The Effect of a Gas-filled Intragastric Balloon or Endoscopic Sleeve Gastroplasty for Weight Loss Compared With a Meal Replacement Weight Loss Program on Gastric Emptying, Hormonal Adaptation to Weight Loss, and Hunger
Phase: NA
Conditions: Obesity
Sponsor: University of Colorado, Denver

 
 
 
Protocol #: 19-0278 
Title: The effect of a gas-filled intragastric balloon or Endoscopic Sleeve Gastroplasty for 
weight loss compared with a meal replacement weight loss program on gastric emptying, 
hormonal adaptation to weight loss, and hunger 
PI: Shelby Sullivan, University of Colorado School of Medicine 
Version Date: 2-Nov-21 
 
SPECIFIC AIMS: The disease obesity continues to be a major health issue in the US with over one 
third of the population having a mass index >30 kg/m2. Obesity is associated with serious 
cardiometabolic complications including diabetes, hypertension, dyslipidemia and myocardial infarction. 
Rates of successful obesity treatment with weight loss and weight maintenance remain low. Several 
endoscopic bariatric therapies and procedures have been approved for use in the United States, 
including three intragastric balloon systems (2 fluid-filled and one gas-filled) and endoscopic sleeve 
gastroplasty (ESG), both of which have lower risks than bariatric surgery and do not alter 
gastrointestinal anatomy. Weight loss with all intragastric balloons and ESG is higher than lifestyle 
therapy or weight loss medications, but less than bariatric surgery. Unlike weight loss medications 
where weight loss from the medication is regained within 6-8 months after therapy ends, weight loss 
maintenance with intragastric balloons remains high with 66-88.5% of the weight loss maintained 6 
months after device removal. Data suggests that space occupying devices with a volume of 400 ml or 
more in the stomach increase feelings of fullness and result in weight loss, but this does not explain the 
prolonged effect of weight loss maintenance after balloon removal. Although few studies have 
investigated the mechanism of action of fluid-filled balloons and one study with 4 patients undergoing 
ESG on weight loss, these data suggest that gastric emptying as well as space occupation contribute 
to weight loss. However, no studies have investigated the mechanisms of action of gas filled 
intragastric balloons on weight loss. 
Understanding the mechanisms responsible for weight loss with the gas filled intragastric balloon 
system and eSG as well as  any weight loss independent effects on blood glucose control would lay 
the groundwork for studies evaluating predictors of response to improve patient selection as well as 
studies understanding the mechanisms behind weight loss maintenance and developing strategies to 
prolong weight loss maintenance. Therefore, the purpose of this pilot study is to determine the 
effects 10% total body weight loss (%TBWL) in patients with obesity treated with the 
intragastric balloon (GF- IGB) system or ESG compared to patients with obesity treated with a 
meal replacement program (MRP) on 1) gastric emptying, 2) hormonal adaptation to weight loss 
and 3) hunger. The following specific aims will be evaluated: 
 
AIM 1. Gastric emptying measured by technetium 99 gastric emptying study. Hypothesis 1. We 
hypothesize that treatment with GF-IGB and ESG will result in greater gastric retention of contents at 2 
hours compared with patients who are treated with MRP. 
AIM 2. Acyl-Ghrelin, glucose and insulin will be measured at multiple times points during a 
mixed meal test (MMT). Hypothesis 2. We hypothesize that weight loss induced increase in active 
ghrelin concentrations seen during a mixed meal tolerance test will be lower in patients treated with GF- 
IGB and ESG compared with patients treated with MRP, but there will be no difference in glucose and 
insulin concentrations. 
Aim 3. Level of hunger will be measured using a visual analog scale. Hypothesis 3. We 
hypothesize that hunger will increase before and during a MMT after weight loss with MRP but will not 
change from baseline after weight loss with GF-IGB or ESG treatment. 

