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.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Drug: Liraglutide (Saxenda) 6Mg/Ml Inj Pen 3Ml or Placebo

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 4

Contacts and Locations

Study Locations

• Switzerland
  • Geneva, Switzerland, 1206
    • University Hospitals of Geneva

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Liraglutide 3.0 mg; 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; 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.
Placebo Comparator: Placebo; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Zoltan Pataky
• Collaborators: University of Geneva, Switzerland
• Investigators: Principal Investigator: Zoltan Pataky, MD, University Hospital, Geneva

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2018
• Primary Completion (Actual): March 18, 2020
• Study Completion (Actual): March 30, 2020

Study Registration Dates

• First Submitted: November 12, 2017
• First Submitted That Met QC Criteria: November 15, 2017
• First Posted (Actual): November 20, 2017

Study Record Updates

• Last Update Posted (Actual): April 30, 2021
• Last Update Submitted That Met QC Criteria: April 29, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: GLP-1; fMRI
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Liraglutide
• Other Study ID Numbers: 2017-01085; U1111-1194-9675 (Registry Identifier: Universal Trial Number)

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No