Clinical trial NCT00707759: Steroid Withdrawal in Pediatric Renal Transplant: Impact on Growth, Bone Metabolism and Acute Rejection
Official title: Multicenter, Open-Label, Randomized Study on Steroid-Free Immunosuppression, in Comparison With Daily Steroid Therapy, in Pediatric Renal Transplant : Impact on Growth, Bone Metabolism and Acute Rejection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Kidney Diseases
Keywords: Pediatric renal transplantation,Bone metabolism (DXA-pQCT)
mRNAFOXP3/IL-17,Steroid withdrawal
Lead sponsor: Fondo Nacional de Desarrollo Científico y Tecnológico, Chile
Sponsor class: OTHER_GOV
First posted: 2008-07-01
Enrollment: 28
Sex: ALL
Minimum age (years): 1
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The present study investigates the safety and efficacy of steroid withdrawal at six days post-transplant in pediatric renal recipients under concomitant immunosuppression based on antibodies anti IL2 (interleukin 2), Tacrolimus (TAC) and Mycophenolate Mofetil (MMF). To investigate the impact of this protocol in growth, bone metabolism, insulin- sensitivity and evaluate the expression of IL17 (interleukin 17) and mRNA FOXP3 (messenger ribonucleic acid forkhead box protein 3) as early markers of acute rejection (blood, urine and renal biopsy).

Hypothesis:Steroid withdrawal in renal pediatric transplant patients improves growth and bone metabolism without increasing the risk of acute rejection. The expression of FoxP3/IL17 in urine cells could be an early molecular markers of acute rejection.

Detailed description: The intention of this investigation is to evaluate a prospective immunosuppressive protocol based on antibodies anti IL-2 (Ac-IL-2), Tacrolimus (TAC) and Mycophenolate Mofetil (MMF)and withdrawal steroids in renal transplant and to compare with a steroid-based protocol.

Objectives:

1. To evaluate growth and the impairment in the GH/IGF (growth hormone/insulin like growth factor) axis
2. To determine the impact of steroids on bone metabolism (biochemical parameters, DXA and pQCT)
3. To determine the steroid effect on metabolic factors (dyslipidemia, insulin- sensitivity and arterial hypertension)
4. To determine acute rejection incidence (protocol renal biopsy)
5. To evaluate the expression of IL-17 and mRNA FoxP3 as early markers of acute rejection (blood, urine and renal biopsy).

Two treatment regimes (Arms)will be compared in randomized form in the course of 12 months after transplantation.

Arm A: TAC + MMF + withdrawal of steroids over a six-days following randomization.

Arm B: TAC + MMF + prednisolone (see schedule)/day

Eligibility criteria: Inclusion Criteria:

* Age \< 16.0 years
* Bone age of boys \< 15 years, of girls \< 13 years
* Prepuberal Tanner Status I
* First or second kidney transplant, living or deceased kidney donation
* Immunosuppression with Tacrolimus (TAC),Mycophenolate mofetil (MMF)
* Patients and parents, respectively, have given their written consent after enlightenment (informed consent)

Exclusion Criteria:

* Irreversible rejection of former transplant
* Highly reactive (\> 30%) lymphocytotoxic antibodies within 12 months prior to transplantation
* Suspected insufficient medication compliance in dialysis
* Patients receiving a basic immunosuppression other than that prescribed in this protocol
* Simultaneous therapy with growth hormone after renal transplant

Primary outcomes:
measure: Stimulation of Growth After 12 Months (Delta Z-score)
timeFrame: 12 months
Secondary outcomes:
measure: Growth-factors (IGF-I, IGFBP-3) Bone Metabolism (FA, Ca/Cru, CaxP, 25(OH)VitD, FGF23, Klotho, PTH, DXA, pQCT) Insulin-sensitivity by ISI Method. Molecular Markers - Acute Rejection (FOXP3/IL-17). Acute Rejection Incidence/Protocol Renal Biopsy
timeFrame: 12 months
Other outcomes:
Locations:
city: Santiago
country: Chile
facility: Calvo Mackenna Children Hospital
state: Metropolitan Region
Study officials:
affiliation: Calvo Mackenna Children´s Hospital-University of Chile
name: Maria Angela Delucchi, MD
role: PRINCIPAL_INVESTIGATOR
References: