Reward Mechanisms in Obesity

Study Overview
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Brief Summary
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The study aims to investigate the effects of 3.0 mg of liraglutide on reward brain circuits in human obesity and to better understand its effects on weight loss (in patients without diabetes). According to the study protocol, 70 obese patient will be evaluated at baseline and at 16-week (end of study) after daily subcutaneous injections of Saxenda® (liraglutide 3.0 mg) or Placebo by pen injector. All participants will first undergo a functional Magnetic Resonance Imaging (fMRI) session while being presented with gustatory stimuli. Second, participants will complete behavioural tasks (i.e., liking versus wanting, in the scanner) and questionnaires aiming at teasing apart reward mechanisms and emotional skills (e.g., emotional regulation ability) associated with food intake. Third, metabolic parameters and hormones involved in appetite regulation will be assessed and studied in relation to fMRI. These measurements will be repeated after 16 weeks in obese individuals. The control group of normal body weight individuals will be evaluated once at Baseline.

Official Title
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Central Nervous System Effects of Liraglutide® 3.0 mg on Reward Mechanisms in Obese Patients Without Diabetes, in Relation to Food Addiction. A Randomized, Single-centre, Double-blind, Placebo Controlled Clinical Trial.

Conditions
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Obesity

Intervention / Treatment
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* Drug: Liraglutide (Saxenda) 6Mg/Ml Inj Pen 3Ml or Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI ≥ 30 kg/m2 and < 40 kg/m2 right-handed current non-smokers with stable body weight (<5% reported change during the previous 3 months) Exclusion Criteria: History of any psychiatric, neurological, cardiovascular, renal or liver disease, malignancies, type 1 and type 2 diabetes mellitus use of centrally acting medication, glucocorticoides, insulin, orlistat any substance abuse food allergies deficits of smell and taste history of pancreatitis family or personal history of multiple endocrine neoplasia type 2 or familial medullary thyroid carcinoma pregnancy contraindications for fMRI

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, single-centre, double-blind, placebo controlled, parallel group, clinical trial.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Liraglutide 3.0 mg<br>35 obese patient will be evaluated at baseline and at 16-week (end of study) after daily subcutaneous injections of Saxenda® (liraglutide 3.0 mg). | Drug: Liraglutide (Saxenda) 6Mg/Ml Inj Pen 3Ml or Placebo<br>* Patients will be evaluated at baseline and at 16-week (end of study) after daily subcutaneous injections of Saxenda® (liraglutide 3.0 mg) or Placebo by pen injector.<br>|
| Placebo Comparator: Placebo<br>35 obese patient will be evaluated at baseline and at 16-week (end of study) after daily subcutaneous injections of Placebo by pen injector. | Drug: Liraglutide (Saxenda) 6Mg/Ml Inj Pen 3Ml or Placebo<br>* Patients will be evaluated at baseline and at 16-week (end of study) after daily subcutaneous injections of Saxenda® (liraglutide 3.0 mg) or Placebo by pen injector.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Bold Oxygenation Level Dependent (BOLD) signal (%) in brain regions involved in the reward system | Bold changes in striatum, amygdala, insula, orbitofrontal complex as detected by fMRI in from baseline to 16-week follow-up | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change of body weight | Weight measurement (kg) | 16 weeks | 
| changes in waist circumference | waist circumference measurement (cm) | 16 weeks | 
| changes in fasting blood sugar | fasting glycaemia measurement (mmol/l) | 16 weeks | 
| changes in glucagon | glucagon measurement (pmol/l) | 16 weeks | 
| changes in ghrelin | ghrelin measurement (mg/dl) | 16 weeks | 
| changes in leptin | leptin measurement (ng/ml) | 16 weeks | 
| changes in obestatin | obestatin measurement (ng/ml) | 16 weeks | 
| changes in reelin | reelin measurement (ng/microL) | 16 weeks | 
| changes in endocannabinoids | measurement of anandamide (AEA), 2-arachidonoylglycerol (2-AG), N-palmitoylethanolamide (PEA), N-oleoylethanolamide (OEA); ng/ml for all | 16 weeks | 
| changes in insulin | fasting insulinaemia measurement (mUI/l) | 16 weeks | 
| change in food addiction score | Assessment by YFAS V.2 questionnaire, 25 questions, total score is reported | 16 weeks | 
| change in liking | Assessment by Pavlovian-Instrumental Transfer (PIT) test during fMRI scanning. Participants will taste the milkshake and tasteless solutions and asked to rate them based on how much they liked tasting the stimulus on a visual analogue scale (ranging from 1 not at all to 100 extremely). | 16 weeks | 
| change in wanting | Assessment by Pavlovian-Instrumental Transfer (PIT) test during fMRI scanning. We will measure the mobilized effort (using a handgrip) the participants mobilized to be delivered with the milkshake. | 16 weeks | 
| change in emotional regulation abilities | Assessed by an emotional regulation task. Subjects will be presented with neutral, positive, negative, and mixed emotional feelings film clips and asked to either attend naturally or decrease their emotional reactions. The clips will be rated on amusement and repulsion scales on a 6-point scale. Based on these ratings, we will calculate a mixed feelings coefficient. | 16 weeks | 
| BOLD in brain regions involved in the reward system | BOLD (%) in striatum, amygdala, insula, orbitofrontal complex as detected by fMRI in the obese groups at baseline in comparison to normal body weight controls | baseline comparison | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GLP-1, fMRI