 
1. Background and Significance 
Obesity is a chronic disease which is associated with and contributes to multiple medical co- 
morbidities including but not limited to cardiovascular disease, diabetes, nonalcoholic fatty liver 
disease, and many different cancers. Obesity is also associated with an increased risk of all-cause 
mortality. Despite these known risks, treatment remains limited. This has contributed to the increase in 
the prevalence of obesity with 42.4%% of adults in the US adults having a body mass index (BMI) >30 
kg/m2 of1. 
Endoscopic bariatric therapies are a new class of treatment for obesity which have 
demonstrated more weight loss than lifestyle therapy alone and fewer complications than bariatric 
surgery with less weight loss than bariatric surgery2-5. Four endoscopic devices are currently approved 
by the FDA for the treatment of obesity, including two intragastric balloons (IGB). One of the balloons 
systems are fluid filled (FF-IGB) and one is gas filled (GF-IGB). Although the GF-IGB system is 
swallowed, all the balloon systems require an endoscopist for endoscopic removal. In clinical registry 
series, these balloons demonstrate similar weight loss at 6 months6-8.  Unlike weight loss medications, 
weight loss maintenance is prolonged after IGB removal, which was demonstrated meta-analysis of 
studies and case series outside of the US of the single FF-IGB demonstrated weight loss maintenance 
after balloon removal 9 and in the US pivotal trials2-4. While the occupancy of space in the stomach by 
IGB is known to induce satiation and satiety10, 11, this mechanism is only present with the IGB in place. 
Therefore, the prolonged effects of weight loss maintenance after IGB removal suggest other 
mechanisms contributing to weight loss with IGB treatment beyond space occupation. ESG is 
completed endoscopically with a device that has FDA 510k clearance for tissue apposition in 
the GI tract. Weight loss with ESG in a recent meta-analysis in 1772 patients demonstrated 16.5% 
TBWL at 12 months and 17.2% TBWL at 18-245 months12. Understanding the mechanisms 
contributing to weight loss with the GF-IGB system and ESG will lay the groundwork for future 
studies to enhance the effect of IGBs and ESG on initial weight loss, patient selection, and 
weight loss maintenance; increasing benefits to patients treated with IGBs or ESG. 
FF-IGB are known to delay gastric emptying 10, 11. This is consistent with practice patterns as 
patients reliably have food left in their stomachs after an overnight fast requiring multiple days of liquid 
diet prior to endoscopic removal to avoid aspiration. In one study,  the FF-IGB delayed gastric 
emptying compared to both baseline and a control group and the change in gastric emptying was 
associated with weight loss (12).  Gastric emptying has been studied in only 4 patients before and after 
ESG.  In these 4 patients, there was a 90 minute increase to the time for 50% of emptying of solid 
foods, however the limited number of patients in that study reduce overall certainty of the effect of ESG 
on gastric emptying13. No  studies have investigated the effects of the GF-IGB on gastric emptying. 
This protocol will clarify the effects of the GF-IGB and ESG on gastric emptying compared with 
a control group matched on weight loss. This will elucidate the weight loss independent effects 
of the devices since patients will be studied at baseline and 10% total body weight loss. 
Another possible mechanism by which IGBs and ESG may induce weight loss and weight loss 
maintenance is through alterations in gut hormones. Ghrelin is a hormone secreted by X/A like cells, 
which are predominantly in the fundus of the stomach14. Ghrelin concentrations fluctuate with eating, 
increasing pre-meals and decreasing in response to food in the stomach. Moreover, infusion of ghrelin 
stimulates eating in humans and is the only known hormone secreted from the GI tract to stimulate 
hunger15. Weight loss with lifestyle therapy alone has been shown to increase fasting and meal test 
“active” or acyl-ghrelin concentrations, which correlated with increased hunger on visual analogue scale 
(VAS) testing16. Acyl-Ghrelin concentrations were still elevated at one year after weight loss despite 
weight regain of almost 50%, which suggests that acyl-ghrelin plays and important role in weight regain. 
Studies investigating ghrelin concentrations in the setting of FF-IGBs have been mixed, demonstrating 
decreased fasting plasma total ghrelin concentrations17, no change in fasting or meal test ghrelin 
concentrations in FF-IGB or control groups18, 19, increased fasting plasma ghrelin compared to a control 
group at months 1 and 6 with decreased ghrelin in the active arm compared to the control arm after 
removal 20 and increased ghrelin concentrations in a single arm 21. However, these studies measured 

