Primary objective: To assess the degree of tacrolimus over-exposure in renal transplant patients with mild diarrhea while on treatment with tacrolimus and mycophenolate mofetil.Secondary objective: To assess the intra-individual variability of…
ID
Source
Brief title
Condition
- Renal disorders (excl nephropathies)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Difference in the ratio AUC:trough level of tacrolimus between subjects with
mild diarrhea and controls.
Secondary outcome
Correlation between two measurements of ratio AUC:trough level of tacrolimus in
the same subject.
Background summary
Diarrhea is a frequent adverse event in patients treated with the combination
of tacrolimus and mycophenolate mofetil and has an important impact on the
pharmacokinetics of tacrolimus. In case of severe diarrhea, the exposure to
tacrolimus can be increased several fold and is reflected in a substantial
increase in trough levels. Mild diarrhea (2-3 stools per day) is more common
and not always reported to the treating physician. In these cases, an increase
in the total tacrolimus exposure may not be accompanied by a marked increase in
tacrolimus trough levels. Consequently, ongoing mild diarrhea may result in
unnoticed chronic tacrolimus overexposure leading to irreversible
nephrotoxicity.
Study objective
Primary objective: To assess the degree of tacrolimus over-exposure in renal
transplant patients with mild diarrhea while on treatment with tacrolimus and
mycophenolate mofetil.
Secondary objective: To assess the intra-individual variability of tacrolimus
pharmacokinetics.
Study design
Cross-sectional study with measurement of tacrolimus pharmacokinetics on two
occasions in subjects with mild diarrhea and in an equal number of controls
with normal stools.
Study burden and risks
The pharmacokinetics of tacrolimus will be measured on two separate days. At
each day blood samples will be collected just before and 1, 2, 4, 6 and 9 hours
after oral intake. Participants will be asked to remain fasted until two hours
after intake of tacrolimus. For blood sampling a dried blood spot method which
includes finger pricks will be used. This method allows that participants take
their own blood samples at home and send the dried blood spot samples to the
hospital. Participants will receive training for using this method during a
regular control visit to the hospital. During the training visit participants
will also complete two questionnaires concerning gastro-intestinal symptoms,
which will take about 20 minutes. The participation with this study does not
require additional examinations or hospital visits. Adverse effects are not
expected.
Postbus 9101
6500 HB Nijmegen
NL
Postbus 9101
6500 HB Nijmegen
NL
Listed location countries
Age
Inclusion criteria
1. Recipient of a renal graft
2. Age: 18 years or older
3. Informed consent
4. At least 2 months after renal transplantation
5. Treatment with the combination of tacrolimus and MMF
6. Tacrolimus trough levels within the target range (5-10 ng/ml) at two subsequent occasions.
Cases: Average stool frequency 2-3 times/day OR unbound stools during last two weeks prior to inclusion.
Controls: Average stool frequency 1 time/day or less AND normal consistency of stools during last two weeks prior to inclusion.
Exclusion criteria
1. History of bowel resection
2. Severe diarrhea (> 3 stools per day)
3. Rectal blood loss
4. Signs of active CMV infection
5. Change in tacrolimus dosage within one week prior to inclusion
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 | NL29414.091.09 |