Type 2 diabetes mellitus Obesity
Conditions
Interventions
Trade Name: Byetta
Product Name: exenatide
Pharmaceutical Form: Concentrate and solvent for solution for injection
Pharmaceutical form of the placebo: Concentrate and solvent for solution for injectio
Sponsors
VU University Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age 18-65 years - BMI 30–40 kg/m2 - Stable bodyweight ( 3 months prior to screening - HbA1C 7.5–10% - Treatment with metformin and/or sulphonylurea at a stable dose for at least 3 months. - Right handed - Both genders; for women: post menopausal (excluding possible menstruation cycle effects) - Caucasian Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 64 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 8
Exclusion criteria
Exclusion criteria: - GLP-1 based therapies, DPP-4 inhibitors, thiazolidinediones 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 21 units/week, for women >14 units/week) - Smoking/ nicotine abuse (defined as: daily smoking / a daily use of nicotine) - 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 exenatide or other GLP-1 RA - Participation in other studies at time of the screening visit - 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the separate and combined actions of the SGLT2 inhibitor dapagliflozin and GLP-1 receptor agonist exenatide BID on activity in central reward and satiety circuits in response to food related stimuli in obese patients with T2DM;Primary end point(s): Difference in neuronal activity in central reward and satiety circuits in response to food related stimuli by BOLD fMRI signal change from baseline compared to 16 weeks of treatment ;Timepoint(s) of evaluation of this end point: fMRI are assessed at baseline, after 10 days en 16 weeks of treatment. ;Secondary Objective: To investigate the separate and combined actions of the SGLT2 inhibitor dapagliflozin and GLP-1 receptor agonist exenatide on quantitative and qualitative aspects of food intake, energy expenditure, anthropometrics, resting state brain activity networks, cardiovascular autonomic nervous function and blood and urine biomarkers Safety objectives: To evaluate the safety and tolerability of the separate and combined actions of the SGLT2 inhibitor dapagliflozin and GLP-1 receptor agonist exenatide Exploratory objectives: -to study the possible influence of concomitant changes in several important hormones and novel hormone measurements that may become available in the near future. -to allow the study of the effects of human genetic variation on the endpoints in the future | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Differences in neuronal activity in the central reward and satiety circuits in response food related stimuli by BOLD fMRI signal compared to baseline and 1.5 weeks of treatment and 1.5 and 16 weeks of treatment between the exenatide+dapagliflozine, exenatide + placebo, dapagliflozin+placebo and double placebo groups • feeding behaviour, measured by quantitative and qualitative changes in food choice, during an ad libitum lunch buffet compared between the groups ( at baseline and 1,5 week , baseline and 16 weeks and 1.5 and 16weeks) • difference in self reported hunger, satiety and fullness by visual analogue scale •difference in resting energy expenditure measured by indirect calorimetry measurements between the groups (at baseline and 1,5 week , baseline and 16 weeks and 1.5 and 16weeks) • Change in bodyweight (kg) and body mass index (kg/m2) between the groups (at baseline and 1,5 week , baseline and 16 weeks and 1.5 and 16weeks) • Difference in bodycomposition measured by bio electrical impedance analysis and other body measurments such as waist and hip circumference between the 4 groups (at baseline and 1,5 week , baseline and 16 weeks and 1.5 and 16weeks) •difference in resting brain activity by fMRI; resting state measurements • effect on cardiovasculair autonomic balance by cardiovasculair reflex tests (bloodpressure, hartfrequency, ECG; assessed by finger plethysmography [NexFin]) • renal measurements by single spot and 24 urine collection; cumulative glucose excretion (0-1,5, 0-16, 1,5-16 ), creatinine clearance (0-1,5, 0-16, 1,5-16 weeks ), tubulair function ; sodium excretion and urinary pH ((0-1,5, 0-16, 1,5-16 weeks), renal damage markers albumin/creatinin ratio (0-1,5, 0-16, 1,5-16weeks ) • resting blood pressure • Change in the plasma/serum biomarkers of metabolism, liver function, estimated renal function (eGFR), electrolytes and haematocrit (0-1,5, 0-8, 0-16, 1,5-16 weeks) The following safety var | — |
Countries
Netherlands
Contacts
Public ContactLotje C.C. van Ruiten
VU University Medical Center
Outcome results
None listed