<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/NCT04497168</url>
  </required_header>
  <id_info>
    <org_study_id>HUM00146905</org_study_id>
    <secondary_id>1R01AG065246</secondary_id>
    <nct_id>NCT04497168</nct_id>
  </id_info>
  <brief_title>Citalopram as a Posterior Cortical Protective Therapy in Parkinson Disease</brief_title>
  <official_title>Citalopram as a Posterior Cortical Protective Therapy in Parkinson Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Michigan</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute on Aging (NIA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Michigan</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This Parkinson disease (PD) trial will test whether 26 months of citalopram, compared to&#xD;
      placebo, can alter the build-up of toxic amyloid-beta plaques in the visuospatial cortex of&#xD;
      the brain linked to visuospatial cognitive impairment in PD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a proof-of-concept Parkinson disease trial aimed at delaying visuospatial&#xD;
      cognitive decline, an important component of Parkinson dementia. In Parkinson disease,&#xD;
      low-range cortical Abeta plaque levels associate with serotonin terminal losses. Multicenter&#xD;
      Parkinson disease observational findings show that selective serotonin reuptake inhibitors&#xD;
      (SSRIs) associate with lower dementia conversion risk and different cerebrospinal fluid&#xD;
      Abeta-42 levels. This study aims to test the hypothesis that citalopram use in Parkinson&#xD;
      disease will reduce visuospatial cortex Abeta plaque accrual, leading to an amelioration of&#xD;
      longitudinal visuospatial cognitive decline linked to Parkinsonian dementia. The study will&#xD;
      test this hypothesis in a randomized placebo-controlled trial of citalopram 20mg daily over&#xD;
      26 months in Parkinson disease subjects (age ≥65) without depression (n=58).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 1, 2021</start_date>
  <completion_date type="Anticipated">September 2025</completion_date>
  <primary_completion_date type="Anticipated">September 2025</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>Prevention</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in visuospatial cortex PiB distribution volume ratio (DVR)</measure>
    <time_frame>Baseline to month 26</time_frame>
    <description>PiB PET can assess the density of amyloid-beta plaques in the brain. This imaging method will be used to quantify the amount of change in amyloid-beta plaques levels--measured specifically within the visuospatial cortex--between month 0 and month 26.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Benton Judgement of Line Orientation (JOLO) test score</measure>
    <time_frame>Baseline to month 26</time_frame>
    <description>This is a standardized test with 30 items that is specific for visual spatial cognition. The minimum score is 0, indicating low visual spatial cognition. The maximum score is 30, indicating high visual spatial cognition.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Montreal Cognitive Assessment (MoCA) score</measure>
    <time_frame>Baseline to month 26</time_frame>
    <description>This scale evaluates different domains of cognition like attention, orientation, memory, language, visuoconstructional capacities, and lastly, executive functions. MoCA is a 30 point test with lower scores indicating impaired cognition. The maximum score is 30.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">58</enrollment>
  <condition>Parkinson Disease</condition>
  <arm_group>
    <arm_group_label>Citalopram</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>20mg daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>matching placebo pills</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Citalopram 20mg</intervention_name>
    <description>20mg daily</description>
    <arm_group_label>Citalopram</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>matching placebo pills</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects with a Parkinson Disease (PD) diagnosis based on the United Kingdom&#xD;
             Parkinson's Disease Society Brain Bank Research Center clinical diagnostic criteria&#xD;
&#xD;
          -  Modified Hoehn and Yahr (HY) scores spanning 2.0 to 3.0&#xD;
&#xD;
          -  Age 65 years or greater&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of an atypical parkinsonian condition&#xD;
&#xD;
          -  Participants on neuroleptics and participants with a history of use of&#xD;
             anti-depressants (including selective serotonin reuptake inhibitors (SSRIs) and&#xD;
             serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants&#xD;
             (TCAs), bupropion, St. John's Wort or other serotoninergic agents in the year&#xD;
             preceding study enrollment&#xD;
&#xD;
          -  Evidence of a large artery stroke or mass lesion on brain imaging&#xD;
&#xD;
          -  Participants with a life threatening comorbid illness&#xD;
&#xD;
          -  Severe claustrophobia precluding PET imaging&#xD;
&#xD;
          -  Inability to participate in research procedures involving ionizing radiation&#xD;
&#xD;
          -  Pregnancy or breastfeeding&#xD;
&#xD;
          -  Participants with active depression as defined by a Geriatric Depression Scale score&#xD;
             of &gt;10 or on the basis of clinical diagnosis by the PI&#xD;
&#xD;
          -  Participants who report active suicidal ideation as defined by an affirmative answer&#xD;
             to questions 1 and 2 on the C-SSRS&#xD;
&#xD;
          -  Participants with baseline HY scores &lt;2.0 or ≥3.0&#xD;
&#xD;
          -  Participants with a QTc interval on baseline EKG &gt;0.45 for men or &gt;0.47 for women&#xD;
&#xD;
          -  Subjects taking certain contraindicated medications at baseline&#xD;
&#xD;
          -  Subjects unable to swallow pills&#xD;
&#xD;
          -  Subjects with a previous history of mania, ongoing hepatic impairment or epilepsy&#xD;
&#xD;
          -  Subjects with a known allergy to citalopram or escitalopram&#xD;
&#xD;
          -  Subjects with substantial cognitive impairment or dementia that would prevent them&#xD;
             from providing informed consent&#xD;
&#xD;
          -  Subjects in another ongoing clinical trial&#xD;
&#xD;
          -  Subjects with treatment-naieve Parkinson disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Vikas Kotagal, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Cate Lewis</last_name>
    <phone>734-232-1199</phone>
