Clinical trial NCT00707759
Conditions: Kidney Diseases
Keywords: Pediatric renal transplantation,Bone metabolism (DXA-pQCT) mRNAFOXP3/IL-17,Steroid withdrawal
Sponsor: Fondo Nacional de Desarrollo Científico y Tecnológico, Chile
Start date: 2008-06-01; Completion date: 2014-12-01
Enrollment: 28 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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

Arms: arm 1: Arms A: TAC + MMF + withdrawal steroids over a six-days following randomization.

1°day: Methylprednisolone iv, 2-3 mg/kg/d 3 doses

2ºday: Methylprednisolone iv, 2-3 mg/kg/d 3 doses

3°day: Prednisone 2 mg/kg/d in 2 doses

4ºday: Prednisone 1 mg/kg/d in 2 doses

5ºday: Prednisone 0.5 mg/kg/d in 2 doses

6ºday: Prednisone 0.25 mg/kg/d in 2 doses

7ºday: Stop Prednisone arm 2: Arms B: TAC + MMF + prednisolone (see schedule)/day

10°days after Tx: 2 mg/kg/d

Day 11 - 20: 1 mg/kg/d

Day 21 - 30: 0.5 mg/kg/d

Day 31 - 60: 0.3 mg/k/d

Week 8 - 12: 0.25 mg/k/d

Week 12 - 16: 0.20 mg/k/d

Week 16 - 20: 0.15 mg/k/d

Month 6 - 12: 0.10 - 0.12 mg/k/d
Interventions: intervention 1: Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + Withdrawal Prednisone intervention 2: Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + prednisolone
Intervention descriptions: intervention 1: Arms A: Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + withdrawal steroids over a six-days following randomization.

1°day: Methylprednisolone iv, 2-3 mg/kg/d 3 doses

2ºday: Methylprednisolone iv, 2-3 mg/kg/d 3 doses

3°day: Prednisone 2 mg/kg/d in 2 doses

4ºday: Prednisone 1 mg/kg/d in 2 doses

5ºday: Prednisone 0.5 mg/kg/d in 2 doses

6ºday: Prednisone 0.25 mg/kg/d in 2 doses

7ºday: Stop Prednisone intervention 2: Arms B: Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + prednisolone (see schedule)/day

10°days after Tx: 2 mg/kg/d

Day 11 - 20: 1 mg/kg/d

Day 21 - 30: 0.5 mg/kg/d

Day 31 - 60: 0.3 mg/k/d

Week 8 - 12: 0.25 mg/k/d

Week 12 - 16: 0.20 mg/k/d

Week 16 - 20: 0.15 mg/k/d

Month 6 - 12: 0.10 - 0.12 mg/k/d

Protocol documents: