The Impact of Gall Bladder Emptying and Bile Acids on the Human GLP-1-secretion
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- GLP-1 response as incremental area under curve (iAUC)
研究概览
简要总结
The last couple of years it has been shown that bile acids not only acts as simple emulsifiers of fat, but constitutes a complex metabolic integrator which not only have an influence on fat digestion and lipid metabolism, but also modulates the energy expenditure in (brown) adipose tissue and muscle tissue. This action is due to stimulation of the receptor TGR5 by bile acids. Recently scientists have discovered that this receptor in rodents is also expressed on the surface of intestinal L-cells (which normally secrets Glucagon-Like Peptide-1 (GLP-1) in response to nutrient stimulation). The stimulation of this receptor has shown a GLP-1 secretion from the intestinal cells which is interesting since GLP-1 has a central role in maintaining normal glucose tolerance and thus blood sugar. Given the above, bile acids has an important impact on intestinal GLP-1 secretion. Whether these scientific findings can be proven in human beings is uncertain.
The primary hypothesis is that stimulating gall bladder emptying via Cholecystokinin (CCK) in healthy subjects will result in a significant GLP-1 response. We also hypothesize that adding orally Metformin or a sequestrant ("a bile acid binder") will further enhance this GLP-1 response.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •HbA1c < 6,0%
- •Not anaemic
- •Written informed consent
排除标准
- •Liver disease
- •Nephropathy
- •fasting plasma glucose > 5,6mM
- •Diabetes running in the family (parents or grandparents)
- •Any medical treatment
- •A former medical history of liver- or bile disease
- •any surgical procedure conducted in the abdomen
- •Body mass index < 18,5 kg/m2 or > 25 kg/m2
研究组 & 干预措施
Acetaminophen+saline
Acetaminophen tablet 1500 mg via nasogastric tube + i.v. saline
干预措施: Acetaminophen (Drug)
Colesevelam+saline
Colesevelam tablet 3750 mg + Acetaminophen tablet 1500 mg via nasogastric tube + iv. saline
干预措施: Acetaminophen (Drug)
Acetaminophen+saline
Acetaminophen tablet 1500 mg via nasogastric tube + i.v. saline
干预措施: Saline (Other)
Acetaminophen+CCK
Acetaminophen tablet 1500 mg via nasogastric tube + iv. CCK-8, 24 pmol/kg/hour
干预措施: Acetaminophen (Drug)
Acetaminophen+CCK
Acetaminophen tablet 1500 mg via nasogastric tube + iv. CCK-8, 24 pmol/kg/hour
干预措施: Cholecystokinin-8 (Other)
Metformin+saline
Metformin tablet 1500 mg + Acetaminophen tablet 1500 mg via nasogastric tube + i.v. saline
干预措施: Acetaminophen (Drug)
Metformin+saline
Metformin tablet 1500 mg + Acetaminophen tablet 1500 mg via nasogastric tube + i.v. saline
干预措施: Metformin (Drug)
Metformin+saline
Metformin tablet 1500 mg + Acetaminophen tablet 1500 mg via nasogastric tube + i.v. saline
干预措施: Saline (Other)
Metformin+CCK
Metformin tablet 1500 mg + Acetaminophen tablet 1500 mg via nasogastric tube + iv. CCK-8, 24 pmol/kg/hour
干预措施: Acetaminophen (Drug)
Metformin+CCK
Metformin tablet 1500 mg + Acetaminophen tablet 1500 mg via nasogastric tube + iv. CCK-8, 24 pmol/kg/hour
干预措施: Metformin (Drug)
Metformin+CCK
Metformin tablet 1500 mg + Acetaminophen tablet 1500 mg via nasogastric tube + iv. CCK-8, 24 pmol/kg/hour
干预措施: Cholecystokinin-8 (Other)
Colesevelam+saline
Colesevelam tablet 3750 mg + Acetaminophen tablet 1500 mg via nasogastric tube + iv. saline
干预措施: Colesevelam (Drug)
Colesevelam+saline
Colesevelam tablet 3750 mg + Acetaminophen tablet 1500 mg via nasogastric tube + iv. saline
干预措施: Saline (Other)
Colesevelam+CCK
Colesevelam tablet 3750 mg + Acetaminophen tablet 1500 mg via nasogastric tube + iv. CCK-8, 24 pmol/kg/hour
干预措施: Acetaminophen (Drug)
Colesevelam+CCK
Colesevelam tablet 3750 mg + Acetaminophen tablet 1500 mg via nasogastric tube + iv. CCK-8, 24 pmol/kg/hour
干预措施: Colesevelam (Drug)
Colesevelam+CCK
Colesevelam tablet 3750 mg + Acetaminophen tablet 1500 mg via nasogastric tube + iv. CCK-8, 24 pmol/kg/hour
干预措施: Cholecystokinin-8 (Other)
结局指标
主要结局
GLP-1 response as incremental area under curve (iAUC)
时间窗: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
次要结局
- Insulin(-30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240)
研究者
Filip Krag Knop
MD, Ph.D.
University Hospital, Gentofte, Copenhagen