Polycystic Liver DiseaseNCT00934791
Polycystic Liver Disease in Kidney Transplant
A study testing Tacrolimus, Sirolimus and Mycophenolate Mofetil in people with Polycystic Liver Disease, run by Mayo Clinic at 1 site in United States.
Trial summary
The purpose of this study is to see if one kind of immunosuppressive drug has better effects for the patient's polycystic liver disease than another type. Tacrolimus and Sirolimus are the two immunosuppressive drugs that will be compared for this study. Both drugs have been commonly prescribed to prevent rejection. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Polycystic Liver Disease
- What is being tested?
- Tacrolimus, Sirolimus and Mycophenolate Mofetil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2009to Dec 2012
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults (> 18 years old) with stage IV or V chronic kidney due to ADPKD
- Primary kidney transplant
- Living or deceased donor kidney transplant
- Estimate total liver volume of 2.5 to 7.5 L
- In addition, at the discretion of the principal investigator(s), certain subjects with numerous liver cysts but with liver volume < 2.5 liters may be enrolled.
Who cannot join
- Pediatric patients (< 18 years of age)
- Patients with Body Mass Index (BMI) greater than or equal to 40 kg/m^2
- Multi-organ transplant (kidney-liver, etc.)
- When people who have one blood type receive blood from someone with a different blood type, it may cause their immune system to react. This is called (ABO) incompatibility. ABO-incompatible or positive cross-match recipients
- Patients with severe hyperlipidemia (serum cholesterol > 350 mg/dl or serum triglycerides > 500 mg/dl)
- Patients with leukopenia (WBC < 3000 10/ml)
Show all 10Show fewer
- Patients unwilling to return to the transplant center for late follow-up visits
- Patients who are currently pregnant or breast-feeding or who expect to be pregnant during the study period
- Female patients of child bearing potential and men with sexual partners of child bearing potential who do not agree to use a medically accepted method of contraception during the study period
- Patients who are not eligible for Thymoglobulin induction
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Single Center, Open-label Randomized Prospective Trial: Effect of Sirolimus on Polycystic Liver Disease
The purpose of this study is to see if one kind of immunosuppressive drug has better effects for the patient's polycystic liver disease than another type. Tacrolimus and Sirolimus are the two immunosuppressive drugs that will be compared for this study. Both drugs have been commonly prescribed to prevent rejection.
Read the detailed description
Autosomal dominant polycystic kidney disease (ADPKD) is a life-threatening monogenic disease with a prevalence of 1 in 400-1000 livebirths. ADPKD is caused by mutations to polycystic kidney disease 1 gene (PKD1) (approximately 85% of cases) or polycystic kidney disease 2 gene (PKD2) (the remaining 15%) gene, encoding polycystin-1 (PC1) and polycystin-2 (PC2), respectively. PC1 is a putative cell-surface, receptor-like protein with yet to-be-identified ligand(s), and PC2 a channel protein with a high conductance to Ca2+.
Polycystic liver disease (PLD) is the most common extra-renal manifestation in ADPKD, present in > 90% of ADPKD patients by age 30. Liver cysts in ADPKD originate from biliary micro-hamartoma or focal proliferations of biliary ductules and from peribiliary glands. Excessive proliferation of biliary epithelial cells, combined with neovascularization, altered cell-extracellular matrix (ECM) interaction/ECM remodeling and cAMP-mediated fluid secretion, is required for the development and expansion of PLD liver cysts.
PLD may become symptomatic with acute complications such as cyst hemorrhage, rupture and infection. Chronic symptoms are frequently associated with massively enlarged PLD, including abdominal distension and pain; dyspnea; gastroesophageal reflux and early satiety which may lead to malnutrition; mechanical lower back pain; obstruction of the inferior vena cava, hepatic and portal veins (leading to dialysis-associated hypotension, hepatic venous outflow obstruction, and portal hypertension) and biliary obstruction. Currently, apart from invasive interventions such as cyst aspiration with sclerosis, cyst fenestration combined hepatic resection and cyst fenestration, liver transplantation and, rarely, selective hepatic artery embolization, no medical therapy is available.
The objective of this study is to conduct a prospective, open-label, randomized trial to examine the effect of sirolimus on total liver volume in kidney transplant recipients with ADPKD.
