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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Stimulation of Growth After 12 Months (Delta Z-score)
研究概览
简要总结
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.
详细描述
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:
- To evaluate growth and the impairment in the GH/IGF (growth hormone/insulin like growth factor) axis
- To determine the impact of steroids on bone metabolism (biochemical parameters, DXA and pQCT)
- To determine the steroid effect on metabolic factors (dyslipidemia, insulin- sensitivity and arterial hypertension)
- To determine acute rejection incidence (protocol renal biopsy)
- 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 16 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
A: withdrawal steroids
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
干预措施: Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + Withdrawal Prednisone (Drug)
B
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
干预措施: Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + prednisolone (Drug)
结局指标
主要结局
Stimulation of Growth After 12 Months (Delta Z-score)
时间窗: 12 months
次要结局
- 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(12 months)
研究者
Maria Angela Delucchi Bicocchi
Physician
Fondo Nacional de Desarrollo Científico y Tecnológico, Chile