Up 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.
Conditions
Interventions
Trade Name: Bezafibrat "Genericon" retard 400 mg
Product Name: Bezafibrat
Product Code: 1-20190
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: BEZAFIBRATE
CAS Number: 41859-67-0
Concentr
Sponsors
Medizinische Universität Graz
Eligibility
Sex/Gender
All
Inclusion criteria
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
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| Secondary end point(s): Liver enzymes Composition and concentrations of VLDL, IDL, LDL and HDL particles Cholesterol precursors and metabolites Markers of inflammation and oxidative stress Vascular morphology and function;Timepoint(s) of evaluation of this end point: Liver enzymes at screening, at weeks 0, 4, 8 Composition and concentrations of VLDL, IDL, LDL and HDL particles at weeks 0, 4, 8 Cholesterol precursors and metabolites at weeks 0, 4, 8 Markers of inflammation and oxidative stress at weeks 0, 4, 8 Vascular morphology and function at weeks 0, 8 | — |
Countries
Austria
Contacts
Public ContactMUG
Medical University of Graz
Outcome results
None listed