Kidney DiseasesPhase 3NCT00707759
Steroid Withdrawal in Pediatric Renal Transplant: Impact on Growth, Bone Metabolism and Acute Rejection
A Phase 3 study testing Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + Withdrawal Prednisone and Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + prednisolone in people with Kidney Diseases, run by Fondo Nacional de Desarrollo Científico y Tecnológico, Chile at 1 site in Chile.
Trial 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). Read more about this study
- Who is it for?
- Ages 1 year to 16 years
- Conditions the study is for
- Kidney Diseases
- What is being tested?
- Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + Withdrawal Prednisone and Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + prednisolone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteChile
- Study dates
- Jun 2008to Dec 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 16 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this 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
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.
Read the 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 (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
- Conditions
- Kidney Diseases
- Being tested
- Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + Withdrawal Prednisone, Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + prednisolone
- Keywords
- Pediatric renal transplantation,Bone metabolism (DXA-pQCT), mRNAFOXP3/IL-17,Steroid withdrawal
- Medical subject headings
- Kidney Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + Withdrawal PrednisoneDrug
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
Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + prednisoloneDrug
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 group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + Withdrawal 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 Receives: Drug: Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + prednisolone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Stimulation of Growth After 12 Months (Delta Z-score)
Measured: 12 months
Secondary outcomes (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
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2008 (estimated)
- Study startJun 2008
- Primary completionDec 2012
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Kidney DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fondo Nacional de Desarrollo Científico y Tecnológico, Chile
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Maria Angela Delucchi Bicocchi, Fondo Nacional de Desarrollo Científico y Tecnológico, Chile
- Investigators
- Maria Angela Delucchi, MD, Principal investigator, Calvo Mackenna Children´s Hospital-University of Chile
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00707759
- Sponsor's protocol ID
- Fondecyt1080166
- Status last verified
- Oct 2015
- First submitted
- 26 Jun 2008
- Last updated
- 10 Nov 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00707759
- Acronym / sponsor ID
- Fondecyt1080166
- Conditions
- Kidney Diseases
- Keywords
- Pediatric renal transplantation,Bone metabolism (DXA-pQCT), mRNAFOXP3/IL-17,Steroid withdrawal
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Fondo Nacional de Desarrollo Científico y Tecnológico, ChileOther government
- Study start
- Jun 2008
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 1 Jul 2008 (estimated)
- Results
- Posted 10 Nov 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A: withdrawal steroids | Experimental | Drug: Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + Withdrawal PrednisoneArms 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 |
| B | Active comparator | Drug: Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + prednisoloneArms 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 |
Who may qualify
- Ages
- 1 year to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + Withdrawal PrednisoneArms 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 | A: withdrawal steroids |
| Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + prednisoloneArms 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 | Drug | B |
Primary outcome
Stimulation of Growth After 12 Months (Delta Z-score)
Time frame: 12 months
1 secondary outcome
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Nov 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Maria Angela Delucchi, MD principal investigator
Calvo Mackenna Children´s Hospital-University of Chile
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + Withdrawal Prednisone and Tacrolimus (TAC)+ Mycophenolate Mofetil (MMF) + prednisolone in people with Kidney Diseases, run by Fondo Nacional de Desarrollo Científico y Tecnológico, Chile at 1 site in Chile.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Chile. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Nov 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Stimulation of Growth After 12 Months (Delta Z-score) (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Nov 2015.