First, to demonstrate whether UDCA-therapy is effective in reducing total liver volume in PLD patients. Second, we want to assess if UDCA modifies quality of life. Finally, we want to assess safety and tolerability.
ID
Source
Brief title
Condition
- Hepatic and biliary neoplasms benign
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Proportional change of total liver volume in UDCA treated patients versus non
treated patients, as assessed by CT at baseline and 6 months.
Secondary outcome
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).
Background summary
Polycystic liver disease (PLD) is a rare disorder characterized by >20
fluid-filled hepatic cysts. (1) 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. We 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.
We hypothesize that UDCA is an effective therapeutic tool in reducing liver
volume in PLD.
Study objective
First, to demonstrate whether UDCA-therapy is effective in reducing total liver
volume in PLD patients. Second, we want to assess if UDCA modifies quality of
life. Finally, we want to assess safety and tolerability.
Study design
International, multicenter, randomized, controlled trial
Intervention
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.
Study burden and risks
When compared to routine clinical care the burden and risk associated with
participation
are:
• In general PLD patients suffering from isolated liver cysts visit an
out-patient department about 1-2 times a year. PLD patients suffering
ADPKD with more advanced renal disease (eGFR <= 60 ml/min/1.73 m2 ) visit an
out-patient department once every 3 months routinely. Therefore this study
imposes at least 6 extra visits to an outpatient department (screening,
baseline, week 4, 12, 24 and 36)
• For patients that are treated outside the participating UMC hospitals, study
visits to the UMCs may lead to extra travel time.
• At screening, baseline and week 24, three blood samples will be drawn. During
visit week 4, 12 and 36, two blood samples will be drawn.
• Two times a CT-scan of liver and kidneys
• Two times two questionnaires need to be completed
• Half of the patients will be exposed to the UDCA-therapy
The potential benefit for participating subjects is that UDCA-therapy may
reduce total liver volume and thereby potentially leading to less complaints
that are related to cyst size and abdominal distension (e.g. abdominal pain,
early satiety and dyspnea).
Geert Grooteplein-Zuid 8
Nijmegen 6525GA
NL
Geert Grooteplein-Zuid 8
Nijmegen 6525GA
NL
Listed location countries
Age
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:
- Abdominal pain
- Abdominal distension
- Abdominal fullness
- Dyspnea
- Early satiety
- Back pain
- Nausea/vomiting
- Anorexia
- Weight loss
- Jaundice
• 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 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 or aluminium hydroxide
• 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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-003207-19-NL |
| CCMO | NL45792.091.13 |