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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

Tracking Information
First Submitted Date  ICMJE June 26, 2008
First Posted Date  ICMJE July 1, 2008
Results First Submitted Date  ICMJE October 13, 2015
Results First Posted Date  ICMJE November 10, 2015
Last Update Posted Date November 10, 2015
Study Start Date  ICMJE June 2008
Actual Primary Completion Date December 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 13, 2015)
Stimulation of Growth After 12 Months (Delta Z-score) [ Time Frame: 12 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: June 27, 2008)
Stimulation of growth after 12 months [ Time Frame: 12 months ]
Change History Complete list of historical versions of study NCT00707759 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 13, 2015)
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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 27, 2008)
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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Steroid Withdrawal in Pediatric Renal Transplant: Impact on Growth, Bone Metabolism and Acute Rejection
Official Title  ICMJE 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
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

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

Study Arms  ICMJE
  • 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
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 13, 2015)
28
Original Estimated Enrollment  ICMJE
 (submitted: June 27, 2008)
70
Actual Study Completion Date  ICMJE December 2014
Actual Primary Completion Date December 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 16 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Chile
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00707759
Other Study ID Numbers  ICMJE Fondecyt1080166
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Maria Angela Delucchi Bicocchi, Fondo Nacional de Desarrollo Científico y Tecnológico, Chile
Study Sponsor  ICMJE Fondo Nacional de Desarrollo Científico y Tecnológico, Chile
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Maria Angela Delucchi, MD Calvo Mackenna Children´s Hospital-University of Chile
PRS Account Fondo Nacional de Desarrollo Científico y Tecnológico, Chile
Verification Date October 2015

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