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

NCT ID: NCT00663455

Last Updated: 2015-06-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-31
• Study Completion Date: 2013-06-30

Brief 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A

Reduction of CSA-dosing over 4 months. Therapy control by safety parameters (serum creatinine, C2-monitoring, renal biopsy).

Group Type: OTHER

Reduction of cyclosporine A (CSA)-dosing

Intervention Type: DRUG

Reduction of CSA-dosing over 4 months. Therapy control by safety parameters (serum creatinine, C2-monitoring, renal biopsy).

B

Standard CSA-dosing without reduction. Therapy control by C2-monitoring.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Reduction of cyclosporine A (CSA)-dosing

Reduction of CSA-dosing over 4 months. Therapy control by safety parameters (serum creatinine, C2-monitoring, renal biopsy).

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Erlangen-Nürnberg Medical School

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jörg Dötsch, MD

Role: PRINCIPAL_INVESTIGATOR

Dept. of Pediatric Nephrology, University Hospital Erlangen, Germany

Locations

Dept. of Pediatric Nephrology, University Hospital Erlangen

Erlangen, , Germany

Dept. of Pediatric Nephrology, University Hospital Freiburg

Freiburg im Breisgau, , Germany

Dept. of Pediatric Nephrology, University Hospital Hamburg

Hamburg, , Germany

Dept. of Pediatric Nephrology, University Hospital Hannover

Hanover, , 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 München

Munich, , Germany

Dept. of Pediatric Nephrology, University Hospital Muenster

Münster, , Germany

Dept. of Pediatric Nephrology, University Hospital Rostock

Rostock, , Germany

Countries

Germany

Other Identifiers

Recaltox-1

Identifier Type: -

Identifier Source: org_study_id