Renal Transplant RejectionPhase 4NCT01413685
Calcineurin Activity in Renal Recipients
A Phase 4 study testing Pharmacokinetics/dynamics in people with Renal Transplant Rejection, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
The purpose is to define if calcineurin activity is a better biological parameter than blood concentration for the therapeutic tacrolimus monitoring. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Transplant Rejection
- What is being tested?
- Pharmacokinetics/dynamics
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteFrance
- Study dates
- Jan 2009to Jul 2010
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- adult renal transplant recipients
- treated by tacrolimus (Prograf or ADVAGRAF), corticoids, Cellcept,
Who cannot join
- patients with a high risk of bad compliance (toxicomania, severe psychiatric troubles)
- multiorgan transplant patients with mTOR inhibitors treatments
- HIV infected patients
- lack of consent for this study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Interest of Calcineurin Activity for the Therapeutic Tacrolimus Monitoring in Renal Recipients
The purpose is to define if calcineurin activity is a better biological parameter than blood concentration for the therapeutic tacrolimus monitoring.
Read the detailed description
Some authors showed that the determination of calcineurin (enzyme of cyclosporin and tacrolimus action) activity was very interesting in bone narrow and hepatic transplant in order to monitor tacrolimus or cyclosporin. Indeed, Furthermore, target Tac concentrations still fail to provide in certain patients an appropriate immunosuppression reflected by rejection. Because a lack of data in renal transplant, we propose to study this population treated by tacrolimus, mycophenolate mofetil and corticoids in the first three months following the transplantation.
Our major aim is to study the relationship between calcineurin activity and immunologic events in 200 renal recipients treated with tacrolimus in the first three months following transplant. Immunologic events could be acute rejections and infraclinical rejections. The second aims are 1) if this relationship exists, to define the threshold predicting acute rejection using ROC-curve, 2) to define variations between pharmacodynamic (calcineurin activity) and pharmacokinetic (whole blood concentrations) tacrolimus monitoring and 3) to compare calcineurin activity in patients with acute rejection and those with borderline rejection. Blood samples will be collected into EDTA-containing vacutainers prior to the tacrolimus morning administration and at 2, 4, 6 and 9 hours following the administration at D7, D14 and D21. Whole blood tacrolimus concentrations and calcineurin activity were measured using LCMSMS and HPLC techniques. After D21, only residual measurements will be carried out at D28, M2 and M3. A comparative statistical analysis will be performed between data defined with and without rejection. In case of difference, a ROC curve analysis could define normal ranges of calcineurin activity.
This is the second study of the Sud FRANCILIEN Institute for Research in Nephrology-Transplantation defined with Nephrology departments in Mondor and BICETRE hospitals and the object "Interest of pharmacodynamics of immunosuppressive drugs in renal-transplant recipients" is a new theme of these teams.
- Conditions
- Renal Transplant Rejection
- Being tested
- Pharmacokinetics/dynamics
- Keywords
- tacrolimus, calcineurin, pharmacodynamic, TDM, pharmacokinetics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pharmacokinetics/dynamicsOther
Determination of tacrolimus concentrations in whole blood and of calcineurin activities in lymphocytes at D8, D15, D21 (pharmacokinetics on 4 times samples), D28, M2 and M3 (residual measurement)
| Study group | Role | What they receive |
|---|---|---|
| Tacrolimus | No intervention | Determination of tacrolimus concentrations in whole blood and of calcineurin activities in lymphocytes at D8, D15, D21 (pharmacokinetics on 4 times samples), D28, M2 and M3 (residual measurement) Receives: Other: Pharmacokinetics/dynamics |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determination of tacrolimus concentrations in whole blood and of calcineurin activities in lymphocytes
Measured: at day 8, day15, day21 (pharmacokinetics on 4 times samples), day 28, month 2 and month 3 (residual measurement)
Secondary outcomes (1)
Pharmacogenetics (3A5)
- Genotyping of CYP3A5 * 3 (A6986G) and mdr-1: mutations of these proteins could explain the changes of absorption of tacrolimus.
- For each patient, during the first month of treatment, 5 ml of blood will be collected on EDTA tube.
