Steroid Withdrawal in Pediatric Renal Transplant: Impact on Growth, Bone Metabolism and Acute Rejection

Kidney Diseases Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00707759
• Other study ID #: Fondecyt1080166
• Status: Completed
• Phase: Phase 3
• First received: June 26, 2008
• Last updated: October 13, 2015
• Start date: June 2008
• Est. completion date: December 2014

Study information

• Verified date: October 2015
• Source: Fondo Nacional de Desarrollo Científico y Tecnológico, Chile
• Contact: n/a
• Is FDA regulated: No
• Health authority: Chile: Comisión Nacional de Investigación Científica y Tecnológica
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: December 2014
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 16 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Kidney Diseases

Intervention

Drug:
• Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + Withdrawal Prednisone
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
• Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + prednisolone
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

Locations

Country	Name	City	State
Chile	Calvo Mackenna Children Hospital	Santiago	Metropolitan Region

Sponsors (1)

Lead Sponsor	Collaborator
Fondo Nacional de Desarrollo Científico y Tecnológico, Chile

Country where clinical trial is conducted

Chile, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Stimulation of Growth After 12 Months (Delta Z-score)		12 months	Yes
Secondary	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	Yes