Kidney TransplantationNCT00999362
Is T-lymphocyte Calcineurin Phosphatase Up-regulated by Treatment With Tacrolimus?
An observational study of Kidney Transplantation, run by University of Aarhus at 1 site in Denmark.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Kidney Transplantation
- How many people
- 40 participants
- Where
- 1 siteDenmark
- Study dates
- Oct 2007to Oct 2009
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Kidney transplant recipients from Department of Nephrology, Aarhus University Hospital, Skejby, Denmark
Who may be able to join
- 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
Show all 13Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Department of Nephrology, Aarhus University Hospital, Skejby
Aarhus, 8200
About this study
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.
Read the 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.
- Conditions
- Kidney Transplantation
- Keywords
- calcineurin activity, real-time PCR, Gene expression of calcineurin, T-lymphocytes, interferon-gamma, Pharmacodynamics, Pharmacokinetics, tacrolimus, western blot, Hoechst
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Gene expression of calcineurin in T-lymphocytes
Measured: Trough level and 2 hours postdose
Calcineurin activity measured in whole blood and in isolated T-lymphocytes
Measured: Trough level and 2 hours postdose
Amount of Calcineurin in T-lymphocytes
Measured: Trough level and 2 hours postdose
Interferon-gamma production
Measured: Trough level and 2 hours postdose
Secondary outcomes (2)
Tacrolimus concentration in whole blood
Measured: Trough level and 2 hours postdose
Number of T-lymphocytes
Measured: Trough level and 2 hours postdose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2009 (estimated)
- Study startOct 2007
- Primary completionMar 2009
- Study completionOct 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney TransplantationStudies of the same condition, open and under way.
- More trials run by University of AarhusThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Time perspective
- Prospective
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Collaborators
- Danish Society of Nephrology, The Danish Kidney Association, Astellas Pharma Inc
- Investigators
- Dorthe M Mortensen, MD, Principal investigator, Department of nephrology, Aarhus University Hospital,Skejby, Denmark
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00999362
- Sponsor's protocol ID
- TAC
- Status last verified
- Oct 2009
- First submitted
- 20 Oct 2009
- Last updated
- 21 Oct 2009
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Is T-lymphocyte Calcineurin Phosphatase Up-regulated by Treatment With Tacrolimus?
- ClinicalTrials.gov ID
- NCT00999362
- Acronym / sponsor ID
- TAC
- Conditions
- Kidney Transplantation
- Keywords
- calcineurin activity, real-time PCR, Gene expression of calcineurin, T-lymphocytes, interferon-gamma, Pharmacodynamics, Pharmacokinetics, tacrolimus
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Collaborators
- Danish Society of Nephrology, The Danish Kidney Association, Astellas Pharma Inc
- Study start
- Oct 2007
- Primary completion
- Mar 2009 (actual)
- Study completion
- Oct 2009 (actual)
- First posted
- 21 Oct 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Kidney transplant recipients from Department of Nephrology, Aarhus University Hospital, Skejby, Denmark
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (7 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
2 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2009.
Related trials for Kidney Transplantation
Enrolling by invitation
Online Exercise Program for Transplant Patients: A Pilot Study
Kidney Transplantation, Physical Function
RecruitingPhase 2
A Study of Mezagitamab in Adults With Late Antibody-Mediated Rejection (AMR) After a Kidney Transplant
Antibody-Mediated Rejection (AMR)
Not yet recruiting
Hypothermic Kidney Machine Perfusion With Omnisol
End Stage Renal Disease (ESRD), Kidney Transplant
Not yet recruitingEarly Phase 1
Biomarker-Guided Mycophenolate Mofetil Elimination in Low-Risk Older Adult Kidney Transplant Recipients
Kidney Transplant Recipient
Recruiting
Non-Invasive Monitoring of Pediatric Kidney Transplant Recipients and Immunosuppression Personalization: an Open-labeled Multicenter Randomized Controlled Study
Pediatric Kidney Disease, Transplant;Failure,Kidney
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dorthe M Mortensen, MD principal investigator
Department of nephrology, Aarhus University Hospital,Skejby, Denmark
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Kidney Transplantation, run by University of Aarhus at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Oct 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Gene expression of calcineurin in T-lymphocytes (time frame: Trough level and 2 hours postdose). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2009.