 
total ghrelin not acyl ghrelin. This limits the reliability of the data especially since no change in ghrelin 
concentrations were seen in control patients with weight loss in which an increase in acyl- ghrelin is 
expected. Moreover, all the studies were with FF-IGB and none were in the GF-IGB system. 
Balloon type may have an effect on acyl-ghrelin concentrations as GF-IGB tend to float in the 
fundus and body of the stomach, which may affect the IGB’s ability to suppress acyl-ghrelin secretion. 
In one of the aforementioned studies a post-hoc analysis demonstrated that the small number of 
patients whose FF-IGBs localized to the fundus had greater suppression of ghrelin19. 
 Fasting ghrelin has been evaluated in one study with 12 patients pre and post ESG.  Fasting 
ghrelin concentrations did not increase with weight loss, but meal testing was not performed 
22Therefore, this protocol will determine the effects of 10% TBWL from either  GF-IGB system 
treatment or ESG treatment  compared to lifestyle and meal replacement therapy on acyl-ghrelin 
concentrations, the active form of ghrelin which stimulates hunger, and the sensation of hunger 
with the VAS. This will allow for the detection of effects that are specific to either procedure and 
independent of weight loss. 
 
2. Innovation and Knowledge to be Gained: This proposal is innovative for several reasons. It will be 
the first ever study to evaluate any mechanisms of action of the GF-IGB system approved for use in the 
US and will add important information to the effect of ESG on gastric emptying as only 4 subjects have 
had gastric emptying measured pre and post ESG  Second, the study will determine a hormonal 
response to weight loss by procedures compared with diet through measuring the active form of 
ghrelin, acyl-ghrelin. Third, no other study investigating mechanisms of action of action of endoscopic 
bariatric therapies have compared outcomes with patients achieving the same amount of weight loss 
through diet alone.  Weight loss itself has many effects, and the only way to mitigate the confounding 
effect of weight loss is to compare changes in these mechanism of action parameters in patients who 
have the same amount of weight loss, but have not undergone these procedures. Fourth, the study 
population will come from three clinically administered weight loss programs with different weight loss 
treatments. Although not a randomized control study, the participant populations in this comparative 
analysis more closely approximate clinical patient populations.  The results from this study will lay the 
groundwork for future studies into additional gut hormone adaptation, optimization of patient selection 
to those with the highest likelihood of response to treatment with the GF-IGB system or ESG and 
studies investigating mechanisms of weight loss maintenance. This information will improve patient 
outcomes with GF-IGB or ESG treatment by endoscopists. 
 
3. Preliminary Data 
The research in this proposal involves using a combination of research techniques including 
imaging, meal testing, and questionnaires to determine the effects of the GF-IGB system and ESG 
on gastric emptying, hormonal adaptation to weight loss, and hunger which I have used in two 
previous studies. 
In one study 18 subjects with obesity and nonalcoholic fatty liver disease were randomized in a 
1:2 ratio to 16 weeks of: 1) no exercise (BMI 40.0 ± 5.4 kg/m2, IHTG 21.3 ± 10.8%) or 2) Exercise at 
45%-55% of VO2 max for 30-60 minutes 5 days/week (BMI 37.1± 4.0 kg/m2, IHTG 20.4± 6.8%). One 
exercise session per week was monitored at our center and subjects were re-fed calories expended 
during exercise by providing a liquid formula meal if any change in weight occurred to maintain weight 
stability. IHTG, measured with magnetic resonance spectroscopy, decreased by 10.3 ± 4.6% in the 
exercise group, but did not change in the control group, p=0.044. Exercise also decreased plasma 
alanine transaminase (ALT) concentrations by 12.8 ± 3.1%, p = 0.04. Exercise did not affect hepatic 
lipoprotein secretion rates 23. 
In a second study, 11 subjects with obesity were studied before and after a 4-week isocaloric diet high in 
high-fructose corn-syrup (HFCS). All meals were made in a bionutrition kitchen with 25% of total calories 
from HFCS. Patients were weighed every 3-4 days at meal pick-up and foods were adjusted to maintain 
weight. No change in weight (98.2±12.8 kg and 97.8±12.6, p=0.336) or IHTG (2.2% [1.6,3.5] and 3.0% 
[2.1,6.5], p=0.424) measured by MRS occurred during the 4-week trial. Meal testing with a liquid mixed 

