NCT01625026

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
40

participants targeted

Target at below P25 for phase_2 obesity

Timeline
Completed

Started Sep 2013

Typical duration for phase_2 obesity

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 19, 2012

Completed
2 days until next milestone

First Posted

Study publicly available on registry

June 21, 2012

Completed
1.2 years until next milestone

Study Start

First participant enrolled

September 1, 2013

Completed
2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2016

Completed
Last Updated

October 18, 2016

Status Verified

October 1, 2016

Enrollment Period

2.6 years

First QC Date

June 19, 2012

Last Update Submit

October 15, 2016

Conditions

Keywords

Morbidly obesityGastric bypassCholecystolithiasis

Outcome Measures

Primary Outcomes (1)

  • 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

    Day 21

Secondary Outcomes (1)

  • Effects of OCA on serum lipid levels

    21 days

Study Arms (4)

Morbid Obesity OCA

ACTIVE COMPARATOR

Obeticholic acid 25 mg/day in three weeks

Drug: Obeticholic acid

Morbid Obesity Placebo

PLACEBO COMPARATOR

Obeticholic acid 25 mg/day matching placebo in three weeks

Drug: Placebo

Gallstones OCA

ACTIVE COMPARATOR

Obeticholic acid 25 mg/day in three weeks

Drug: Obeticholic acid

Gallstones Placebo

PLACEBO COMPARATOR

Obeticholic acid 25 mg/day matching placebo in three weeks

Drug: Placebo

Interventions

Obeticholic acid 25 mg/day in three weeks

Also known as: INT-747
Gallstones OCAMorbid Obesity OCA

Placebo to obeticholic acid

Also known as: Placebo INT-747
Gallstones PlaceboMorbid Obesity Placebo

Eligibility Criteria

Age20 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • In the obesity group: BMI ≥35 kg/m2
  • In the gallstone group: symptomatic, ultrasound verified gallstone disease

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hanns-Ulrich Marschall

Gothenburg, 411 31, Sweden

Location

Related Publications (1)

  • Al-Dury S, Wahlstrom A, Panzitt K, Thorell A, Stahlman M, Trauner M, Fickert P, Backhed F, Fandriks L, Wagner M, Marschall HU. Obeticholic acid may increase the risk of gallstone formation in susceptible patients. J Hepatol. 2019 Nov;71(5):986-991. doi: 10.1016/j.jhep.2019.06.011. Epub 2019 Jun 27.

MeSH Terms

Conditions

ObesityGallstonesCholecystolithiasis

Interventions

obeticholic acid

Condition Hierarchy (Ancestors)

OverweightOvernutritionNutrition DisordersNutritional and Metabolic DiseasesBody WeightSigns and SymptomsPathological Conditions, Signs and SymptomsCholelithiasisBiliary Tract DiseasesDigestive System DiseasesGallbladder DiseasesCalculiPathological Conditions, Anatomical

Study Officials

  • Hanns-Ulrich Marschall, MD, PhD

    Sahlgrenska University Hospital Gothenburg

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Clinical Hepatology

Study Record Dates

First Submitted

June 19, 2012

First Posted

June 21, 2012

Study Start

September 1, 2013

Primary Completion

April 1, 2016

Study Completion

April 1, 2016

Last Updated

October 18, 2016

Record last verified: 2016-10

Locations