Pilot Study of the Effect of Liraglutide on Weight Loss and Gastric Functions in Obesity

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT02647944
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH), Novo Nordisk A/S (Industry)
• Enrollment: 40
• Location: 1
• Arms: 2
• Actual Duration (Months): 12.4
• Patients Per Site Per Month: 3.2

Study Details

Study Description

Brief Summary

This study was 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.

Condition or Disease	Intervention/Treatment	Phase
Obesity	Drug: Liraglutide; Drug: Placebo	Phase 2

Detailed Description

The objective of this study was to compare effects of liraglutide and placebo over 16 weeks on gastric motor functions, satiation, satiety and weight in obese patients. Subjects were randomized to liraglutide or placebo. Liraglutide or placebo was escalated by 0.6mg/day each week for 5 weeks and continued until week 16. At baseline and after 16 weeks' treatment, the investigators measured weight, gastric emptying of solids (GES), gastric volumes, satiation (maximum tolerated volume of liquid nutrient drink), and satiety. GES was also measured at 5 weeks.

During the study, the subjects received standardized dietetic and behavioral advice for weight reduction therapy. All subjects were given a standard text for information and met with a behavioral psychologist who has expertise in obesity treatment at the baseline visit and at visits at weeks 4,8, and 12. Additionally, the subjects had brief contact with a member of the study team every 4 weeks to inquire about their adherence to study protocol, any difficulties they were experiencing, whether they were reading their text assignments, and to answer any additional questions.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Pilot Study of the Effect of Liraglutide on Weight Loss and Gastric Functions in Obesity
• Actual Study Start Date: Dec 18, 2015
• Actual Primary Completion Date: Dec 30, 2016
• Actual Study Completion Date: Dec 30, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Liraglutide Saxenda 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.	Drug: Liraglutide; 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.; Other Names: Saxenda
Placebo Comparator: Placebo 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.	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Gastric Emptying of Solids Half-time (T1/2) at 5 Weeks [5 weeks]

   Gastric emptying of solids was assessed by scintigraphy using a 320 Kcal 99mTc-radiolabeled egg, solid-liquid meal. Gastric Emptying Half-time was the linear interpretation of time to when 50% of radiolabeled meal emptied from the stomach.

2. Gastric Emptying of Solids Half-time (T1/2) at 16 Weeks [16 weeks]

   Gastric emptying of solids was assessed by scintigraphy using a 320 Kcal 99mTc-radiolabeled egg, solid-liquid meal. Gastric Emptying Half-time was the linear interpretation of time to when 50% of radiolabeled meal emptied from the stomach.

Secondary Outcome Measures

1. Weight Change at 5 Weeks [baseline, 5 weeks]

   Body weight in kg was measured at 5 weeks and compared to baseline.

2. Weight Change at 16 Weeks [baseline, 16 weeks]

   Body weight in kg was measured at 16 weeks and compared to baseline.

3. Satiety by Buffet Meal, Total Calories Ingested at 16 Weeks [16 weeks]

   Satiety (a measure of appetite) was appraised by "free feeding" buffet meal consisting of standard foods of known nutrient composition. The total amount of food consumed was analyzed by the study dietitian.

4. Satiation Volume to Fullness at 16 Weeks [16 weeks]

   After drinking Ensure, participants recorded 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 and level 5 corresponding to the maximal tolerated volume (maximum or unbearable fullness/satiation).

5. Satiation Maximum Tolerated Volume at 16 Weeks [16 weeks]

   After drinking Ensure, participants recorded 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 and level 5 corresponding to the maximal tolerated volume (maximum or unbearable fullness/satiation).

6. Gastric Fasting Volume at 16 Weeks [16 weeks]

   Gastric fasting volume was measured by single photon emission computed tomography (SPECT) imaging of the stomach after intravenous injection of 99mTC-pertechnetate, which is taken up by the gastric mucosa.

7. Gastric Postprandial Volume at 16 Weeks [16 weeks]

   Gastric fasting volume was measured by single photon emission computed tomography (SPECT) imaging of the stomach after intravenous injection of 99mTC-pertechnetate, which is taken up by the gastric mucosa.

