<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/NCT03242499</url>
  </required_header>
  <id_info>
    <org_study_id>NCTRC201702</org_study_id>
    <nct_id>NCT03242499</nct_id>
  </id_info>
  <brief_title>Lovastatin as a Neuroprotective Treatment for Early Stage Parkinson's Disease</brief_title>
  <official_title>Lovastatin as a Neuroprotective Treatment for Early Stage Parkinson's Disease: a Single-center, Double-blind, Placebo-controlled Randomized Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Taiwan University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Taiwan University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background: Recent evidence has shown that statins, especially lipophilic statins, may have a&#xD;
      neuroprotective benefit in Parkinson's disease (PD). We aim to perform a randomized&#xD;
      placebo-controlled trial evaluating the disease-modifying efficacy of lovastatin in patients&#xD;
      with early stage PD.&#xD;
&#xD;
      Methods and Study Design: This study will be a phase II, single-center, double-blind,&#xD;
      randomized, placebo-controlled parallel-group study. In this trial, we are going to examine&#xD;
      the possibility that lovastatin, a highly potent lipophilic statin, has disease-modifying&#xD;
      effects in PD. We are going to enroll 80 patients with early stage PD patients. Subjects will&#xD;
      then be randomized to a 48-week double-blind treatment period of lovastatin 80mg/day or&#xD;
      placebo. Primary endpoints are changes in motor severity based on Movement Disorder&#xD;
      Society-Unified Parkinson's Disease Rating Scale motor sub-score (MDS-UPDRS part III, with&#xD;
      higher numbers indicating more severe disease). During the follow-up period, the dose of&#xD;
      anti-parkinsonism could be added if both the patients and doctors thought the clinical&#xD;
      condition deteriorated. Changes in PD medication as measured by levodopa-equivalent dose&#xD;
      (LED) will be recorded at each visit. The secondary endpoints measured include MDS-UPDRS&#xD;
      total scores, Part I and Part II sub-scores, the timing and dose of added anti-parkinsonism&#xD;
      medication during the treatment period, the changes of 18F-DOPA PET uptake and MMSE scores,&#xD;
      and global impression scale (GCI) of patients and investigators at the end of the study.&#xD;
&#xD;
      Expected results: We hypothesize that lovastatin would slow down both motor and cognitive&#xD;
      symptoms deterioration and dopaminergic neuronal degeneration in patients with early stage&#xD;
      PD.&#xD;
&#xD;
      Importance of the study: Our study will provide Class II evidence that intensive lipid&#xD;
      lowering with lovastatin 80 mg/day decrease the disease progression in patients with early&#xD;
      stage PD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase 2, single-center, randomized, double-blind, placebo-controlled,&#xD;
      parallel-group, 2-arm study in patients with mild to moderate PD. There will be three phases&#xD;
      to the study. An initial 12-week screening phase was performed to determine eligibility.&#xD;
      After informed consents, early-stage PD patients with Hoehn-Yahr stage 1 will be enrolled and&#xD;
      participants will be asked to stop previously used anti-parkinsonism medications for at least&#xD;
      one month to see the baseline disease severity. At the start of the study, participants will&#xD;
      receive a comprehensive parkinsonism symptoms evaluation using Movement Disorder&#xD;
      Society-Unified Parkinson's disease rating scale (MDS-UPDRS), global cognitive test using&#xD;
      MMSE, and will be arranged for 18F-DOPA PET scan to evaluate the dopaminergic reserve in the&#xD;
      striatum. Participants will also be asked to fasting for at least 8 hours to check the&#xD;
      baseline laboratory test, including liver/renal functions, lipid profiles and serum CK level.&#xD;
      Subjects will then be randomized to a 48-week double-blind treatment period of oral&#xD;
      lovastatin 80mg/day or placeboSubjects in both groups will attend a further 5 clinic visits&#xD;
      after 4, 12, 24, 36, and 48 weeks, where they are asked about their neurological symptoms and&#xD;
      are evaluated by MDS-UPDRS. During the follow-up period, the dose of anti-parkinsonism could&#xD;
      be added if both the patients and doctors thought the clinical condition deteriorated.&#xD;
      Changes in PD medication as measured by levodopa-equivalent dose (LED) will be recorded at&#xD;
      each visit. At final visit, patients will be arranged to receive the follow up 18F-DOPA PET&#xD;
      scan to evaluate the dopaminergic reservation in the striatum and received MDS-UPDRS and MMSE&#xD;
      evaluation. The secondary endpoints measured include MDS-UPDRS total scores, Part I and Part&#xD;
      II sub-scores, the timing and dose of added anti-parkinsonism medication during the treatment&#xD;
      period, the changes of 18F-DOPA PET uptake and MMSE scores, and global impression scale (GCI)&#xD;
      of patients and investigators at the end of the study.&#xD;
&#xD;
      After informed consent form is completed, each patient will participate in the study for up&#xD;
      to 48 weeks (a Screening Period of ≤12 weeks, followed by a Baseline Visit, 48 weeks of&#xD;
      double-blind treatment, and a 4-week post-dose Safety Follow-up Visit) The post-dose Safety&#xD;
      Follow-up Visit is for patients early terminating or not willing to participate in the&#xD;
      open-label extension study):&#xD;
&#xD;
        -  Screening Period: 16 weeks&#xD;
&#xD;
        -  Treatment Period: 48 weeks&#xD;
&#xD;
        -  Safety Follow-Up Period: 4 weeks After completion of the Treatment Period in this&#xD;
