ObesityLIBRANCT01363609
Effects of Glucagon Like Peptide-1(GLP-1) and Liraglutide on Brain Satiety and Reward Circuits and Feeding Behavior in Diabetes
A study testing Liraglutide treatment 12 weeks, insulin glargine treatment and GLP-1 receptor antagonist in people with Obesity and Type 2 Diabetes, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Obesity, Type 2 Diabetes
- What is being tested?
- Liraglutide treatment 12 weeks, insulin glargine treatment and GLP-1 receptor antagonist
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteNetherlands
- Study dates
- Oct 2011to Jan 2015
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Obesity, Type 2 Diabetes
- Being tested
- Liraglutide treatment 12 weeks, insulin glargine treatment, GLP-1 receptor antagonist
- Medical subject headings
- Obesity, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Liraglutide treatment 12 weeksDrug
liraglutide will be started with a titration period of 2 weeks: week 1 0.6mg once daily, week 2 1.2mg once daily. If well tolerated, treatment will be continued for 10 more weeks in dosage of 1.8mg once daily
insulin glargine treatmentDrug
Insulin glargine treatment consist a treatment period of 12 weeks. Treatment will start with a dosage of 10 IU once daily. Patient will self-titrate the insulin glargine dosage based on self-monitored fasting blood glucose (FBG) concentrations for the previous 3 days using the following guideline: If FBG levels are above 5.6 mmol/L (100-153 mg/dL) on 3 consecutive mornings, the daily dose is to be increased by 2 IU/day. If hypoglycemia documented by glucose concentration < 3.3 mmol/L (60 mg/dL) or requiring assistance occurs without an easily identifiable reason (skipped meal, excessive physical activity), the daily dose is to be downregulated, with -2 IU/day
GLP-1 receptor antagonistDrug
Exendin 9-39 will be infused intravenously at doses of 600 pM/kg • min. This will only be during one of the visit for the healthy lean controls and the T2DM group, and during two visits in the group with obesity planned for gastric bypass surgery
| Study group | Role | What they receive |
|---|---|---|
| Liraglutide | Experimental | 12 week treatment with liraglutide in fixed dosage Receives: Drug: Liraglutide treatment 12 weeks |
| Insulin glargine | Active comparator | 12 week treatment, once daily, with insulin glargine. Dosage based on fasting blood glucose measurements Receives: Drug: insulin glargine treatment |
| before start of treatment period | Other | before start of the treatment period, one day with tests will be performed. During this test a GLP-1 receptor antagonist will be administered In the group with obesity and planned gastric bypass surgery, the GLP-1 receptor agonist will be administered during 1 test before and 1 test after the surgery Receives: Drug: GLP-1 receptor antagonist |
What is being measured
The primary outcome is the main question the study is designed to answer.
food-stimuli related neuronal activity in reward and satiety circuits as represented by BOLD fMRI signal change from baseline (%)
- differences between obese T2DM patients and healthy lean subjects food-stimuli related neuronal activity in reward and satiety circuits as represented by BOLD fMRI signal change from baseline (%)
- the involvement of endogenous GLP-1 food-stimuli related neuronal activity in reward and satiety circuits as represented by BOLD fMRI signal change from baseline (%)
- Effects of treatment with the GLP-1 analog liraglutide in obese patients with type 2 diabetes in food-stimuli related neuronal activity in reward and satiety circuits as represented by BOLD fMRI signal change from baseline (%)
- - To investigate the involvement of the increased meal-related endogenous GLP-1 levels after gastric bypass surgery in these food-stimuli related CNS satiety and reward responses and to investigate whether pharmacological blocking of endogenous GLP-1 receptor activation, using a GLP-1 antagonist, differentially affects these responses before and after gastric bypass surgery in obese individuals.
