Obeticholic Acid in Morbidly Obese Patients and Healthy Volunteers
Kulcsszavak
Absztrakt
Leírás
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.
Dátumok
| Utolsó ellenőrzés: | 03/31/2018 |
| Első benyújtás: | 08/20/2015 |
| Becsült beiratkozás benyújtva: | 08/23/2015 |
| Első közzététel: | 08/24/2015 |
| Utolsó frissítés beküldve: | 04/25/2018 |
| Utolsó frissítés közzétéve: | 04/26/2018 |
| A tanulmány tényleges kezdési dátuma: | 07/31/2015 |
| Becsült elsődleges befejezési dátum: | 09/30/2019 |
| A tanulmány becsült befejezési dátuma: | 09/30/2019 |
Állapot vagy betegség
Beavatkozás / kezelés
Drug: Obeticholic acid
Drug: Obeticholic acid placebo
Fázis
Karcsoportok
| Kar | Beavatkozás / kezelés |
|---|---|
| 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 |
Jogosultsági kritériumok
| Tanulásra alkalmas korok | 18 Years Nak nek 18 Years |
| Tanulásra alkalmas nemek | All |
| Egészséges önkénteseket fogad | Igen |
| Kritériumok | 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. |
Eredmény
Elsődleges eredménymérők
1. ChIP-assay in biopsies as a measure of Activation of FXR-dependent genes in small intestine [Three weeks]
Másodlagos eredménymérők
1. Shot-gun metagenomics as a measure of Impact of FXR activation on gut microbiota [Three weeks]
