The Effect of GLP-1 Receptor Activation on Central Reward and Satiety in Obesity and Diabetes (Braini-Ex)
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|ClinicalTrials.gov Identifier: NCT01281228|
Recruitment Status : Completed
First Posted : January 21, 2011
Last Update Posted : June 3, 2015
|Condition or disease||Intervention/treatment||Phase|
|Diabetes Mellitus Diabetes Mellitus, Type 2 Obesity||Drug: exenatide Drug: exenatide + exendin (9-39) Drug: placebo||Not Applicable|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||48 participants|
|Intervention Model:||Crossover Assignment|
|Official Title:||The Effect of GLP-1 Receptor Activation on Central Reward and Satiety Circuits in Response to Food Stimuli in Obesity and Diabetes|
|Study Start Date :||September 2011|
|Actual Primary Completion Date :||October 2013|
|Actual Study Completion Date :||October 2013|
Infusion of exenatide; loading dose 50 ng/min during 30 min, followed by a maintenance dose 20ng/min for the rest of the tests.
The loading dose is 50 ng/min during 30 min, followed by a maintenance dose 20 ng/min for the rest of the tests.
Other Name: Byetta
Experimental: exenatide + exendin (9-39)
exenatide infusion: loading dose 50 ng/min during 30 min, followed by a maintenance dose 20 ng/min for the rest of the test. And infusion of exendin(9-39) 600pM/kg/min.
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.
Placebo Comparator: saline
saline infusion, with the same infusion speed
- Differences in neuronal activity in CNS reward and satiety circuits [ Time Frame: 1 hour ]Differences in neuronal activity in CNS reward and satiety circuits (including striatum, amygdala, orbitofrontal cortex, insula, hypothalamus), as represented by BOLD fMRI signal change from baseline (%) in response to food(-related) stimuli, between obese T2DM patients, normoglycemic obese individuals and normoglycemic healthy lean subjects.
- Feeding behavior [ Time Frame: 2 hours ]Feeding behavior, measured as quantitative (kcal) and qualitative (energy density as well as nutrient composition; carbohydrate/fat/protein) changes in food choice during a choice-buffet lunch, will be compared between groups and conditions.
- Self-reported hunger [ Time Frame: 2 hours ]Self-reported hunger, satiety, fullness and prospective food consumption, will be rated on 100 mm visual analogue scales before and after the meal.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01281228
|VU University Medical Center|
|Amsterdam, De Boelelaan 1117, Netherlands, 1007MB|
|Principal Investigator:||Michaela Diamant, MD PhD||VU University Medical Center, Diabetes Center|