Measured: approximately 3 years
Secondary outcomes (9)
GLP-1 analog treatment related changes in obese patients with type 2 diabetes in self-reported hunger, satiety, fullness
Measured: approximately 3 years
GLP-1 analog treatment related changes in obese patients with type 2 diabetes in basal metabolic rate and post-prandial energy expenditure
Measured: approximately 3 years
GLP-1 analog treatment related changes in obese patients with type 2 diabetes in microvascular function and vasomotion
Measured: approximately 3 years
GLP-1 analog treatment related changes in obese patients with type 2 diabetes in cardiovascular autonomic nervous balance
Measured: approximately 3 years
GLP-1 analog treatment related changes in obese patients with type 2 diabetes in concomitant changes in metabolic and humoral markers
Measured: approximately 3 years
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
Measured: approximately 3 years
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
Measured: approximately 3 years
GLP-1 analog treatment related changes in obese patients with type 2 diabetes in resting state brain activity networks.
Measured: approximately 3 years
GLP-1 analog treatment related changes in obese patients with type 2 diabetes in brain arterial blood flow.
Measured: approximately 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2011 (estimated)
- Study startOct 2011
- Primary completionJan 2015
- Study completionJan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, RG IJzerman, Amsterdam UMC, location VUmc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01363609
- Sponsor's protocol ID
- DC2011LiBrain001
- Acronym
- LIBRA
- Status last verified
- Feb 2015
- First submitted
- 26 May 2011
- Last updated
- 18 Feb 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Ten Kulve JS, Veltman DJ, Gerdes VEA, van Bloemendaal L, Barkhof F, Deacon CF, Holst JJ, Drent ML, Diamant M, IJzerman RG. Elevated Postoperative Endogenous GLP-1 Levels Mediate Effects of Roux-en-Y Gastric Bypass on Neural Responsivity to Food Cues. Diabetes Care. 2017 Nov;40(11):1522-1529. doi: 10.2337/dc16-2113.
PubMed 29025878ten Kulve JS, Veltman DJ, van Bloemendaal L, Barkhof F, Deacon CF, Holst JJ, Konrad RJ, Sloan JH, Drent ML, Diamant M, IJzerman RG. Endogenous GLP-1 mediates postprandial reductions in activation in central reward and satiety areas in patients with type 2 diabetes. Diabetologia. 2015 Dec;58(12):2688-98. doi: 10.1007/s00125-015-3754-x. Epub 2015 Sep 18.
PubMed 26385462
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01363609
- Acronym / sponsor ID
- LIBRA / DC2011LiBrain001
- Conditions
- Obesity, Type 2 Diabetes
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Study start
- Oct 2011
- Primary completion
- Jan 2015 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 1 Jun 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Liraglutide | Experimental | Drug: Liraglutide treatment 12 weeks12 week treatment with liraglutide in fixed dosage |
| Insulin glargine | Active comparator | Drug: insulin glargine treatment12 week treatment, once daily, with insulin glargine. Dosage based on fasting blood glucose measurements |
| before start of treatment period | Other | Drug: GLP-1 receptor antagonistbefore start of the treatment period, one day with tests will be performed. During this test a GLP-1 receptor antagonist will be administered In the group with obesity and planned gastric bypass surgery, the GLP-1 receptor agonist will be administered during 1 test before and 1 test after the surgery |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- 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).