           double-blind, placebo-controlled study, patients will be offered the option to enroll in&#xD;
           an open-label extension study until 5 years. The end of the study is defined as the date&#xD;
           of the last visit of the last patient in the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">May 15, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2019</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2019</primary_completion_date>
  <phase>Phase 2</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>Other</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes of MDS-UPDRS Part III (motor subscale) from baseline to week 48</measure>
    <time_frame>After informed consent form is completed, each patient will participate in the study for up to 48 weeks (a Screening Period of ≤12 weeks, followed by a Baseline Visit, 48 weeks of double-blind treatment, and a 4-week post-dose Safety Follow-up Visit</time_frame>
    <description>Measure the motor symptoms severity changes of Parkinson's disease</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Parkinson Disease</condition>
  <arm_group>
    <arm_group_label>Active</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Lovastatin 80mg per day for 48 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo 80mg per day for 48 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lovastatin</intervention_name>
    <description>Lovastatin 80mg or placebo use for 48 weeks.</description>
    <arm_group_label>Active</arm_group_label>
    <other_name>LOVASTATIN &quot;YUNG SHIN&quot;</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>placebo for 48 weeks</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient is informed and given ample time and opportunity to think about his/her&#xD;
             participation in this study and has given his/her written informed consent on an&#xD;
             Independent Review Board (IRB) approved consent form.&#xD;
&#xD;
          -  Patient is considered reliable and capable of adhering to the protocol, visit&#xD;
             schedule, or medication administration according to the judgment of the investigator.&#xD;
&#xD;
          -  Patient has a documented history of idiopathic PD consistent with the UK Parkinson's&#xD;
             Disease Society Brain Bank Diagnostic criteria [14] prior to the Screening Visit.&#xD;
&#xD;
          -  Modified Hoehn and Yahr stage =1 in the off medication state (stop medications for 1&#xD;
             month)&#xD;
&#xD;
          -  Patients did not previously receive any anti-parkinsonism medications (drug naïve) or&#xD;
             had stopped medications for at least 1 month.&#xD;
&#xD;
          -  Age 30-90 years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient has any form of secondary or atypical parkinsonism (e.g., drug-induced, post&#xD;
             stroke).&#xD;
&#xD;
          -  Patient has known abnormality on brain CT or MRI imaging considered to be causing&#xD;
             symptoms or signs of neurological dysfunction.&#xD;
&#xD;
          -  Prior intracerebral surgical intervention for PD including deep brain stimulation&#xD;
             (DBS).&#xD;
&#xD;
          -  Prior or current use of statins as a lipid lowering therapy&#xD;
&#xD;
          -  End stage renal disease (creatinine clearance eGFR &lt;30 mL/min) or history of severe&#xD;
             cardiac disease (angina, myocardial infarction or cardiac surgery in preceding two&#xD;
             years)&#xD;
&#xD;
          -  Abnormal liver function with aspartate transaminase (AST) or alanine transaminase&#xD;
             (ALT) &gt;2 x upper normal limit.&#xD;
&#xD;
          -  Creatine kinase (CK) &gt;2 x upper normal limit of normal.&#xD;
&#xD;
          -  History of myopathy or rhabdolyolysis.&#xD;
&#xD;
          -  Females who are pregnant or breast feeding.&#xD;
&#xD;
          -  Patient has a history of chronic alcohol or drug abuse within the last 2 years.&#xD;
&#xD;
          -  Exposure to neuroleptics (antipsychotic drugs) for more than 1 month within the past 2&#xD;
             years, or any exposure within the past year (except for quetiapine).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chin-Hsien Lin, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Taiwan University Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Chin-Hsien Lin, MD, PhD</last_name>
    <phone>886-2-23123456</phone>
    <phone_ext>65335</phone_ext>
    <email>chlin@ntu.edu.tw</email>
  </overall_contact>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>100</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Chin-Hsien Lin, MD,PhD</last_name>
      <phone>886-2-3123456</phone>
      <phone_ext>65335</phone_ext>
      <email>chlin@ntu.edu.tw</email>
    </contact>
    <investigator>
      <last_name>Chin-Hsien Lin, MD,PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>August 1, 2017</study_first_submitted>
  <study_first_submitted_qc>August 7, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 8, 2017</study_first_posted>
  <last_update_submitted>October 15, 2017</last_update_submitted>
  <last_update_submitted_qc>October 15, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 17, 2017</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>Parkinson Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lovastatin</mesh_term>
    <mesh_term>L 647318</mesh_term>
    <mesh_term>Dihydromevinolin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03242499
org study id: NCTRC201702
nct id: NCT03242499
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Background: Recent evidence has shown that statins, especially lipophilic statins, may have a
      neuroprotective benefit in Parkinson's disease (PD). We aim to perform a randomized
      placebo-controlled trial evaluating the disease-modifying efficacy of lovastatin in patients
      with early stage PD.

