The Impact of Lixisenatide on Postprandial Glucose Tolerance in Pancreatectomised Subjects -a Delineation of Extrapancreatic Effects
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 主要终点
- PPG excursions measured as incremental area under curve (iAUC)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Pancreatectomised + Lixisenatide
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
干预措施: Lixisenatide (Drug)
Pancreatectomised + Lixisenatide
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
干预措施: Standardized liquid meal (Other)
Pancreatectomized + lixisenatide-placebo
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.
干预措施: Lixisenatide-Placebo (Drug)
Pancreatectomized + lixisenatide-placebo
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.
干预措施: Standardized liquid meal (Other)
Healthy + Lixisenatide
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
干预措施: Lixisenatide (Drug)
Healthy + Lixisenatide
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
干预措施: Standardized liquid meal (Other)
Healthy + lixisenatide-placebo
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
干预措施: Lixisenatide-Placebo (Drug)
Healthy + lixisenatide-placebo
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
干预措施: Standardized liquid meal (Other)
结局指标
主要结局
PPG excursions measured as incremental area under curve (iAUC)
时间窗: -120,-45,-30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes
次要结局
- differences in gastric emptying, measurement of s-paracetamol(-30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes)
- resting energy expenditure (REE)(-90,30,150 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)
- food intake and appetite(at time 0,30,60,90,120,150,180 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)
- 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)
研究者
Filip Krag Knop
Associated Professor, MD, P.h.D.
University Hospital, Gentofte, Copenhagen