Ursodeoxycholic Acid as Treatment for Polycystic Liver Disease

Brief Title

Ursodeoxycholic Acid as Treatment for Polycystic Liver Disease

Official Title

An International, Multicenter, Randomized Controlled Clinical Trial Assessing the Efficacy of Ursodeoxycholic Acid as a Volume Reducing Treatment in Symptomatic Polycystic Liver Disease

Brief 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.

Study Phase

Phase 2

Study Type


Primary Outcome

Effect of UDCA on total liver volume

Secondary Outcome

 Effect of UDCA-therapy on absolute total liver volume


Polycystic Liver Disease


Ursodeoxycholic Acid

Study Arms / Comparison Groups

 Control group
Description:  This group will receive standard care (no treatment)


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

December 2013

Completion Date

October 2015

Primary Completion Date

October 2015

Eligibility Criteria

        Inclusion Criteria:

          -  18 ≤ age ≤ 80 years

          -  Polycystic liver disease with underlying diagnosis of (PCLD or ADPKD), defined as ≥ 20
             liver cysts

          -  Total liver volume ≥ 2500 mL

          -  Symptomatic defined as ECOG-PS ≥ 1 (2), and having at least three out of ten PCLD

          -  Informed consent, patients are willing and able to comply with the study drug regimen
             and all other study requirements.

        Exclusion Criteria:

          -  Use of oral anticonceptives or estrogen supplementation

          -  Use of UDCA in 3 months before baseline

          -  Females who are pregnant or breast-feeding or patients of reproductive potential not
             employing an effective method of birth control.

          -  Intervention (aspiration or surgical intervention) within six months before baseline

          -  Treatment with somatostatin analogues within six months before baseline

          -  Renal dysfunction (MDRD-Glomerular filtration rate< 30 ml/min/1.73m2)

          -  Patients with a kidney transplant

          -  Hypersensitivity reaction to UDCA or patients with galactose-intolerance, lactase
             deficiency or glucose-galactose malabsorption

          -  Acute cholecystitis or frequent biliary colic attacks

          -  Acute stomach or duodenal ulcers

          -  Inflammation of small intestine or colon

          -  Use of drugs that can interact with UDCA, such as colestyramine, aluminium hydroxide
             or cyclosporin

          -  Enrolment in another clinical trial of an investigational agent while participating in
             this study

          -  History or other evidence of severe illness or any other conditions which would make
             the patient, in the opinion of the investigator, unsuitable for the study

          -  Mental illness that interferes with the patient ability to comply with the protocol




18 Years - 80 Years

Accepts Healthy Volunteers



Joost PH Drenth, dr., , 

Location Countries


Location Countries


Administrative Informations



Organization ID

PLD 11-01

Responsible Party


Study Sponsor

Radboud University Medical Center


 Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Study Sponsor

Joost PH Drenth, dr., Principal Investigator, Radboud University Medical Centre Nijmegen, the Netherlands

Verification Date

April 2016