8. Gastric Accommodation Volume at 16 Weeks [16 weeks (approximately 1 hour after 99mTC injection)]

   Change between postprandial and fasting whole gastric volume by 99mTc-SPECT Imaging. A noninvasive SPECT method was used to measure gastric volume during fasting and 32 min after a liquid nutritional supplement meal. Subjects reported to the clinic after an overnight fast. 99mTC was given by an intravenous injection in the forearm. The first fasting scan was obtained, and the study medication was given s.c. After 10 min, a 2nd fasting post medication scan was obtained, and the meal consumed; then two serial postprandial scans were obtained. Each scan required 9-12 min. Tomographic images of the gastric wall were obtained throughout the long axis of the stomach using a dual-head gamma camera that rotates around the body. This allows assessment of the radiolabeled circumference of the gastric wall, rather than the intragastric content.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Overweight and obese adults (≥30 kg/m^{2 or ≥27 kg/m}2 with an obesity-related co-morbidity).

• Subjects residing within 125 miles of Mayo Clinic in Rochester, Minnesota.

• 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 type 2 diabetes mellitus on metformin) disorders.

• Women of childbearing potential will be using an effective form of contraception, and have negative pregnancy tests within 48 hours of enrolment and before each radiation exposure.

• Subjects must have the ability to provide informed consent before any trial-related activities.

Exclusion criteria:

• Weight exceeding 137 kilograms (safety limit of camera for measuring gastric volumes).

• Abdominal surgery other than appendectomy, Caesarian section or tubal ligation.

• Positive history of chronic gastrointestinal diseases, systemic disease that could affect gastrointestinal motility, or use of medications that may alter gastrointestinal motility, appetite or absorption, e.g., orlistat.

• Patients with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia-type 2.

• Patients with a personal history of pancreatitis (acute or chronic)

• Significant untreated psychiatric dysfunction based upon screening with the Hospital Anxiety and Depression Inventory, a self-administered alcoholism screening test (AUDIT-C), and the Questionnaire on Eating and Weight Patterns (binge eating disorders and bulimia). If such a dysfunction is identified by a Hospital Anxiety Depression (HAD) score >8 or difficulties 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.

• Intake of medication, whether prescribed or over the counter (except multivitamins), within 7 days of the study. Exceptions are birth control pill, estrogen replacement therapy, thyroxin replacement therapy and any medication administered for co-morbidities as long as they do not alter gastrointestinal motility including gastric emptying (GE) and gastric accommodation. For example, statins for hyperlipidemia, diuretics, β-adrenergic blockers,Angiotensin Converting Enzyme (ACE) inhibitors and angiotensin antagonists for hypertension, and metformin for type 2 diabetes mellitus or prediabetes are permissible. In contrast, resin sequestrants for hyperlipidemia [which may reduce GE and reduce appetite, α2-adrenergic agonists for hypertension, or other glucagon-like peptide-1 receptor agonists (GLP-1) receptor agonists (exenatide) or amylin analogs (pramlintide) are not permissible because they significantly affect GE and/or gastric accommodation.

• Hypersensitivity to the study medication, liraglutide.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Novo Nordisk A/S

Investigators

• Principal Investigator: Michael Camilleri, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

• Halawi H, Khemani D, Eckert D, O'Neill J, Kadouh H, Grothe K, Clark MM, Burton DD, Vella A, Acosta A, Zinsmeister AR, Camilleri M. Effects of liraglutide on weight, satiation, and gastric functions in obesity: a randomised, placebo-controlled pilot trial. Lancet Gastroenterol Hepatol. 2017 Dec;2(12):890-899. doi: 10.1016/S2468-1253(17)30285-6. Epub 2017 Sep 27.

• Responsible Party: Michael Camilleri, Principle Investigator, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT02647944
• Other Study ID Numbers: 15-001783; R56DK067071; UL1TR000135
• First Posted: Jan 6, 2016
• Last Update Posted: Oct 27, 2017
• Last Verified: Oct 1, 2017

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Obesity; Weight Loss; Liraglutide

Study Results

Participant Flow

Recruitment Details	Participants were enrolled between December 18, 2015 and September 1, 2016 at the Mayo Clinic in Rochester, Minnesota.

