<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/NCT03840837</url>
  </required_header>
  <id_info>
    <org_study_id>HP-00084074</org_study_id>
    <secondary_id>3P30AG028747-13S3</secondary_id>
    <nct_id>NCT03840837</nct_id>
  </id_info>
  <brief_title>Cholinergic Neurotransmission in Mobility and Cognition in Parkinson Disease</brief_title>
  <official_title>Cholinergic Neurotransmission - A Common Underlying Mechanism of Cognitive and Gait Impairment in Parkinson Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Maryland, Baltimore</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 Maryland, Baltimore</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 is a single-site non-randomized open label pilot study. The investigators will use&#xD;
      accelerometer-based instrumented gait analysis and computerized cognitive testing to study&#xD;
      the interaction of motor and cognitive dysfunction in Parkinson disease dementia (PDD), and&#xD;
      the effect of rivastigmine on motor and cognitive performance. All study participants will be&#xD;
      tested for motor and cognitive performance at baseline (arm 1). A subgroup of study&#xD;
      participants will then be treated with rivastigmine for 12 weeks (arm 2), and the effect of&#xD;
      this treatment on gait measures and cognitive measures will be analyzed at the follow-up&#xD;
      visit 12 weeks after the baseline visit. Specifically, we will determine which components of&#xD;
      motor and cognitive impairment are associated with each other, and which components of the&#xD;
      two domains respond to rivastigmine-mediated stimulation of cholinergic neurotransmission.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single-site non-randomized open label clinical trial in patients with Parkinson&#xD;
      disease (PD) and mild to moderate cognitive deficits, designed to 1) identify associations&#xD;
      between cognitive impairment and gait impairment, and 2) identify cognitive domains and gait&#xD;
      measures that improve after 12 weeks of treatment with rivastigmine. Aim 1 will be addressed&#xD;
      with a cross-sectional approach (arm 1, baseline only, all participants), and aim 2 will be&#xD;
      addressed with a longitudinal interventional approach (arm 2, 12 week-treatment with&#xD;
      rivastigmine, subgroup of participants).&#xD;
&#xD;
      Patients with idiopathic Parkinson disease (PD) and mild to moderate cognitive deficits&#xD;
      amounting to PD dementia (PDD) will be enrolled. At baseline (arm 1), all participants will&#xD;
      perform the timed-up-and-go test (TUG), wearing a light-weight sensor device strapped to the&#xD;
      lower back with a neoprene belt. Participants will also complete a computerized cognitive&#xD;
      test battery (NeuroTrax Mild Cognitive Impairment &amp; Early Dementia Battery by MindStreams). A&#xD;
      subgroup of participants (arm 2) will then be treated with transdermal rivastigmine for 12&#xD;
      weeks, with dose increases every 4 weeks and titration up to 13.3 mg/24h, if tolerated. The&#xD;
      same assessment (quantitative gait testing and NeuroTrax computerized cognitive test battery)&#xD;
      will be repeated after 12 weeks, with the participant on a stable dose of transdermal&#xD;
      rivastigmine.&#xD;
&#xD;
      The investigators will analyze correlation of iTUG measures and cognitive measures at&#xD;
      baseline (cross-sectional analysis). The investigators will also analyze change in iTUG&#xD;
      measures and cognitive measures between baseline and follow-up for the subgroup of&#xD;
      participants in arm 2 (in other words, before and after rivastigmine treatment; longitudinal&#xD;
      analysis).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 2, 2019</start_date>
  <completion_date type="Actual">April 1, 2020</completion_date>
  <primary_completion_date type="Actual">April 1, 2020</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>All participants perform a baseline assessment (arm 1 - cross-sectional). A subgroup of participants (based on physician and participant choice) proceed to a 12-week treatment phase with the study drug (transdermal rivastigmine) and subsequent follow-up assessment (arm 2 - longitudinal).</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Timed-Up-and-Go (TUG) duration [s]</measure>
    <time_frame>Data analysis will be completed within 6 months of completing study enrollment.</time_frame>
    <description>Time participant needs to complete the TUG.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>NeuroTrax Executive Function score</measure>
    <time_frame>Data analysis will be completed within 6 months of completing study enrollment.</time_frame>
    <description>Result of the NeuroTrax computerized cognitive test of executive function.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>Parkinson Disease</condition>
  <condition>Parkinson Disease Dementia</condition>
  <arm_group>
