Calcineurin Activity in Renal Recipients

This study has been terminated.
(no patient corresponding to criteria)
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01413685
First received: June 24, 2011
Last updated: December 26, 2011
Last verified: June 2011
  Purpose

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


Condition Intervention Phase
Renal Transplant Rejection
Other: Pharmacokinetics/dynamics
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Interest of Calcineurin Activity for the Therapeutic Tacrolimus Monitoring in Renal Recipients

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pharmacogenetics (3A5) [ Time Frame: at day 8, day 15, day 21, day 28, month 2 and month 3 ] [ Designated as safety issue: No ]
    • 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


Enrollment: 25
Study Start Date: January 2009
Study Completion Date: July 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)
Other Name: 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01413685

Locations
France
Hôpital Henri Mondor
Créteil, France, 94000
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Philippe GRIMBERT Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01413685     History of Changes
Other Study ID Numbers: P071004
Study First Received: June 24, 2011
Last Updated: December 26, 2011
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
tacrolimus
calcineurin
pharmacodynamic
TDM
pharmacokinetics

Additional relevant MeSH terms:
Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 28, 2014