THE TREMOR STUDY: TACROLIMUS EXTENDED RELEASE, MOVEMENT DISORDERS AND OTHER NEUROCOGNITIVE EFFECTS

Renal transplantation is the optimal form of renal replacement therapy.
Compared to dialysis, it increases patient survival and quality of life.
Moreover, renal transplantation decreases the economic burden of
end-stage-renal replacement therapy to society. After renal transplantation
maintenance immunosuppressive therapy is necessary to control graft rejection.
These immunosuppressive regimens are frequently associated with side effects,
which might detract from the potential gain of the renal transplant. Conversion
to another regimen or formula of a specific drug can then be beneficial to
reduce side effects.

The main objective of this study is to investigate whether kidney transplant
recipient suffering from a tacrolimus-induced tremor can benefit from switching
from conventional tacrolimus to LCPT, a new extended release preparation of
tacrolimus (Envarsus®), or cyclosporine (Neoral®).

Investigator-driven, open-label, prospective, randomized controlled trial.

At baseline, participants will undergo pharmacokinetic testing, a quality of
life assessment and a computerized neuropsychological test battery (the
Amsterdam Neuropsychological Tasks or ANT battery). The ANT battery consists of
several computerized tests measuring the basal cognitive processes that
regulate daily functioning, including two modules that are well-suited to
quantify tremors. At one month, participants will be randomized to (1)
continuing their current tacrolimus preparation, (2) switching to Envarsus®, or
(3) switching to Neoral®. After one month, the tests will be repeated. Then,
the participants in the control group will also be switched to Envarsus®. After
one month, all tests will again be repeated.

Participants will be asked to undergo three test cycles. Each cycle is expected
to last 8 hours, so that the total required time for completing the study will
amount to 24 hours over a period of three months. In each cycle, participants
will give at least four 5ml blood samples over a period of six hours for
pharmacokinetic testing (more if drug levels are out of range), fill out two
questionnaires and undergo a 45-minute neuropsychological assessment.
Participating in this study can be beneficial because it may result in a
diminished tremor and an improved neurocognitive function. In addition,
participants will receive 50 euros per cycle plus compensation for travel
expenses and the option of choosing the drug that suited them best at the end
of the study.