 
meal (without HFCS at baseline and with 25% of calories as HFCS at end study testing) revealed trends 
towards increased fasting plasma uric acid concentrations (5.3±0.8 mg/dl baseline and 5.9±1.4 mg/dl end-
study, p=0.062) and Uric Acid Area Under the Curve (1188±154 baseline and 1343±335 end-study, 
p=0.091). The high HFCS intervention resulted in a 12.8 ± 7% increase in plasma total cholesterol 
concentration, 25.4±31% increase in plasma triglyceride concentration, and a trend towards an increase 
in very low-density lipoprotein-triglyceride rate of secretion. No changes were seen in glucose kinetics 
measured by hyperinsulinemic euglycemic clamp testing (manuscript in preparation). 
 
4. Approach 
4.1 Subjects: The study population will consist of 11 patients with a BMI 30-40 kg/m2 and age 22-65 
years old who are weight stable (defined as <5% weight change in the last 3 months) and initiating clinical 
treatment with the GF-IGB system, 11 patients with a BMI 30-40 kg/m2 and age 22-65 years old who are 
weight stable (defined as <5% weight change in the last 3 months) and initiating clinical treatment with 
ESG, and 11 patients with a BMI 30-40 kg/m2 and age 22-65 who are weight stable and initiating clinical 
treatment with a medically supervised MRP (My New Weigh; University of Colorado, Anschutz Health and 
Wellness Center). After undergoing any required laboratory testing or imaging for the patient’s self-chosen 
treatments, patient will present for screening. The screening visit will consist of a history and physical 
examination, the Patient Health Questionnaire- 9 (PHQ-9) 24, and the Questionnaire on Eating and Weight 
Patterns – 5 25 (Appendix A). Patients with a history of liver disease, uncontrolled thyroid disease, anemia, 
diabetes, eating disorder, uncontrolled depression defined as a score ≥10 PHQ-9, on weight loss 
medications in the last 3 months, history of gastroparesis, bariatric surgery, or history to allergy or 
intolerance to any component of the meal used in the gastric emptying study or mixed meal test will be 
excluded. Women who are pregnant or lactating, prisoners, non-English speakers, and decisionally 
challenged adults will also be excluded. We anticipate consenting 25 patients in each arm to achieve the 
required number of patients completing all study testing in each arm for achieve adequate statistical 
power (See 5.2 Power Calculation). We will attempt to match enrollment based on BMI in categories of 
BMI 30-34.9 kg/m2 and 35-40 kg/m2. 
 
