A Phase 2 interventional study of Obeticholic acid and Placebo in Obesity and Gallstones, sponsored by Sahlgrenska University Hospital. Completed at 1 site in Sweden. Open to participants aged 20 Years to 65 Years. Per ClinicalTrials.gov, last updated 2016-10-18.
Sponsored by Sahlgrenska University Hospital · Phase 2, Interventional, and Basic science
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.
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.
346 studies on the registry are indexed under Gallstones; 46 are open to participants now.
This study's enrollment of 40 is below the median of 99 across 232 interventional studies indexed under Gallstones.
Browse Gallstones studies →Sahlgrenska University Hospital is the lead sponsor of 259 studies on the registry; 68 are open to participants now.
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Obeticholic acid 25 mg/day in three weeks
Drug: Obeticholic acid
Obeticholic acid 25 mg/day matching placebo in three weeks
Drug: Placebo
Obeticholic acid 25 mg/day in three weeks
Drug: Obeticholic acid
Obeticholic acid 25 mg/day matching placebo in three weeks
Drug: Placebo
Obeticholic acid 25 mg/day in three weeks
Also known as: INT-747
Placebo to obeticholic acid
Also known as: Placebo INT-747
Effects of OCA on FXR-dependent metabolism
Primary endpoints * relative changes in markers for insulin resistance * relative changes in FA and TG * relative changes in hepatic and adipose tissue lipase expression and activity * relative changes in hepatic apical transport proteins ABCG5/8, BSEP, MDR3, MRP2 * relative changes in hepatic ER stress markers
Time frame: Day 21
Effects of OCA on serum lipid levels
Secondary endpoints * relative changes in m RNA expression levels of genes listed under 3.ix * relative changes in hepatic basolateral transport proteins listed under 3.x * relative change in serum bile acids as listed under 3.xii, including INT-747 * relative changes in biliary lipids (cholesterol, phospholipids, bile acids) * relative change in plasma 7α-hydroxy-4-cholesten-3-one and FGF-19 * relative changes in total cholesterol, LDL-C, HDL-C, Apo A1, Apo B, in Lp(A)
Time frame: 21 days
This study is completed, as verified in Oct 2016. You cannot join it, but the record below documents what was studied.
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Sahlgrenska University Hospital