Skip to main content
OpenTrials
Completed

NCT Number: NCT02021110

Ursodeoxycholic Acid as Treatment for Polycystic Liver Disease

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Polycystic Liver Disease Abnormalities, Multiple Ciliopathies Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genetic Diseases, Inborn Kidney Diseases Kidney Diseases, Cystic Male Urogenital Diseases Polycystic Kidney Diseases Polycystic Kidney, Autosomal Dominant Urogenital Diseases Urologic Diseases

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Radboud University Medical Centre Nijmegen, Nijmegen, Gelderland, Netherlands

Loading trial locations.

About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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 symptoms:
  • 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

Treatment and study plan

Ursodeoxycholic acid

Drug

The intervention group will receive 15-20mg/kg/day UDCA for 24 weeks

Other names: Ursochol

Primary outcomes

  1. Effect of UDCA on total liver volume

    Time frame: Baseline to week 24

    Proportional change of total liver volume in UDCA treated patients versus non treated patients, as assessed by CT at baseline and week 24

Secondary outcomes

  1. Effect of UDCA-therapy on absolute total liver volume

    Time frame: Baseline to week 24

    Absolute total liver volume at baseline and end of treatment (week 24) will be measured

  2. Effect of UDCA on gastro-intestinal symptoms measured by a GI-questionnaire

    Time frame: Baseline to week 24

    Improvement in Gastrointestinal Symptom score

  3. Effect of UDCA on health related quality of life as measured by Study Form -36

    Time frame: Baseline to week 24

    Improvement in Study Form -36 score

  4. Proportion of patients with any reduction in total liver volume after 24 weeks

    Time frame: Baseline to week 24

    Proportion reduction in total liver volume

  5. Effect of UDCA on absolute total kidney volume

    Time frame: Baseline to week 24

    Change in total kidney volume after 24 weeks

Other outcomes

  1. Adverse events as a measure of tolerability and safety of UDCA

    Time frame: Baseline to week 24

    All adverse events

Sponsors and collaborators

Lead sponsor

Radboud University Medical Center

Other

Collaborators

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

Registry information

Official study title

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

Acronym: CURSOR

Important dates

Study start
2013
Primary completion
2015
Study completion
2015
First posted
Dec 27, 2013
Registry last updated
Sep 23, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.