Reward Mechanisms in Obesity (LIRAOB)

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.

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.

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).

35 obese patient will be evaluated at baseline and at 16-week (end of study) after daily subcutaneous injections of Placebo by pen injector.

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.

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

measurement of anandamide (AEA), 2-arachidonoylglycerol (2-AG), N-palmitoylethanolamide (PEA), N-oleoylethanolamide (OEA); ng/ml for all

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").

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.

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.

BOLD (%) in striatum, amygdala, insula, orbitofrontal complex as detected by fMRI in the obese groups at baseline in comparison to normal body weight controls

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