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Ursodeoxycholic Acid as Treatment for Polycystic Liver Disease (CURSOR)

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ClinicalTrials.gov Identifier: NCT02021110
Recruitment Status : Completed
First Posted : December 27, 2013
Last Update Posted : September 23, 2021
Sponsor:
Collaborator:
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Information provided by (Responsible Party):
Radboud University

Tracking Information
First Submitted Date  ICMJE December 12, 2013
First Posted Date  ICMJE December 27, 2013
Last Update Posted Date September 23, 2021
Study Start Date  ICMJE December 2013
Actual Primary Completion Date October 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 16, 2021)
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
Original Primary Outcome Measures  ICMJE
 (submitted: December 19, 2013)
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 andweek 24
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 16, 2021)
  • 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
  • Effect of UDCA on gastro-intestinal symptoms measured by a GI-questionnaire [ Time Frame: Baseline to week 24 ]
    Improvement in Gastrointestinal Symptom score
  • 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
  • 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
  • Effect of UDCA on absolute total kidney volume [ Time Frame: Baseline to week 24 ]
    Change in total kidney volume after 24 weeks
Original Secondary Outcome Measures  ICMJE
 (submitted: December 19, 2013)
  • Effect of UDCA-therapy on absolute total liver volume [ Time Frame: Baseline to week 24 ]
    Absolute TLV at baseline and end of treatment (week 24) will be measured
  • Effect of UDCA on gastro-intestinal symptoms measured by a GI-questionnaire [ Time Frame: Baseline to week 24 ]
  • Effect of UDCA on health related quality of life as measured by SF-36 [ Time Frame: Baseline to week 24 ]
  • Proportion of patients with any reduction in total liver volume after 24 weeks [ Time Frame: Baseline to week 24 ]
  • Effect of UDCA on abslute total kidney volume [ Time Frame: Baseline to week 24 ]
Current Other Pre-specified Outcome Measures
 (submitted: September 16, 2021)
Adverse events as a measure of tolerability and safety of UDCA [ Time Frame: Baseline to week 24 ]
All adverse events
Original Other Pre-specified Outcome Measures
 (submitted: December 19, 2013)
Adverse events as a measure of tolerability and safety of UDCA [ Time Frame: Baseline to week 24 ]
 
Descriptive Information
Brief Title  ICMJE Ursodeoxycholic Acid as Treatment for Polycystic Liver Disease
Official Title  ICMJE 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Polycystic Liver Disease
  • Polycystic Kidney, Autosomal Dominant
Intervention  ICMJE Drug: Ursodeoxycholic Acid
The intervention group will receive 15-20mg/kg/day UDCA for 24 weeks
Other Name: Ursochol
Study Arms  ICMJE
  • No Intervention: Control group
    This group will receive standard care (no treatment)
  • Experimental: Ursodeoxycholic Acid
    The intervention group will receive 15-20mg/kg/day UDCA for 24 weeks
    Intervention: Drug: Ursodeoxycholic Acid
Publications * D'Agnolo HM, Kievit W, Takkenberg RB, Riaño I, Bujanda L, Neijenhuis MK, Brunenberg EJ, Beuers U, Banales JM, Drenth JP. Ursodeoxycholic acid in advanced polycystic liver disease: A phase 2 multicenter randomized controlled trial. J Hepatol. 2016 Sep;65(3):601-7. doi: 10.1016/j.jhep.2016.05.009. Epub 2016 May 17.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 19, 2013)
34
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE October 2015
Actual Primary Completion Date October 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands,   Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02021110
Other Study ID Numbers  ICMJE PLD 11-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Radboud University
Study Sponsor  ICMJE Radboud University
Collaborators  ICMJE Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Investigators  ICMJE
Principal Investigator: Joost PH Drenth, dr. Radboud University Medical Centre Nijmegen, the Netherlands
PRS Account Radboud University
Verification Date April 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP