Effects of the activation of PPARs in the orphan hepatic disease primary biliary cirrhosis

• Conditions: p to 67% of PBC patients have an incomplete biochemical response to UDCA and remain at increased risk for progression to cirrhosis and liver-related death. In this study we will prospectively examine the therapeutic effects of bezafibrate (a pan-agonist activating PPARalpha/delta/gamma) in patients with early-stage PBC with a specific focus on improvement of liver functions, inflammation, lipid profile, oxidative status and endothelial function.; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2011-004681-15-AT
• Lead Sponsor: Medizinische Universität Graz

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-10-19
• Last Update Posted: 9 December 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Incomplete responders to standard UDCA therapy (AP > 1.5x ULN after one year)
PBC stage I – II (biopsy proven and/or positive AMA)
Male or female gender
Age 18 – 70 years
Normal kidney function
Signed informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion Criteria

PBC stage III – IV
Age > 70 years
Decompensated liver disease (Child-Pugh class B/C, presence of ascites, esophageal varices)
Cholelithiasis
ALT or AST > 3x ULN
CK > 5x ULN or CK >3x ULN with muscle pain, tenderness or weakness
Pregnancy or breastfeeding
Premenopausal women without certain contraception
Known hypersensitivity to fibrates
Current treatment with lipid-lowering drugs, immunosuppressants, coumarin-based anticoagulants, monoamine oxidase inhibitors

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Our major hypothesis is that the treatment with bezafibrate will improve levels of AP in early-stage PBC patients with an incomplete biochemical response to UCDA through a combination of metabolic and anti-inflammatory effects. ;Secondary Objective: Moreover, we will focus on mechanistic effects on markers of liver function, chronic low-grade inflammation, dyslipidemia, oxidative stress and endothelial function.;Primary end point(s): alkaline phosphatase (AP);Timepoint(s) of evaluation of this end point: Screening (within 4 weeks prior to baseline visit), at weeks 0 (baseline), 4, 8

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Liver enzymes<br>Composition and concentrations of VLDL, IDL, LDL and HDL particles<br>Cholesterol precursors and metabolites<br>Markers of inflammation and oxidative stress<br>Vascular morphology and function;Timepoint(s) of evaluation of this end point: Liver enzymes at screening, at weeks 0, 4, 8<br>Composition and concentrations of VLDL, IDL, LDL and HDL particles at weeks 0, 4, 8<br>Cholesterol precursors and metabolites at weeks 0, 4, 8<br>Markers of inflammation and oxidative stress at weeks 0, 4, 8<br>Vascular morphology and function at weeks 0, 8