    <arm_group_label>Arm 1: baseline only (cross-sectional)</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>At baseline, all participants will undergo instrumented gait/balance testing, using a wearable sensor (Dynaport MT), and cognitive testing, using a computerized cognitive test battery (NeuroTrax Mild Cognitive Impairment &amp; Early Dementia Battery by MindStreams). In other words, all participants will be part of arm 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2: rivastigmine (longitudinal)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>As study intervention, a subgroup of participants will then be treated with transdermal rivastigmine patch for 12 weeks, with dose increases every 4 weeks and titration up to 13.3 mg/24h, if tolerated. For the arm 2 subgroup of participants, the same assessment that was performed at baseline (quantitative gait testing and NeuroTrax computerized cognitive test battery) will be repeated after 12 weeks, with the patient on a stable dose of transdermal rivastigmine.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rivastigmine transdermal patch</intervention_name>
    <description>Titration of transdermal rivastigmine, as per arm description.</description>
    <arm_group_label>Arm 2: rivastigmine (longitudinal)</arm_group_label>
    <other_name>Exelon transdermal patch</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years.&#xD;
&#xD;
          -  Diagnosis of idiopathic Parkinson disease.&#xD;
&#xD;
          -  Mild to moderate cognitive impairment, as determined by a MoCA score of ≤ 25 and ≥ 10.&#xD;
&#xD;
          -  Patient passes the Evaluation to Sign Consent (ESC) or a legally authorized&#xD;
             representative (LAR) is present at the time of enrollment and signs the informed&#xD;
             consent form on behalf of the patient.&#xD;
&#xD;
          -  Patient is enrolled (or willing to be enrolled) in the University of Maryland&#xD;
             Parkinson Disease and Movement Disorders Center PD Research Database (HP 42195)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Advanced Parkinson disease (Hoehn &amp; Yahr stage 5), with inability to walk unassisted.&#xD;
&#xD;
          -  Other medical condition(s) that significantly interfere(s) with gait and balance&#xD;
             (e.g., advanced arthritis).&#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>Rainer von Coelln, Dr. med.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Maryland School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Maryland School of Medicine, Dept. of Neurology</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>February 11, 2019</study_first_submitted>
  <study_first_submitted_qc>February 12, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 15, 2019</study_first_posted>
  <disposition_first_submitted>January 21, 2022</disposition_first_submitted>
  <disposition_first_submitted_qc>January 21, 2022</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">January 26, 2022</disposition_first_posted>
  <last_update_submitted>January 25, 2022</last_update_submitted>
  <last_update_submitted_qc>January 25, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 31, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Maryland, Baltimore</investigator_affiliation>
    <investigator_full_name>F. Rainer von Coelln, MD</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>cognitive impairment</keyword>
  <keyword>Parkinson disease dementia</keyword>
  <keyword>wearable sensor</keyword>
  <keyword>gait analysis</keyword>
  <keyword>rivastigmine</keyword>
  <keyword>cholinesterase inhibitor</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinson Disease</mesh_term>
    <mesh_term>Dementia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rivastigmine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>All data generated during this project will be shared with the scientific community through peer-reviewed publications and presentations at national and international conferences.&#xD;
We will share our raw data with qualified collaborating scientists upon request. Only aggregated data of study participants will be made available to other researchers.</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT03840837
org study id: HP-00084074
secondary id: 3P30AG028747-13S3
nct id: NCT03840837
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This is a single-site non-randomized open label pilot study. The investigators will use
      accelerometer-based instrumented gait analysis and computerized cognitive testing to study
      the interaction of motor and cognitive dysfunction in Parkinson disease dementia (PDD), and
      the effect of rivastigmine on motor and cognitive performance. All study participants will be
      tested for motor and cognitive performance at baseline (arm 1). A subgroup of study
      participants will then be treated with rivastigmine for 12 weeks (arm 2), and the effect of
      this treatment on gait measures and cognitive measures will be analyzed at the follow-up
      visit 12 weeks after the baseline visit. Specifically, we will determine which components of
      motor and cognitive impairment are associated with each other, and which components of the
      two domains respond to rivastigmine-mediated stimulation of cholinergic neurotransmission.