Key exclusion criteria (25 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Liraglutide treatment 12 weeksliraglutide will be started with a titration period of 2 weeks: week 1 0.6mg once daily, week 2 1.2mg once daily. If well tolerated, treatment will be continued for 10 more weeks in dosage of 1.8mg once daily | Drug | Liraglutide |
| insulin glargine treatmentInsulin glargine treatment consist a treatment period of 12 weeks. Treatment will start with a dosage of 10 IU once daily. Patient will self-titrate the insulin glargine dosage based on self-monitored fasting blood glucose (FBG) concentrations for the previous 3 days using the following guideline: If FBG levels are above 5.6 mmol/L (100-153 mg/dL) on 3 consecutive mornings, the daily dose is to be increased by 2 IU/day. If hypoglycemia documented by glucose concentration < 3.3 mmol/L (60 mg/dL) or requiring assistance occurs without an easily identifiable reason (skipped meal, excessive physical activity), the daily dose is to be downregulated, with -2 IU/day | Drug | Insulin glargine |
| GLP-1 receptor antagonistExendin 9-39 will be infused intravenously at doses of 600 pM/kg • min. This will only be during one of the visit for the healthy lean controls and the T2DM group, and during two visits in the group with obesity planned for gastric bypass surgery | Drug | before start of treatment period |
Primary outcome
food-stimuli related neuronal activity in reward and satiety circuits as represented by BOLD fMRI signal change from baseline (%)
Time frame: approximately 3 years
* differences between obese T2DM patients and healthy lean subjects food-stimuli related neuronal activity in reward and satiety circuits as represented by BOLD fMRI signal change from baseline (%) * the involvement of endogenous GLP-1 food-stimuli related neuronal activity in reward and satiety circuits as represented by BOLD fMRI signal change from baseline (%) * Effects of treatment with the GLP-1 analog liraglutide in obese patients with type 2 diabetes in food-stimuli related neuronal activity in reward and satiety circuits as represented by BOLD fMRI signal change from baseline (%) * - To investigate the involvement of the increased meal-related endogenous GLP-1 levels after gastric bypass surgery in these food-stimuli related CNS satiety and reward responses and to investigate whether pharmacological blocking of endogenous GLP-1 receptor activation, using a GLP-1 antagonist, differentially affects these responses before and after gastric bypass surgery in obese individuals.
9 secondary outcomes
GLP-1 analog treatment related changes in obese patients with type 2 diabetes in self-reported hunger, satiety, fullness
Time frame: approximately 3 years
GLP-1 analog treatment related changes in obese patients with type 2 diabetes in basal metabolic rate and post-prandial energy expenditure
Time frame: approximately 3 years
GLP-1 analog treatment related changes in obese patients with type 2 diabetes in microvascular function and vasomotion
Time frame: approximately 3 years
GLP-1 analog treatment related changes in obese patients with type 2 diabetes in cardiovascular autonomic nervous balance
Time frame: approximately 3 years
GLP-1 analog treatment related changes in obese patients with type 2 diabetes in concomitant changes in metabolic and humoral markers
Time frame: approximately 3 years
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
Time frame: approximately 3 years
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
Time frame: approximately 3 years
GLP-1 analog treatment related changes in obese patients with type 2 diabetes in resting state brain activity networks.
Time frame: approximately 3 years
GLP-1 analog treatment related changes in obese patients with type 2 diabetes in brain arterial blood flow.
Time frame: approximately 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2015.
- Derived from this study: PubMed 29025878Ten Kulve JS, Veltman DJ, Gerdes VEA, van Bloemendaal L, Barkhof F, Deacon CF, Holst JJ, Drent ML, Diamant M, IJzerman RG. Elevated Postoperative Endogenous GLP-1 Levels Mediate Effects of Roux-en-Y Gastric Bypass on Neural Responsivity to Food Cues. Diabetes Care. 2017 Nov;40(11):1522-1529. doi: 10.2337/dc16-2113.
- Derived from this study: PubMed 26385462ten Kulve JS, Veltman DJ, van Bloemendaal L, Barkhof F, Deacon CF, Holst JJ, Konrad RJ, Sloan JH, Drent ML, Diamant M, IJzerman RG. Endogenous GLP-1 mediates postprandial reductions in activation in central reward and satiety areas in patients with type 2 diabetes. Diabetologia. 2015 Dec;58(12):2688-98. doi: 10.1007/s00125-015-3754-x. Epub 2015 Sep 18.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Liraglutide treatment 12 weeks, insulin glargine treatment and GLP-1 receptor antagonist in people with Obesity and Type 2 Diabetes, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
food-stimuli related neuronal activity in reward and satiety circuits as represented by BOLD fMRI signal change from baseline (%) (time frame: approximately 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01363609, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Feb 2015.