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

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.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Drug: Placebo; Drug: Liraglutide

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 Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	5 weeks
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.	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight Change at 5 Weeks	Body weight in kg was measured at 5 weeks and compared to baseline.	baseline, 5 weeks
Weight Change at 16 Weeks	Body weight in kg was measured at 16 weeks and compared to baseline.	baseline, 16 weeks
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.	16 weeks
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).	16 weeks
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).	16 weeks
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.	16 weeks
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.	16 weeks
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.	16 weeks (approximately 1 hour after 99mTC injection)

Collaborators and Investigators

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

Publications and helpful links

General 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2015
• Primary Completion (Actual): December 30, 2016
• Study Completion (Actual): December 30, 2016

Study Registration Dates

• First Submitted: December 31, 2015
• First Submitted That Met QC Criteria: January 5, 2016
• First Posted (Estimate): January 6, 2016

Study Record Updates

• Last Update Posted (Actual): October 27, 2017
• Last Update Submitted That Met QC Criteria: October 25, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Body Weight Changes; Obesity; Weight Loss; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Liraglutide
• Other Study ID Numbers: 15-001783; UL1TR000135 (U.S. NIH Grant/Contract); R56DK067071 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• 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