Obeticholic Acid in Morbidly Obese Patients and Healthy Volunteers

NCT02532335 | Unknown Phase 1

• 1 other identifier: OCAPUSH
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

OCAPUSH (EudraCT 2014-002313-33) is a double-blind placebo-controlled parallel-arms study of the effects of obeticholic acid on farnesoid X receptor expression in jejunum and on gut microbiota in morbidly obese patients and healthy volunteers. Obeticholic acid (OCA, 6-ethyl-chenodeoxycholic acid, INT-747) is a semi-synthetic derivative of the major human bile acid chenodeoxycholic acid and will be administered orally at a dose of 25 mg/day during three weeks to 20 morbidly obese patients awaiting Roux-en-Y gastric bypass and to 20 healthy volunteers. On the days before the first and after the last dose faeces and blood are sampled for the analyses of bile acids and the gut microbiota. On the day after the last dose a push-enteroscopy is performed in conscious sedation for biopsy taking in the jejunum.These procedures are repeated 6 month after surgery in the morbid obese patients. Inclusion criteria are male or female gender, 20-65 years of age and morbid obesity (BMI \>35 kg/m2) eligible for bariatric surgery. Exclusion criteria are liver diseases other that fatty liver disease, other significant morbidity, medications known to interact with OCA, pregnancy, uncertainty about safe and reliable contraception, and problems to understand or adhere to the protocol. The primary objectives of this pharmacodynamic trial are the study of the effect of OCA on the expression of FXR in the jejunum and small intestinal permeability, and on fecal bile acids and gut microbiota. The secondary objectives are the study of the effects of OCA on the genome-wide FXR DNA binding sites (cistromics) with the global gene expression profile (transcriptomics) in human jejunum.

Conditions

Obesity

Keywords

FXR; bile acids; FGF19; C4; gut microbiota; Pharmacodynamics of FXR activation in the small bowel

Outcome Measures

Primary Outcomes (1)

• ChIP-assay in biopsies as a measure of Activation of FXR-dependent genes in small intestine

  ChIP-assay in biopsies

  Three weeks

Secondary Outcomes (1)

• Shot-gun metagenomics as a measure of Impact of FXR activation on gut microbiota

  Three weeks

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: Obeticholic acid; Drug: Obeticholic acid placebo

Healthy Volunteers OCA

ACTIVE COMPARATOR

Obeticholic acid Obeticholic acid 25 mg/day in three weeks

Drug: Obeticholic acid

Healthy volunteers Placebo

PLACEBO COMPARATOR

Obeticholic acid 25 mg/day matching placebo in three weeks

Drug: Obeticholic acid; Drug: Obeticholic acid placebo

Interventions

Obeticholic acid DRUG

active drug

Also known as: INT-747

Healthy Volunteers OCA; Healthy volunteers Placebo; Morbid Obesity OCA; Morbid Obesity Placebo

Obeticholic acid placebo DRUG

matching placebo

Also known as: INT-747 placebo

Healthy volunteers Placebo; Morbid Obesity Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Morbid obesity awaiting gastric bypass surgery, ≥35 kg/m2
• Male subjects, pre-, and post-menopausal female subjects
• Women of childbearing potential can only be included if a safe and reliable contraception is used, e.g., oral contraceptives
• Patients eligible to laparoscopic bariatric surgery
• Patients must give their signed and dated written consent to participate in this study based on written information of all pertinent aspects of the trial provided at least 24 hours before undertaking any trial related activity.

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.
• Hypothyroidism, unless the subject is clinically euthyroid, receiving a stable dose thyroid hormone replacement therapy and serum TSH is within the normal range.

Sponsors & Collaborators

• Sahlgrenska University Hospital: lead

Study Sites (2)

Hanns-Ulrich Marschall

Gothenburg, 411 31, Sweden

RECRUITING

Sahlgrenska Academy

Gothenburg, Sweden

ENROLLING BY INVITATION

MeSH Terms

Conditions

Obesity

Interventions

obeticholic acid

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Hanns-Ulrich Marschall

  Sahlgrenska University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hanns-Ulrich Marschall, MD, PhD, MSc

CONTACT

+46708774073; hanns-ulrich.marschall@gu.se

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Clinical Hepatology, Sponsor

Study Record Dates

• First Submitted: August 21, 2015
• First Posted: August 25, 2015
• Study Start: August 1, 2015
• Primary Completion: December 1, 2020
• Study Completion: June 1, 2021
• Last Updated: August 25, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

SE (2)