NCT01363609

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
50

participants targeted

Target at P25-P50 for not_applicable obesity

Timeline
Completed

Started Oct 2011

Typical duration for not_applicable obesity

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 26, 2011

Completed
6 days until next milestone

First Posted

Study publicly available on registry

June 1, 2011

Completed
4 months until next milestone

Study Start

First participant enrolled

October 1, 2011

Completed
3.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2015

Completed
Last Updated

February 18, 2015

Status Verified

February 1, 2015

Enrollment Period

3.3 years

First QC Date

May 26, 2011

Last Update Submit

February 17, 2015

Conditions

ObesityType 2 Diabetes

Outcome Measures

Primary Outcomes (1)

  • 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.

    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

    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

    approximately 3 years

  • GLP-1 analog treatment related changes in obese patients with type 2 diabetes in microvascular function and vasomotion

    approximately 3 years

  • GLP-1 analog treatment related changes in obese patients with type 2 diabetes in cardiovascular autonomic nervous balance

    approximately 3 years

  • GLP-1 analog treatment related changes in obese patients with type 2 diabetes in concomitant changes in metabolic and humoral markers

    approximately 3 years

  • +4 more secondary outcomes

Study Arms (3)

Liraglutide

EXPERIMENTAL

12 week treatment with liraglutide in fixed dosage

Drug: Liraglutide treatment 12 weeks

Insulin glargine

ACTIVE COMPARATOR

12 week treatment, once daily, with insulin glargine. Dosage based on fasting blood glucose measurements

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

Drug: GLP-1 receptor antagonist

Interventions

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

Liraglutide
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

Insulin glargine
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

before start of treatment period

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.
  • +8 more criteria

You may not qualify if:

  • 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
  • +10 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

VU University Medical Center

Amsterdam, 1081 HV, Netherlands

Location

Related Publications (2)

  • 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.

    PMID: 29025878DERIVED

  • ten 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.

    PMID: 26385462DERIVED

MeSH Terms

Conditions

ObesityDiabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

OverweightOvernutritionNutrition DisordersNutritional and Metabolic DiseasesBody WeightSigns and SymptomsPathological Conditions, Signs and SymptomsDiabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesEndocrine System Diseases

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD, PhD

Study Record Dates

First Submitted

May 26, 2011

First Posted

June 1, 2011

Study Start

October 1, 2011

Primary Completion

January 1, 2015

Study Completion

January 1, 2015

Last Updated

February 18, 2015

Record last verified: 2015-02

Locations

NL(1)