The Influence of Liraglutide on the Reward Properties of Food: an fMRI Study on Healthy Volunteers
Condition: Healthy Human Male Subjects
Study type: Interventional
Phase: Phase 4

Summary: 
      Clinical experience has confirmed the anorexic effect of Glucagon-like-peptide 1 (GLP-1)
      mimetics in comparison to DPP-4 inhibitors. A possible mechanism of this effect might be
      associated with changes in food choices, as suggested by animal studies. It has been shown
      that functional magnetic resonance imaging (fMRI) of the brain is a valuable tool in obesity
      research and can be used to study the response of several brain regions to the visual
      presentation of preferred in comparison to non preferred food items and to non food items The
      aim of this study is to search for possible effects of liraglutide in comparison to placebo
      on 1. food choices and 2. changes in brain function as evidenced by fMRI in healthy
      volunteers.

      Findings of this study will help not only to get deeper insight into the mechanism of the
      anorexic effect of GLP-1 mimetics, but also into the regulation of food choices per se. In
      the future, it is planned to extend the results of this study in normal weight volunteers to
      obese diabetic subjects.
    

Detailed description: 
      Design: The study is designed as a double blind, placebo controlled, randomized crossover
      intervention study with two arms (liraglutide first followed by placebo vs. placebo first
      followed by liraglutide) in 16 healthy male volunteers. fMRI results and food intake are
      compared between groups baseline vs. end of treatment period and placebo vs. liraglutide.

      Intervention: A standard dose of 0.6 mg Liraglutide (oder placebo) will be used, and will be
      applied subcutaneously each morning for three subsequent days by the study personnel. Study
      sessions will be performed on the fourth day after placebo/liraglutide interventions.

      Study sessions: On study days participants arrive at the trial centre at 8.00 am after a 12h
      fast. Participants are instructed to eat a light dinner around 8.00 pm the previous day and
      to spend around 8h resting during the night before the study days. Upon arrival, blood
      pressure and heart rate is measured and an iv line is started, from which a blood sample is
      taken from the antecubital vein for blood glucose, insulin and plasma hormone concentrations
      determination. The occurrence of nausea, vomiting, dizziness or any other adverse events
      (AE's) is reviewed together with the subject.

      Instructions for the fMRI examination are reviewed together with the subject. The subject is
      advised to leave all ferromagnetic items behind, and baseline hunger/satiety visual analogue
      scales (VAS) are recorded. Then, the fMRI session with the food items paradigm (together with
      repeated recordings of hunger/satiety VAS) takes place. Afterwards, another blood sample and
      hunger/satiety VAS is taken and the subject is allowed to eat ad libitum from a buffet
      breakfast. Food intake is recorded in detail, including meal choices and calorie intake.
      After a final hunger/satiety VAS recording and another blood sample subjects are dismissed
      from the trial centre.

      Outcome variables: Main outcome variables are fMRI activity in the brain during the high
      calorie/low calorie food items paradigm and food intake at the buffet liraglutide vs. placebo
      at the end of treatment. Secondary outcome parameters are hunger/satiety VAS ratings, total
      and active plasma ghrelin, peptide YY (PYY), glucose and insulin concentrations.
    

Intervention name(s): Liraglutide; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): sc injections of 0.6 mg Liraglutide daily for three continuous days.; 0.9% NaCl, 0.2 ml
Other intervention name(s): Victoza; Isotonic saline
Intervention MeSH terms: Liraglutide
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Basic Science
Keywords: GLP1; obesity; fMRI; ghrelin