The purpose of this study is to assess cognitive outcome and quality of life in stable renal transplant patients treated with twice daily tacrolimus at baseline and after switching to Envarsus XL. The study is designed to see if switching patients from Tacrolimus to Envarsus treatment improves cognitive function.
Patients with chronic kidney disease most commonly show cognitive impairments involving attention, memory, executive functions, and mental processing speed. Although data have demonstrated improvements in cognition following kidney transplant and the reversibility of the memory problems evidenced in dialysis, neurotoxicity in transplant patients occurs in \>40-50% of the patients treated with tacrolimus. Attention and working memory impairment have been observed in patients treated with sirolimus or tacrolimus, while cyclosporine-treated patients demonstrated performance similar to that of healthy volunteer controls, which may indicate that the cognitive deficit found was partly related to treatment. ENVARSUS XR is a new FDA-approved formulation of tacrolimus. A hallmark difference between ENVARSUS XR and other forms of once- and twice-daily tacrolimus products is the unique, proprietary MeltDose® drug delivery technology (Veloxis Pharmaceuticals, Hørsholm, Denmark) which reduces tacrolimus' particle size to a molecular level. The decreased surface area of the drug particles results in complete absorption and increased bioavailability in a once-daily dosing formulation. In stable kidney transplant patients, ENVARSUS XR pharmacokinetics are characterized by a steadier and more consistent concentration time profile over 24 hours, reduced peak and peak-to-trough fluctuations and similar exposure while benefiting from \~ 20% less total daily dose than twice daily tacrolimus. This open-label, prospective phase clinical trial is designed to evaluate whether switching patients from TAC-IR to ENVARSUS XR treatment improves cognitive function.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
60
Change from Tacrolimus taken twice a day to Envarsus XR taken once a day
VUMC
Nashville, Tennessee, United States
Change in cognitive function-Global on RBANS
Measured by the Global Composite Score on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Total score can range from 40 to 160. Low score indicates cognitive impairment.
Time frame: Baseline to month 4
Change in cognitive function-Global on Covid-19 telephone battery
Measured by the global composite score of the Covid-19 Telephone Battery, should that be the primary outcome battery that we employ due to COVID limitation. Total score can range from 40 to 160. Low score indicates cognitive impairment.
Time frame: Baseline to month 4
Change in cognitive function on Trail making part A
Measured by Trail making Part A. Maximum time given for TMT A is 150 seconds. Results are reported as the number of seconds required to complete the task; therefore, higher scores reveal greater impairment.
Time frame: Baseline to month 4
Change in cognitive function on Trail making part B
Measured by Trail making Part B. Maximum time given for TMT B is 300 seconds. Results are reported as the number of seconds required to complete the task; therefore, higher scores reveal greater impairment.
Time frame: Baseline to month 4
Change in quality of life
Change in quality of life measured by WHODAS. The total score of WHODAS is the sum of all the 12 sub-scores and ranges from 0 to 48, with lower scores indicating better functioning. Total scores of 1-4 belong to mild disability, 5-9 to moderate disability, and 10-48 to severe disability
Time frame: Baseline to Month 4
Impression of Improvement by PGI
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measured by PGI-I (Patient's Global Impression of Improvement). The PGI-I measures change since initiating a medication and is assessed on a 7-point Likert-type scale ranging from very much better (1) to very much worse (7)
Time frame: baseline to month 4
Impression of Improvement by CGI
measured by CGI-I (Clinical Global Impression of Improvement). The CGI-I measures change since initiating a medication and is assessed on a 7-point Likert-type scale ranging from very much improved (1) to very much worse (7).
Time frame: baseline to month 4
Change of quality of sleep
measured by PIRS-20 (Pittsburgh Insomnia Rating Scale). The PIRS-20 total score is the sum of all items and ranges from 0 (good sleep) to 60 (bad sleep).3
Time frame: Baseline to month 4