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	Saxenda 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.	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.
Period Title: Overall Study
STARTED	19	21
COMPLETED	17	18
NOT COMPLETED	2	3

Baseline Characteristics

Arm/Group Title	Liraglutide	Placebo	Total
Arm/Group Description	Saxenda 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.	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.	Total of all reporting groups
Overall Participants	19	21	40
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.95 (11.08)	37.81 (12.14)	39.30 (11.61)
Sex: Female, Male (Count of Participants)
Female	17 89.5%	18 85.7%	35 87.5%
Male	2 10.5%	3 14.3%	5 12.5%
Race/Ethnicity, Customized (Count of Participants)
White Non-Hispanic	17 89.5%	19 90.5%	36 90%
Asian	1 5.3%	0 0%	1 2.5%
Hispanic or Latino	0 0%	2 9.5%	2 5%
Other	1 5.3%	0 0%	1 2.5%
Region of Enrollment (Count of Participants)
United States	19 100%	21 100%	40 100%
Body Mass Index (BMI) (kg/m^2) [Mean (Inter-Quartile Range) ]
Mean (Inter-Quartile Range) [kg/m^2]	37.2	34.6	36.65
Body Weight (kg) [Mean (Inter-Quartile Range) ]
Mean (Inter-Quartile Range) [kg]	103.7	99.1	103

Outcome Measures

1. Primary Outcome

Title	Gastric Emptying of Solids Half-time (T1/2) at 5 Weeks
Description	Gastric emptying of solids was assessed by scintigraphy using a 320 Kcal 99mTc-radiolabeled egg, solid-liquid meal. Gastric Emptying Half-time was the linear interpretation of time to when 50% of radiolabeled meal emptied from the stomach.
Time Frame	5 weeks

Outcome Measure Data

Analysis Population Description

Intent to treat analysis; data were imputed for the 5 participants who dropped out.

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	Saxenda 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.	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.
Measure Participants	19	21
Median (Inter-Quartile Range) [minutes]	180	117

2. Primary Outcome

Title	Gastric Emptying of Solids Half-time (T1/2) at 16 Weeks
Description	Gastric emptying of solids was assessed by scintigraphy using a 320 Kcal 99mTc-radiolabeled egg, solid-liquid meal. Gastric Emptying Half-time was the linear interpretation of time to when 50% of radiolabeled meal emptied from the stomach.
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

Intent to treat analysis; data were imputed for the 5 participants who dropped out.

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	Saxenda 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.	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.
Measure Participants	19	21
Median (Inter-Quartile Range) [minutes]	142	113

3. Secondary Outcome

Title	Weight Change at 5 Weeks
Description	Body weight in kg was measured at 5 weeks and compared to baseline.
Time Frame	baseline, 5 weeks

Outcome Measure Data

Analysis Population Description

Intent to treat analysis; data were imputed for the 5 participants who dropped out.

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	Saxenda 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.	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.
Measure Participants	19	21
Median (Inter-Quartile Range) [kg]	3.70	0.60

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Secondary Outcome

Title	Weight Change at 16 Weeks
Description	Body weight in kg was measured at 16 weeks and compared to baseline.
Time Frame	baseline, 16 weeks

Outcome Measure Data

Analysis Population Description

Intent to treat analysis; data were imputed for the 5 participants who dropped out.

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	Saxenda 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.	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.
Measure Participants	19	21
Median (Inter-Quartile Range) [kg]	5.30	2.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

5. Secondary Outcome

Title	Satiety by Buffet Meal, Total Calories Ingested at 16 Weeks
Description	Satiety (a measure of appetite) was appraised by "free feeding" buffet meal consisting of standard foods of known nutrient composition. The total amount of food consumed was analyzed by the study dietitian.
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

Intent to treat analysis; data were imputed for the 5 participants who dropped out.

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	Saxenda 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.	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.
Measure Participants	19	21
Median (Inter-Quartile Range) [kcal]	554.0	680.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.27
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

6. Secondary Outcome

Title	Satiation Volume to Fullness at 16 Weeks
Description	After drinking Ensure, participants recorded 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 and level 5 corresponding to the maximal tolerated volume (maximum or unbearable fullness/satiation).
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

Intent to treat analysis; data were imputed for the 5 participants who dropped out.

