Ursodeoxycholic Acid as Treatment for Polycystic Liver Disease
Status:
Completed
Trial end date:
2015-10-01
Target enrollment:
Participant gender:
Summary
Rationale: Polycystic liver disease (PLD) is a rare disorder characterized by >20
fluid-filled hepatic cysts. Polycystic livers are present in the combination with renal cysts
as a manifestation of autosomal dominant polycystic kidney disease (ADPKD), or isolated in
the absence of renal cysts as autosomal dominant polycystic liver disease (ADPLD or PCLD).
PLD patients are confronted with symptoms caused by the mass effect of their polycystic liver
every day for the rest of their life. There is no standard therapeutic option for symptomatic
PLD patients. Current options are fairly invasive or their efficacy is only moderate.
Preliminary data in our research lab have shown that ursodeoxycholic acid (UDCA) inhibited
the proliferation of polycystic human cholangiocytes in vitro through the normalization of
the intracellular calcium levels in cystic cholangiocytes. The investigators also found that
daily oral administration of UDCA for 5 months to polycystic kidney disease (PCK) rats, an
animal model of ARPKD that spontaneously develops hepato-renal cystogenesis, resulted in
inhibition of hepatic cystogenesis.
The investigators hypothesize that UDCA is an effective therapeutic tool in reducing liver
volume in PLD.
Objective: First, to demonstrate whether UDCA-therapy is effective in reducing total liver
volume in PLD patients. Second, the investigators want to assess if UDCA modifies quality of
life. Finally, the investigators want to assess safety and tolerability.
Study design: International, multicenter, randomized, controlled trial Study population: 34
subjects (18 ≤age ≤ 80 years) suffering from symptomatic polycystic liver disease with
underlying diagnosis of (PCLD or ADPKD), defined as ≥ 20 liver cysts on CT-scan and liver
volume of ≥ 2500. Symptomatic is defined as Eastern Cooperative Oncology Group- Performance
Score (ECOG-PS) ≥ 1 and having at least three out of ten PLD symptoms.
Intervention: The patients will be randomized (1:1) into two groups. One group of patients
will receive 15-20mg/kg/day UDCA for 24 weeks. The other group will receive standard care.
Main study endpoint: Proportional change of total liver volume in UDCA treated patients
versus non treated patients, as assessed by CT at baseline and 6 months.
Phase:
Phase 2
Details
Lead Sponsor:
Radboud University
Collaborators:
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) Biodonostia Health Research Institute