Effect of Endoplasmic Reticulum Stress on Metabolic Function
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 101
- 试验地点
- 1
- 主要终点
- Body Composition
研究概览
简要总结
Normally, the hormone insulin works to help keep blood sugar normal. However, as a person gains weight, insulin does not work as well and blood sugar tends to be a little higher than normal. This is called "insulin resistance".
Two investigational drugs (not approved by the Food and Drug Administration) for the treatment of high lipid levels or insulin resistance are being examined in this study: one drug is called tauroursodeoxycholic acid (TUDCA), the other is called sodium phenylbutyrate (PBA). This study is designed to test if TUDCA and/or PBA is effective in people who are obese with insulin resistance and high lipids. We hypothesize that pharmacologically-induced decreases in ER stress will improve insulin action and hepatic lipid metabolism in obese subjects.
详细描述
A 4-week randomized, controlled trial will be conducted to evaluate the following specific aims in obese subjects:
Determine the effect of treatment with TUDCA or PBA on:
- Body fat distribution: a) intrahepatic triglyceride (IHTG) content, b) intramyocellular triglyceride (IMTG) content, and c) intra-abdominal fat content, assessed by using magnetic resonance spectroscopy and magnetic resonance imaging.
- In vivo insulin sensitivity in adipose tissue (suppression of lipolysis), liver (suppression of glucose production), and skeletal muscle (stimulation of glucose uptake), assessed by using the hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotope tracer infusion.
- VLDL-triglyceride (TG) and VLDL-apolipoprotein-B100 (apoB-100) secretion rates, assessed by stable isotopically labeled tracer infusion methods.
- Skeletal muscle intracellular insulin signaling, fatty acid oxidation, and markers of inflammation, assessed by evaluating skeletal muscle biopsies ex vivo.
- Adipose tissue insulin signaling, ER stress, and inflammation, assessed by evaluating adipose tissue biopsies ex vivo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •BMI range 30 to 45
- •sedentary (defined as regular exercise < 1 h per week or < 2 x/week for the last 6 months)
排除标准
- •active or previous infection with hepatitis B or C
- •liver diseases
- •history of alcohol abuse
- •current alcohol consumption > 20 g/day
- •severe hypertriglyceridemia ( > 400 mg/dL)
- •active peptic ulcer disease
- •taking cholestyramine or oral contraceptives
- •women who are pregnant or lactating
研究组 & 干预措施
Placebo
Subjects will be given a placebo rather than tauroursodeoxycholic acid.
干预措施: placebo (Other)
tauroursodeoxycholic acid
Subjects will receive tauroursodeoxycholic acid for four weeks.
干预措施: tauroursodeoxycholic acid (Drug)
PBA
Subjects will receive sodium phenylbutyrate for four weeks.
干预措施: sodium phenylbutyrate (Drug)
结局指标
主要结局
Body Composition
时间窗: Baseline and four weeks
Fat mass (%)
次要结局
- Insulin Sensitivity in the Liver(Baseline and four weeks)
- VLDL-triglyceride (TG) Concentration(Baseline and four weeks)