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Trial record 1 of 1 for:    NCT00934791
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Polycystic Liver Disease in Kidney Transplant

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00934791
Recruitment Status : Terminated (Terminated due to inadequate enrollment)
First Posted : July 8, 2009
Results First Posted : March 8, 2013
Last Update Posted : March 8, 2013
Wyeth is now a wholly owned subsidiary of Pfizer
Information provided by (Responsible Party):
Patrick G. Dean, Mayo Clinic

Tracking Information
First Submitted Date  ICMJE July 6, 2009
First Posted Date  ICMJE July 8, 2009
Results First Submitted Date  ICMJE February 4, 2013
Results First Posted Date  ICMJE March 8, 2013
Last Update Posted Date March 8, 2013
Study Start Date  ICMJE February 2009
Actual Primary Completion Date December 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 4, 2013)
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).
Original Primary Outcome Measures  ICMJE
 (submitted: July 7, 2009)
To examine the changes in native liver volume at year 1, 2, and 3 after kidney transplantation. [ Time Frame: 3 years ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: July 7, 2009)
To examine the changes in native kidney volumes and to examine additional safety data (serum lipid profile and blood counts) in ADPKD patients population. [ Time Frame: 3 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Polycystic Liver Disease in Kidney Transplant
Official Title  ICMJE Single Center, Open-label Randomized Prospective Trial: Effect of Sirolimus on Polycystic Liver Disease
Brief 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.
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  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Polycystic Liver Disease
Intervention  ICMJE
  • Drug: Tacrolimus
    Tacrolimus 6-10 mg/day (maintain trough levels of 8-10 ng/mL)
    Other Name: Prograf
  • Drug: Sirolimus
    Sirolimus 3-5 mg/day (maintain high-performance liquid chromatography (HPLC) blood level 10-15 ng/mL)
    Other Names:
    • Rapamune
    • Rapamycin
  • Drug: Mycophenolate Mofetil
    Mycophenolate Mofetil 750 mg twice daily
    Other Name: Cellcept
  • Drug: Prednisone
    Prednisone tapered to 5 mg/day by day 92
    Other Name: Deltasone
Study Arms  ICMJE
  • Active Comparator: Control Group
    Tacrolimus, mycophenolate mofetil, and prednisone
    • Drug: Tacrolimus
    • Drug: Mycophenolate Mofetil
    • Drug: Prednisone
  • Active Comparator: Sirolimus Group
    Sirolimus, mycophenolate mofetil, and prednisone
    • Drug: Sirolimus
    • Drug: Mycophenolate Mofetil
    • Drug: Prednisone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: January 9, 2013)
Original Estimated Enrollment  ICMJE
 (submitted: July 7, 2009)
Actual Study Completion Date  ICMJE December 2012
Actual Primary Completion Date December 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00934791
Other Study ID Numbers  ICMJE 08-004315
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Patrick G. Dean, Mayo Clinic
Study Sponsor  ICMJE Mayo Clinic
Collaborators  ICMJE Wyeth is now a wholly owned subsidiary of Pfizer
Investigators  ICMJE
Principal Investigator: Patrick Dean, M.D. Mayo Clinic
Principal Investigator: QI Qian, MD Mayo Clinic
PRS Account Mayo Clinic
Verification Date February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP