Obeticholic Acid in Bariatric and Gallstone Disease
Kulcsszavak
Absztrakt
Leírás
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.
Dátumok
| Utolsó ellenőrzés: | 09/30/2016 |
| Első benyújtás: | 06/18/2012 |
| Becsült beiratkozás benyújtva: | 06/19/2012 |
| Első közzététel: | 06/20/2012 |
| Utolsó frissítés beküldve: | 10/14/2016 |
| Utolsó frissítés közzétéve: | 10/17/2016 |
| A tanulmány tényleges kezdési dátuma: | 08/31/2013 |
| Becsült elsődleges befejezési dátum: | 03/31/2016 |
| A tanulmány becsült befejezési dátuma: | 03/31/2016 |
Állapot vagy betegség
Beavatkozás / kezelés
Drug: Obeticholic acid
Drug: 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: Gallstones OCA Obeticholic acid 25 mg/day in three weeks | |
| Placebo Comparator: Gallstones Placebo Obeticholic acid 25 mg/day matching placebo in three weeks |
Jogosultsági kritériumok
| Tanulásra alkalmas korok | 20 Years Nak nek 20 Years |
| Tanulásra alkalmas nemek | All |
| Egészséges önkénteseket fogad | Igen |
| Kritériumok | 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. |
Eredmény
Elsődleges eredménymérők
1. Effects of OCA on FXR-dependent metabolism [Day 21]
Másodlagos eredménymérők
1. Effects of OCA on serum lipid levels [21 days]
