The effects of the hormone GLP-1 in the brain regarding satiety and reward circuits and feeding behavior in diabetes.

Conditions: diabetes mellitusobesity
MedDRA version: 16.1Level: LLTClassification code 10012594Term: DiabetesSystem Organ Class: 10027433 - Metabolism and nutrition disorders
MedDRA version: 16.1Level: PTClassification code 10029883Term: ObesitySystem Organ Class: 10027433 - Metabolism and nutrition disorders
Therapeutic area: Body processes [G] - Metabolic Phenomena [G03]

Registration Number: EUCTR2011-000753-24-NL

Lead Sponsor: VU University Medical Center

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: Not specified

Inclusion Criteria

For the healthy, lean individuals:
- Age 18–65 years
- Women: post menopausal (excluding possible menstruation cycle effects)
- Body-mass index (BMI) of <25 kg/m2,
- Stable bodyweight (<5% reported change during the previous 3 months).
- Normal fasting and 2h postload glucose as ascertained during a 75-g oral glucose tolerance test (OGTT)
- Right handed

For the obese individuals scheduled for gastric bypass surgery:
-Age 18–65 years
- Women: preferably post menopausal (excluding possible menstruation cycle effects)
- Body-mass index (BMI) of >30 kg/m2,
- Stable bodyweight (<5% reported change during the previous 1 months).
- Normal or impaired fasting and 2h post load glucose as ascertained during a 75-g oral glucose tolerance test (OGTT) (defined normal; fasting < 5.6 mmol/l and after OGTT t=120min. < 7.8 mmol/l, impaired; fasting 5.7-7.1 mmol/l and after OGTT t=120min 7.9-11.0 mmol/l)
- Right handed

For the obese individuals with T2DM:
- Age 18-65 years
- Women: post menopausal (excluding possible menstruation cycle effects)
- BMI 25–40 kg/m2
- Stable bodyweight (<5% reported change during the previous 3 months).
- Diagnosed with T2DM > 3 months prior to screening
- HbA1C 6.5–8.5%
- Treatment with metformin at a stable dose for at least 3 months.
- Right handed

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

- GLP-1 based therapies, thiazolidinediones, sulphonylurea or insulin within 3 months before screening
- Weight-lowering agents within 3 months before screening.
- 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))
- Liver disease
- History of gastrointestinal disorders (including gastroparese, pancreatitis and cholelithiasis)
- Neurological illness
- Malignancy
- History of major heart disease
- History of major renal disease
- 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
- Chronic use of centrally acting agents or glucocorticoids within 2 weeks immediately prior to screening.
- Use of cytostatic or immune modulatory agents
- History of allergy for acetaminophen.
- History of allergy for insulin analog
- History of allergy for liraglutide or other GLP-1 RA/analog
- Participation in other studies
- Individuals who have received treatment within the last 30 days with a drug that has not received
regulatory approval for any indication at the time of study entry
- Individuals who are investigator site personnel, directly affiliated with the study, or are immediate family
of investigator site personnel directly affiliated with the study. Immediate family is defined as a spouse,
parent, child, or sibling, whether biological or legally adopted.
- Individuals who have previously completed or withdrawn from this study or any other study investigating
GLP-1 receptor agonist or dipeptidyl peptidase (DPP)-4 within 6 months
- Left handed.
- Individuals who, in the opinion of the investigator, are unsuitable in any other way to participate in this
study.
- Individuals who are employed by NovoNordisk & comp. (that is, employees, temporary contract workers,
or designees responsible for conducting the study).
- Poor commandment of the Dutch language or any (mental) disorder that precludes full understanding
the purpose, instruction and hence participation in the study.
- Further exclusion criteria will be in compliance with the EMeA SPC of liraglutide.