Ursodeoxycholic Acid as Treatment for Polycystic Liver Disease (CURSOR)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Radboud University
Sponsor:
Collaborators:
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Donostia University Hospital Spain
Information provided by (Responsible Party):
Radboud University
ClinicalTrials.gov Identifier:
NCT02021110
First received: December 12, 2013
Last updated: December 19, 2013
Last verified: December 2013
  Purpose

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 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 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.

Main secondary outcome variables:

  • To demonstrate whether UDCA-therapy changes absolute total liver volume
  • To demonstrate whether UDCA-therapy changes gastro-intestinal symptoms measured by a GI-questionnaire
  • To demonstrate whether UDCA-therapy changes quality of life as measured by SF-36
  • To demonstrate which proportion of patients has any reduction in total liver volume after 24 weeks
  • To demonstrate whether UDCA is well tolerated
  • To demonstrate whether UDCA-therapy changes absolute total kidney volume (TKV).

Condition Intervention Phase
Polycystic Liver Disease (PLD):
Polycystic Kidney, Autosomal Dominant
Polycystic Liver Disease
Drug: Ursodeoxycholic Acid
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • Effect of UDCA on total liver volume [ Time Frame: Baseline to week 24 ] [ Designated as safety issue: No ]
    Proportional change of total liver volume in UDCA treated patients versus non treated patients, as assessed by CT at baseline andweek 24


Secondary Outcome Measures:
  • Effect of UDCA-therapy on absolute total liver volume [ Time Frame: Baseline to week 24 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Effect of UDCA on health related quality of life as measured by SF-36 [ Time Frame: Baseline to week 24 ] [ Designated as safety issue: No ]
  • Proportion of patients with any reduction in total liver volume after 24 weeks [ Time Frame: Baseline to week 24 ] [ Designated as safety issue: No ]
  • Effect of UDCA on abslute total kidney volume [ Time Frame: Baseline to week 24 ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Adverse events as a measure of tolerability and safety of UDCA [ Time Frame: Baseline to week 24 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 34
Study Start Date: December 2013
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: Ursodeoxycholic Acid
The intervention group will receive 15-20mg/kg/day UDCA for 24 weeks
Other Name: Ursochol

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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-GFR < 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02021110

Contacts
Contact: Hedwig MA D'Agnolo, drs. hedwig.dagnolo@radboudumc.nl

Locations
Netherlands
Radboud University Medical Centre Nijmegen Recruiting
Nijmegen, Gelderland, Netherlands
Contact: Hedwig MA D'Agnolo, dr.    0031 24 3619190    hedwig.dagnolo@radboudumc.nl   
Contact: Joost PH Drenth, drs.    031 24 3619190    joostphdrenth@cs.com   
Principal Investigator: Hedwig MA D'Agnolo, drs.         
Academic Medical Centre Amsterdam Active, not recruiting
Amsterdam, Netherlands
Spain
Donostia University Hospital Not yet recruiting
San Sebastian, Spain
Contact: JM Banales    +34 627401179    JESUS.BANALES@biodonostia.org   
Contact: JI Arenas, MD    +34 943 006067    juanignacio.arenasruiztapiador@osakidetza.net   
Sub-Investigator: L Bujanda, MD, PhD         
Sub-Investigator: Juan I Arenas, MD         
Principal Investigator: JM Banales         
Sponsors and Collaborators
Radboud University
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Donostia University Hospital Spain
Investigators
Principal Investigator: Joost PH Drenth, dr. Radboud University Medical Centre Nijmegen, the Netherlands
  More Information

No publications provided

Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT02021110     History of Changes
Other Study ID Numbers: PLD 11-01
Study First Received: December 12, 2013
Last Updated: December 19, 2013
Health Authority: Netherlands: Medical Ethics Review Committee (METC)

Additional relevant MeSH terms:
Liver Diseases
Polycystic Kidney Diseases
Multicystic Dysplastic Kidney
Polycystic Kidney, Autosomal Dominant
Cysts
Kidney Diseases, Cystic
Kidney Diseases
Urologic Diseases
Urogenital Abnormalities
Congenital Abnormalities
Digestive System Diseases
Neoplasms
Pathological Conditions, Anatomical
Ursodeoxycholic Acid
Cholagogues and Choleretics
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 20, 2014