NCT01281228

The Effect of GLP-1 Receptor Activation on Central Reward and Satiety in Obesity and Diabetes

The Effect of GLP-1 Receptor Activation on Central Reward and Satiety Circuits in Response to Food Stimuli in Obesity and Diabetes

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 48 (actual)
• Sponsor: Amsterdam UMC, location VUmc · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Accepted

Summary

Glucagon-like peptide 1 (GLP-1) based therapies, such as exenatide, are already successfully employed in the treatment of Type 2 Diabetes (T2DM). Exenatide improves glycemic control and is associated with reduced food intake and body weight. The investigators hypothesize that it affects central reward and satiety circuits and that this may contribute to the weight loss.

Detailed description

The aim of the project is to determine 1) whether GLP-1 receptor activation of CNS reward and satiety circuits occurs, in the context of food(-related) stimuli; if this effect is altered in obese and diabetic compared to lean individuals 2) if it is independent of other postprandial metabolic and hormonal changes 3) if this effect is GLP-1-receptor-mediated 4) if the CNS changes correlate with subsequent feeding behaviour. Methods The investigators will compare 16 obese T2DM-patients, 16 normoglycemic obese and 16 healthy lean individuals, with respect to food(-related) neuronal activity in central reward and satiety circuits by blood oxygen level-dependent (BOLD) fMRI. fMRI will be performed during intravenous infusion of a) the GLP-1 receptor agonist exenatide; b) exenatide and a GLP-1 receptor antagonist (exendin 9-39)(to investigate whether the exenatide-induced effects are GLP-1-receptor mediated) or c) saline; in randomized order, on separate days. To tease out concomitant postprandial metabolic and hormonal influences, measurements will be performed during a somatostatin pancreatic clamp with replacement of basal insulin, glucagon and growth hormone. Finally, to correlate changes in brain activity with subsequent feeding behavior, the investigators will measure food intake, self-reported hunger, satiety and mood, during a choice-buffet after the scanning. Expected Results This project will gain insight into (CNS) mechanisms underlying the observed effects of the GLP-1 receptor agonist exenatide on food intake and body weight in obese, diabetic and healthy lean individuals. These findings may increase our understanding of the development of obesity and weight loss problems in obese and diabetic individuals and the role of GLP-1 in the central regulation of feeding behavior/appetite control.

Conditions

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Obesity

Interventions

Type	Name	Description
DRUG	exenatide	The loading dose is 50 ng/min during 30 min, followed by a maintenance dose 20 ng/min for the rest of the tests.
DRUG	exenatide + exendin (9-39)	The loading dose is 50 ng/min during 30 min, followed by a maintenance dose 20 ng/min for the rest of the tests. Exendin 9-39 will be infused intravenously at doses of 600 pM/kg • min.
DRUG	placebo	saline infusion

Timeline

• Start date: 2011-09-01
• Primary completion: 2013-10-01
• Completion: 2013-10-01
• First posted: 2011-01-21
• Last updated: 2015-06-03

Locations

1 site across 1 country: Netherlands