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Obeticholic Acid in Bariatric and Gallstone Disease (OCABSGS)

This study has been completed.
Medical University of Vienna
Information provided by (Responsible Party):
Hanns-Ulrich Marschall, Sahlgrenska University Hospital, Sweden Identifier:
First received: June 19, 2012
Last updated: October 15, 2016
Last verified: October 2016
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.

Condition Intervention Phase
Drug: Obeticholic acid
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: Effects of Obeticholic Acid on Hepatic Fatty Acid/Triglyceride Metabolism and Hepatobiliary Detoxification/Elimination in Morbidly Obese and Gallstone Patients

Resource links provided by NLM:

Further study details as provided by Sahlgrenska University Hospital, Sweden:

Primary Outcome Measures:
  • Effects of OCA on FXR-dependent metabolism [ Time Frame: Day 21 ]

    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

Secondary Outcome Measures:
  • Effects of OCA on serum lipid levels [ Time Frame: 21 days ]

    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)

Enrollment: 40
Study Start Date: September 2013
Study Completion Date: April 2016
Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Morbid Obesity OCA
Obeticholic acid 25 mg/day in three weeks
Drug: Obeticholic acid
Obeticholic acid 25 mg/day in three weeks
Other Name: INT-747
Placebo Comparator: Morbid Obesity Placebo
Obeticholic acid 25 mg/day matching placebo in three weeks
Drug: Placebo
Placebo to obeticholic acid
Other Name: Placebo INT-747
Active Comparator: Gallstones OCA
Obeticholic acid 25 mg/day in three weeks
Drug: Obeticholic acid
Obeticholic acid 25 mg/day in three weeks
Other Name: INT-747
Placebo Comparator: Gallstones Placebo
Obeticholic acid 25 mg/day matching placebo in three weeks
Drug: Placebo
Placebo to obeticholic acid
Other Name: Placebo INT-747

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.

Ages Eligible for Study:   20 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.
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Please refer to this study by its identifier: NCT01625026

Hanns-Ulrich Marschall
Göteborg, Sweden, 411 31
Sponsors and Collaborators
Sahlgrenska University Hospital, Sweden
Medical University of Vienna
Principal Investigator: Hanns-Ulrich Marschall, MD, PhD Sahlgrenska University Hospital Gothenburg
  More Information

Responsible Party: Hanns-Ulrich Marschall, Professor of Clinical Hepatology, Sahlgrenska University Hospital, Sweden Identifier: NCT01625026     History of Changes
Other Study ID Numbers: OCABSGS
Study First Received: June 19, 2012
Last Updated: October 15, 2016

Keywords provided by Sahlgrenska University Hospital, Sweden:
Morbidly obesity
Gastric bypass

Additional relevant MeSH terms:
Biliary Tract Diseases
Digestive System Diseases
Gallbladder Diseases
Pathological Conditions, Anatomical
Chenodeoxycholic Acid
Gastrointestinal Agents processed this record on May 23, 2017