Influence of Liraglutide, a GLP-1 Receptor Agonist, on Brown Adipose Tissue (BAT) Activity in Humans (i-LAB)

The purpose of this study is to access liraglutide influence brown adipose tissue recruitment and its thermogenic effect through hypothalamic activation in obese individuals.

Study Overview

• Status: Unknown
• Conditions: Obesity; Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Liraglutide 3.0 mg

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Bruno Geloneze, MD, PhD; Phone Number: +55 19 35218589; Email: bgeloneze@terra.com.br

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Body mass index over 30 kg/m2.

Exclusion Criteria:

• Hypersensitivity to liraglutide or any of its vehicle components;
• History of diabetes or pre-diabetes - either by fasting glycemia, oGTT or HbA1c;
• Previous treatment within the last 3 months with glucagon like peptide-1 agonists, iDPP4 or any medication that is associated with BAT activation, including propranolol and benzodiazepines;
• Liver diseases, except non-alcoholic steatohepatitis (NASH);
• Infection by HIV, hepatitis B or hepatitis C;
• Addiction to cannabis, heroin, morphine, cocaine, benzodiazepines or amphetamine;
• Obesity induced by other disorders such as Cushing syndrome, hypothyroidism, lipodystrophy
• Current or history of treatment with medications that may cause significant weight gain within 3 months prior to screening, including systemic corticosteroids (except for a short course of treatment, i.e. 7-10 days), tricyclic antidepressants, atypical antipsychotic and mood stabilizers (e.g. imipramine, amitriptyline, mirtazapine, paroxetine, phenelzine, chlorpromazine, thioridazine, clozapine, olanzapine, valproic acid and its derivatives, and lithium);
• Current participation (or within the last 3 months) in an organized weight reduction program
• Currently or previous using within 3 months before screening of pramlintide, sibutramine, orlistat, topiramate, or metformin (either by prescription or as part of a clinical trial)
• Participation in a clinical trial within the last 3 months prior to screening
• Simultaneous participation in any other clinical trial of an investigational drug
• Previous surgical treatment of obesity;
• Cancer (past or present, except basal cell skin cancer or squamous cell skin cancer), which in the investigator's opinion could interfere with the results of the trial
• Liver enzyme (ALT and AST) above 2.5 x of reference range
• Pancreatic enzymes (amylase, lipase) above 3 x the reference range
• Chronic kidney disease stages 3, 4, or 5
• Relevant inflammatory or acute or chronic infectious disease; hyperthyroidism; neurological, psychiatric, gastrointestinal, respiratory, renal, hepatic or cardiac relevant disease, that could interfere with trial results per the judgment of investigator
• Any condition that at the discretion of investigator could interfere with treatment adhesion on patient safety
• Blood donation or transfusion within the last 3 months
• Pregnancy or intention of pregnancy
• History of Multiple Endocrine Neoplasia Syndrome Type 2 (MEN 2)
• History of pancreatitis
• Less than 80% of liraglutide adherence
• Calcitonin above the reference range at the screening visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Liraglutide 3.0 mg; Subjects will use liraglutide 3.0 mg for 2 weeks.	Drug: Liraglutide 3.0 mg; Subjects will use liraglutide 3.0 mg for 2 weeks; Other Names: Victoza

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the effect of liraglutide administration on brown adipose tissue (BAT) activation in humans	Activation of BAT, as considered Standard Uptake Value (SUV) threshold of 2.0 on 18-FDG-PET CT, prior to liraglutide use and after 2 weeks on liraglutide 3.0 mg	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the effect of liraglutide administration on hypothalamic activation in humans	Evaluate the effect of liraglutide administration on hypothalamic tract activation as assessed by magnetic resonance image in humans prior and after 2 weeks on liraglutide 3.0 mg	2 weeks
Evaluate the effect of liraglutide administration on non-shivering thermogenesis in humans	Evaluate the effect of liraglutide administration on non-shivering thermogenesis by infrared thermography and indirect calorimetry in humans prior and after 2 weeks on liraglutide 3.0 mg	2 weeks
Evaluate the effect of liraglutide administration on body weight in humans	Evaluate the effect of liraglutide administration on total body weight (kg) in humans prior and after 2 weeks on liraglutide 3.0 mg	2 weeks
Evaluate the effect of liraglutide administration on metabolic basal rate in humans	Evaluate the effect of liraglutide administration on basal kilocalories/day in humans prior and after 2 weeks on liraglutide 3.0 mg	2 weeks
Evaluate the effect of liraglutide administration on body composition in humans	Evaluate the effect of liraglutide administration on lean mass and fat percentage as assessed by dual x-ray absorptiometry (DXA) in humans prior and after 2 weeks on liraglutide 3.0 mg	2 weeks

Collaborators and Investigators

• Sponsor: University of Campinas, Brazil
• Investigators: Principal Investigator: Bruno Geloneze, MD, PhD, University of Campinas; Principal Investigator: Lício A Velloso, MD, PhD, University of Campinas; Study Chair: José C Lima Júnior, MD, University of Campinas; Study Chair: Riobaldo M Cintra, MD, University of Campinas

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Anticipated): March 1, 2017
• Study Completion (Anticipated): April 1, 2017

Study Registration Dates

• First Submitted: March 18, 2016
• First Submitted That Met QC Criteria: March 23, 2016
• First Posted (Estimate): March 24, 2016

Study Record Updates

• Last Update Posted (Estimate): March 24, 2016
• Last Update Submitted That Met QC Criteria: March 23, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Liraglutide; Body Composition; Body weight; Brown Adipose Tissue; Basal Metabolic Rate; Victoza; Hypothalamic Activation; Non-shivering Thermogenesis; Adipose Tissue Biopsy
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Liraglutide
• Other Study ID Numbers: i-LAB; U1111-1178-4180 (Registry Identifier: Universal Trial Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No