4.1 Study Protocol 
4.1.a. Overview. All patients will undergo study testing at baseline prior to initiating treatment with the 
GF-IGB system, ESG, or MRP. Study testing will consist of two separate visits within 7 days of each 
other at both baseline and at 10% total body weight loss (TBWL). On visit one, patients will undergo a 
gastric emptying study and on visit two, patients will undergo a mixed meal test and VAS for hunger. 
All subjects will be called weekly to review weight loss and rate of weight loss in order to appropriately 
time end study testing. 
4.1.b. Treatments (Standard of Care): The three groups will consist of patients undergoing the 
following clinical treatments as part of their clinical care.  These treatments are not affected by study 
participation. 
GF-IGB System Treatment: After the patients meet all clinical GF-IGB system treatment (FDA 
approved, Appendix B) criteria and pre-placement activities, patients report to the endoscopy lab after 
an overnight fast for balloon administration at their own expense. The balloon, contained in a hard, 
cellulose food grade capsule and attached to a thin catheter, is swallowed by the patient in a standing 
position. Once the two-step verification of balloon passage into the stomach by both fluoroscopy and 
pressure reading, the balloon is inflated to a volume of 250 ml with a nitrogen-mix gas, additional 
imaging of the inflated balloon is obtained, the catheter is ejected from the balloon, and the catheter is 
pulled out through the patient’s mouth. The process is repeated at week 2 for the second balloon and 
between weeks 4-8 for the third balloon based on patient preference. All patients are given an 
individualized calorie prescription by a registered dietitian for a goal of up to 2 pounds of weight loss 
per week. The balloons are removed endoscopically 6 months after placement of the first balloon(5). 
Patients also attend monthly virtual individual diet coaching and monthly virtual group behavior 
coaching sessions both delivered by a registered dietitian for twelve months focused on long-term 
behavior change, 6 months while the balloons are in place and six months after the balloons are 
removed. 

 
 
ESG Treatment: After the patients meet all clinical ESG treatment criteria, patients report to the 
endoscopy lab after an overnight fast for the ESG procedure at their own expense. Endoscopic 
sleeve gastroplasty is a weight loss procedure that uses an FDA 510K cleared endoscopic suturing 
device known as Overstitch to reduce the size of the gastric body. The procedure is completed with 
an endoscope, which is a flexible tube with a camera, with the suturing device attached at the distal 
tip. suturing device attached to it. It is inserted through the mouth, down the esophagus, and into the 
stomach. Sutures with 8-10 bites 1.5-2 cm apart in a U-shape pattern are placed starting distally 6 
cm proximal to the pylorus. When the suture is tightened the greater curve of the stomach is reduced 
in size.  Additional sutures are placed moving proximally up to 2 cm distal to the gastroesophageal 
junction. An additional row of sutures is then placed again in the distal to proximal stomach to 
complete the gastroplasty. The final shape of the gastric body is a tube 3-4 cm in diameter.    This 
decreases the amount of food one can consume, which leads to the consumption of fewer calories 
throughout the day, resulting in weight loss. However, for long-term success and maintenance of 
weight loss, a healthy diet and exercise are also required with the consumption of smaller portion 
sizes. All patients are given an individualized calorie prescription by a registered dietitian for a goal of 
up to 2 pounds of weight loss per week. Patients also attend monthly virtual individual diet coaching 
and monthly virtual group behavior coaching sessions both delivered by a registered dietitian for 
twelve months focused on long-term behavior change.  
 
MRP: After patients meet all criteria for the medically supervised MRP program and enroll in the 
program at their own expense, patients are given an individualized calorie prescription by a 
registered dietitian for a goal of 2 pounds weight loss per week. Patients are seen in a group-based 
program once a week focused on long-term behavior change and use meal replacements for a 
nutritionally balanced very low-calorie diet for 20 weeks. 
 
4.1.c. Gastric emptying study (research related). After an overnight fast, patients will report to the 
radiology suite at the University of Colorado Hospital. Subjects will consume a meal consisting of 118 
ml (4 oz) of liquid egg substitute mixed with technetium colloidal sulfur and cooked until firm, two pieces 
of white bread, and 29 gm of a jam as well as 120 ml of water ingested upright over 10 minutes. 
Immediately after ingestion, planar static imaging of the anterior and posterior abdomen with the patient 
in the upright position will be performed. Radiotracer activity in the stomach will be obtained with 
anterior and posterior regions of interest placed over the stomach, and percent retention calculated 
using the geometric mean at baseline, 0.5 hour, 1 hour, 2 hours, 3 hours, and 4hours after ingestion. If 
there is less than 10% food remaining in the stomach at the 3 hour mark the gastric emptying study will 
stop at 3 hours.  
 
