Clinical trial NCT02647944: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Obesity
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Novo Nordisk A/S
First posted: 2016-01-06
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Gastric Emptying of Solids Half-time (T1/2) at 5 Weeks
timeFrame: 5 weeks
measure: Gastric Emptying of Solids Half-time (T1/2) at 16 Weeks
timeFrame: 16 weeks
Secondary outcomes:
measure: Weight Change at 5 Weeks
timeFrame: baseline, 5 weeks
measure: Weight Change at 16 Weeks
timeFrame: baseline, 16 weeks
measure: Satiety by Buffet Meal, Total Calories Ingested at 16 Weeks
timeFrame: 16 weeks
measure: Satiation Volume to Fullness at 16 Weeks
timeFrame: 16 weeks
measure: Satiation Maximum Tolerated Volume at 16 Weeks
timeFrame: 16 weeks
measure: Gastric Fasting Volume at 16 Weeks
timeFrame: 16 weeks
measure: Gastric Postprandial Volume at 16 Weeks
timeFrame: 16 weeks
measure: Gastric Accommodation Volume at 16 Weeks
timeFrame: 16 weeks (approximately 1 hour after 99mTC injection)
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Michael Camilleri, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.