Envarsus Neurotoxicity Burden in Liver Transplant Patients

Study Overview
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Brief Summary
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This study will compare neurologic side effects associated with two immunosuppressant medications used in liver transplant patients. The standard therapy of twice daily immediate release Tacrolimus will be compared to Envarsus once daily. We hypothesize that Envarsus will show a lower rate of neurologic side effects than immediate release tacrolimus.

Official Title
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The Effect of Conversion to Once-Daily Envarsus® on the Neurologic Toxicity Burden in Liver Transplant Recipients

Conditions
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Liver Transplant; Complications, Neurotoxicity

Intervention / Treatment
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* Drug: Envarsus
* Drug: Tacrolimus Immediate release


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female adult (≥18 years old) with a history of liver or liver/kidney transplant within the first 6 months of transplant. Patients must be capable of understanding the purposes and risks of the study and have the ability to give written informed consent and be willing to participate and comply with the study. Exclusion Criteria: Patients will be excluded if they are pregnant or nursing females or males with a pregnant female partner HIV positive (HIV ab +) Unable to tolerate oral medications Use of another investigational product within thirty days prior to receiving study medication Moderate acute cellular rejection (RAI ≥ 5) within the past month A condition that is known to cause tremor such as essential tremor, Parkinson disease, or enhanced physiologic tremor. Patients taking medications known to induce tremors or dopamine blocking agents A condition or disorder that, in the opinion of the investigator, may adversely affect the outcome of the study or the safety of the subject

Ages Eligible for Study
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Minimum Age: 18 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1: Control<br>Tacrolimus immediate release twice daily for 6 months | Drug: Tacrolimus Immediate release<br>* Subjects in this group will take Tacrolimus immediate release for 6 months of treatment (goal 12 hour trough: 3-10 ng/mL) +/- adjunctive agent and prednisone.<br>|
| Experimental: Arm 2: Intervention<br>Envarsus daily for 6 months. | Drug: Envarsus<br>* Subjects in this group will take Envarsus daily for 6 months of treatment (goal 24 hour trough: 3-10 ng/mL) +/- adjunctive agent and prednisone.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in neurotoxicity burden | Estimate the change from baseline to six months in neurotoxicity burden measured by a composite Patient Global Impression of Improvement score | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in mean Fahn-Tolosa-Marin (FTM) score | Estimate the change in the mean FTM score among patients with self-reported tremors from baseline to six months. | 6 months |