Four weeks following kidney transplant, subjects will undergo iothalamate clearance measurement, 24-hour urine collection and protein measurement and physical examination by a transplant surgeon. Patients will be randomized to receive either sirolimus-based immunosuppression or to continue tacrolimus-based immunosuppression unless one of the following conditions are noted:
- Complications of the kidney transplant incision, including, but not limited to: superficial wound infection, deep wound infection, and fascial dehiscence
- Iothalamate clearance measurement less than 40 mL/min/1.72m^2
- Urinary protein excretion greater than 800 mg/24 hours. Subjects with the above conditions will continue to receive tacrolimus-based immunosuppression at the discretion of the treating physician/surgeon.
Enrolled subjects will undergo abdominal and pelvic CT scans within 3 months before or after kidney transplantation and at one, two, and three years after kidney transplantation.
- Conditions
- Polycystic Liver Disease
- Being tested
- Tacrolimus, Sirolimus, Mycophenolate Mofetil, Prednisone
- Keywords
- Kidney Transplant, Autosomal dominant polycystic kidney disease, Polycystic liver disease
- 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.
TacrolimusDrug
Also called Prograf
Tacrolimus 6-10 mg/day (maintain trough levels of 8-10 ng/mL)
SirolimusDrug
Also called Rapamune, Rapamycin
Sirolimus 3-5 mg/day (maintain high-performance liquid chromatography (HPLC) blood level 10-15 ng/mL)
Also called Cellcept
Mycophenolate Mofetil 750 mg twice daily
PrednisoneDrug
Also called Deltasone
Prednisone tapered to 5 mg/day by day 92
| Study group | Role | What they receive |
|---|---|---|
| Control Group | Active comparator | Tacrolimus, mycophenolate mofetil, and prednisone Receives: Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Drug: Prednisone |
| Sirolimus Group | Active comparator | Sirolimus, mycophenolate mofetil, and prednisone Receives: Drug: Sirolimus; Drug: Mycophenolate Mofetil; Drug: Prednisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Liver Volume at 2 Years After Kidney Transplantation
Liver volume at 2 years will be compared between the sirolimus and control (tacrolimus) groups using analysis of covariance (ANCOVA).
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2009 (estimated)
- Study startFeb 2009
- Primary completionDec 2012
- Study completionDec 2012
Why it stopped: Terminated due to inadequate enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Polycystic Liver DiseaseStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- Wyeth is now a wholly owned subsidiary of Pfizer
- Responsible party
- Principal investigator, Patrick G. Dean, Mayo Clinic
- Investigators
- Patrick Dean, M.D., Principal investigator, Mayo ClinicQI Qian, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00934791
- Sponsor's protocol ID
- 08-004315
- Status last verified
- Feb 2013
- First submitted
- 6 Jul 2009
- Last updated
- 8 Mar 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single Center, Open-label Randomized Prospective Trial: Effect of Sirolimus on Polycystic Liver Disease
- ClinicalTrials.gov ID
- NCT00934791
- Acronym / sponsor ID
- 08-004315
- Conditions
- Polycystic Liver Disease
- Keywords
- Kidney Transplant, Autosomal dominant polycystic kidney disease, Polycystic liver disease
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated due to inadequate enrollment
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- Wyeth is now a wholly owned subsidiary of Pfizer
- Study start
- Feb 2009
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 8 Jul 2009 (estimated)
- Results
- Posted 8 Mar 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to see if one kind of immunosuppressive drug has better effects for the patient's polycystic liver disease than another type. Tacrolimus and Sirolimus are the two immunosuppressive drugs that will be compared for this study. Both drugs have been commonly prescribed to prevent rejection.
Detailed description
Autosomal dominant polycystic kidney disease (ADPKD) is a life-threatening monogenic disease with a prevalence of 1 in 400-1000 livebirths. ADPKD is caused by mutations to polycystic kidney disease 1 gene (PKD1) (approximately 85% of cases) or polycystic kidney disease 2 gene (PKD2) (the remaining 15%) gene, encoding polycystin-1 (PC1) and polycystin-2 (PC2), respectively. PC1 is a putative cell-surface, receptor-like protein with yet to-be-identified ligand(s), and PC2 a channel protein with a high conductance to Ca2+.
Polycystic liver disease (PLD) is the most common extra-renal manifestation in ADPKD, present in > 90% of ADPKD patients by age 30. Liver cysts in ADPKD originate from biliary micro-hamartoma or focal proliferations of biliary ductules and from peribiliary glands. Excessive proliferation of biliary epithelial cells, combined with neovascularization, altered cell-extracellular matrix (ECM) interaction/ECM remodeling and cAMP-mediated fluid secretion, is required for the development and expansion of PLD liver cysts.
