Pilot Study of the Effect of Liraglutide 3.0 mg on Weight Loss and Gastric Functions in Obesity

Michael Camilleri, MD

Status and phase: Completed; Phase 2

Conditions: Obesity

Treatments: Drug: Placebo; Drug: Liraglutide

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT03523273

UL1TR000135 (U.S. NIH Grant/Contract)

R56DK067071 (U.S. NIH Grant/Contract)

15-001783 Part B

Details and patient eligibility

About

This study is 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.

Enrollment: 136 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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.
• The investigators plan to recruit equal proportions of men and women.
• Women of childbearing potential will be using an effective form of contraception, and have negative pregnancy tests within 48 hours of enrollment and before each radiation exposure. In addition, since liraglutide 3.0 mg is classified as Pregnancy Category X, monthly urine pregnancy testing will be performed in any female participant with childbearing potential.
• 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, cholecystectomy, 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 past or current history of pancreatitis, gallstones, history of alcoholism, blood triglyceride levels >500 mg/dL.
• Significant untreated psychiatric dysfunction based upon screening with the Hospital Anxiety and Depression Inventory (HAD), 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 HAD score >11 on either the Anxiety or Depression subscales, 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 any medication (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.
• Delayed gastric emptying at 2 and 4 hours
• Hypersensitivity to the study medication, liraglutide
• Participate in highly intense physical activity program that could potentially interfere with study interpretation.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Double Blind

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136 participants in 2 patient groups

Liraglutide

Experimental group

Description:

Liraglutide 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.

Treatment:

Drug: Liraglutide

Placebo

Experimental group

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.

Treatment:

Drug: Placebo