Is T-lymphocyte Calcineurin Phosphatase Up-regulated by Treatment With Tacrolimus?
|ClinicalTrials.gov Identifier: NCT00999362|
Recruitment Status : Completed
First Posted : October 21, 2009
Last Update Posted : October 21, 2009
|Condition or disease|
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.
The aim of the project is find out if long-term treatment with tacrolimus results in up-regulation of CaN in lymphocytes.
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.
|Study Type :||Observational|
|Actual Enrollment :||40 participants|
|Official Title:||Is T-lymphocyte Calcineurin Phosphatase Up-regulated by Treatment With Tacrolimus?|
|Study Start Date :||October 2007|
|Actual Primary Completion Date :||March 2009|
|Actual Study Completion Date :||October 2009|
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
- Gene expression of calcineurin in T-lymphocytes [ Time Frame: Trough level and 2 hours postdose ]
- Calcineurin activity measured in whole blood and in isolated T-lymphocytes [ Time Frame: Trough level and 2 hours postdose ]
- Amount of Calcineurin in T-lymphocytes [ Time Frame: Trough level and 2 hours postdose ]
- Interferon-gamma production [ Time Frame: Trough level and 2 hours postdose ]
- Tacrolimus concentration in whole blood [ Time Frame: Trough level and 2 hours postdose ]
- Number of T-lymphocytes [ Time Frame: Trough level and 2 hours postdose ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00999362
|Department of Nephrology, Aarhus University Hospital, Skejby|
|Aarhus, Denmark, 8200|
|Principal Investigator:||Dorthe M Mortensen, MD||Department of nephrology, Aarhus University Hospital,Skejby, Denmark|