Steroid Withdrawal in Pediatric Renal Transplant: Impact on Growth, Bone Metabolism and Acute Rejection
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| ClinicalTrials.gov Identifier: NCT00707759 |
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Recruitment Status :
Completed
First Posted : July 1, 2008
Results First Posted : November 10, 2015
Last Update Posted : November 10, 2015
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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 |
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 (growth hormone/insulin like growth factor) axis
- To determine the impact of steroids on bone metabolism (biochemical parameters, 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
| 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 |
| Arm | Intervention/treatment |
|---|---|
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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 |
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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 |
- Stimulation of Growth After 12 Months (Delta Z-score) [ Time Frame: 12 months ]
- 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 ]
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| Ages Eligible for Study: | 1 Year to 16 Years (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
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
| Chile | |
| Calvo Mackenna Children Hospital | |
| Santiago, Metropolitan Region, Chile | |
| 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:
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Pediatric renal transplantation,Bone metabolism (DXA-pQCT) mRNAFOXP3/IL-17,Steroid withdrawal |
Additional relevant MeSH terms:
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Kidney Diseases Urologic Diseases Prednisone Prednisolone Methylprednisolone Acetate Methylprednisolone Methylprednisolone Hemisuccinate Prednisolone acetate 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 |