Effects of Glucagon Like Peptide-1(GLP-1) and Liraglutide on Brain Satiety and Reward Circuits and Feeding Behavior in Diabetes
Information source: VU University Medical Center
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Obesity; Type 2 Diabetes
Intervention: Liraglutide treatment 12 weeks (Drug); insulin glargine treatment (Drug); GLP-1 receptor antagonist (Drug)
Phase: N/A
Status: Completed
Sponsored by: VU University Medical Center
Summary
The aim of this study is to investigate if endogenous Glucagon Like Peptide - 1 (GLP-1) has
an effect on brain satiety and reward systems and if there are alterations in obese patients
with type 2 diabetes (T2DM). Secondly, the aim is to investigate whether treatment with a
GLP-1 analog, liraglutide, restores these signals in obese patients with type 2 diabetes.
Finally, also the endogenous GLP-1 effects will be investigated in obese individuals before
and after gastric bypass surgery on brain satiety and reward systems.
Clinical Details
Official title: Central Effects of Endogenous Glucagon Like Peptide-1 (GLP-1) and the GLP-1 Analog Liraglutide on Brain Satiety and Reward Circuits and Feeding Behavior in Diabetes
Study design: Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Open Label
Primary outcome: food-stimuli related neuronal activity in reward and satiety circuits as represented by BOLD fMRI signal change from baseline (%)
Secondary outcome: GLP-1 analog treatment related changes in obese patients with type 2 diabetes in self-reported hunger, satiety, fullnessGLP-1 analog treatment related changes in obese patients with type 2 diabetes in basal metabolic rate and post-prandial energy expenditure GLP-1 analog treatment related changes in obese patients with type 2 diabetes in microvascular function and vasomotion GLP-1 analog treatment related changes in obese patients with type 2 diabetes in cardiovascular autonomic nervous balance GLP-1 analog treatment related changes in obese patients with type 2 diabetes in concomitant changes in metabolic and humoral markers Alterations in resting state brain activity networks in obese patients with type 2 diabetes compared to lean, healthy individuals and the involvement of endogenous GLP-1 Alterations in brain arterial blood flow in obese patients with type 2 diabetes compared to lean, healthy individuals and the involvement of endogenous GLP-1 GLP-1 analog treatment related changes in obese patients with type 2 diabetes in resting state brain activity networks. GLP-1 analog treatment related changes in obese patients with type 2 diabetes in brain arterial blood flow.
Detailed description:
First aim will be addressed in a cross-sectional randomized study. 20 healthy, lean and 20
obese individuals with type 2 diabetes (T2DM) will be exposed to food cues and with
concomitant infusion of glucagon Like peptide-1 (GLP-1) receptor antagonist or saline, to
assess the involvement of endogenous GLP-1, secreted in response to a meal. Measurements
activation of CNS circuits involved in satiety and reward will be performed using blood
oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI).
The second aim will be addressed in cross-over randomized-controlled trial (RCT) in the T2DM
patients only. Patients will be randomly assigned liraglutide vs insulin glargine treatment,
during a treatment period of 12 weeks each with a 12-week washout period in between. The
investigators will perform the same fMRI protocol.
The third aim will be addressed in a study with obese individuals who are scheduled for a
gastric bypass surgery. The same protocol as for the first aim will be performed and this
will be before and after the surgery in the same individuals.
Eligibility
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
Criteria:
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 post load glucose as ascertained during a 75-g oral glucose
tolerance test (OGTT) (34)
- Right handed
For the obese T2DM individuals:
- 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
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 as glucose fasting < 7. 1 mmol/l and after OGTT
t=120min < 11. 0 mmol/l) (39)
- Right handed
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 gastropareses, pancreatitis and
cholelithiasis)
- Neurological illness
- Malignancy
- Other type of bariatric surgery (Redo-GBP, sleeve, distal GBP, adj banding,
Scopinaro)
- 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 or known allergy for acetaminophen.
- History of allergy for insulin analog
- History of allergy for liraglutide
- 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
Locations and Contacts
VU University Medical Center, Amsterdam 1081 HV, Netherlands
Additional Information
Starting date: October 2011
Last updated: February 17, 2015
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