be to a breast-fed infant 
or to an unborn child carried by a woman who takes part in this study. Breast-feeding mothers 
must stop breast-feeding to take part in this study.  
 
As part of this study a pregnancy test is required for all women who are able to become pregnant. 
Urine pregnancy tests will be done (at the beginning and end of the study and throughout the 
study whenever you will be exposed to radiation and/or start your medication) on all women of 
child bearing potential. You will be told the results of the pregnancy test. If the pregnancy test is 
positive, you will not be able to take part in the study. If you are postmenopausal, it must be 
documented in your medical history. This will confirm your postmenopausal status and no urine 
pregnancy testing will be required of you. 
 
There may be other risks of Liraglutide that are currently unknown. 
 
 
7. 
Are there reasons you might leave this research study early? 
 
 
You may decide to stop at any time. You should tell the Principal Investigator if you decide to 
stop and you will be advised whether any additional tests may need to be done for your safety.  
 
In addition, the Principal Investigator or Mayo Clinic may stop you from taking part in this study 
at any time:  
• if it is in your best interest,  
• if you don’t follow the study procedures,  
• if the study is stopped.  
 
If you leave this research study early, or are withdrawn from the study, no more information 
about you will be collected; however, information already collected about you in the study may 
continue to be used.  
 
We will tell you about any new information that may affect your willingness to stay in the 
research study. 


 
 
Approval Date:  
June 3, 2020 
Not to be used after: June 2, 2021 
 
 
IRB#: 15-001783 01  
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8. 
What if you are injured from your participation in this research study? 
 
 
Where to get help:  
 
If you think you have suffered a research-related injury, you should promptly notify the Principal 
Investigator listed in the Contact Information at the beginning of this form. Mayo Clinic will 
offer care for research-related injuries, including first aid, emergency treatment and follow-up 
care as needed. 
 
Who will pay for the treatment of research related injuries:  
 
Care for such research-related injuries will be billed in the ordinary manner, to you or your 
insurance. Treatment costs for research-related injuries not covered by your insurance will be 
paid by Mayo Clinic. 
 
 
9. 
What are the possible benefits from being in this research study? 
 
 
Others who are overweight or obese may benefit in the future from what we learn in this research 
study. 
 
 
10. 
What alternative do you have if you choose not to participate 
in this research study? 
 
 
This study is only being done to gather information. You may choose not to take part in this 
study. 


 
 
Approval Date:  
June 3, 2020 
Not to be used after: June 2, 2021 
 
 
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11. 
What tests or procedures will you need to pay for if you take part  
in this research study?  
 
 
You won’t need to pay for tests and procedures which are done just for this research study. These 
tests and procedures are:  
• Vital signs  
• Physical exam  
• Questionnaires 
• Blood tests  
• Urine pregnancy tests  
 
 
• Electrocardiogram (ECG) 
• Body Measurements 
• Height and Weight 
• Placebo/Study Medication (syringes 
and needles if needed) 
• Gastric Emptying test 
• Nutrient Drink test 
• Gastric Volume test 
• DEXA-Body Composition scan  
• Buffet Meal test
However, you and/or your insurance will need to pay for all other tests and procedures that you 
would have as part of your clinical care, including co-payments and deductibles.  
 
If you have billing or insurance questions call Patient Account Services at the telephone 
number provided in the Contact Information section of this form. 
 
 
12. 
Will you be paid for taking part in this research study? 
 
 
You will be paid $1200 if you complete the whole study. If you don’t complete the study, we 
will pay you part of the money. At your randomization visit, you will receive a copy of The 
Mayo Clinic Diet and at week 8 a token of thanks (Mayo Clinic water bottle). 


 
 
Approval Date:  
June 3, 2020 
Not to be used after: June 2, 2021 
 
 
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13. 
What will happen to your samples? 
 
 
Your samples will be used for this study, but we would also like to keep some of your samples 
for future research. You can still take part in this current study even if you don’t want your 
sample used for future research. If you agree to give your sample, it will be the property of Mayo 
Clinic. Your sample will be stored in a coded format, which protects your identity. Mayo Clinic 
may destroy the sample at any time without telling you. 
 
Other researchers at Mayo Clinic who aren’t involved with this study may ask to use your 
sample for future research. Researchers at other institutions may also ask for a part of your 
sample for future studies. Your sample will be sent to researchers in a coded format, which 
protects your identity. 
 
Some future studies may examine your DNA, which is the genetic information you inherited 
from your parents (genetic testing).  The Principal Investigator may contact you if there are 
findings which may be useful for your health care. You would be given general information on 
the potential risks, benefits, and costs of choosing to learn about the findings.   
 
