Calcineurin Activity in Renal Recipients

Renal Transplant Rejection Clinical Trial

Official title:

Interest of Calcineurin Activity for the Therapeutic Tacrolimus Monitoring in Renal Recipients

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01413685
• Other study ID #: P071004
• Status: Terminated
• Phase: Phase 4
• First received: June 24, 2011
• Last updated: November 13, 2014
• Start date: January 2009
• Est. completion date: July 2010

Study information

• Verified date: November 2014
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

The purpose is to define if calcineurin activity is a better biological parameter than blood concentration for the therapeutic tacrolimus monitoring.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 23
• Est. completion date: July 2010
• Est. primary completion date: July 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• adult renal transplant recipients

• treated by tacrolimus (Prograf or ADVAGRAF), corticoids, Cellcept,

Exclusion Criteria:

• 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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Renal Transplant Rejection

Intervention

Other:
• Pharmacokinetics/dynamics
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)

Locations

Country	Name	City	State
France	Hôpital Henri Mondor	Créteil

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determination of tacrolimus concentrations in whole blood and of calcineurin activities in lymphocytes		at day 8, day15, day21 (pharmacokinetics on 4 times samples), day 28, month 2 and month 3 (residual measurement)	No
Secondary	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	at day 8, day 15, day 21, day 28, month 2 and month 3	No