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Diabetes MellitusBraini-ExNCT01281228

The Effect of GLP-1 Receptor Activation on Central Reward and Satiety in Obesity and Diabetes

A study testing exenatide and exenatide + exendin (9-39) in people with Diabetes Mellitus and Diabetes Mellitus, Type 2, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 yearsHealthy volunteers can take part
What is being tested?
exenatide and exenatide + exendin (9-39)
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
48 participants
Where
1 siteNetherlands
Study dates
Sep 2011to Oct 2013
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 70 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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.
  • For the healthy lean subjects, inclusion criteria will be:
  • body-mass index (BMI) of <25 kg/m2
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  • 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)
  • For the normoglycemic obese individuals, inclusion criteria will be:
  • 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)
  • For the obese T2DM individuals, inclusion criteria will be:
  • 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.

Who cannot join

  • 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.
  • For all individuals, exclusion criteria will be:
  • 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
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  • 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
  • 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
  • individuals, who in the opinion of the investigator, are unsuitable in any other way to participate in this study
  • individuals who are employed by Amylin Pharmaceutical Inc. or Eli Lilly \& company (that is, employees, temporary contract workers, or designees responsible for conducting the study). Immediate family of Amylin or Lilly employees may participate in sponsored clinical trials, but are not permitted to participate at an Amylin or Lilly facility. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted
  • poor commandment of the Dutch language or any (mental) disorder that precludes full understanding the purpose, instruction and hence participation in the study.

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • VU University Medical Center

    Amsterdam, De Boelelaan 1117, 1007MB

Other trials in Netherlands

About this study

Official title: The Effect of GLP-1 Receptor Activation on Central Reward and Satiety Circuits in Response to Food Stimuli in Obesity and Diabetes

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.

Read the detailed description

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.

Being tested
exenatide, exenatide + exendin (9-39), placebo
Keywords
Exenatide, Type 2 diabetes mellitus, Incretin hormones, GLP-1 agonist, Satiety, Reward
Medical subject headings
Diabetes Mellitus, Diabetes Mellitus, Type 2, Obesity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • exenatideDrug

    Also called Byetta

    The loading dose is 50 ng/min during 30 min, followed by a maintenance dose 20 ng/min for the rest of the tests.

  • exenatide + exendin (9-39)Drug

    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.

  • placeboDrug

    saline infusion

Study groups in NCT01281228
Study groupRoleWhat they receive
exenatideExperimentalInfusion of exenatide; loading dose 50 ng/min during 30 min, followed by a maintenance dose 20ng/min for the rest of the tests.
Receives: Drug: exenatide
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.
Receives: Drug: exenatide + exendin (9-39)
salinePlacebo comparatorsaline infusion, with the same infusion speed
Receives: Drug: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 1 hour

Secondary outcomes (2)

  1. Feeding behavior

    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.

    Measured: 2 hours

  2. Self-reported hunger

    Self-reported hunger, satiety, fullness and prospective food consumption, will be rated on 100 mm visual analogue scales before and after the meal.

    Measured: 2 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jan 2011 (estimated)
  2. Study startSep 2011
  3. Primary completionOct 2013
  4. Study completionOct 2013

Resources

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
Single blind
Who is masked
Participant
Enrolment
48 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01281228
Sponsor's protocol ID
DC2010Exbrain001
Other IDs
2010-023635-42
Acronym
Braini-Ex
Status last verified
Jun 2015
First submitted
20 Jan 2011
Last updated
3 Jun 2015
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 25071023

Questions about this trial

What is this clinical trial studying?

A study testing exenatide and exenatide + exendin (9-39) in people with Diabetes Mellitus and Diabetes Mellitus, Type 2, 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 17 inclusion and 23 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 3 Jun 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. Some participants in this study may receive a placebo. 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?

Differences in neuronal activity in CNS reward and satiety circuits (time frame: 1 hour). 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 NCT01281228, which also lists 1 linked publication.

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 3 Jun 2015.

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