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

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

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

Conditions
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Obesity, Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Liraglutide 3.0 mg


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Liraglutide 3.0 mg<br>Subjects will use liraglutide 3.0 mg for 2 weeks. | Drug: Liraglutide 3.0 mg<br>* Subjects will use liraglutide 3.0 mg for 2 weeks<br>* Other names: Victoza;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Brown Adipose Tissue, Hypothalamic Activation, Non-shivering Thermogenesis, Basal Metabolic Rate, Liraglutide, Victoza, Body Composition, Body weight, Adipose Tissue Biopsy