GLP-1-mediated Gluco-metabolic Effects of Bile Acid Sequestration
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- plasma glucose
研究概览
简要总结
The objective of this study is to investigate the potential GLP-1-mediated contribution to the well-established glucose-lowering effect of sevelamer-induced bile acid sequestration . Exendin9-39 has been demonstrated to act as a potent and specific GLP-1 receptor antagonist with no partial agonistic potential and is considered a useful tool in the assessment of GLP-1 physiology. The aim is to evaluate any contribution of sevelamer-induced GLP-1 secretion to the reduced plasma glucose concentrations observed after treatment with sevelamer. A randomised placebo-controlled cross-over study involving two 17-day treatment periods with sevelamer and placebo, respectively, in metformin-treated patients with type 2 diabetes, will be conducted. The impact of bile acid sequestration on GLP-1 secretion and effect will be examined during two randomised experimental days after 15 and 17 days of treatment with sevelamer (1,600 mg three times a day) and placebo, respectively. During each of these two experimental days, a meal test with concomitant exendin9-39 infusion or placebo will be performed (for evaluation of any GLP-1-mediated effects). Postprandial plasma glucose excursion is the primary endpoint, and secondary endpoints include postprandial plasma/serum excursions of insulin, C-peptide, GLP-1, glucagon, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-2 (GLP-2), peptide YY (PYY), oxyntomodulin, ghrelin, fibroblast growth factor (FGF)-19, FGF-21, C4 (an intermediate in the de novo synthesis of bile acids), cholecystokinin (CCK), bile acids and plasma lipids. Furthermore, gastric emptying, gallbladder emptying, liver fat content, appetite and ad libitum food intake will be examined.
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
- 40 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Type 2 diabetes for at least 3 months (diagnosed according to the criteria of the World Health Organization (WHO))
- •Men and postmenopausal women
- •Metformin applied as the only glucose-lowering drug
- •Caucasian ethnicity
- •Normal haemoglobin
- •Age above 40 years and below 75 years
- •BMI >23 kg/m2 and <35 kg/m2
- •Informed and written consent
排除标准
- •Liver disease (alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) >2 times normal values) or history of hepatobiliary disorder
- •Gastrointestinal disease, previous intestinal resection, cholecystectomy or any major intra-abdominal surgery
- •Nephropathy (serum creatinine >150 µM and/or albuminuria)
- •Hypo- or hyperthyroidism
- •Hypo- or hypercalcaemia
- •Hypo- or hyperphosphataemia
- •Active or recent malignant disease
- •Treatment with medicine that cannot be paused for 12 hours
- •Treatment with oral anticoagulants
- •Any treatment or condition requiring acute or sub-acute medical or surgical intervention
- •Any condition considered incompatible with participation by the investigators
研究组 & 干预措施
sevelamer
Patients with type 2 diabetes treated with sevelamer
干预措施: Sevelamer (Drug)
placebo
Patients with type 2 diabetes treated with placebo
干预措施: Placebo (Drug)
结局指标
主要结局
plasma glucose
时间窗: -30 minutes to 240 minutes with ingestion of a meal at 0 minutes
Postprandial plasma glucose (PG) excursion (AUC240 min)
次要结局
- Postprandial responses of Bile acids(-30 minutes to 240 minutes with ingestion of a meal at 0 minutes)
- Postprandial responses of Amino acids(-30 minutes to 240 minutes with ingestion of a meal at 0 minutes)
- Postprandial responses of Insulin and c-peptide(-30 minutes to 240 minutes with ingestion of a meal at 0 minutes)
- Postprandial responses of Glucagon(-30 minutes to 240 minutes with ingestion of a meal at 0 minutes)
- Postprandial responses of glucose-dependent insulinotropic polypeptide (GIP)(-30 minutes to 240 minutes with ingestion of a meal at 0 minutes)
- Postprandial responses of Ghrelin(-30 minutes to 240 minutes with ingestion of a meal at 0 minutes)
- Postprandial responses of fibroblast growth factor (FGF)-19(-30 minutes to 240 minutes with ingestion of a meal at 0 minutes)
- Postprandial responses of fibroblast growth factor (FGF)-21(-30 minutes to 240 minutes with ingestion of a meal at 0 minutes)
- Postprandial responses of peptide YY (PYY)(-30 minutes to 240 minutes with ingestion of a meal at 0 minutes)
- Postprandial responses of plasma lipids(-30 minutes to 240 minutes with ingestion of a meal at 0 minutes)
- Postprandial responses of glucagon-like peptide-1 (GLP-1)(-30 minutes to 240 minutes with ingestion of a meal at 0 minutes)
- Postprandial responses of glucagon-like peptide-2 (GLP-2)(-30 minutes to 240 minutes with ingestion of a meal at 0 minutes)
- Postprandial responses of cholecystokinin (CCK)(-30 minutes to 240 minutes with ingestion of a meal at 0 minutes)
- Rate of gall bladder emptying(-30 minutes to 240 minutes with ingestion of a meal at 0 minutes)
- Liver stiffness and fat(At initiation and after 15 days of treatment with sevelamer/placebo)
- Appetite measured by visual analog scale(-30 minutes to 240 minutes with ingestion of a meal at 0 minutes)
- Gastric emptying(-30 minutes to 240 minutes with ingestion of a meal and paracetamol at 0 minutes)