ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
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

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.


Condition or disease Intervention/treatment Phase
Kidney Diseases Drug: Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + Withdrawal Prednisone Drug: Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + prednisolone Phase 3

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 : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : June 2008
Actual Primary Completion Date : December 2012
Actual Study Completion Date : December 2014

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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

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


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

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





Primary Outcome Measures :
  1. Stimulation of Growth After 12 Months (Delta Z-score) [ Time Frame: 12 months ]

Secondary Outcome Measures :
  1. 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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   1 Year to 16 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00707759


Locations
Chile
Calvo Mackenna Children Hospital
Santiago, Metropolitan Region, Chile
Sponsors and Collaborators
Fondo Nacional de Desarrollo Científico y Tecnológico, Chile
Investigators
Principal Investigator: Maria Angela Delucchi, MD Calvo Mackenna Children´s Hospital-University of Chile

Responsible Party: Maria Angela Delucchi Bicocchi, Physician, Fondo Nacional de Desarrollo Científico y Tecnológico, Chile
ClinicalTrials.gov Identifier: NCT00707759     History of Changes
Other Study ID Numbers: Fondecyt1080166
First Posted: July 1, 2008    Key Record Dates
Results First Posted: November 10, 2015
Last Update Posted: November 10, 2015
Last Verified: October 2015

Keywords provided by Maria Angela Delucchi Bicocchi, Fondo Nacional de Desarrollo Científico y Tecnológico, Chile:
Pediatric renal transplantation,Bone metabolism (DXA-pQCT)
mRNAFOXP3/IL-17,Steroid withdrawal

Additional relevant MeSH terms:
Kidney Diseases
Urologic Diseases
Prednisolone acetate
Methylprednisolone acetate
Prednisone
Prednisolone
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone hemisuccinate
Prednisolone phosphate
Mycophenolic Acid
Tacrolimus
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antiemetics