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

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ClinicalTrials.gov Identifier: NCT00707759
Recruitment Status : Completed
First Posted : July 1, 2008
Results First Posted : November 10, 2015
Last Update Posted : November 10, 2015
Sponsor:
Information provided by (Responsible Party):
Maria Angela Delucchi Bicocchi, Fondo Nacional de Desarrollo Científico y Tecnológico, Chile

June 26, 2008
July 1, 2008
October 13, 2015
November 10, 2015
November 10, 2015
June 2008
December 2012   (Final data collection date for primary outcome measure)
Stimulation of Growth After 12 Months (Delta Z-score) [ Time Frame: 12 months ]
Stimulation of growth after 12 months [ Time Frame: 12 months ]
Complete list of historical versions of study NCT00707759 on ClinicalTrials.gov Archive Site
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 [ Time Frame: 12 months ]
Growth-factors by IGF-I, IGFBP-3 plasma levels Bone metabolism (FA, Ca/Cru, CaxP, 25(OH)VitD, PTH,DXA, pQCT Insulin-sensitivity by ISI method. Molecular markers - acute rejection (FOXP3/IL-17). Acute rejection incidence/protocol renal biopsy [ Time Frame: 12 months ]
Not Provided
Not Provided
 
Steroid Withdrawal in Pediatric Renal Transplant: Impact on Growth, Bone Metabolism and Acute Rejection
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

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.

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

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Kidney Diseases
  • 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

  • Drug: 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

  • Experimental: 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

    Intervention: Drug: Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + Withdrawal Prednisone
  • Active Comparator: 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

    Intervention: Drug: Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + prednisolone
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
28
70
December 2014
December 2012   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
1 Year to 16 Years   (Child)
No
Contact information is only displayed when the study is recruiting subjects
Chile
 
 
NCT00707759
Fondecyt1080166
Yes
Not Provided
Not Provided
Maria Angela Delucchi Bicocchi, Fondo Nacional de Desarrollo Científico y Tecnológico, Chile
Fondo Nacional de Desarrollo Científico y Tecnológico, Chile
Not Provided
Principal Investigator: Maria Angela Delucchi, MD Calvo Mackenna Children´s Hospital-University of Chile
Fondo Nacional de Desarrollo Científico y Tecnológico, Chile
October 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP