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
  Purpose

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.


Condition
Kidney Transplantation

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Is T-lymphocyte Calcineurin Phosphatase Up-regulated by Treatment With Tacrolimus?

Resource links provided by NLM:


Further study details as provided by University of Aarhus:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 40
Study Start Date: October 2007
Study Completion Date: October 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Groups/Cohorts
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

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

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00999362

Locations
Denmark
Department of Nephrology, Aarhus University Hospital, Skejby
Aarhus, Denmark, 8200
Sponsors and Collaborators
University of Aarhus
Danish Society of Nephrology
The Danish Kidney Association
Astellas Pharma Inc
Investigators
Principal Investigator: Dorthe M Mortensen, MD Department of nephrology, Aarhus University Hospital,Skejby, Denmark
  More Information

No publications provided

Responsible Party: MD Dorthe M Mortensen, Department of Nephrology, Aarhus University Hospital, Skejby, Denmark
ClinicalTrials.gov Identifier: NCT00999362     History of Changes
Other Study ID Numbers: TAC
Study First Received: October 20, 2009
Last Updated: October 20, 2009
Health Authority: Denmark: The Regional Committee on Biomedical Research Ethics
Denmark: Danish Dataprotection Agency

Keywords provided by University of Aarhus:
calcineurin activity
real-time PCR
Gene expression of calcineurin
T-lymphocytes
interferon-gamma
Pharmacodynamics
Pharmacokinetics
tacrolimus
western blot
Hoechst

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

ClinicalTrials.gov processed this record on July 22, 2014