Obesity
Conditions
Keywords
GLP-1, fMRI
Brief summary
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.
Interventions
DRUGLiraglutide (Saxenda) 6Mg/Ml Inj Pen 3Ml or Placebo
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.
Sponsors
University of Geneva, Switzerland
Zoltan Pataky
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomized, single-centre, double-blind, placebo controlled, parallel group, clinical trial.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of Bold Oxygenation Level Dependent (BOLD) signal (%) in brain regions involved in the reward system | 16 weeks | Bold changes in striatum, amygdala, insula, orbitofrontal complex as detected by fMRI in from baseline to 16-week follow-up |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| changes in waist circumference | 16 weeks | waist circumference measurement (cm) |
| changes in fasting blood sugar | 16 weeks | fasting glycaemia measurement (mmol/l) |
| changes in glucagon | 16 weeks | glucagon measurement (pmol/l) |
| changes in ghrelin | 16 weeks | ghrelin measurement (mg/dl) |
| changes in leptin | 16 weeks | leptin measurement (ng/ml) |
| changes in obestatin | 16 weeks | obestatin measurement (ng/ml) |
| changes in reelin | 16 weeks | reelin measurement (ng/microL) |
| change of body weight | 16 weeks | Weight measurement (kg) |
| changes in insulin | 16 weeks | fasting insulinaemia measurement (mUI/l) |
| change in food addiction score | 16 weeks | Assessment by YFAS V.2 questionnaire, 25 questions, total score is reported |
| change in liking | 16 weeks | 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). |
| change in wanting | 16 weeks | 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. |
| change in emotional regulation abilities | 16 weeks | 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 brain regions involved in the reward system | baseline comparison | BOLD (%) in striatum, amygdala, insula, orbitofrontal complex as detected by fMRI in the obese groups at baseline in comparison to normal body weight controls |
| changes in endocannabinoids | 16 weeks | measurement of anandamide (AEA), 2-arachidonoylglycerol (2-AG), N-palmitoylethanolamide (PEA), N-oleoylethanolamide (OEA); ng/ml for all |
Countries
Switzerland
Outcome results
None listed