Is T-lymphocyte Calcineurin Phosphatase Up-regulated by Treatment With Tacrolimus?

This study has been completed.
Sponsor:
Collaborators:
Danish Society of Nephrology
The Danish Kidney Association
Astellas Pharma Inc
Information provided by:
University of Aarhus
ClinicalTrials.gov Identifier:
NCT00999362
First received: October 20, 2009
Last updated: NA
Last verified: October 2009
History: No changes posted

October 20, 2009
October 20, 2009
October 2007
March 2009   (final data collection date for primary outcome measure)
  • Gene expression of calcineurin in T-lymphocytes [ Time Frame: Trough level and 2 hours postdose ] [ Designated as safety issue: No ]
  • Calcineurin activity measured in whole blood and in isolated T-lymphocytes [ Time Frame: Trough level and 2 hours postdose ] [ Designated as safety issue: No ]
  • Amount of Calcineurin in T-lymphocytes [ Time Frame: Trough level and 2 hours postdose ] [ Designated as safety issue: No ]
  • Interferon-gamma production [ Time Frame: Trough level and 2 hours postdose ] [ Designated as safety issue: No ]
Same as current
No Changes Posted
  • Tacrolimus concentration in whole blood [ Time Frame: Trough level and 2 hours postdose ] [ Designated as safety issue: No ]
  • Number of T-lymphocytes [ Time Frame: Trough level and 2 hours postdose ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Is T-lymphocyte Calcineurin Phosphatase Up-regulated by Treatment With Tacrolimus?
Is T-lymphocyte Calcineurin Phosphatase Up-regulated by Treatment With Tacrolimus?

The purpose of this study is to determine whether calcineurin phosphatase in the T-lymphocytes is up-regulated after long-term treatment with tacrolimus, a calcineurin inhibitor.

Background:

The immunosuppressive effect of both tacrolimus and cyclosporine is believed to be through inhibition of the enzyme calcineurin phosphatase (CaN) in T-lymphocytes. We have demonstrated, that tacrolimus decreases CaN activity in patients early after renal transplantation. In stable renal transplant patients treated this inhibition was hardly seen in patients treated with tacrolimus, while it was clearly demonstrated in patients treated cyclosporine. One explanation to this finding could be, that calcineurin phosphatase is up-regulated by long-term treatment with tacrolimus. The findings seem to imply, that tacrolimus has mechanisms of immunosuppression apart from inhibiting CaN. This could have implications for side-effects due to CaN inhibition. Among side-effects thought to be due to CaN inhibition is nephrotoxicity. The results may therefore be and indication of tacrolimus being less nephrotoxic compared to cyclosporine in long-term stable renal transplant patients.

Purpose:

The aim of the project is find out if long-term treatment with tacrolimus results in up-regulation of CaN in lymphocytes.

Study plan:

The general plan of the investigation is to compare CaN in lymphocytes in two groups of renal transplant patients treated with tacrolimus. One group just prior and just after transplantation compared to a group of stable renal transplanted patients a long time after transplantation. CaN is determined as enzyme activity, amount of protein, and by gen-activation.

Observational
Time Perspective: Prospective
Not Provided
Not Provided
Probability Sample

Kidney transplant recipients from Department of Nephrology, Aarhus University Hospital, Skejby, Denmark

Kidney Transplantation
Not Provided
  • Early kidney-transplant recipients
    Patients receiving a kidney transplantation at Aarhus University Hospital, Skejby and receiving tacrolimus as part of their immunosuppressive regime.
  • stable kidney transplant recipients
    Tacrolimus treated kidney-transplant recipients from the out-door clinic at Aarhus University Hospital, Skejby and more than two years after transplantation
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
40
October 2009
March 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

Group 1 (early kidney-transplant recipients)

  • Age over 18 years
  • 20 consecutively kidney-transplant recipients at Department of Nephrology, Aarhus University Hospital, Skejby, Denmark
  • receiving tacrolimus as part of their immunosuppressive treatment
  • receipt of graft from either deceased or living-related donor
  • written consent to participate

Group 2 (stable kidney-transplant recipients)

  • Age over 18 years
  • Stable renal allograft function defined as S-creatinine <200 µmol/l
  • variation in S-creatinine <20% for 6 months prior to inclusion
  • kidney transplantation more than 2 years before inclusion
  • receipt of graft from either deceased or living-related donor
  • written consent to participate

Exclusion Criteria:

Group 1 (early kidney-transplant recipients)

  • patients suspected of non-compliance
  • patients receiving medications known to interact with tacrolimus pharmacokinetics
  • patients who on day 8 after transplantation have not reached a trough level for blood tacrolimus concentration above 8 µg/l.

Group 2 (stable kidney-transplant recipients)

  • patients suspected of non-compliance
  • patients receiving medications known to interact with tacrolimus pharmacokinetics
Both
18 Years to 75 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Denmark
 
NCT00999362
TAC
Yes
MD Dorthe M Mortensen, Department of Nephrology, Aarhus University Hospital, Skejby, Denmark
University of Aarhus
  • Danish Society of Nephrology
  • The Danish Kidney Association
  • Astellas Pharma Inc
Principal Investigator: Dorthe M Mortensen, MD Department of nephrology, Aarhus University Hospital,Skejby, Denmark
University of Aarhus
October 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP