Obeticholic Acid in Bariatric and Gallstone Disease
关键词
抽象
描述
In a placebo-controlled double-blind randomized trial, 20 otherwise healthy morbidly obese patients scheduled for bariatric surgery, and 20 otherwise healthy gallstone patients will be administered 25 mg/day INT-747 or placebo for three weeks until the day before surgery. Serum from days 1 and 21 will be analyzed for routine liver tests, bile acids, a complete lipid profile including FA and in addition for 7α-hydroxy-4-cholesten-3-one and FGF-19, markers for bile acid synthesis and its intestinal stimulation. For the evaluation of insulin resistance and possible pre-diabetes, plasma will be taken for the estimation of HOMA index and oral glucose tolerance test (OGTT) will be performed at days 1 and 21. At surgery, a liver biopsy (0.5-1 g) and a white adipose tissue (WAT) specimen (1 cm2) will be taken and immediately frozen in liquid nitrogen for mRNA and protein preparation for quantitative RT-PCR and Western analysis, respectively, histopathological NAFLD grading, and measuring of hepatic and WAT lipase activity. In gallstone patients, gallbladder bile will be sampled for the measurements of biliary lipids (cholesterol, phospholipids, bile acids) and the calculation of the cholesterol saturation index.
日期
| 最后验证: | 09/30/2016 |
| 首次提交: | 06/18/2012 |
| 提交的预估入学人数: | 06/19/2012 |
| 首次发布: | 06/20/2012 |
| 上次提交的更新: | 10/14/2016 |
| 最近更新发布: | 10/17/2016 |
| 实际学习开始日期: | 08/31/2013 |
| 预计主要完成日期: | 03/31/2016 |
| 预计完成日期: | 03/31/2016 |
状况或疾病
干预/治疗
Drug: Obeticholic acid
Drug: Placebo
相
手臂组
| 臂 | 干预/治疗 |
|---|---|
| Active Comparator: Morbid Obesity OCA Obeticholic acid 25 mg/day in three weeks | |
| Placebo Comparator: Morbid Obesity Placebo Obeticholic acid 25 mg/day matching placebo in three weeks | |
| Active Comparator: Gallstones OCA Obeticholic acid 25 mg/day in three weeks | |
| Placebo Comparator: Gallstones Placebo Obeticholic acid 25 mg/day matching placebo in three weeks |
资格标准
| 有资格学习的年龄 | 20 Years 至 20 Years |
| 有资格学习的性别 | All |
| 接受健康志愿者 | 是 |
| 标准 | Inclusion Criteria: - In the obesity group: BMI ≥35 kg/m2 - In the gallstone group: symptomatic, ultrasound verified gallstone disease Exclusion Criteria: - Chronic liver disease other than NAFLD (viral hepatitis, autoimmune liver disease, hemochromatosis, homozygous alpha1-antitrypsin deficiency and Wilson disease) - Previous gastric or small bowel surgery - Inflammatory bowel disease - Uncontrolled diabetes mellitus (fasting blood glucose >6.7 mmol/L), hypothyroidism or hyperthyroidism, or other significant endocrine disease. - Pregnancy. A urine pregnancy test will be performed the day before start of medication. Women of childbearing potential can only be included if a safe and reliable contraception is used, e.g., oral contraceptives. - Elevations of transaminases (ALAT/ASAT) or alkaline phosphatase or bilirubin above 2xULN (upper limit of normal) the day before start of medication. - Other serious disease, including depressive disorders treated by medication - Patients who will not comply with the protocol. - A subject who is euthyroid on a stable replacement dose of thyroid hormone is acceptable provided the TSH is within normal range. |
结果
主要结果指标
1. Effects of OCA on FXR-dependent metabolism [Day 21]
次要成果指标
1. Effects of OCA on serum lipid levels [21 days]