Please read the following statements and mark your choices: 
 
1.  I permit my sample to be stored and used in future research of weight loss at Mayo Clinic: 
 
  Yes 
  No  
Please initial here: ________Date: ________ 
 
2.  I permit my sample to be stored and used in future research at Mayo Clinic to learn about, 
prevent, or treat any other health problems: 
 
  Yes 
  No  
Please initial here: ________Date: ________ 
 
3.  I permit Mayo Clinic to give my sample to researchers at other institutions: 
 
  Yes 
  No  
Please initial here: ________Date: ________ 
 
There is a very small chance that some commercial value may result from the use of your 
donated sample.  If that happens, you won’t be offered a share in any profits. 
 


 
 
Approval Date:  
June 3, 2020 
Not to be used after: June 2, 2021 
 
 
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You may request to have your sample destroyed by writing to the Principal Investigator. 
The address is found in the “Contact Information" section of this consent form. 
 
Because we cannot predict how your sample will be used in the future, we cannot promise that 
samples can be retrieved and destroyed. 
 
 
14. 
How will your privacy and the confidentiality of your records be protected? 
 
 
Mayo Clinic is committed to protecting the confidentiality of information obtained about you in 
connection with this research study. Your information will be stored in secured areas and 
password-protected computers. 
 
During this research, information about your health will be collected. Under Federal law called 
the Privacy Rule, health information is private. However, there are exceptions to this rule, and 
you should know who may be able to see, use and share your health information for research and 
why they may need to do so. Information about you and your health cannot be used in this 
research study without your written permission. If you sign this form, it will provide that 
permission.   
 
Health information may be collected about you from: 
• Past, present and future medical records. 
• Research procedures, including research office visits, tests, interviews and 
questionnaires. 
 
Why will this information be used and/or given to others? 
• To do the research. 
• To report the results. 
• To see if the research was done correctly. 
 
If the results of this study are made public, information that identifies you will not be used. 
 
Who may use or share your health information? 
• Mayo Clinic research staff involved in this study.  
 


 
 
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With whom may your health information be shared?  
• The Mayo Clinic Institutional Review Board that oversees the research.  
• Other Mayo Clinic physicians involved in your clinical care.  
• Researchers involved in this study at other institutions. 
• Federal and State agencies (such as the Food and Drug Administration, the Department of 
Health and Human Services, the National Institutes of Health and other United States 
agencies) or government agencies in other countries that oversee or review research. 
• A group that oversees the data (study information) and safety of this research. 
 
In addition, individuals involved in study oversight and not employed by Mayo Clinic may be 
allowed to review your health information included in past, present, and future medical and/or 
research records. This review may be done on-site at Mayo Clinic or remotely (from an off-site 
location). These records contain information that directly identifies you. However, the 
individuals will not be allowed to record, print, or copy (using paper, digital, photographic or 
other methods), or remove your identifying information from Mayo Clinic. 
 
Is your health information protected after it has been shared with others? 
Mayo Clinic asks anyone who receives your health information from us to protect your privacy; 
however, once your information is shared outside Mayo Clinic, we cannot promise that it will 
remain private and it may no longer be protected by the Privacy Rule. 
 
Your Privacy Rights 
You do not have to sign this form, but if you do not, you cannot take part in this research study. 
 
If you cancel your permission to use or share your health information, your participation in this 
study will end and no more information about you will be collected; however, information 
already collected about you in the study may continue to be used. 
 
If you choose not to take part or if you withdraw from this study, it will not harm your 
relationship with your own doctors or with Mayo Clinic. 
 
You can cancel your permission to use or share your health information at any time by sending a 
letter to the address below: 
 
Mayo Clinic 
Office for Human Research Protection 
ATTN:  Notice of Revocation of Authorization 
200 1st Street SW 
Rochester, MN  55905 
 
Alternatively, you may cancel your permission by emailing the Mayo Clinic Research Subject 
Advocate at: researchsubjectadvocate@mayo.edu. 


 
 
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Name and Clinic Number 
 
Please be sure to include in your letter or email: 
• The name of the Principal Investigator, 
• The study IRB number and /or study name, and 
• Your contact information. 
 
Your permission lasts forever, unless you cancel it.  
 
 
ENROLLMENT AND PERMISSION SIGNATURES 
 
 
Your signature documents your permission to take part in this research.  
 
 
 
  
 
 
 
/        /  
 
 
   : 
       AM/PM   
Printed Name  
 
 
 
Date 
 
 
 
Time   
 
 
 
 
_______________________________ 
Signature 
 
 
Person Obtaining Consent  
• I have explained the research study to the participant. 
• I have answered all questions about this research study to the best of my ability. 
 
 
 
  
 
 
 
/        /  
 
 
   : 
       AM/PM   
Printed Name  
 
 
 
Date 
 
 
 
Time           
 
 
_______________________________ 
Signature