    <email>cathlewi@med.umich.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Michigan</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Vikas Kotagal</last_name>
      <phone>734-647-4331</phone>
      <email>vikaskot@umich.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>July 29, 2020</study_first_submitted>
  <study_first_submitted_qc>July 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 4, 2020</study_first_posted>
  <last_update_submitted>February 13, 2023</last_update_submitted>
  <last_update_submitted_qc>February 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Michigan</investigator_affiliation>
    <investigator_full_name>Vikas Kotagal</investigator_full_name>
    <investigator_title>Assistant Professor of Neurology</investigator_title>
  </responsible_party>
  <keyword>Serotonin</keyword>
  <keyword>Selective Serotonin Reuptake Inhibitor</keyword>
  <keyword>Amyloid-beta</keyword>
  <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>Citalopram</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Participant data will be uploaded in a timely manner in the &quot;openICPSR&quot; Data Management Resource (DMR) of ICPSR (Inter-University Consortium for Political and Social Research). Biospecimens (DNA) will be banked in the NIA NCRAD biorepository. Uploaded datasets will be stripped of identifiers in order to prevent the possibility of identifying human subjects participants in this study from the publically available dataset.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_time_frame>Consistent with NIA policies, the study team will ensure the dataset is shared by the occurrence of the earlier of the following two milestones: either the date of primary publication or within 9 months of lifting of the data lock.</ipd_time_frame>
    <ipd_access_criteria>Access to the coded dataset that is uploaded to openICPSR is available to any individual who applies to the openICPSR for data access. This process involves providing a brief description of the intended use of the data to be downloaded, a data use agreement and data security plan, and documentation of IRB approval or exemption.</ipd_access_criteria>
    <ipd_url>https://www.openicpsr.org/openicpsr/</ipd_url>
  </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/NCT04497168
org study id: HUM00146905
secondary id: 1R01AG065246
nct id: NCT04497168
lead sponsor: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
This Parkinson disease (PD) trial will test whether 26 months of citalopram, compared to
      placebo, can alter the build-up of toxic amyloid-beta plaques in the visuospatial cortex of
      the brain linked to visuospatial cognitive impairment in PD.
This study is a proof-of-concept Parkinson disease trial aimed at delaying visuospatial
      cognitive decline, an important component of Parkinson dementia. In Parkinson disease,
      low-range cortical Abeta plaque levels associate with serotonin terminal losses. Multicenter
      Parkinson disease observational findings show that selective serotonin reuptake inhibitors
      (SSRIs) associate with lower dementia conversion risk and different cerebrospinal fluid
      Abeta-42 levels. This study aims to test the hypothesis that citalopram use in Parkinson
      disease will reduce visuospatial cortex Abeta plaque accrual, leading to an amelioration of
      longitudinal visuospatial cognitive decline linked to Parkinsonian dementia. The study will
      test this hypothesis in a randomized placebo-controlled trial of citalopram 20mg daily over
      26 months in Parkinson disease subjects (age ≥65) without depression (n=58).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Participant, Investigator)
measure: Change in visuospatial cortex PiB distribution volume ratio (DVR)
time frame: Baseline to month 26
description: PiB PET can assess the density of amyloid-beta plaques in the brain. This imaging method will be used to quantify the amount of change in amyloid-beta plaques levels--measured specifically within the visuospatial cortex--between month 0 and month 26.
measure: Change in Benton Judgement of Line Orientation (JOLO) test score
time frame: Baseline to month 26
description: This is a standardized test with 30 items that is specific for visual spatial cognition. The minimum score is 0, indicating low visual spatial cognition. The maximum score is 30, indicating high visual spatial cognition.
measure: Change in Montreal Cognitive Assessment (MoCA) score
time frame: Baseline to month 26
description: This scale evaluates different domains of cognition like attention, orientation, memory, language, visuoconstructional capacities, and lastly, executive functions. MoCA is a 30 point test with lower scores indicating impaired cognition. The maximum score is 30.
arm group label: Citalopram
arm group type: Experimental
description: 20mg daily
arm group label: Placebo
arm group type: Placebo Comparator
description: matching placebo pills
intervention type: Drug
intervention name: Citalopram 20mg
description: 20mg daily
arm group label: Citalopram
intervention type: Drug
intervention name: Placebo
description: matching placebo pills
arm group label: Placebo
criteria: 
gender: All
minimum age: 65 Years
maximum age: N/A
healthy volunteers: No
last name: Vikas Kotagal, MD
role: Principal Investigator
affiliation: University of Michigan
last name: Cate Lewis
phone: 734-232-1199
email: cathlewi@med.umich.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Michigan
investigator full name: Vikas Kotagal
investigator title: Assistant Professor of Neurology
mesh term: Parkinson Disease
mesh term: Citalopram
sharing ipd: Yes
ipd description: Participant data will be uploaded in a timely manner in the "openICPSR" Data Management Resource (DMR) of ICPSR (Inter-University Consortium for Political and Social Research). Biospecimens (DNA) will be banked in the NIA NCRAD biorepository. Uploaded datasets will be stripped of identifiers in order to prevent the possibility of identifying human subjects participants in this study from the publically available dataset.
ipd info type: Study Protocol
ipd time frame: Consistent with NIA policies, the study team will ensure the dataset is shared by the occurrence of the earlier of the following two milestones: either the date of primary publication or within 9 months of lifting of the data lock.
ipd access criteria: Access to the coded dataset that is uploaded to openICPSR is available to any individual who applies to the openICPSR for data access. This process involves providing a brief description of the intended use of the data to be downloaded, a data use agreement and data security plan, and documentation of IRB approval or exemption.
ipd url: https://www.openicpsr.org/openicpsr/