Calcineurin Activity in Renal Recipients

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.

Study Overview

• Status: Terminated
• Conditions: Renal Transplant Rejection
• Intervention / Treatment: Other: Pharmacokinetics/dynamics

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 Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Créteil, France, 94000
    • Hôpital Henri Mondor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Tacrolimus; 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)	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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Philippe GRIMBERT, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: June 24, 2011
• First Submitted That Met QC Criteria: August 9, 2011
• First Posted (Estimate): August 10, 2011

Study Record Updates

• Last Update Posted (Estimate): November 14, 2014
• Last Update Submitted That Met QC Criteria: November 13, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: pharmacokinetics; pharmacodynamic; tacrolimus; TDM; calcineurin
• Other Study ID Numbers: P071004