Ursodeoxycholic Acid as Treatment for Polycystic Liver Disease
Condition: Polycystic Liver Disease; Polycystic Kidney, Autosomal Dominant
MeSH terms: Cysts; Liver Diseases; Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      We investigated whether ursodeoxycholic acid was able to reduce total liver volume in
      polycystic liver disease.
    

Intervention name(s): Ursodeoxycholic Acid
Intervention type(s): Drug
Intervention description(s): The intervention group will receive 15-20mg/kg/day UDCA for 24 weeks
Other intervention name(s): Ursochol
Intervention MeSH terms: Ursodeoxycholic Acid
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment