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

• Register: EUCTR
• Last refreshed on: 9 December 2013
• Main ID: EUCTR2011-004681-15-AT
• Date of registration: 19/10/2011
• Prospective Registration: Yes
• Primary sponsor: Medizinische Universität Graz
• Public title: Effects of the activation of PPARs in the orphan hepatic disease primary biliary cirrhosis
• Scientific title: Effects of the activation of peroxisome proliferator-activated receptors in patients with primary biliary cirrhosis - Effects of the activation of PPARs in patients with PBC
• Date of first enrolment: 09/11/2011
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-004681-15
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Austria

Contacts

• Name: MUG
• Affiliation: Medical University of Graz

• Name: MUG
• Affiliation: Medical University of Graz

Key inclusion & exclusion 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:
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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

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.

Intervention(s)

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
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 400-

Product Name: Ursodeoxycholsäure
Pharmaceutical Form: Capsule
CAS Number: 128-13-2
Other descriptive name: URSODEOXYCHOLIC ACID
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-

Primary Outcome(s)

Secondary Objective: Moreover, we will focus on mechanistic effects on markers of liver function, chronic low-grade inflammation, dyslipidemia, oxidative stress and endothelial function.

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.

Timepoint(s) of evaluation of this end point: Screening (within 4 weeks prior to baseline visit), at weeks 0 (baseline), 4, 8

Primary end point(s): alkaline phosphatase (AP)

Secondary Outcome(s)

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

Secondary ID(s)

KIMCL_TS_2011-09

Source(s) of Monetary Support

Medical University of Graz, Clinical Institute of Medical and Chemical Laboratory Diagnostics