PLD may become symptomatic with acute complications such as cyst hemorrhage, rupture and infection. Chronic symptoms are frequently associated with massively enlarged PLD, including abdominal distension and pain; dyspnea; gastroesophageal reflux and early satiety which may lead to malnutrition; mechanical lower back pain; obstruction of the inferior vena cava, hepatic and portal veins (leading to dialysis-associated hypotension, hepatic venous outflow obstruction, and portal hypertension) and biliary obstruction. Currently, apart from invasive interventions such as cyst aspiration with sclerosis, cyst fenestration combined hepatic resection and cyst fenestration, liver transplantation and, rarely, selective hepatic artery embolization, no medical therapy is available.
The objective of this study is to conduct a prospective, open-label, randomized trial to examine the effect of sirolimus on total liver volume in kidney transplant recipients with ADPKD.
Four weeks following kidney transplant, subjects will undergo iothalamate clearance measurement, 24-hour urine collection and protein measurement and physical examination by a transplant surgeon. Patients will be randomized to receive either sirolimus-based immunosuppression or to continue tacrolimus-based immunosuppression unless one of the following conditions are noted:
- Complications of the kidney transplant incision, including, but not limited to: superficial wound infection, deep wound infection, and fascial dehiscence
- Iothalamate clearance measurement less than 40 mL/min/1.72m^2
- Urinary protein excretion greater than 800 mg/24 hours. Subjects with the above conditions will continue to receive tacrolimus-based immunosuppression at the discretion of the treating physician/surgeon.
Enrolled subjects will undergo abdominal and pelvic CT scans within 3 months before or after kidney transplantation and at one, two, and three years after kidney transplantation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control Group | Active comparator | Drug: Tacrolimus, Drug: Mycophenolate Mofetil, Drug: PrednisoneTacrolimus, mycophenolate mofetil, and prednisone |
| Sirolimus Group | Active comparator | Drug: Sirolimus, Drug: Mycophenolate Mofetil, Drug: PrednisoneSirolimus, mycophenolate mofetil, and prednisone |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adults (> 18 years old) with stage IV or V chronic kidney due to ADPKD
- Primary kidney transplant
- Living or deceased donor kidney transplant
- Estimate total liver volume of 2.5 to 7.5 L
- In addition, at the discretion of the principal investigator(s), certain subjects with numerous liver cysts but with liver volume < 2.5 liters may be enrolled.
Key exclusion criteria (10 listed)
- Pediatric patients (< 18 years of age)
- Patients with Body Mass Index (BMI) greater than or equal to 40 kg/m^2
- Multi-organ transplant (kidney-liver, etc.)
- When people who have one blood type receive blood from someone with a different blood type, it may cause their immune system to react. This is called (ABO) incompatibility. ABO-incompatible or positive cross-match recipients
- Patients with severe hyperlipidemia (serum cholesterol > 350 mg/dl or serum triglycerides > 500 mg/dl)
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 |
|---|---|---|
| TacrolimusAlso: PrografTacrolimus 6-10 mg/day (maintain trough levels of 8-10 ng/mL) | Drug | Control Group |
| SirolimusAlso: Rapamune, RapamycinSirolimus 3-5 mg/day (maintain high-performance liquid chromatography (HPLC) blood level 10-15 ng/mL) | Drug | Sirolimus Group |
| Mycophenolate MofetilAlso: CellceptMycophenolate Mofetil 750 mg twice daily | Drug | Control Group, Sirolimus Group |
| PrednisoneAlso: DeltasonePrednisone tapered to 5 mg/day by day 92 | Drug | Control Group, Sirolimus Group |
Primary outcome
Liver Volume at 2 Years After Kidney Transplantation
Time frame: 2 years
Liver volume at 2 years will be compared between the sirolimus and control (tacrolimus) groups using analysis of covariance (ANCOVA).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Patrick Dean, M.D. principal investigator
Mayo Clinic
QI Qian, MD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Tacrolimus, Sirolimus and Mycophenolate Mofetil in people with Polycystic Liver Disease, run by Mayo Clinic at 1 site in United States.
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 10 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: stopped early, as of the sponsor's last update on 8 Mar 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Mar 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Liver Volume at 2 Years After Kidney Transplantation (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Mar 2013.