Obeticholic Acid in Morbidly Obese Patients and Healthy Volunteers
关键词
抽象
描述
Obeticholic acid will be administered orally at a dose of 25 mg/day during three weeks to 20 morbidly obese patients awaiting Roux-en-Y gastric bypass and to 20 healthy volunteers. On the days before the first and after the last dose faeces and blood are sampled for the analyses of bile acids and the gut microbiota. On the day after the last dose a push-enteroscopy is performed in conscious sedation for biopsy taking in the jejunum. These procedures are repeated 6 month after surgery in the morbid obese patients. Inclusion criteria are male or female gender, 20-65 years of age and morbid obesity (BMI >35 kg/m2) eligible for bariatric surgery. Exclusion criteria are liver diseases other that fatty liver disease, other significant morbidity, medications known to interact with OCA, pregnancy, uncertainty about safe and reliable contraception, and problems to understand or adhere to the protocol. The primary objectives of this pharmacodynamic trial are the study of the effect of OCA on the expression of FXR in the jejenum and small intestinal permeability, and on fecal bile acids and gut microbiota. The secondary objectives are the study of the effects of OCA on the genome-wide FXR DNA binding sites (cistromics) with the global gene expression profile (transcriptomics) in human jejunum.
日期
| 最后验证: | 03/31/2018 |
| 首次提交: | 08/20/2015 |
| 提交的预估入学人数: | 08/23/2015 |
| 首次发布: | 08/24/2015 |
| 上次提交的更新: | 04/25/2018 |
| 最近更新发布: | 04/26/2018 |
| 实际学习开始日期: | 07/31/2015 |
| 预计主要完成日期: | 09/30/2019 |
| 预计完成日期: | 09/30/2019 |
状况或疾病
干预/治疗
Drug: Obeticholic acid
Drug: Obeticholic acid 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: Healthy Volunteers OCA Obeticholic acid Obeticholic acid 25 mg/day in three weeks | |
| Placebo Comparator: Healthy volunteers Placebo Obeticholic acid 25 mg/day matching placebo in three weeks |
资格标准
| 有资格学习的年龄 | 18 Years 至 18 Years |
| 有资格学习的性别 | All |
| 接受健康志愿者 | 是 |
| 标准 | Inclusion Criteria: Morbid obesity awaiting gastric bypass surgery, ≥35 kg/m2 Male subjects, pre-, and post-menopausal female subjects Women of childbearing potential can only be included if a safe and reliable contraception is used, e.g., oral contraceptives Patients eligible to laparoscopic bariatric surgery Patients must give their signed and dated written consent to participate in this study based on written information of all pertinent aspects of the trial provided at least 24 hours before undertaking any trial related activity. 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. Hypothyroidism, unless the subject is clinically euthyroid, receiving a stable dose thyroid hormone replacement therapy and serum TSH is within the normal range. |
结果
主要结果指标
1. ChIP-assay in biopsies as a measure of Activation of FXR-dependent genes in small intestine [Three weeks]
次要成果指标
1. Shot-gun metagenomics as a measure of Impact of FXR activation on gut microbiota [Three weeks]
