Ursodeoxycholic Acid as Treatment for Polycystic Liver Disease (CURSOR)

Radboud University Medical Center

Status and phase

Completed

Phase 2

Conditions

Polycystic Liver Disease

Polycystic Kidney, Autosomal Dominant

Treatments

Drug: Ursodeoxycholic Acid

Study type

Interventional

Funder types

Other

Identifiers

NCT02021110

PLD 11-01

Details and patient eligibility

About

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.

Full description

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

Enrollment

34 patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

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