NCT00663455

Randomized Study to Reduce Calcineurininhibitor Toxicity in Pediatric and Adolescent Kidney Transplant Recipients

A Multicenter, Randomized, Parallel-group, Trial to Reduce Toxicity of Calcineurininhibitor-therapy in Steroid-free Longterm Immunosuppression in Pediatric and Adolescent Kidney Transplant Recipients

• Status: Terminated
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 50 (actual)
• Sponsor: University of Erlangen-Nürnberg Medical School · Academic / Other
• Sex: All
• Age: 3 Years – 16 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine if a safe reduction of cyclosporine A in pediatric and adolescent patients with stable renal graft function, reduces signs of calcineurin-inhibitor toxicity.

Detailed description

Chronic transplant nephropathy is one of the major causes of graft loss after renal transplantation. Toxicity of calcineurin-inhibitors is suspected to be one cause for loss of graft function. Therefore reduction of cyclosporine A dosing can result in longer graft survival and better graft function in patients after renal-transplantation. However, reduction of immunosuppression can result in acute rejection episodes, although it is less likely in patients with stable graft function 12 months or longer after successful renal transplantation. Therefore the aim of this randomized, controlled study in pediatric and adolescent renal transplant recipients, is to compare the impact of reduced cyclosporine A-dosing to standard CSA-dosing on renal graft function. Therapy monitoring in both groups will be performed by obtaining CSA blood levels two hours after intake, as they provide an individual insight in pharmacokinetics in comparison to conventional trough level (C0)-measurements. Secondary objectives to evaluate are 1. the evaluation of the health-related Quality of life and psychosocial burden in the two treatment arms. 2. measurement of the NFAT-regulated gene expression (nuclear factor of activated t-cells) of intracellular cytokines \[Interleukin-2, TNF-alpha, Interferon-gamma and GMCSF) by quantitative PCR as measurement of CSA activity. 3. To obtain new insights by screening for metabolites conjunct with clinic features of nephrotoxicity or graft rejections a metabolomic screening and a targeted analysis (trimethylamine-N-oxide, neopterin and kynurenine/tryptophan ratio) will be performed.

Conditions

• Kidney Transplant

Interventions

Type	Name	Description
DRUG	Reduction of cyclosporine A (CSA)-dosing	Reduction of CSA-dosing over 4 months. Therapy control by safety parameters (serum creatinine, C2-monitoring, renal biopsy).

Timeline

• Start date: 2008-12-01
• Primary completion: 2012-12-01
• Completion: 2013-06-01
• First posted: 2008-04-22
• Last updated: 2015-06-04

Locations

10 sites across 1 country: Germany