      Methods and Study Design: This study will be a phase II, single-center, double-blind,
      randomized, placebo-controlled parallel-group study. In this trial, we are going to examine
      the possibility that lovastatin, a highly potent lipophilic statin, has disease-modifying
      effects in PD. We are going to enroll 80 patients with early stage PD patients. Subjects will
      then be randomized to a 48-week double-blind treatment period of lovastatin 80mg/day or
      placebo. Primary endpoints are changes in motor severity based on Movement Disorder
      Society-Unified Parkinson's Disease Rating Scale motor sub-score (MDS-UPDRS part III, with
      higher numbers indicating more severe disease). During the follow-up period, the dose of
      anti-parkinsonism could be added if both the patients and doctors thought the clinical
      condition deteriorated. Changes in PD medication as measured by levodopa-equivalent dose
      (LED) will be recorded at each visit. The secondary endpoints measured include MDS-UPDRS
      total scores, Part I and Part II sub-scores, the timing and dose of added anti-parkinsonism
      medication during the treatment period, the changes of 18F-DOPA PET uptake and MMSE scores,
      and global impression scale (GCI) of patients and investigators at the end of the study.

      Expected results: We hypothesize that lovastatin would slow down both motor and cognitive
      symptoms deterioration and dopaminergic neuronal degeneration in patients with early stage
      PD.

