Alterations in Cognitive Function and Cerebral Blood Flow After Conversion From Immediate Release Tacrolimus to Slow Release Envarsus

Study Overview
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Brief Summary
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The purpose of this study is to learn if conversion from immediate release tacrolimus to Envarsus improves cerebral blood flow, brain blood flow response to exercise, and cognition.

Detailed Description
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Each patient will have two study assessments: one at baseline and another one at 12 weeks after the baseline assessment. Each assessment may be divided into 2 visits to accommodate the MRI and TCD (Transcranial Doppler ultrasound). Detailed medical history will be extracted from the patients' medical records, interviews and questionnaires. We will obtain brain MRI (without gadolinium contrast) in enrolled patients. Neuropsychological test (NP) tests will include a standard battery to detect subclinical changes in cognition which can be missed by screening tests like the mini mental state exam.

Official Title
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Alterations in Cognitive Function and Cerebral Blood Flow After Conversion From Immediate Release Tacrolimus to Slow Release Envarsus

Conditions
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End Stage Renal Disease

Intervention / Treatment
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* Drug: Envarsus
* Drug: Tacrolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age between 18 and 85 years English speaking (NP tests will be in English); able to sign informed consent able to arrange transportation to and from study sites without acute stroke, concussion or traumatic brain injury received a kidney transplant at least 12 weeks before recruitment stable kidney function with serum creatinine <3mg/dl Exclusion Criteria: are claustrophobic or have other contra-indication for MRI have hearing or visual impairment are unable to read, write, speak or understand English have uncontrolled psychosis or seizure disorder or are currently using antipsychotics or anti-epileptics dual organ transplant oxygen-dependent chronic obstructive pulmonary disease diagnosis of dementia unable to perform exercise on the Nustep (muscle weakness or cardiac safety concern) uncontrolled blood pressure

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Study Arm<br>The patients in the study arm will be converted from immediate release Tacrolimus to Envarsus. After obtaining informed consent, participants will undergo baseline tests for cognitive function and cerebral blood flow. After 12 weeks, cognition and brain blood flow will be assesses again in all enrolled patients. | Drug: Envarsus<br>* Patients will then be randomized in the ratio of 2:1 with 20 being in the study arm and 10 in the control arm. Envarsus will be prescribed by the transplant team per conversion guidelines. The transplant team will monitor drug levels, per the dosing guidelines.<br>|
| Control Arm<br>Patients in the control arm will remain on the immediate release Tacrolimus. After obtaining informed consent, participants will undergo baseline tests for cognitive function and cerebral blood flow. After 12 weeks, cognition and brain blood flow will be assesses again in all enrolled patients. | Drug: Tacrolimus<br>* The patient's physician will prescribe drug according to standard practice.<br>* Other names: Prograf;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cognitive function using a battery of neuropsychological tests | Battery aggregate scores include such tests as: Mini Mental Sate Exam, Montreal Cognitive Assessment, Digit Span, Logical Memory, Category Fluency, Trail Making, Digit Symbol, Block Design, Stroop, Buschke Free and Cued Reminding Test. | Change from Baseline to Week 12 | 
| Change in cerebral blood flow | including brain blood flow response curve to exercise or cerebral reactivity | Change from Baseline to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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End Stage Renal Disease