Polycystic Liver Disease in Kidney Transplant

February 4, 2013 updated by: Patrick G. Dean, Mayo Clinic

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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:

  1. Complications of the kidney transplant incision, including, but not limited to: superficial wound infection, deep wound infection, and fascial dehiscence
  2. Iothalamate clearance measurement less than 40 mL/min/1.72m^2
  3. 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 Type

Interventional

Enrollment (Actual)

2

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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)
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Control Group
Tacrolimus, mycophenolate mofetil, and prednisone
Drug: Tacrolimus
Tacrolimus 6-10 mg/day (maintain trough levels of 8-10 ng/mL)
Other Names:
  • Prograf
Drug: Mycophenolate Mofetil
Mycophenolate Mofetil 750 mg twice daily
Other Names:
  • Cellcept
Drug: Prednisone
Prednisone tapered to 5 mg/day by day 92
Other Names:
  • Deltasone
Active Comparator: Sirolimus Group
Sirolimus, mycophenolate mofetil, and prednisone
Drug: Mycophenolate Mofetil
Mycophenolate Mofetil 750 mg twice daily
Other Names:
  • Cellcept
Drug: Prednisone
Prednisone tapered to 5 mg/day by day 92
Other Names:
  • Deltasone
Drug: Sirolimus
Sirolimus 3-5 mg/day (maintain high-performance liquid chromatography (HPLC) blood level 10-15 ng/mL)
Other Names:
  • Rapamycin
  • Rapamune

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mayo Clinic

Collaborators

Wyeth is now a wholly owned subsidiary of Pfizer

Investigators

  • Principal Investigator: Patrick Dean, M.D., Mayo Clinic
  • Principal Investigator: Qi Qian, MD, Mayo Clinic

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2009

Primary Completion (Actual)

December 1, 2012

Study Completion (Actual)

December 1, 2012

Study Registration Dates

First Submitted

July 6, 2009

First Submitted That Met QC Criteria

July 7, 2009

First Posted (Estimate)

July 8, 2009

Study Record Updates

Last Update Posted (Estimate)

March 8, 2013

Last Update Submitted That Met QC Criteria

February 4, 2013

Last Verified

February 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 08-004315

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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