4.1.d. Mixed Meal Test (research related): On a day separate from the gastric emptying study, 
patients will report to the Clinical Translational Research Center (CTRC) at the University of Colorado 
School of Medicine after an overnight fast. An intravenous catheter will be inserted into a hand or 
forearm vein for blood draws. Immediately before and at 15, 30, 60, 90, 120, 150, and 180 minutes 
after consumptions of a mixed meal, blood will be drawn for measurement of acyl-ghrelin, plasma 
insulin, and plasma glucose concentrations. The mixed meal will be a mixture of liquids and solids and 
contain 550 kcal with a macronutrient content of 51% carbohydrate, 33% fat, and 16% protein. 
4.1.e. Visual Analogue Scales to assess Hunger (Research Related): A validated questionnaire 
(The Visual Analogue Scales for measurement of appetite sensations) 26 will be given to patients 
during the mixed meal test. Subjects will fill out the questionnaire immediately before the mixed meal 
and at 15, 30, 60, 90, 120, 150, and 180 minutes after consuming the mixed meal. 
4.1.f. Follow-up weight at 12 months: patients will report for a follow-up visit at 12 months after 
initiating therapy for weight. 

 
 
5. Statistical Analysis. 
5.1 Data analysis. The primary analysis will be a group by study-time repeated (baseline-end study) 
measures analysis of variance which will include an evaluation of statistical contrasts that compare 
between group differences in changes from baseline to end. Analyses will be performed on the 
following variables: percent of gastric retention at 2 hours, fasting and Area Under the Curve (AUC) for 
acyl ghrelin, insulin, glucose, and VAS-hunger. A Student’s t-test for paired samples will also be 
performed on each variable from baseline to end-study testing. All data will be analyzed using SPSS 
(IBM, Armonk, NY) 
5.2 Power calculation. The primary endpoints used for the power calculation in this study are change 
in gastric emptying at 2 hours, acyl-ghrelin concentrations, and visual analog scale. In assessing 
statistical power, we will use statistical contrasts of change from baseline between the groups, 
assuming 11 patients in each group. Based on previous work, a conservative estimate of standard 
deviation of the change is assumed to be roughly 80% of the amount of change for fasting acyl-ghrelin 
and VAS Hunger (16) and 60% for percent gastric retention at 2 hours 11. All tests are two-sided and 
performed at the 0.05 level of significance. GPower 3.1 (Universitat Duesseldorf, Germany) was used 
for power calculations. The impact of these assumptions is as follows (Table 1): 
 
 
Table 1. Power Calculations 
 
 
Variable 
Baseline 
Response to Weight Loss 
Between Group 
(compared with MRP) 
 
 
MRP 
GF-IGB 
ESG 
GF-IGB 
ESG 
% Retention at 2 hours 
25±14.5% 
0 
+12.5 
(50%) 
+12.5 
(50%) 
96% 
96% 
Acyl Ghrelin pg/ml 
125±100 
+50 (40%) 
+10 (8%) 
+10 (8%) 
86% 
86% 
Visual Analog Scale 
32±25 
+11 (40%) 
0 
0 
80% 
80% 
 
 
6.0. Study timeline. 
Subjects will be recruited over two years from patient populations already at the University of Colorado. 
Our current practice had 15 GF-IGB patients per year since the start of the program with 80% of the 
current patient population meeting study criteria. Our current practice also had 18 ESG patients in the 
last 12 year months with 75% of the current patient population meeting study criteria. The MRP at the 
University of Colorado enrolls >40 patients per year with >50% meeting study inclusion criteria. 
Baseline to End-Study Testing is expected to take 16 weeks per patient. Consenting will need to be 
performed on 25 subjects in each group (total of 75 subjects). Assuming an attrition rate of 20% for 
patients undergoing baseline testing, all study testing should be completed with 11 subjects in each 
group within two years. If a participant has not reached 10% TBWL by the end of the clinic program, 
they will be withdrawn from the study. 
 
