NCT01625026

Obeticholic Acid in Bariatric and Gallstone Disease

Effects of Obeticholic Acid on Hepatic Fatty Acid/Triglyceride Metabolism and Hepatobiliary Detoxification/Elimination in Morbidly Obese and Gallstone Patients

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (actual)
• Sponsor: Sahlgrenska University Hospital · Academic / Other
• Sex: All
• Age: 20 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

By binding to the nuclear receptor FXR, bile acids not only regulate their own turn-over but presumably also pivotal steps in cholesterol, triglyceride and glucose metabolism as shown in laboratory animals. Obeticholic acid (OCA) is a semisynthetic bile acid with very high affinity to FXR. In a pharmacodynamic study the effects of OCA on bile acid, lipid and glucose turn-over are studied in 20 morbidly obese and 20 gallstones patents, respectively, that are administered OCA at 25 mg/day in three weeks before bariatric (BS) or gallstone (GS) surgery where in addition to blood samples also biopsies are taken from the liver and in the case of BS, omental and subcutaneous adipose tissue and in case of GS, gallbladder bile.

Detailed description

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.

Conditions

• Obesity
• Gallstones

Interventions

Type	Name	Description
DRUG	Obeticholic acid	Obeticholic acid 25 mg/day in three weeks
DRUG	Placebo	Placebo to obeticholic acid

Timeline

• Start date: 2013-09-01
• Primary completion: 2016-04-01
• Completion: 2016-04-01
• First posted: 2012-06-21
• Last updated: 2016-10-18

Locations

1 site across 1 country: Sweden