Polycystic Liver DiseasePhase 2CURSORNCT02021110
Ursodeoxycholic Acid as Treatment for Polycystic Liver Disease
A Phase 2 study testing Ursodeoxycholic Acid in people with Polycystic Liver Disease and Polycystic Kidney, Autosomal Dominant, run by Radboud University Medical Center at 3 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Polycystic Liver Disease, Polycystic Kidney, Autosomal Dominant
- What is being tested?
- Ursodeoxycholic Acid
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 3 sitesin 2 countries
- Study dates
- Dec 2013to Oct 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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)
Show all 15Show fewer
- 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
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
Netherlands2 sites
Academic Medical Centre Amsterdam
Amsterdam
Radboud University Medical Centre Nijmegen
Nijmegen, Gelderland
About this study
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
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.
Read more
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.
Read the detailed description
We investigated whether ursodeoxycholic acid was able to reduce total liver volume in polycystic liver disease.
- Being tested
- Ursodeoxycholic Acid
- Medical subject headings
- Polycystic liver disease, Polycystic Kidney, Autosomal Dominant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ursodeoxycholic AcidDrug
Also called Ursochol
The intervention group will receive 15-20mg/kg/day UDCA for 24 weeks
| Study group | Role | What they receive |
|---|---|---|
| Control group | No intervention | This group will receive standard care (no treatment) |
| Ursodeoxycholic Acid | Experimental | The intervention group will receive 15-20mg/kg/day UDCA for 24 weeks Receives: Drug: Ursodeoxycholic Acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effect of UDCA on total liver volume
Proportional change of total liver volume in UDCA treated patients versus non treated patients, as assessed by CT at baseline and week 24
Measured: Baseline to week 24
Secondary outcomes (5)
Effect of UDCA-therapy on absolute total liver volume
Absolute total liver volume at baseline and end of treatment (week 24) will be measured
Measured: Baseline to week 24
Effect of UDCA on gastro-intestinal symptoms measured by a GI-questionnaire
Improvement in Gastrointestinal Symptom score
Measured: Baseline to week 24
Effect of UDCA on health related quality of life as measured by Study Form -36
Improvement in Study Form -36 score
Measured: Baseline to week 24
Proportion of patients with any reduction in total liver volume after 24 weeks
Proportion reduction in total liver volume
Measured: Baseline to week 24
Effect of UDCA on absolute total kidney volume
Change in total kidney volume after 24 weeks
Measured: Baseline to week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Dec 2013 (estimated)
- Study startDec 2013
- Primary completionOct 2015
- Study completionOct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Polycystic Liver DiseaseStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Joost PH Drenth, dr., Principal investigator, Radboud University Medical Centre Nijmegen, the Netherlands
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02021110
- Sponsor's protocol ID
- PLD 11-01
- Acronym
- CURSOR
- Status last verified
- Apr 2016
- First submitted
- 12 Dec 2013
- Last updated
- 23 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 27212247
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02021110
- Acronym / sponsor ID
- CURSOR / PLD 11-01
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Study start
- Dec 2013
- Primary completion
- Oct 2015 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 27 Dec 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control group | No intervention | –This group will receive standard care (no treatment) |
| Ursodeoxycholic Acid | Experimental | Drug: Ursodeoxycholic AcidThe intervention group will receive 15-20mg/kg/day UDCA for 24 weeks |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ursodeoxycholic AcidAlso: UrsocholThe intervention group will receive 15-20mg/kg/day UDCA for 24 weeks | Drug | Ursodeoxycholic Acid |
Primary outcome
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
5 secondary outcomes
Effect of UDCA-therapy on absolute total liver volume
Time frame: Baseline to week 24
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 Study Form -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 absolute total kidney volume
Time frame: Baseline to week 24
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2021.
- Derived from this study: PubMed 27212247D'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.
Related trials for Polycystic Liver Disease
RecruitingObservational study
Longitudinal Study of Ultra-rare Inherited Metabolic and Degenerative Neurological Diseases.
Inherited Disease, Rare Diseases
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
Not yet recruitingObservational study
Chinese Overweight/Obesity Cohort: Metabolic & Comorbidity Risks
Obesity & Overweight, Diabetes Mellitus, Type 2
Not yet recruitingObservational study
Biomarker Panel for PCOS-Associated Liver Steatosis in Adolescent Girls (COMPASS-pedPCOS)
Polycystic Ovary Syndrome (PCOS), Metabolic Dysfunction-Associated Steatotic Liver Disease
Active, not recruitingPhase 2/3
A Trial to Assess the Efficacy and Safety of Octreotide Subcutaneous Depot in Patients With PLD
Polycystic Liver Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joost PH Drenth, dr. principal investigator
Radboud University Medical Centre Nijmegen, the Netherlands
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ursodeoxycholic Acid in people with Polycystic Liver Disease and Polycystic Kidney, Autosomal Dominant, run by Radboud University Medical Center at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Netherlands, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effect of UDCA on total liver volume (time frame: Baseline to week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02021110, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2021.