NCT01655563

Pharmacogenetic Trial of Tacrolimus After Pediatric Transplantation

A Pharmacogenetic Trial of Tacrolimus Dosing After Pediatric Transplantation

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 75 (actual)
• Sponsor: The Hospital for Sick Children · Academic / Other
• Sex: All
• Age: 1 Day – 18 Years
• Healthy volunteers: Not accepted

Summary

Tacrolimus is a standard and widely used maintenance immunosuppressive agent after solid organ transplantation.The purpose of this trial is to determine if dosing of tacrolimus through genetics will help in early attainment and maintenance of the correct dosage level in the early post-transplant period. This pilot dose-finding trial will help to determine a dosing strategy guided by genotypes and age for solid organ transplant recipients that will be further validated through a multi-centre trial as an immediate next step. The study hypothesizes that dosage levels determined through age and genotype will be attained faster and more accurately than the standard dosing procedures in the 14-days after the transplant. Further, this study hypothesizes that a genotype and age dosing strategy will cause a faster recovery (tested through the kidneys' ability to clear creatine from the blood) and result in lower frequencies of adverse effects and rejection of the transplant.

Conditions

• Heart Transplantation
• Liver Transplantation
• Kidney Transplantation

Interventions

Type	Name	Description
DRUG	Tacrolimus	Tacrolimus, a calcineurin inhibitor, is the commonest immunosuppressive agent used for maintenance immunosuppression after solid organ transplantation. The mechanism of action involves binding to an intracellular protein, FKBP-12. A complex of tacrolimus-FKBP-12, calcium, calmodulin and calcineurin is then formed and the phosphatase activity of calcineurin is inhibited. This prevents the generation of nuclear factor of activated T-cells, a nuclear component, resulting in inhibition of transcription of lymphokines (interleukin-2, γ-interferon). The net result is the inhibition of T-lymphocyte activation.Tacrolimus is metabolized primarily by the CYP3A enzymes in the liver particularly the CYP3A5.

Timeline

• Start date: 2011-09-01
• Primary completion: 2016-02-01
• Completion: 2016-02-01
• First posted: 2012-08-02
• Last updated: 2019-12-13
• Results posted: 2019-08-28

Locations

1 site across 1 country: Canada