Back to resultsPilot Study of the Effect of Liraglutide on Weight Loss and Gastric Functions in Obesity
Primary Purpose
Obesity
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Liraglutide
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Obesity
Eligibility Criteria
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.
Sites / Locations
- Mayo Clinic in Rochester
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Liraglutide
Placebo
Arm 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.
Outcomes
Primary Outcome Measures
Gastric Emptying of Solids Half-time (T1/2) at 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.
Gastric Emptying of Solids Half-time (T1/2) at 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
Weight Change at 5 Weeks
Body weight in kg was measured at 5 weeks and compared to baseline.
Weight Change at 16 Weeks
Body weight in kg was measured at 16 weeks and compared to baseline.
Satiety by Buffet Meal, Total Calories Ingested at 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.
Satiation Volume to Fullness at 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).
Satiation Maximum Tolerated Volume at 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).
Gastric Fasting Volume at 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.
Gastric Postprandial Volume at 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.
Gastric Accommodation Volume at 16 Weeks
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.
Full Information
NCT ID
NCT02647944
First Posted
December 31, 2015
Last Updated
October 25, 2017
Sponsor
Mayo Clinic
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Novo Nordisk A/S
1. Study Identification
Unique Protocol Identification Number
NCT02647944
Brief Title
Pilot Study of the Effect of Liraglutide on Weight Loss and Gastric Functions in Obesity
Official Title
Pilot Study of the Effect of Liraglutide on Weight Loss and Gastric Functions in Obesity
Study Type
Interventional
2. Study Status
Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
December 18, 2015 (Actual)
Primary Completion Date
December 30, 2016 (Actual)
Study Completion Date
December 30, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mayo Clinic
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Novo Nordisk A/S
4. Oversight
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
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obesity
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Factorial Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Liraglutide
Arm Type
Active Comparator
Arm 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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Liraglutide
Other Intervention Name(s)
Saxenda
Intervention Description
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 Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
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
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
Secondary Outcome Measure Information:
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
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
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
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
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
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
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
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Camilleri, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
28958851
Citation
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.
Results Reference
background
PubMed Identifier
35894080
Citation
Maselli D, Atieh J, Clark MM, Eckert D, Taylor A, Carlson P, Burton DD, Busciglio I, Harmsen WS, Vella A, Acosta A, Camilleri M. Effects of liraglutide on gastrointestinal functions and weight in obesity: A randomized clinical and pharmacogenomic trial. Obesity (Silver Spring). 2022 Aug;30(8):1608-1620. doi: 10.1002/oby.23481.
Results Reference
derived
PubMed Identifier
31665455
Citation
Kadouh H, Chedid V, Halawi H, Burton DD, Clark MM, Khemani D, Vella A, Acosta A, Camilleri M. GLP-1 Analog Modulates Appetite, Taste Preference, Gut Hormones, and Regional Body Fat Stores in Adults with Obesity. J Clin Endocrinol Metab. 2020 May 1;105(5):1552-63. doi: 10.1210/clinem/dgz140.
Results Reference
derived
Learn more about this trial
Pilot Study of the Effect of Liraglutide on Weight Loss and Gastric Functions in Obesity
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