Metabolic Pattern of Cyclosporine A and Acute Renal Failure

Sponsor

University of Oslo School of Pharmacy (Other)

Overall Status

Completed

CT.gov ID

NCT00264355

Collaborator

(none)

Enrollment

Location

Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Heart Transplantation Acute Renal Failure	Drug: cyclosporine A	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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

Study Start Date :

Dec 1, 2005

Actual Study Completion Date :

Jun 1, 2007

Outcome Measures

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. []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	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