- Genotyping is realized by the allelic discrimination technique Taqman, on a ABI Prism 7000 (TaqMan ®) in the Molecular Biology unit, Pharmacogenetics and Hormonology Bicêtre Hospital
Measured: at day 8, day 15, day 21, day 28, month 2 and month 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2011 (estimated)
- Study startJan 2009
- Primary completionJul 2010
- Study completionJul 2010
Why it stopped: no patient corresponding to criteria
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal Transplant RejectionStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Philippe GRIMBERT, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01413685
- Sponsor's protocol ID
- P071004
- Status last verified
- Nov 2014
- First submitted
- 24 Jun 2011
- Last updated
- 14 Nov 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Interest of Calcineurin Activity for the Therapeutic Tacrolimus Monitoring in Renal Recipients
- ClinicalTrials.gov ID
- NCT01413685
- Acronym / sponsor ID
- P071004
- Conditions
- Renal Transplant Rejection
- Keywords
- tacrolimus, calcineurin, pharmacodynamic, TDM, pharmacokinetics
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: no patient corresponding to criteria
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Jan 2009
- Primary completion
- Jul 2010 (actual)
- Study completion
- Jul 2010 (actual)
- First posted
- 10 Aug 2011 (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 is to define if calcineurin activity is a better biological parameter than blood concentration for the therapeutic tacrolimus monitoring.
Detailed description
Some authors showed that the determination of calcineurin (enzyme of cyclosporin and tacrolimus action) activity was very interesting in bone narrow and hepatic transplant in order to monitor tacrolimus or cyclosporin. Indeed, Furthermore, target Tac concentrations still fail to provide in certain patients an appropriate immunosuppression reflected by rejection. Because a lack of data in renal transplant, we propose to study this population treated by tacrolimus, mycophenolate mofetil and corticoids in the first three months following the transplantation.
Our major aim is to study the relationship between calcineurin activity and immunologic events in 200 renal recipients treated with tacrolimus in the first three months following transplant. Immunologic events could be acute rejections and infraclinical rejections. The second aims are 1) if this relationship exists, to define the threshold predicting acute rejection using ROC-curve, 2) to define variations between pharmacodynamic (calcineurin activity) and pharmacokinetic (whole blood concentrations) tacrolimus monitoring and 3) to compare calcineurin activity in patients with acute rejection and those with borderline rejection. Blood samples will be collected into EDTA-containing vacutainers prior to the tacrolimus morning administration and at 2, 4, 6 and 9 hours following the administration at D7, D14 and D21. Whole blood tacrolimus concentrations and calcineurin activity were measured using LCMSMS and HPLC techniques. After D21, only residual measurements will be carried out at D28, M2 and M3. A comparative statistical analysis will be performed between data defined with and without rejection. In case of difference, a ROC curve analysis could define normal ranges of calcineurin activity.
This is the second study of the Sud FRANCILIEN Institute for Research in Nephrology-Transplantation defined with Nephrology departments in Mondor and BICETRE hospitals and the object "Interest of pharmacodynamics of immunosuppressive drugs in renal-transplant recipients" is a new theme of these teams.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tacrolimus | No intervention | Other: Pharmacokinetics/dynamicsDetermination of tacrolimus concentrations in whole blood and of calcineurin activities in lymphocytes at D8, D15, D21 (pharmacokinetics on 4 times samples), D28, M2 and M3 (residual measurement) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- adult renal transplant recipients
- treated by tacrolimus (Prograf or ADVAGRAF), corticoids, Cellcept,
Key exclusion criteria (4 listed)
- patients with a high risk of bad compliance (toxicomania, severe psychiatric troubles)
- multiorgan transplant patients with mTOR inhibitors treatments
- HIV infected patients
- lack of consent for this study
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 |
|---|---|---|
| Pharmacokinetics/dynamicsDetermination of tacrolimus concentrations in whole blood and of calcineurin activities in lymphocytes at D8, D15, D21 (pharmacokinetics on 4 times samples), D28, M2 and M3 (residual measurement) | Other | Tacrolimus |
Primary outcome
Determination of tacrolimus concentrations in whole blood and of calcineurin activities in lymphocytes
Time frame: at day 8, day15, day21 (pharmacokinetics on 4 times samples), day 28, month 2 and month 3 (residual measurement)
1 secondary outcome
Pharmacogenetics (3A5)
Time frame: at day 8, day 15, day 21, day 28, month 2 and month 3
Results and safety
The study was stopped early (reason given: no patient corresponding to criteria). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2014.
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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.
Philippe GRIMBERT principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Pharmacokinetics/dynamics in people with Renal Transplant Rejection, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 2 inclusion and 4 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 14 Nov 2014. 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 France. 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: no patient corresponding to criteria). 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?
Determination of tacrolimus concentrations in whole blood and of calcineurin activities in lymphocytes (time frame: at day 8, day15, day21 (pharmacokinetics on 4 times samples), day 28, month 2 and month 3 (residual measurement)). 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 14 Nov 2014.