Metabolic Pattern of Cyclosporine A and Acute Renal Failure

NCT00264355 | Completed Phase 4

• 1 other identifier: HeartTx-ARF
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Heart Transplantation; Acute Renal Failure

Keywords

cyclosporine; metabolites; metabolic pattern; genotypes

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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.

Interventions

cyclosporine A DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• None

Sponsors & Collaborators

• University of Oslo School of Pharmacy: lead

Study Sites (1)

Rikshospitalet, Department of Thoracic surgery

Oslo, Oslo, Norway

Location

MeSH Terms

Conditions

Acute Kidney Injury

Interventions

Cyclosporine

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Anders Åsberg, Ph.D.

  University of Oslo School of Pharmacy

  STUDY DIRECTOR

• Arnt Fiane, MD, Ph.D.

  Rikshospitalet, Department of Thoracic surgery

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 9, 2005
• First Posted: December 12, 2005
• Study Start: December 1, 2005
• Study Completion: June 1, 2007
• Last Updated: September 6, 2007

Record last verified: 2007-09

Locations

NO (1)