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	Saxenda 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.	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.
Measure Participants	19	21
Median (Inter-Quartile Range) [mL]	360	600

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.069
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

7. Secondary Outcome

Title	Satiation Maximum Tolerated Volume at 16 Weeks
Description	After drinking Ensure, participants recorded 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 and level 5 corresponding to the maximal tolerated volume (maximum or unbearable fullness/satiation).
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

Intent to treat analysis; data were imputed for the 5 participants who dropped out.

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	Saxenda 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.	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.
Measure Participants	19	21
Median (Inter-Quartile Range) [mL]	750	1126

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.054
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

8. Secondary Outcome

Title	Gastric Fasting Volume at 16 Weeks
Description	Gastric fasting volume was measured by single photon emission computed tomography (SPECT) imaging of the stomach after intravenous injection of 99mTC-pertechnetate, which is taken up by the gastric mucosa.
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

Intent to treat analysis; data were imputed for the 5 participants who dropped out.

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	Saxenda 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.	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.
Measure Participants	19	21
Median (Inter-Quartile Range) [mL]	231	192

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.13
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

9. Secondary Outcome

Title	Gastric Postprandial Volume at 16 Weeks
Description	Gastric fasting volume was measured by single photon emission computed tomography (SPECT) imaging of the stomach after intravenous injection of 99mTC-pertechnetate, which is taken up by the gastric mucosa.
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

Intent to treat analysis; data were imputed for the 5 participants who dropped out.

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	Saxenda 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.	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.
Measure Participants	19	21
Median (Inter-Quartile Range) [mL]	705	668

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.68
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

10. Secondary Outcome

Title	Gastric Accommodation Volume at 16 Weeks
Description	Change between postprandial and fasting whole gastric volume by 99mTc-SPECT Imaging. A noninvasive SPECT method was used to measure gastric volume during fasting and 32 min after a liquid nutritional supplement meal. Subjects reported to the clinic after an overnight fast. 99mTC was given by an intravenous injection in the forearm. The first fasting scan was obtained, and the study medication was given s.c. After 10 min, a 2nd fasting post medication scan was obtained, and the meal consumed; then two serial postprandial scans were obtained. Each scan required 9-12 min. Tomographic images of the gastric wall were obtained throughout the long axis of the stomach using a dual-head gamma camera that rotates around the body. This allows assessment of the radiolabeled circumference of the gastric wall, rather than the intragastric content.
Time Frame	16 weeks (approximately 1 hour after 99mTC injection)

Outcome Measure Data

Analysis Population Description

Intent to treat analysis; data were imputed for the 5 participants who dropped out.

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	Saxenda 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.	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.
Measure Participants	19	21
Median (Inter-Quartile Range) [mL]	453	433

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.95
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Time Frame	16 weeks
Arm/Group Title	Liraglutide		Placebo
Arm/Group Description	Saxenda 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.		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.
All Cause Mortality
	Liraglutide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/21 (0%)
Serious Adverse Events
	Liraglutide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/21 (0%)
Other (Not Including Serious) Adverse Events
	Liraglutide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/19 (89.5%)		14/21 (66.7%)
Gastrointestinal disorders
Nausea	12/19 (63.2%)	31	2/21 (9.5%)	5
Bloating	2/19 (10.5%)	4	2/21 (9.5%)	2
Constipation	2/19 (10.5%)	5	2/21 (9.5%)	2
Diarrhea	1/19 (5.3%)	1	3/21 (14.3%)	3
Abdominal pain/discomfort	4/19 (21.1%)	5	2/21 (9.5%)	3
Abdominal Cramping	3/19 (15.8%)	4	2/21 (9.5%)	3
Loose stools	3/19 (15.8%)	3	1/21 (4.8%)	2
Decreased appetite	3/19 (15.8%)	3	1/21 (4.8%)	1
General disorders
Headache	5/19 (26.3%)	7	4/21 (19%)	5
Lightheaded	1/19 (5.3%)	1	2/21 (9.5%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.