To prospectively measure the intracellular tacrolimus concentration in CD3+ T lymphocytes in kidney transplant recipients. The area under the concentration-vs-time curve (AUC) of the intracellular tacrolimus concentration will be determined and used…
ID
Source
Brief title
Condition
- Renal disorders (excl nephropathies)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The intracellular tacrolimus concentration in CD3+ T lymphocytes and a
population pharmacokinetic model to describe tacrolimus.
Secondary outcome
The association between the intracellular tacrolimus concentration in CD3+ T
lymphocytes and IL-2 and IFN-* production by these same cells.
The association between the intracellular tacrolimus concentration in CD3+ T
lymphocytes and clinical events (post-transplant diabetes mellitus and acute
rejection).
Background summary
The immunosuppressive drug tacrolimus is routinely monitored after kidney
transplantation by measuring the whole blood, pre-dose concentration (C0).
However, the C0 has a poor correlation with clinical events, most notably the
risk of acute rejection. Since tacrolimus* site of action is within immune
cells, the intracellular tacrolimus concentration in peripheral blood
mononuclear cells (PBMCs) has recently been proposed to better represent the
active concentration. However, several studies could not demonstrate an
association between the intracellular tacrolimus concentration and acute
rejection. One of the possible explanations for this surprising finding is the
fact the PBMC fraction is composed of several cells including lymphocytes and
monocytes. In this study, the tacrolimus concentration in CD3+ T lymphocytes
will be investigated as this may be a more relevant cell population than PBMCs.
Study objective
To prospectively measure the intracellular tacrolimus concentration in CD3+ T
lymphocytes in kidney transplant recipients. The area under the
concentration-vs-time curve (AUC) of the intracellular tacrolimus concentration
will be determined and used for the development of a population pharmacokinetic
model. The pharmacokinetics of intra-CD3+ tacrolimus will be compared with the
whole-blood concentration and will be related to important clinical events.
Study design
Observational study with additional blood sampling.
Study burden and risks
The participants in this study are de novo kidney transplant recipients
transplanted at the Erasmus MC. These patients will receive routine medical
care. Twenty mL of venous blood will be sampled from each participant on 4
occasions, including time 0 (pre-dose concentration), 4, and 8 hours after
tacrolimus administration on day 5-7 post-kidney transplant and time 0 at day
14 (20 mL at each timepoint for a total of 80 mL per patient for the whole
study). No extra-visits are required.
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Listed location countries
Age
Inclusion criteria
- Age * 18 years.
- Recipient of a kidney transplant at the Erasmus MC.
- Use once-daily tacrolimus as part of routine maintenance immunosuppression
starting the day of surgery.
- Written informed consent.
Exclusion criteria
Patients who receive lymphocyte depleting agents (thymoglobuline,
anti-thymocyte globulin, and alemtuzumab) as an induction therapy or
anti-rejection treatment before enrolment. Recipients using medication known to
have a pharmacokinetic (drug-drug) interaction with tacrolimus: Antibiotics
(Clarithromycin, Doxycyclin, Erythromycin, Rifampicin), Antiepileptics
(Carbamazepine, Phenobarbital, Phenytoin), Antihypertensive and antiarrhythmic
agents (Amiodarone, Diltiazem, Verapamil), Antimycotic drugs (Fluconazole,
Itraconazole, Ketoconazole), Other (HIV protease inhibitors, Theophyllin)
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL80363.078.22 |