Effect of Tacrolimus Formulation on Neurological Side Effects in Older Kidney Transplant Recipients

University of California, Davis64 enrolled

Overview

Previous studies have shown that elderly patients experience higher trough levels of tacrolimus and are more sensitive to the effects of medications, they experience higher occurrence and severity of such medication related toxicities. Therefore, the investigators hypothesize that by transitioning patients from tacrolimus immediate release to Envarsus ®, the peak-dose effect will be eliminated or attenuated, leading to a significant decrease in neurocognitive toxicities in the older patient population.

The investigators will conduct a single-center, prospective, open-label, randomized study to evaluate the difference in neurocognitive side effects between Envarsus and immediate release tacrolimus. Eligible patients will be enrolled within 8 weeks post-transplantation. They will be administered a baseline panel of neurocognitive tests. They will then be randomized to either continue on immediate release tacrolimus or Envarsus. 6 weeks after randomization, the neurocognitive tests will be repeated.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Kidney Transplant; Complications Toxicity Drug Toxicity

Eligibility

Sex: ALLMin age: 60 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Recipient of a kidney transplant 2. Age 60 or greater at the time of transplant 3. Kidney graft is functional (not dialysis dependent) by 4 weeks post-transplant 4. Have IR tacrolimus as maintenance therapy 5. Have BMI \< 35 at time of transplant 6. Achieve therapeutic tacrolimus level within 4 weeks post-transplant Exclusion Criteria: 1. Recipient of a simultaneous non-kidney transplant (pancreas) 2. Had an episode of rejection before study enrollment 3. Had a TIA/CVA after transplantation and before study enrollment 4. Had a neurologic injury after transplantation and before study enrollment 5. Blindness 6. Have an mTOR inhibitor as maintenance therapy 7. Nonadherence, as determined by a trough level less than 7 ng/mL after achieving therapeutic level with no other rationale for sub-therapeutic levels. 8. Adults unable to consent 9. Pregnant women 10. Prisoners

Outcomes

Primary Outcomes

Change in Neurocognitive Side Effects

Change in MOCA (Montreal Cognitive Assessment) from baseline to study end. MOCA scale runs from 0 to 30 with higher being a better outcome. Change in DSST (Digital Symbol Substitution Test) from baseline to study end. DSST scale runs from 1 to 125 with higher being a better outcome.

Time frame: 6 weeks after randomization and baseline testing

Secondary Outcomes

Change in Self-reported Side Effects

Quality of life in Essential Tremor questionnaire (QUEST) Summary Score: A 30-item scale assessing the impact of tremor on various domains of quality of life, such as communication, work and hobbies. In the QUEST questionnaire scale, a lower score is indicative of better quality of life while higher scores indicate poorer quality of life. The score is a percentage ranging from zero to 100.

Time frame: 6 weeks after randomization and baseline testing

Kidney Graft Survival

Number of kidney grafts still functioning at the end of the study

Time frame: 6 months after transplant

Patient Survival

Number patients who survived during the study