Polycystic Liver Disease in Kidney Transplant

This study has been terminated.
(Terminated due to inadequate enrollment)
Sponsor:
Collaborator:
Wyeth is now a wholly owned subsidiary of Pfizer
Information provided by (Responsible Party):
Patrick G. Dean, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00934791
First received: July 6, 2009
Last updated: February 4, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention
Polycystic Liver Disease
Drug: Tacrolimus
Drug: Sirolimus
Drug: Mycophenolate Mofetil
Drug: Prednisone

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Single Center, Open-label Randomized Prospective Trial: Effect of Sirolimus on Polycystic Liver Disease

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Liver Volume at 2 Years After Kidney Transplantation [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Liver volume at 2 years will be compared between the sirolimus and control (tacrolimus) groups using analysis of covariance (ANCOVA).


Enrollment: 2
Study Start Date: February 2009
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Prograf
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
Active Comparator: Sirolimus Group
Sirolimus, mycophenolate mofetil, and prednisone
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00934791

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
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
  More Information

No publications provided

Responsible Party: Patrick G. Dean, PI, Mayo Clinic
ClinicalTrials.gov Identifier: NCT00934791     History of Changes
Other Study ID Numbers: 08-004315
Study First Received: July 6, 2009
Results First Received: February 4, 2013
Last Updated: February 4, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Mayo Clinic:
Kidney Transplant
Autosomal dominant polycystic kidney disease
Polycystic liver disease

Additional relevant MeSH terms:
Liver Diseases
Digestive System Diseases
Pathological Conditions, Anatomical
Cysts
Neoplasms
Mycophenolate mofetil
Sirolimus
Everolimus
Tacrolimus
Mycophenolic Acid
Prednisone
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Anti-Inflammatory Agents
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on July 22, 2014