 
7.0 Recruitment and Consenting: 
Study participants in the GF-IGB and ESG group will be recruited from the endoscopic 
bariatric therapy clinical practice who have passed all clinical pre-procedure testing and are scheduled 
to undergo device placement. Study participants in the MRP group will be recruited from the My New 
Weigh meal replacement program who have met all clinical program entry criteria. Medical records will 
be reviewed for inclusion and exclusion criteria prior to consent and subjects will be asked face to face, 
or over the phone if they would like to participate in this study. Patients will then be scheduled for 
consent and screening. The consenting process will be performed by the study coordinator in a face to 

 
face visit. Only the study participant will be allowed to provide consent for the study. 
 
8.0 Potential Risks for Patients 
8.1 General: We anticipate no psychological, social or legal risks beyond those of participation in 
health-related research in general. The potential risks associated with participation in this study are 
small. They will be explained to all subjects who desire to participate in this research project. In 
addition, subjects will be informed that there is a possibility of unforeseeable risk, although we consider 
this unlikely. The research coordinator and/or the PI will ensure understanding of the consent and study 
procedures, as well as laboratory results; in addition, the research coordinator and/or PI will explain the 
various procedures and answer any questions the subjects may have before initiating any procedures. 
Whenever concerns arise, subjects will be informed that they are free to withdraw from the study at any 
time with no bias or prejudice. 
 
8.2 Confidentiality: All key personnel involved in the design or conduct of the research involving the 
human subjects will receive the required education on the protection of human research participants 
prior to the start of this project. All specimens will be obtained solely for research purposes. Study 
samples and datasheets will be coded with an identification number for each subject. All data will be 
treated confidentially, and the subjects' names and identities will not be disclosed in any published 
reports. Clinic records are maintained in EPIC and study related data will be maintained on de-identified 
case report forms that will be entered into RedCap. A locked excel spreadsheet on a secured server 
will be used to maintain the key to the identification of study subject ID numbers. 
 
8.3 Questionnaires: Patients could screen positive for moderate or severe depression or an eating 
disorder. Patients will be notified of these results and referral resources will be given to patients. If the 
patient wants these results sent to their primary care physicians, a copy of the results and referral 
resources will be sent to the subject’s primary care physician. 
8.4 Gastric Emptying Study: This research involves exposure to radiation equivalent to 40 mrems per 
study from the gastric emptying study. This is equivalent to <13%% of the amount of average radiation 
exposure adults in the US receive each year. Participants could also have an allergic reaction to the 
food components of the test. All subjects will be advised of the radiation exposure and will be 
questioned about food allergies and if they have a known allergy to any component of the test meal, 
they will be excluded from the study. 
 
8.5 Intravenous catheter insertion: Possible side effects of intravenous catheter insertion are 
discomfort, bruising, and/or bleeding at the site of needle insertion. Occasionally some people 
experience dizziness or feel faint. An infection can occur at the site of catheter insertion. Aseptic 
technique for intravenous catheter insertion will be used to prevent infection, participants will have IV 
catheter insertion while seated or reclined, and the site will be monitored during the mixed meal test for 
any signs of intravenous catheter malfunction. 
 
9.0 Data Monitoring: 
This the study related procedures in this protocol (questionnaires, visual analog scale, gastric emptying 
study, and mixed meal tests with blood draws) are low risk. The PI will review any adverse events that 
occur from study related procedures as they occur. There will not be a formal interim analysis. 
10.0 Potential Scientific Problems: 
This is an ambitious protocol which will require enough patient volume for adequate enrollment, 
however we have adequate patient populations to recruit for this study. Detailed follow-up of patients is 
necessary to ensure testing at 10% TBWL, and I have experience with two other trials that required 
carefully monitoring weight to eliminate confounding from change in weight. I will employ similar 
strategies in this study to test patients at the required %TBWL and we have budgeted for an assumed 
20% attrition rate after enrollment and baseline testing to have adequate sample to achieve sufficient 

 
power. 
 
11.0 Funding: 
Grant funding is currently pending for this study from the American Society for Gastrointestinal 
Endoscopy, but PI start-up funds are currently available to complete all study testing. 
 
 
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