An open, non-randomized, parallel-group pharmokinetic and -dynamic, investigator-initiated study on effects of obeticholic acid (OCA) in bile of patients with primary biliary cholangitis (PBC) and non-alcoholic steatohepatitis (NASH) in comparison to healthy controls

Phase 2

Completed

• Conditions: fatty liver disease; non-alcoholic steatohepatitis; Primary biliary cholangitis; 10019654; small bile duct injury

• Registration Number: NL-OMON47216
• Lead Sponsor: Academisch Medisch Centrum

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Last Update Posted: 28 February 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 33

Inclusion Criteria

- Male or female patients / volunteers of 18 to 75 years of age.
- Body mass index within 18 to 40 kg/m2
- Positive AMA (anti-mitochondrial antibody) testing (for PBC patients).
- Proven non-cirrhotic liver disease compatible with PBC stage I, II, III or NASH, no reliable signs of portal hypertension such as esophageal varices or ascites and/or pylephlebectasia > 15 mm, and a fibroscan < 15 kPa.
- The diagnosis of NASH must be confirmed by a liver biopsy (e.g. according Brunt criteria) in the last 24 months

Exclusion Criteria

- Existing cardiac / hematological / renal / gastrointestinal diseases which might interfere with the drugs' safety, tolerability, absorption, pharmacokinetics and / or endoscopy.
- Other acute or chronic diseases which might affect absorption or metabolism of OCA
- Existing disorders of the coagulation system or treatment with anticoagulants or agents inhibiting thrombocyte aggregation
- Positive anti-HIV-test, HBsAg-test or anti-HCV-test.
- Acute inflammation of the gallbladder.
- Cholecystectomy
- Histologically proven cirrhotic liver disease or total bilirubin > 2 mg/dl or reliable signs of portal hypertension such as esophageal varices or ascites and/or pylephlebectasia > 15 mm and / or fibroscan > 15 kPa.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Assess the effect of obeticholic acid (OCA) in patients with PBC [in<br /><br>combination with long-term UDCA treatment (15 mg/kg/d)], patients with NASH and<br /><br>healthy volunteers on the bile acid and lipid composition of bile and serum, </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Assess the effect of obeticholic acid (OCA) in patients with PBC [in<br /><br>combination with long-term UDCA treatment (15 mg/kg/d)], patients with NASH and<br /><br>healthy volunteers on the biliary and serum levels of cytokines (e.g., IL-6,<br /><br>IL-8, TNF*), chemokines and enterohepatic hormones (e.g., FGF-19)<br /><br><br /><br>Assess the effect of obeticholic acid (OCA) in patients with PBC [in<br /><br>combination with long-term UDCA treatment (15 mg/kg/d)], patients with NASH and<br /><br>healthy volunteers on the bile acid composition and microbiome in faeces<br /><br><br /><br>Assess the effect of obeticholic acid (OCA) in patients with PBC [in<br /><br>combination with long-term UDCA treatment (15 mg/kg/d)], patients with NASH and<br /><br>healthy volunteers on the expression of duodenal transport proteins and enzymes<br /><br>contributing to the biliary and intestinal detoxification machinery </p><br>