      Importance of the study: Our study will provide Class II evidence that intensive lipid
      lowering with lovastatin 80 mg/day decrease the disease progression in patients with early
      stage PD.
This is a Phase 2, single-center, randomized, double-blind, placebo-controlled,
      parallel-group, 2-arm study in patients with mild to moderate PD. There will be three phases
      to the study. An initial 12-week screening phase was performed to determine eligibility.
      After informed consents, early-stage PD patients with Hoehn-Yahr stage 1 will be enrolled and
      participants will be asked to stop previously used anti-parkinsonism medications for at least
      one month to see the baseline disease severity. At the start of the study, participants will
      receive a comprehensive parkinsonism symptoms evaluation using Movement Disorder
      Society-Unified Parkinson's disease rating scale (MDS-UPDRS), global cognitive test using
      MMSE, and will be arranged for 18F-DOPA PET scan to evaluate the dopaminergic reserve in the
      striatum. Participants will also be asked to fasting for at least 8 hours to check the
      baseline laboratory test, including liver/renal functions, lipid profiles and serum CK level.
      Subjects will then be randomized to a 48-week double-blind treatment period of oral
      lovastatin 80mg/day or placeboSubjects in both groups will attend a further 5 clinic visits
      after 4, 12, 24, 36, and 48 weeks, where they are asked about their neurological symptoms and
      are evaluated by MDS-UPDRS. During the follow-up period, the dose of anti-parkinsonism could
      be added if both the patients and doctors thought the clinical condition deteriorated.
      Changes in PD medication as measured by levodopa-equivalent dose (LED) will be recorded at
      each visit. At final visit, patients will be arranged to receive the follow up 18F-DOPA PET
      scan to evaluate the dopaminergic reservation in the striatum and received MDS-UPDRS and MMSE
      evaluation. The secondary endpoints measured include MDS-UPDRS total scores, Part I and Part
      II sub-scores, the timing and dose of added anti-parkinsonism medication during the treatment
      period, the changes of 18F-DOPA PET uptake and MMSE scores, and global impression scale (GCI)
      of patients and investigators at the end of the study.

      After informed consent form is completed, each patient will participate in the study for up
      to 48 weeks (a Screening Period of ≤12 weeks, followed by a Baseline Visit, 48 weeks of
      double-blind treatment, and a 4-week post-dose Safety Follow-up Visit) The post-dose Safety
      Follow-up Visit is for patients early terminating or not willing to participate in the
      open-label extension study):

        -  Screening Period: 16 weeks

        -  Treatment Period: 48 weeks

        -  Safety Follow-Up Period: 4 weeks After completion of the Treatment Period in this
           double-blind, placebo-controlled study, patients will be offered the option to enroll in
           an open-label extension study until 5 years. The end of the study is defined as the date
           of the last visit of the last patient in the study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Double (Participant, Investigator)
measure: Changes of MDS-UPDRS Part III (motor subscale) from baseline to week 48
time frame: After informed consent form is completed, each patient will participate in the study for up to 48 weeks (a Screening Period of ≤12 weeks, followed by a Baseline Visit, 48 weeks of double-blind treatment, and a 4-week post-dose Safety Follow-up Visit
description: Measure the motor symptoms severity changes of Parkinson's disease
arm group label: Active
arm group type: Experimental
description: Lovastatin 80mg per day for 48 weeks.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo 80mg per day for 48 weeks.
intervention type: Drug
intervention name: Lovastatin
description: Lovastatin 80mg or placebo use for 48 weeks.
arm group label: Active
other name: LOVASTATIN "YUNG SHIN"
intervention type: Drug
intervention name: Placebo
description: placebo for 48 weeks
arm group label: Placebo
criteria: 
gender: All
minimum age: 30 Years
maximum age: 90 Years
healthy volunteers: No
last name: Chin-Hsien Lin, MD, PhD
role: Principal Investigator
affiliation: National Taiwan University Hospital
last name: Chin-Hsien Lin, MD, PhD
phone: 886-2-23123456
phone ext: 65335
email: chlin@ntu.edu.tw
facility: 
status: Recruiting
contact: 
investigator: 
country: Taiwan
responsible party type: Sponsor
mesh term: Parkinson Disease
mesh term: Lovastatin
mesh term: L 647318
mesh term: Dihydromevinolin
sharing ipd: No