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

Kidney Transplant Clinical Trial

— Recaltox  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00663455
• Other study ID #: Recaltox-1
• Status: Terminated
• Phase: Phase 4
• First received: April 21, 2008
• Last updated: June 3, 2015
• Start date: December 2008
• Est. completion date: June 2013

Study information

• Verified date: June 2015
• Source: University of Erlangen-Nürnberg Medical School
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 50
• Est. completion date: June 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Years to 16 Years

Eligibility

Inclusion Criteria:

• age at inclusion 3-16 years

• male or female patients

• recipient of first or second renal transplant

• graft age > 24 months

• last acute rejection episode > 6 months ago

• Immune suppression comedication Mycophenolatmofetil (MMF) in a dose range of 1200 +/- 200 mg/m² BSA/d within at least 6 months or minimal MPA-AUC = 45 mg x h/l. If MPA-AUC < 45 mg x h/l adjustment of dosage with re-screening in = 4 weeks is possible.

• Application of CSA in stable dosing within the last 3 months before study inclusion and CSA-C2-level > 500 ng/ml. If CSA-C2-level < 500 ng/ml adjustment of dosage with re-screening in = 4 weeks is possible.

• steroid-free immunosuppression for at least 6 months before enrollment

• biopsy of the renal graft without any signs of acute rejection (def. according to BANFF classification), within 3 months before enrollment

• written informed consent of parents/legal guardians and, if applicable, patient's consent

Exclusion Criteria:

• glomerular filtration rate < 40 ml/min/1.73 m2 BSA (acc. to Schwartz' formula) at time of enrollment

• > 2 episodes of acute graft rejection within 12 months prior to enrollment

• condition after steroid-resistant graft rejection

• actual participation in another clinical trial

• Recurrence of primary renal disease in the graft

• proven infection with EBV and/ or CMV and antiviral therapy within 3 months prior to enrollment

• proven infection with polyoma virus within 3 months prior to enrolment

• pregnant or nursing women

• hemoglobin < 8 g/dl at screening visit

• non-treated arterial hypertension

• uncontrolled infectious disease

• history of malignancy of any organ system, treated or non-treated

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Kidney Transplant

Intervention

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).

Locations

Country	Name	City	State
Germany	Dept. of Pediatric Nephrology, University Hospital Erlangen	Erlangen
Germany	Dept. of Pediatric Nephrology, University Hospital Freiburg	Freiburg
Germany	Dept. of Pediatric Nephrology, University Hospital Hamburg	Hamburg
Germany	Dept. of Pediatric Nephrology, University Hospital Hannover	Hannover
Germany	Dept. of Pediatric Nephrology, University Hospital Heidelberg	Heidelberg
Germany	Dept. of Pediatric Nephrology, University Hospital Jena	Jena
Germany	Dept. of Pediatric Nephrology, Community Hospital Memmingen	Memmingen
Germany	Dept. of Pediatric Nephrology, University Hospital Muenster	Muenster
Germany	Dept. of Pediatric Nephrology, University Hospital München	Munich
Germany	Dept. of Pediatric Nephrology, University Hospital Rostock	Rostock

Sponsors (1)

Lead Sponsor	Collaborator
University of Erlangen-Nürnberg Medical School

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean decline per month in glomerular filtration rate (calculated acc. to Schwartz' formula) during the clinical trial - comparison between the two study arms (CSA-dose reduction group and group with constant CSA-dosing)		24 months	Yes
Secondary	Evaluation 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		24 months	Yes
Secondary	Health-related Quality of life evaluation using validated questionnaires (TACQoL) to determine differences between the two study arms		24 months	No