<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03823768</url>
  </required_header>
  <id_info>
    <org_study_id>00083855</org_study_id>
    <nct_id>NCT03823768</nct_id>
  </id_info>
  <brief_title>Envarsus Neurotoxicity Burden in Liver Transplant Patients</brief_title>
  <official_title>The Effect of Conversion to Once-Daily Envarsus® on the Neurologic Toxicity Burden in Liver Transplant Recipients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of South Carolina</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Veloxis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Medical University of South Carolina</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will compare neurologic side effects associated with two immunosuppressant&#xD;
      medications used in liver transplant patients. The standard therapy of twice daily immediate&#xD;
      release Tacrolimus will be compared to Envarsus once daily. We hypothesize that Envarsus will&#xD;
      show a lower rate of neurologic side effects than immediate release tacrolimus.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 31, 2020</start_date>
  <completion_date type="Anticipated">September 30, 2023</completion_date>
  <primary_completion_date type="Actual">April 30, 2023</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in neurotoxicity burden</measure>
    <time_frame>6 months</time_frame>
    <description>Estimate the change from baseline to six months in neurotoxicity burden measured by a composite Patient Global Impression of Improvement score</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in mean Fahn-Tolosa-Marin (FTM) score</measure>
    <time_frame>6 months</time_frame>
    <description>Estimate the change in the mean FTM score among patients with self-reported tremors from baseline to six months.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Neurotoxicity</condition>
  <condition>Liver Transplant; Complications</condition>
  <arm_group>
    <arm_group_label>Arm 1: Control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Tacrolimus immediate release twice daily for 6 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2: Intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Envarsus daily for 6 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Envarsus</intervention_name>
    <description>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.</description>
    <arm_group_label>Arm 2: Intervention</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tacrolimus Immediate release</intervention_name>
    <description>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.</description>
    <arm_group_label>Arm 1: Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female adult (≥18 years old) with a history of liver or liver/kidney&#xD;
             transplant within the first 6 months of transplant.&#xD;
&#xD;
          2. Patients must be capable of understanding the purposes and risks of the study and have&#xD;
             the ability to give written informed consent and be willing to participate and comply&#xD;
             with the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients will be excluded if they are pregnant or nursing females or males with a&#xD;
             pregnant female partner&#xD;
&#xD;
          2. HIV positive (HIV ab +)&#xD;
&#xD;
          3. Unable to tolerate oral medications&#xD;
&#xD;
          4. Use of another investigational product within thirty days prior to receiving study&#xD;
             medication&#xD;
&#xD;
          5. Moderate acute cellular rejection (RAI ≥ 5) within the past month&#xD;
&#xD;
          6. A condition that is known to cause tremor such as essential tremor, Parkinson disease,&#xD;
             or enhanced physiologic tremor.&#xD;
&#xD;
          7. Patients taking medications known to induce tremors or dopamine blocking agents&#xD;
&#xD;
          8. A condition or disorder that, in the opinion of the investigator, may adversely affect&#xD;
             the outcome of the study or the safety of the subject&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Derek Dubay, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical University of South Carolina</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Medical University of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>January 29, 2019</study_first_submitted>
  <study_first_submitted_qc>January 29, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 30, 2019</study_first_posted>
  <last_update_submitted>May 22, 2023</last_update_submitted>
  <last_update_submitted_qc>May 22, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neurotoxicity Syndromes</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tacrolimus</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03823768
org study id: 00083855
nct id: NCT03823768
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in neurotoxicity burden
time frame: 6 months
description: Estimate the change from baseline to six months in neurotoxicity burden measured by a composite Patient Global Impression of Improvement score
measure: Change in mean Fahn-Tolosa-Marin (FTM) score
time frame: 6 months
description: Estimate the change in the mean FTM score among patients with self-reported tremors from baseline to six months.
arm group label: Arm 1: Control
arm group type: Active Comparator
description: Tacrolimus immediate release twice daily for 6 months
arm group label: Arm 2: Intervention
arm group type: Experimental
description: Envarsus daily for 6 months.
intervention type: Drug
intervention name: Envarsus
description: 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.
arm group label: Arm 2: Intervention
intervention type: Drug
intervention name: Tacrolimus Immediate release
description: 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.
arm group label: Arm 1: Control
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Derek Dubay, MD
role: Principal Investigator
affiliation: Medical University of South Carolina
facility: 
country: United States
responsible party type: Sponsor
mesh term: Neurotoxicity Syndromes
mesh term: Tacrolimus