Effects of Colesevelam HCl On Bile Acid Pools And Kinetic Parameters in Normal Subjects, Subjects With Impaired Glucose Tolerance, And Subjects With Type 2 Diabetes Mellitus
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Bile Acid Pool Size and Kinetic Parameters
研究概览
简要总结
This project will compare the amount of bile acids and their kinetics in overweight and obese people with normal glucose metabolism, impaired glucose tolerance and frank type 2 diabetes. We hypothesize that bile acids will behave differently in these groups. We will also explore the effects of Colesevelam HCl, a medicine that lowers LDL cholesterol by binding bile acids, on bile acids in those groups. We hypothesize the drug may have different actions on bile acids in subjects with different degrees of abnormal glucose metabolism.
详细描述
Bile acids, which are synthesized from cholesterol in the liver, play a key role in digestion as they solubilize dietary lipids and aid their absorption in the digestive tract. While for many years bile acids have been characterized by this digestive role, recent research indicates that bile acids play other important roles. Because bile acids have been shown to act in signaling pathways that affect metabolism, there has been renewed interest in investigations of their effects. This study explores potential differences in bile acid kinetics based on insulin resistance or type 2 diabetes at baseline.
Colesevelam HCl is a bile acid sequestrant, which in addition to its primary role in lowering serum LDL-C levels, has secondarily been implicated in lowering blood glucose levels. This study explores the relationship between insulin resistance and type 2 diabetes and changes in bile acid pool sizes and kinetics with colesevelam treatment. Isotopically labeled bile acids will be administered to subjects before and after treatment with colesevelam and comparisons will be made in bile acid pool size, fractional turnover rate, and synthesis rate in the three study groups.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 40 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Have given written informed consent
- •BMI 25-35 kg/m^2, inclusive
- •Normal liver and thyroid function
- •No history of liver, biliary, or intestinal disease
- •Diabetic Subjects
- •Diagnosed Type 2 Diabetes Mellitus
- •HbA1C = 6.7-10%
- •Normal Subjects
- •2 hr OGTT glucose < 140 mg/dL
- •fasting glucose < 100 mg/dL
- •TG < 150 mg/dL
- •HDL cholesterol >= 40 mg/dL
- •Impaired Glucose Tolerance Subjects
- •2 hr OGTT glucose >= 140 and < 200 mg/dL
排除标准
- •T1DM or history of diabetic ketoacidosis
- •treatment with blood pressure lowering therapy that has not been stable for three months before screening
- •colesevelam HCl, cholestyramine, or colestipol treatment for hyperlipidemia within the last three months
- •treatment with thiazolidinedione (TZD) at any time
- •treatment with insulin within past 6 months
- •treatment with antibiotics within last 3 months
- •extreme sportsmen
- •treatment with medication affecting liver or intestinal function within the last 3 months
- •allergic or toxic rxn to colesevelam HCl
- •history of dysphagia, swallowing disorders, or intestinal motility disorder
- •Serum Triglycerides > 500 mg/dL at visit 1
- •Serum LDL-C < 60 mg/dL at visit 1
- •any condition or therapy investigator believes not in subjects best interest
- •use of any investigational drug within 30 days before screening
- •chronic treatment with oral corticosteroids at any time or acute treatment within last three months
- •hyperthyroidism or treatment with thyroid hormone/levothyroxine
研究组 & 干预措施
Normal Glucose Metabolism
Overweight and obese individuals that have normal glucose metabolism and their response to Colesevelam HCl
干预措施: Colesevelam HCl (Drug)
Impaired Glucose Tolerance
Overweight and obese individuals that have impaired glucose tolerance and their response to Colesevelam HCl
干预措施: Colesevelam HCl (Drug)
Frank type 2 diabetes
Overweight and obese individuals that have frank type 2 diabetes and their response to Colesevelam HCl
干预措施: Colesevelam HCl (Drug)
结局指标
主要结局
Bile Acid Pool Size and Kinetic Parameters
时间窗: 60 days of treatment
次要结局
- Resting Metabolic Rate(60 days of treatment)