Steroid Withdrawal in Pediatric Renal Transplant Immunosuppression : Impact on Growth, Bone Metabolism and Acute Rejection - Full Text View

Sponsored by:	Fondo Nacional de Desarrollo Científico y Tecnológico, Chile
Information provided by:	Fondo Nacional de Desarrollo Científico y Tecnológico, Chile
ClinicalTrials.gov Identifier:	NCT00707759

Purpose

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 IL-2 (Ac-IL-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 IL-17 and mRNA FOXP3 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 MNSP and urine cells could be an early molecular markers of acute rejection.

Condition	Intervention	Phase
Kidney Diseases	Drug: Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + Withdrawal Prednisone Drug: Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + prednisolone	Phase III

MedlinePlus related topics: Kidney Transplantation

Drug Information available for: Prednisolone 6-Methylprednisolone Depo-medrol Medrol veriderm Methylprednisolone Methylprednisolone hemisuccinate Methylprednisolone Sodium Succinate Prednisolone acetate Prednisolone sodium phosphate Prednisolone Sodium Succinate Prednisone Tacrolimus Mycophenolate Mofetil Mycophenolate mofetil hydrochloride Tacrolimus anhydrous

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
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

Further study details as provided by Fondo Nacional de Desarrollo Científico y Tecnológico, Chile:

Primary Outcome Measures:

Stimulation of growth after 12 months [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	70
Study Start Date:	June 2008
Estimated Study Completion Date:	December 2011
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: withdrawal steroids: Experimental 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	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
B: Active Comparator 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	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

Arms

Assigned Interventions

A: withdrawal steroids: Experimental

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

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

B: Active Comparator

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

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

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:

To evaluate growth and the impairment in the GH/IGF axis
To determine the impact of steroids on bone metabolism (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.

Arm B: TAC + MMF + prednisolone (see schedule)/day

Eligibility

Ages Eligible for Study:	1 Year to 16 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age < 16.0 years
Bone age of boys < 15 years, of girls < 13 years
First or second kidney transplant, living or cadaver 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00707759

Contacts

Contact: Angela Delucchi, MD	56-2-2351189	angeladelucchi@vtr.net
Contact: Francisco Cano, MD	56-2-2361592	fcano@med.uchile.cl

Locations

Chile, Metropolitan Region
Calvo Mackenna Children Hospital	Recruiting
Santiago, Metropolitan Region, Chile
Contact: Angela Delucchi, MD 56-2-2351189 angeladelucchi@vtr.net
Contact: Francisco Cano, MD 56-2-2361592 fcano@med.uchile.cl
Principal Investigator: Angela Delucchi, MD
Sub-Investigator: Loreto Reyes, MD
Sub-Investigator: Veronica Mericq, MD
Sub-Investigator: Francisco Cano, MD

Sponsors and Collaborators

Fondo Nacional de Desarrollo Científico y Tecnológico, Chile

Investigators

Principal Investigator:

Angela Delucchi, MD

Calvo Mackenna Children´s Hospital-University of Chile

More Information

Steroid Project Web Page This link exits the ClinicalTrials.gov site

Responsible Party:	University of Chile ( Maria Angela Delucchi Bicocchi )
Study ID Numbers:	Fondecyt1080166
Study First Received:	June 26, 2008
Last Updated:	January 5, 2009
ClinicalTrials.gov Identifier:	NCT00707759
Health Authority:	Chile: Comisión Nacional de Investigación Científica y Tecnológica

Keywords provided by Fondo Nacional de Desarrollo Científico y Tecnológico, Chile:

Pediatric renal transplantation,Bone metabolism (DXA-pQCT)
mRNAFOXP3/IL-17,Steroid withdrawal

Study placed in the following topic categories:

Prednisone
Urologic Diseases
Methylprednisolone
Prednisolone
Mycophenolic Acid
Mycophenolate mofetil

Methylprednisolone acetate
Prednisolone acetate
Tacrolimus
Kidney Diseases
Methylprednisolone Hemisuccinate

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Enzyme Inhibitors
Antibiotics, Antineoplastic

Immunosuppressive Agents
Protective Agents
Neuroprotective Agents
Glucocorticoids
Hormones
Pharmacologic Actions
Autonomic Agents
Therapeutic Uses
Peripheral Nervous System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 16, 2009