This is a single-site non-randomized open label clinical trial in patients with Parkinson
      disease (PD) and mild to moderate cognitive deficits, designed to 1) identify associations
      between cognitive impairment and gait impairment, and 2) identify cognitive domains and gait
      measures that improve after 12 weeks of treatment with rivastigmine. Aim 1 will be addressed
      with a cross-sectional approach (arm 1, baseline only, all participants), and aim 2 will be
      addressed with a longitudinal interventional approach (arm 2, 12 week-treatment with
      rivastigmine, subgroup of participants).

      Patients with idiopathic Parkinson disease (PD) and mild to moderate cognitive deficits
      amounting to PD dementia (PDD) will be enrolled. At baseline (arm 1), all participants will
      perform the timed-up-and-go test (TUG), wearing a light-weight sensor device strapped to the
      lower back with a neoprene belt. Participants will also complete a computerized cognitive
      test battery (NeuroTrax Mild Cognitive Impairment & Early Dementia Battery by MindStreams). A
      subgroup of participants (arm 2) will then be treated with transdermal rivastigmine for 12
      weeks, with dose increases every 4 weeks and titration up to 13.3 mg/24h, if tolerated. The
      same assessment (quantitative gait testing and NeuroTrax computerized cognitive test battery)
      will be repeated after 12 weeks, with the participant on a stable dose of transdermal
      rivastigmine.

      The investigators will analyze correlation of iTUG measures and cognitive measures at
      baseline (cross-sectional analysis). The investigators will also analyze change in iTUG
      measures and cognitive measures between baseline and follow-up for the subgroup of
      participants in arm 2 (in other words, before and after rivastigmine treatment; longitudinal
      analysis).
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: All participants perform a baseline assessment (arm 1 - cross-sectional). A subgroup of participants (based on physician and participant choice) proceed to a 12-week treatment phase with the study drug (transdermal rivastigmine) and subsequent follow-up assessment (arm 2 - longitudinal).
primary purpose: Treatment
masking: None (Open Label)
measure: Timed-Up-and-Go (TUG) duration [s]
time frame: Data analysis will be completed within 6 months of completing study enrollment.
description: Time participant needs to complete the TUG.
measure: NeuroTrax Executive Function score
time frame: Data analysis will be completed within 6 months of completing study enrollment.
description: Result of the NeuroTrax computerized cognitive test of executive function.
arm group label: Arm 1: baseline only (cross-sectional)
arm group type: No Intervention
description: At baseline, all participants will undergo instrumented gait/balance testing, using a wearable sensor (Dynaport MT), and cognitive testing, using a computerized cognitive test battery (NeuroTrax Mild Cognitive Impairment & Early Dementia Battery by MindStreams). In other words, all participants will be part of arm 1.
arm group label: Arm 2: rivastigmine (longitudinal)
arm group type: Experimental
description: As study intervention, a subgroup of participants will then be treated with transdermal rivastigmine patch for 12 weeks, with dose increases every 4 weeks and titration up to 13.3 mg/24h, if tolerated. For the arm 2 subgroup of participants, the same assessment that was performed at baseline (quantitative gait testing and NeuroTrax computerized cognitive test battery) will be repeated after 12 weeks, with the patient on a stable dose of transdermal rivastigmine.
intervention type: Drug
intervention name: Rivastigmine transdermal patch
description: Titration of transdermal rivastigmine, as per arm description.
arm group label: Arm 2: rivastigmine (longitudinal)
other name: Exelon transdermal patch
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Rainer von Coelln, Dr. med.
role: Principal Investigator
affiliation: University of Maryland School of Medicine
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Maryland, Baltimore
investigator full name: F. Rainer von Coelln, MD
investigator title: Assistant Professor
mesh term: Parkinson Disease
mesh term: Dementia
mesh term: Rivastigmine
sharing ipd: No
ipd description: All data generated during this project will be shared with the scientific community through peer-reviewed publications and presentations at national and international conferences.
We will share our raw data with qualified collaborating scientists upon request. Only aggregated data of study participants will be made available to other researchers.