Ursodeoxycholic Acid as Treatment for Polycystic Liver Disease (CURSOR)

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

Tracking Information

• First Submitted Date: December 12, 2013
• First Posted Date: December 27, 2013
• Last Update Posted Date: September 23, 2021
• Study Start Date: December 2013
• Actual Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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

Current Secondary Outcome Measures (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 (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: 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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Polycystic Liver Disease
• Polycystic Kidney, Autosomal Dominant

Intervention

Drug: Ursodeoxycholic Acid

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

Other Name: Ursochol

Study Arms

• 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, Riano 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 19, 2013): 34
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: October 2015
• Actual Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)

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 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

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Netherlands, Spain

Administrative Information

• NCT Number: NCT02021110
• Other Study ID Numbers: PLD 11-01
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Radboud University Medical Center
• Original Responsible Party: Same as current
• Current Study Sponsor: Radboud University Medical Center
• Original Study Sponsor: Same as current
• Collaborators: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Investigators

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

• PRS Account: Radboud University Medical Center
• Verification Date: April 2016