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| Name | Class |
|---|---|
| MCM Vaccines B.V. | INDUSTRY |
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Postprandial glucose (PPG) excursions are not only determined by insulin-mediated glucose disposal and endogenous glucose production (regulated by insulin and glucagon); also the rate of gastric emptying constitutes an important determinant of PPG levels 1. The short-acting glucagon-like peptide-1 (GLP-1) receptor agonist lixisenatide is used in the treatment of type 2 diabetes. It increases glucose-dependent insulin secretion, suppresses glucagon secretion and reduces gastric emptying of meals 2. These three mechanisms most likely constitute the weightiest mechanisms behind the potent impact of lixisenatide on exaggerated PPG excursions in patients with type 2 diabetes - which often are normalised during lixisenatide treatment 3. However, the separate impact of lixisenatide-induced reduction of gastric emptying (independently of the pancreatic effects) has been difficult to determine. Importantly, treatment with lixisenatide also decreases appetite and food intake and may, like native GLP-1, increase energy expenditure 4. So far an exact demarcation of the pancreatic and extrapancreatic effects of lixisenatide in humans remains to be established.
The present project serves to determine whether effects of lixisenatide on gastric emptying, appetite, food intake and resting energy expenditure are dependent on the endocrine pancreas.
The study is a randomised, placebo-controlled, double-blinded, cross-over study.
12 healthy persons and 12 pancreatectomized patients (i.e. patients who have had their pancreata removed due to pancreatic cancer or severe chronic pancreatitis) will be subjected to two experimental days on which they will undergo a liquid meal test followed by a fasting period and finished off with an ad libitum meal with lixisenatide and placebo, respectively.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pancreatectomised + Lixisenatide | Active Comparator | During the experimental day the patient will ingest a standardized liquid meal (200 ml containing 1,650 kJ (394 kcal): carbohydrate 50%, protein 15%, fat 35%, consisting of glucose (48.4 g + 1.6 g [U-13C6]-glucose), rapeseed oil (14.1 g), whey protein (15.2 g) and 1.5 g paracetamol). Before the meal a Lixisenatide-injection will be given subcutaneously |
|
| Pancreatectomized + lixisenatide-placebo | Placebo Comparator | During the experimental day the patient will ingest a standardized liquid meal (200 ml containing 1,650 kJ (394 kcal): carbohydrate 50%, protein 15%, fat 35%, consisting of glucose (48.4 g + 1.6 g [U-13C6]-glucose), rapeseed oil (14.1 g), whey protein (15.2 g) and 1.5 g paracetamol). Before the meal a placebo-injection will be given subcutaneously. |
|
| Healthy + Lixisenatide | Active Comparator | During the experimental day the subject will ingest a standardized liquid meal (200 ml containing 1,650 kJ (394 kcal): carbohydrate 50%, protein 15%, fat 35%, consisting of glucose (48.4 g + 1.6 g [U-13C6]-glucose), rapeseed oil (14.1 g), whey protein (15.2 g) and 1.5 g paracetamol). Before the meal a Lixisenatide-injection will be given subcutaneously |
|
| Healthy + lixisenatide-placebo | Placebo Comparator | During the experimental day the subject will ingest a standardized liquid meal (200 ml containing 1,650 kJ (394 kcal): carbohydrate 50%, protein 15%, fat 35%, consisting of glucose (48.4 g + 1.6 g [U-13C6]-glucose), rapeseed oil (14.1 g), whey protein (15.2 g) and 1.5 g paracetamol). Before the meal a placebo-injection will be given subcutaneously |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lixisenatide | Drug | single injection of 20 µg lixisenatide subcutaneously |
|
| Measure | Description | Time Frame |
|---|---|---|
| PPG excursions measured as incremental area under curve (iAUC) | -120,-45,-30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes |
| Measure | Description | Time Frame |
|---|---|---|
| differences in gastric emptying, measurement of s-paracetamol | measurement of time to peak and incremental area under the curve (iAUC) | -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes |
| food intake and appetite |
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Inclusion criteria Pancreatectomised patients
Exclusion criteria Pancreatectomised patients
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| Name | Affiliation | Role |
|---|---|---|
| Filip K Knop, Assoc. Prof. | Center for Diabetes Research, Gentofte Hospital, Kildegaardsvej 28, 2900 Hellerup, Denmark | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32394228 | Derived | Juel CTB, Lund A, Andersen MM, Hansen CP, Storkholm JH, Rehfeld JF, van Hall G, Hartmann B, Wewer Albrechtsen NJ, Holst JJ, Vilsboll T, Knop FK. The GLP-1 receptor agonist lixisenatide reduces postprandial glucose in patients with diabetes secondary to total pancreatectomy: a randomised, placebo-controlled, double-blinded crossover trial. Diabetologia. 2020 Jul;63(7):1285-1298. doi: 10.1007/s00125-020-05158-9. Epub 2020 May 11. |
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| ID | Term |
|---|---|
| C479460 | lixisenatide |
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|
| Lixisenatide-Placebo | Drug |
|
| Standardized liquid meal | Other | standardized liquid meal (200 ml containing 1,650 kJ (394 kcal): carbohydrate 50%, protein 15%, fat 35%, consisting of glucose (48.4 g + 1.6 g [U-13C6]-glucose), rapeseed oil (14.1 g), whey protein (15.2 g) and 1.5 g paracetamol). |
|
assessed by a visual analogue scale (VAS)
| at time 0,30,60,90,120,150,180 minutes |
| resting energy expenditure (REE) | measured by calorimetry | -90,30,150 minutes |
| p-glucose mmol/L | -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes |
| p-C-peptide pmol/l | -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes |
| glucagon, gastrin, cholecystokinin, GIP, GLP-1, oxyntomodulin | -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes |