Kidney TransplantPhase 4RecaltoxNCT00663455
Randomized Study to Reduce Calcineurininhibitor Toxicity in Pediatric and Adolescent Kidney Transplant Recipients
A Phase 4 study testing Reduction of cyclosporine A (CSA)-dosing in people with Kidney Transplant, run by University of Erlangen-Nürnberg Medical School at 10 sites in Germany.
Trial summary
The purpose of this study is to determine if a safe reduction of cyclosporine A in pediatric and adolescent patients with stable renal graft function, reduces signs of calcineurin-inhibitor toxicity. Read more about this study
- Who is it for?
- Ages 3 to 16 years
- Conditions the study is for
- Kidney Transplant
- What is being tested?
- Reduction of cyclosporine A (CSA)-dosing
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 10 sitesGermany
- Study dates
- Dec 2008to Jun 2013
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 3 to 16 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- age at inclusion 3-16 years
- male or female patients
- recipient of first or second renal transplant
- graft age > 24 months
- last acute rejection episode > 6 months ago
- Immune suppression comedication Mycophenolatmofetil (MMF) in a dose range of 1200 +/- 200 mg/m² BSA/d within at least 6 months or minimal MPA-AUC ≥ 45 mg x h/l. If MPA-AUC < 45 mg x h/l adjustment of dosage with re-screening in ≥ 4 weeks is possible.
Show all 10Show fewer
- Application of CSA in stable dosing within the last 3 months before study inclusion and CSA-C2-level > 500 ng/ml. If CSA-C2-level < 500 ng/ml adjustment of dosage with re-screening in ≥ 4 weeks is possible.
- steroid-free immunosuppression for at least 6 months before enrollment
- biopsy of the renal graft without any signs of acute rejection (def. according to BANFF classification), within 3 months before enrollment
- written informed consent of parents/legal guardians and, if applicable, patient's consent
Who cannot join
- glomerular filtration rate < 40 ml/min/1.73 m2 BSA (acc. to Schwartz' formula) at time of enrollment
- > 2 episodes of acute graft rejection within 12 months prior to enrollment
- condition after steroid-resistant graft rejection
- actual participation in another clinical trial
- Recurrence of primary renal disease in the graft
- proven infection with EBV and/ or CMV and antiviral therapy within 3 months prior to enrollment
Show all 12Show fewer
- proven infection with polyoma virus within 3 months prior to enrolment
- pregnant or nursing women
- hemoglobin < 8 g/dl at screening visit
- non-treated arterial hypertension
- uncontrolled infectious disease
- history of malignancy of any organ system, treated or non-treated
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
Germany10 sites
Dept. of Pediatric Nephrology, University Hospital Erlangen
Erlangen
Dept. of Pediatric Nephrology, University Hospital Freiburg
Freiburg im Breisgau
Dept. of Pediatric Nephrology, University Hospital Hamburg
Hamburg
Dept. of Pediatric Nephrology, University Hospital Hannover
Hanover
Dept. of Pediatric Nephrology, University Hospital Heidelberg
Heidelberg
Dept. of Pediatric Nephrology, University Hospital Jena
Jena
Dept. of Pediatric Nephrology, Community Hospital Memmingen
Memmingen
Dept. of Pediatric Nephrology, University Hospital München
Munich
Dept. of Pediatric Nephrology, University Hospital Muenster
Münster
Dept. of Pediatric Nephrology, University Hospital Rostock
Rostock
About this study
Official title: A Multicenter, Randomized, Parallel-group, Trial to Reduce Toxicity of Calcineurininhibitor-therapy in Steroid-free Longterm Immunosuppression in Pediatric and Adolescent Kidney Transplant Recipients
The purpose of this study is to determine if a safe reduction of cyclosporine A in pediatric and adolescent patients with stable renal graft function, reduces signs of calcineurin-inhibitor toxicity.
Read the detailed description
Chronic transplant nephropathy is one of the major causes of graft loss after renal transplantation. Toxicity of calcineurin-inhibitors is suspected to be one cause for loss of graft function. Therefore reduction of cyclosporine A dosing can result in longer graft survival and better graft function in patients after renal-transplantation. However, reduction of immunosuppression can result in acute rejection episodes, although it is less likely in patients with stable graft function 12 months or longer after successful renal transplantation.
Therefore the aim of this randomized, controlled study in pediatric and adolescent renal transplant recipients, is to compare the impact of reduced cyclosporine A-dosing to standard CSA-dosing on renal graft function. Therapy monitoring in both groups will be performed by obtaining CSA blood levels two hours after intake, as they provide an individual insight in pharmacokinetics in comparison to conventional trough level (C0)-measurements.
Secondary objectives to evaluate are
- the evaluation of the health-related Quality of life and psychosocial burden in the two treatment arms.
- measurement of the NFAT-regulated gene expression (nuclear factor of activated t-cells) of intracellular cytokines [Interleukin-2, TNF-alpha, Interferon-gamma and GMCSF) by quantitative PCR as measurement of CSA activity.
- To obtain new insights by screening for metabolites conjunct with clinic features of nephrotoxicity or graft rejections a metabolomic screening and a targeted analysis (trimethylamine-N-oxide, neopterin and kynurenine/tryptophan ratio) will be performed.
- Conditions
- Kidney Transplant
- Being tested
- Reduction of cyclosporine A (CSA)-dosing
- Keywords
- kidney transplant recipients, children and adolescents with kidney transplants
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Reduction of cyclosporine A (CSA)-dosingDrug
Reduction of CSA-dosing over 4 months. Therapy control by safety parameters (serum creatinine, C2-monitoring, renal biopsy).
| Study group | Role | What they receive |
|---|---|---|
| A | Other | Reduction of CSA-dosing over 4 months. Therapy control by safety parameters (serum creatinine, C2-monitoring, renal biopsy). Receives: Drug: Reduction of cyclosporine A (CSA)-dosing |
| B | No intervention | Standard CSA-dosing without reduction. Therapy control by C2-monitoring. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean decline per month in glomerular filtration rate (calculated acc. to Schwartz' formula) during the clinical trial - comparison between the two study arms (CSA-dose reduction group and group with constant CSA-dosing)
Measured: 24 months
Secondary outcomes (2)
Evaluation of the NFAT-regulated gene expression (nuclear factor of activated t-cells) of intracellular cytokines [Interleukin-2, TNF-alpha, Interferon-gamma and GMCSF) by quantitative PCR as measurement of CSA activity
Measured: 24 months
Health-related Quality of life evaluation using validated questionnaires (TACQoL) to determine differences between the two study arms
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2008 (estimated)
- Study startDec 2008
- Primary completionDec 2012
- Study completionJun 2013
Why it stopped: Recruitment goals were not achieved. Extension of the trial concept had to be abjected due to methodological reasons.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney TransplantStudies of the same condition, open and under way.
- More trials run by University of Erlangen-Nürnberg Medical SchoolThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Erlangen-Nürnberg Medical School
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jörg Dötsch, MD, Principal investigator, Dept. of Pediatric Nephrology, University Hospital Erlangen, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00663455
- Sponsor's protocol ID
- Recaltox-1
- Acronym
- Recaltox
- Status last verified
- Jun 2015
- First submitted
- 21 Apr 2008
- Last updated
- 4 Jun 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Parallel-group, Trial to Reduce Toxicity of Calcineurininhibitor-therapy in Steroid-free Longterm Immunosuppression in Pediatric and Adolescent Kidney Transplant Recipients
- ClinicalTrials.gov ID
- NCT00663455
- Acronym / sponsor ID
- Recaltox / Recaltox-1
- Conditions
- Kidney Transplant
- Keywords
- kidney transplant recipients, children and adolescents with kidney transplants
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Recruitment goals were not achieved. Extension of the trial concept had to be abjected due to methodological reasons.
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University of Erlangen-Nürnberg Medical SchoolUniversity, hospital or other
- Study start
- Dec 2008
- Primary completion
- Dec 2012 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 22 Apr 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine if a safe reduction of cyclosporine A in pediatric and adolescent patients with stable renal graft function, reduces signs of calcineurin-inhibitor toxicity.
Detailed description
Chronic transplant nephropathy is one of the major causes of graft loss after renal transplantation. Toxicity of calcineurin-inhibitors is suspected to be one cause for loss of graft function. Therefore reduction of cyclosporine A dosing can result in longer graft survival and better graft function in patients after renal-transplantation. However, reduction of immunosuppression can result in acute rejection episodes, although it is less likely in patients with stable graft function 12 months or longer after successful renal transplantation.
Therefore the aim of this randomized, controlled study in pediatric and adolescent renal transplant recipients, is to compare the impact of reduced cyclosporine A-dosing to standard CSA-dosing on renal graft function. Therapy monitoring in both groups will be performed by obtaining CSA blood levels two hours after intake, as they provide an individual insight in pharmacokinetics in comparison to conventional trough level (C0)-measurements.
Secondary objectives to evaluate are
- the evaluation of the health-related Quality of life and psychosocial burden in the two treatment arms.
- measurement of the NFAT-regulated gene expression (nuclear factor of activated t-cells) of intracellular cytokines [Interleukin-2, TNF-alpha, Interferon-gamma and GMCSF) by quantitative PCR as measurement of CSA activity.
- To obtain new insights by screening for metabolites conjunct with clinic features of nephrotoxicity or graft rejections a metabolomic screening and a targeted analysis (trimethylamine-N-oxide, neopterin and kynurenine/tryptophan ratio) will be performed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Other | Drug: Reduction of cyclosporine A (CSA)-dosingReduction of CSA-dosing over 4 months. Therapy control by safety parameters (serum creatinine, C2-monitoring, renal biopsy). |
| B | No intervention | –Standard CSA-dosing without reduction. Therapy control by C2-monitoring. |
Who may qualify
- Ages
- 3 to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (10 listed)
- age at inclusion 3-16 years
- male or female patients
- recipient of first or second renal transplant
- graft age > 24 months
- last acute rejection episode > 6 months ago
Key exclusion criteria (12 listed)
- glomerular filtration rate < 40 ml/min/1.73 m2 BSA (acc. to Schwartz' formula) at time of enrollment
- > 2 episodes of acute graft rejection within 12 months prior to enrollment
- condition after steroid-resistant graft rejection
- actual participation in another clinical trial
- Recurrence of primary renal disease in the graft
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 |
|---|---|---|
| Reduction of cyclosporine A (CSA)-dosingReduction of CSA-dosing over 4 months. Therapy control by safety parameters (serum creatinine, C2-monitoring, renal biopsy). | Drug | A |
Primary outcome
Mean decline per month in glomerular filtration rate (calculated acc. to Schwartz' formula) during the clinical trial - comparison between the two study arms (CSA-dose reduction group and group with constant CSA-dosing)
Time frame: 24 months
2 secondary outcomes
Evaluation of the NFAT-regulated gene expression (nuclear factor of activated t-cells) of intracellular cytokines [Interleukin-2, TNF-alpha, Interferon-gamma and GMCSF) by quantitative PCR as measurement of CSA activity
Time frame: 24 months
Health-related Quality of life evaluation using validated questionnaires (TACQoL) to determine differences between the two study arms
Time frame: 24 months
Results and safety
The study was stopped early (reason given: Recruitment goals were not achieved. Extension of the trial concept had to be abjected due to methodological reasons.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2015.
Related trials for Kidney Transplant
Enrolling by invitation
Online Exercise Program for Transplant Patients: A Pilot Study
Kidney Transplantation, Physical Function
RecruitingPhase 2
A Study of Mezagitamab in Adults With Late Antibody-Mediated Rejection (AMR) After a Kidney Transplant
Antibody-Mediated Rejection (AMR)
Not yet recruiting
Hypothermic Kidney Machine Perfusion With Omnisol
End Stage Renal Disease (ESRD), Kidney Transplant
Not yet recruitingEarly Phase 1
Biomarker-Guided Mycophenolate Mofetil Elimination in Low-Risk Older Adult Kidney Transplant Recipients
Kidney Transplant Recipient
Recruiting
Non-Invasive Monitoring of Pediatric Kidney Transplant Recipients and Immunosuppression Personalization: an Open-labeled Multicenter Randomized Controlled Study
Pediatric Kidney Disease, Transplant;Failure,Kidney
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.
Jörg Dötsch, MD principal investigator
Dept. of Pediatric Nephrology, University Hospital Erlangen, Germany
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Reduction of cyclosporine A (CSA)-dosing in people with Kidney Transplant, run by University of Erlangen-Nürnberg Medical School at 10 sites in Germany.
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 10 inclusion and 12 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: stopped early, as of the sponsor's last update on 4 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Germany. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Recruitment goals were not achieved. Extension of the trial concept had to be abjected due to methodological reasons.). Results are not available in the source record.
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?
Mean decline per month in glomerular filtration rate (calculated acc. to Schwartz' formula) during the clinical trial - comparison between the two study arms (CSA-dose reduction group and group with constant CSA-dosing) (time frame: 24 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 4 Jun 2015.