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Metabolic Pattern of Cyclosporine A and Acute Renal Failure

This study has been completed.
Sponsor:
Information provided by:
University of Oslo School of Pharmacy
ClinicalTrials.gov Identifier:
NCT00264355
First received: December 9, 2005
Last updated: September 5, 2007
Last verified: September 2007
History of Changes
  Purpose

Following heart transplantation many patients develop acute renal failure in the early posttransplant phase and some are in need of renal replacement therapy for shorter or longer time. The cause of this acute renal failure is most probably multi factorial but many reports indicate that cyclosporine has a central role in the pathophysiology and it is generally recommended to lower the cyclosporine load to patients developing acute renal failure in this population.

Several in vitro studies on renal cells in culture indicate that the primary metabolites of cyclosporine (AM1, AM9, AM4N) are less toxic to the kidney than cyclosporine itself. However, the secondary metabolite AM19 as well as the cyclic metabolites AM1c and AM1c9 has been associated with decreased renal function and nephrotoxicity renal transplant recipients.

The primary objective of this pilot study is to investigate if the concentrations of secondary- and cyclic metabolites of cyclosporine (AM19, AM1c, AM1c9) is related to development of acute renal failure in the early posttransplant phase following heart transplantation.

Secondary objectives are to investigate associations between genotypes of P-glycoprotein and CYP3A5 and the metabolic pattern of cyclosporine.


Condition Intervention Phase
Heart Transplantation
Acute Renal Failure
 Drug: cyclosporine A
 Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Metabolic Pattern of Cyclosporine A - Association of Secondary- and Cyclic Metabolites With Acute Renal Failure in Heart Transplant Recipients

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Oslo School of Pharmacy:

Primary Outcome Measures:
  • The primary analysis of cyclosporine and metabolite concentrations and ratios will be compared between the patients developing acute renal failure and those who do not

Secondary Outcome Measures:
  • Regression analysis comparing concentrations/ratios and actual renal function (continuously parameter)
  • Descriptive listing of cyclosporine and metabolites concentrations in CYP3A5*3/*3 patients compared to the other patients. It is anticipated that an exploratory analysis will be performed to compare the two groups.
  • Descriptive listing of CsA and metabolites concentrations in patients with different combinations of MDR-1 genotypes compared to the other patients. It is anticipated that an exploratory analysis will be performed to compare the two groups.

Estimated Enrollment: 30
Study Start Date: December 2005
Study Completion Date: June 2007
  Eligibility

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

Inclusion Criteria:

  • Heart transplant recipients receiving CsA as part of their immunosuppressive therapy.
  • 18 years of age or older.
  • Signed informed consent.

Exclusion Criteria:

  • None
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00264355

Locations
Norway
Rikshospitalet, Department of Thoracic surgery
Oslo, Norway, Oslo
Sponsors and Collaborators
University of Oslo School of Pharmacy
Investigators
Study Director: Anders Åsberg, Ph.D. University of Oslo School of Pharmacy
Principal Investigator: Arnt Fiane, MD, Ph.D. Rikshospitalet, Department of Thoracic surgery
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00264355     History of Changes
Other Study ID Numbers: HeartTx-ARF
Study First Received: December 9, 2005
Last Updated: September 5, 2007
Health Authority: Norway: Norwegian Medicines Agency

Keywords provided by University of Oslo School of Pharmacy:
cyclosporine
metabolites
metabolic pattern
genotypes

Additional relevant MeSH terms:
Acute Kidney Injury
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Cyclosporins
Cyclosporine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
 Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on May 16, 2013