The Effect of GLP-1 Receptor Activation on Central Reward and Satiety in Obesity and Diabetes
Braini-Ex
2 other identifiers
interventional
48
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for not_applicable diabetes-mellitus
Started Sep 2011
Typical duration for not_applicable diabetes-mellitus
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 20, 2011
CompletedFirst Posted
Study publicly available on registry
January 21, 2011
CompletedStudy Start
First participant enrolled
September 1, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2013
CompletedJune 3, 2015
June 1, 2015
2.1 years
January 20, 2011
June 2, 2015
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Differences in neuronal activity in CNS reward and satiety circuits
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.
1 hour
Secondary Outcomes (2)
Feeding behavior
2 hours
Self-reported hunger
2 hours
Study Arms (3)
exenatide
EXPERIMENTALInfusion of exenatide; loading dose 50 ng/min during 30 min, followed by a maintenance dose 20ng/min for the rest of the tests.
exenatide + exendin (9-39)
EXPERIMENTALexenatide 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.
saline
PLACEBO COMPARATORsaline infusion, with the same infusion speed
Interventions
The loading dose is 50 ng/min during 30 min, followed by a maintenance dose 20 ng/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. Exendin 9-39 will be infused intravenously at doses of 600 pM/kg • min.
Eligibility Criteria
You may qualify if:
- For all 3 study groups:
- age 18-70 years.
- Men and women. For women, only postmenopausal women (as ascertained by serum FSH) will be included in order to avoid variations related to the menstrual cycle.
- To promote comparability and to overcome the interference of lateralization, only right-handed persons will be included.
- body-mass index (BMI) of \<25 kg/m2
- stable bodyweight (\<5% reported change during the previous 3 months)
- Normal fasting and 2-h postload glucose as ascertained during a 75-g oral glucose tolerance test (OGTT)
- body-mass index (BMI) ≥30 kg/m2
- stable bodyweight (\<5% reported change during the previous 3 months)
- Normal fasting and 2-h postload glucose as ascertained during a 75-g oral glucose tolerance test (OGTT)
- Diagnosed with T2DM (20) \> 3 months prior to screening
- BMI ≥30 kg/m2
- HbA1c 6.2-8.5%
- Treatment with metformin at a stable dose for at least 3 months.
You may not qualify if:
- In the obese T2DM patients, no blood glucose- and weight lowering agents will be allowed within 3 months before screening except for metformin. The normoglycemic lean and obese individuals will not be allowed to take blood glucose-lowering agents at any time before and during the study.
- congestive heart failure (NYHA II-IV)
- chronic renal failure (glomerular filtration rate \< 60 mL/min/1.73m2 per Modification of Diet in Renal Disease (MDRD)) or serious liver impairment
- a history of gastrointestinal disorders, including gastroparesis, pancreatitis and cholelithiasis
- neurological illness
- malignancy
- pregnancy or breast feeding
- implantable devices
- substance abuse
- addiction
- contra-indication for MRI, such as claustrophobia or pacemaker
- any psychiatric illness, including eating disorders and depression
- hypersensitivity to the active substance or to any of the excipients
- chronic use of glucocorticoids or centrally acting drugs within 2 weeks immediately prior to screening
- use of cytostatic or immuno-modulatory agents
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Amsterdam UMC, location VUmclead
- Eli Lilly and Companycollaborator
- Bristol-Myers Squibbcollaborator
Study Sites (1)
VU University Medical Center
Amsterdam, De Boelelaan 1117, 1007MB, Netherlands
Related Publications (1)
van Bloemendaal L, IJzerman RG, Ten Kulve JS, Barkhof F, Konrad RJ, Drent ML, Veltman DJ, Diamant M. GLP-1 receptor activation modulates appetite- and reward-related brain areas in humans. Diabetes. 2014 Dec;63(12):4186-96. doi: 10.2337/db14-0849. Epub 2014 Jul 28.
PMID: 25071023DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Michaela Diamant, MD PhD
VU University Medical Center, Diabetes Center
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- PARTICIPANT
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Dr.
Study Record Dates
First Submitted
January 20, 2011
First Posted
January 21, 2011
Study Start
September 1, 2011
Primary Completion
October 1, 2013
Study Completion
October 1, 2013
Last Updated
June 3, 2015
Record last verified: 2015-06