Obeticholic Acid in Bariatric and Gallstone Disease (OCABSGS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Sahlgrenska University Hospital, Sweden
Sponsor:
Collaborator:
Medical University of Vienna
Information provided by (Responsible Party):
Hanns-Ulrich Marschall, Sahlgrenska University Hospital, Sweden
ClinicalTrials.gov Identifier:
NCT01625026
First received: June 19, 2012
Last updated: May 13, 2014
Last verified: May 2014
  Purpose

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
Obesity
Gallstones
Drug: Obeticholic acid
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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)


Estimated Enrollment: 40
Study Start Date: September 2013
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Obeticholic acid
Obeticholic acid 25 mg/day in three weeks
Drug: Obeticholic acid
Obeticholic acid 25 mg/day in three weeks
Placebo Comparator: Placebo Drug: Placebo
Placebo to obeticholic acid

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.

  Eligibility

Ages Eligible for Study:   20 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01625026

Contacts
Contact: Hanns-Ulrich Marschall, MD, PhD +46708774073 hanns-ulrich.marschall@gu.se

Locations
Sweden
Hanns-Ulrich Marschall Recruiting
Göteborg, Sweden, 411 31
Contact: Hanns-Ulrich Marschall    +4670774073    hanns-ulrich.marschall@gu.se   
Principal Investigator: Hanns-Ulrich Marschall, MD, PhD         
Sponsors and Collaborators
Sahlgrenska University Hospital, Sweden
Medical University of Vienna
Investigators
Principal Investigator: Hanns-Ulrich Marschall, MD, PhD Sahlgrenska University Hospital Gothenburg
  More Information

No publications provided

Responsible Party: Hanns-Ulrich Marschall, Professor of Clinical Hepatology, Sahlgrenska University Hospital, Sweden
ClinicalTrials.gov Identifier: NCT01625026     History of Changes
Other Study ID Numbers: OCABSGS
Study First Received: June 19, 2012
Last Updated: May 13, 2014
Health Authority: Sweden: Medical Products Agency

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

Additional relevant MeSH terms:
Obesity
Gallstones
Cholelithiasis
Cholecystolithiasis
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Biliary Tract Diseases
Digestive System Diseases
Gallbladder Diseases
Calculi
Pathological Conditions, Anatomical

ClinicalTrials.gov processed this record on September 22, 2014