<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/NCT04403399</url>
  </required_header>
  <id_info>
    <org_study_id>HUM00093188-a</org_study_id>
    <nct_id>NCT04403399</nct_id>
  </id_info>
  <brief_title>Crossover Target Engagement Study of Cholinergic Mechanisms of Gait Dysfunction in Parkinson's Disease (Project #3 - Experiment 3 [UdallP3E3])</brief_title>
  <acronym>UdallP3E3</acronym>
  <official_title>Cholinergic Mechanisms of Gait Dysfunction in Parkinson's Disease Experiment 3 - Project #3</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Michigan</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Michigan</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>
      With an appropriate oral dose of Varenicline (VCN) identified from experiments 1 &amp; 2 of the&#xD;
      study (see NCT02933372), the investigators will administer VCN to Parkinson Disease (PD)&#xD;
      participants to determine if VCN improves walking speed and measures of balance. PD&#xD;
      participants will receive VCN or a placebo (fake drug) for 3 weeks to assess the effects of&#xD;
      VCN administration on gait speed and balance. Participants will undergo examinations to&#xD;
      assess the intensity of their Parkinsonism and asked questions to assess their mood and&#xD;
      thinking.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      To demonstrate that α4β2* nAChRs are appropriate therapeutic targets in Parkinson's Disease&#xD;
      (PD), it is necessary to study key pharmacokinetic-pharmacodynamic features of α4β2* nAChR in&#xD;
      the context of the PD brain with loss of nerve cells that produce the neurotransmitter&#xD;
      acetylcholine, a pathologic environment in which they may exhibit unique features. This&#xD;
      personalized medicine approach focuses our studies on the subgroup of PD subjects with loss&#xD;
      of nerve cells that produce the neurotransmitter acetylcholine identified by Project II and&#xD;
      the Clinical Resource Core. The investigators will assess α4β2* nAChR features using PET&#xD;
      imaging with the α4β2* nAChR ligand [18-Fluorine]flubatine, subacute administration of the&#xD;
      α4β2* nAChR partial agonist Varenicline (VCN), and laboratory measures of gait, balance, and&#xD;
      attention. The investigators will use [18-Fluorine] flubatine PET to assess VCN occupancy of&#xD;
      brain α4β2* nAChRs (experiments 1 &amp; 2). VCN will be administered to both PD participants&#xD;
      (experiment 1) and healthy controls (experiment 2) and both populations will undergo a&#xD;
      flubatine PET scan to assess VCN occupancy. Using this PET data to select an appropriate VCN&#xD;
      dose, the investigators will perform a pharmacodynamic study (experiment 3) with subacute VCN&#xD;
      administration to determine if α4β2* nAChR stimulation improves laboratory measures of gait&#xD;
      function, postural control, and attentional function in PD subjects with loss of nerve cells&#xD;
      that produce the neurotransmitter acetylcholine.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 29, 2017</start_date>
  <completion_date type="Actual">June 26, 2019</completion_date>
  <primary_completion_date type="Actual">June 26, 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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Gait Speed</measure>
    <time_frame>end of each period: 22 and 64 days</time_frame>
    <description>Gait speed, how fast a person can walk down a corridor, at normal pace with no distractors (i.e., no dual task).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>JERK</measure>
    <time_frame>end of each period: 22 and 64 days</time_frame>
    <description>JERK is the time based derivative of spontaneous lower trunk accelerations during standing. It was assessed with the Ambulatory Parkinson's Disease Monitoring (APDM) wearable sensor system (APDM Wearable Technologies, Inc.) using the iSWAY protocol, with participants standing on a foam pad with eyes closed. JERK was calculated using the manufacturer's software (Mobility Lab Version 1).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Attention</measure>
    <time_frame>end of period: days 22 and 64</time_frame>
    <description>Attention function will be measured with a standard computer test, the Sustained Attention Test (SAT), without a distractor condition. Results are reported as the vigilance index, a measure that corrects estimates of accurate detection with penalties for false detection and not confounded by errors of omission. (Frey PW, Colliver JA. Sensitivity and responsivity measures for discrimination learning. Learn Motiv 1973; 4:327-342.) The minimum score is -1.00 (indicating that all recorded responses were misses or false alarms) and maximum is +1 (indicating that all recorded responses were hits or correct rejections). Higher values indicate better attentional performance.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">34</enrollment>
  <condition>Parkinson's Disease</condition>
  <arm_group>
    <arm_group_label>Varenicline then Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Varenicline 0.5 mg BID orally for 3 weeks, followed by a 3-week washout period, then placebo BID orally for 3 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo then Varenicline</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Placebo BID orally for 3 weeks, followed by a 3-week washout period, then Varenicline 0.5 mg BID orally for 3 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Varenicline</intervention_name>
    <description>Initial 0.25 mg oral dose of varenicline administered with monitoring over 4 hours, then total daily dose escalated over the next 2 days until final 0.5 mg BID oral varenicline administered for the remaining 3 weeks.</description>
    <arm_group_label>Placebo then Varenicline</arm_group_label>
    <arm_group_label>Varenicline then Placebo</arm_group_label>
    <other_name>Chantix</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Initial placebo oral dose administered with monitoring over 4 hours, then total daily dose escalated over the next 2 days until final placebo BID dosing administered orally for the remaining 3 weeks.</description>
    <arm_group_label>Placebo then Varenicline</arm_group_label>
    <arm_group_label>Varenicline then Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. PD diagnosis will be based on the United Kingdom Parkinson's Disease Society Brain&#xD;
             Bank Research Center (UKPDSBRC) clinical diagnostic criteria. The investigators will&#xD;
             enrich the cohort by recruiting subjects at modified Hoehn and Yahr stages 2 or&#xD;
             higher, duration of motor disease 5 years or longer, age &gt;65 years, or the Postural&#xD;
             Instability and Gait Disorder (PIGD) phenotype. Duration of motor disease will be&#xD;
             defined as the time between onset of motor symptoms and time of entry into the study.&#xD;
             The PIGD phenotype is defined as described previously. PD subjects with defined&#xD;
             cholinergic deficits will be recruited as described in Project II. PD subjects will&#xD;
             have cortical cholinergic deficits based on 5th percentile cutoff of the normal&#xD;
             controls as defined previously.&#xD;
&#xD;
          2. Stable dopaminergic replacement therapy for 3 months prior to enrollment and expected&#xD;
             to maintain stable dopaminergic therapy for duration of study participation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Other disorders which may resemble PD with or without dementia, such as vascular&#xD;
             dementia, normal pressure hydrocephalus, progressive supranuclear palsy, multiple&#xD;
             system atrophy, corticobasal ganglionic degeneration, or toxic causes of parkinsonism.&#xD;
             Prototypical cases have distinctive clinical profiles, like vertical supranuclear gaze&#xD;
             palsy, early and severe dysautonomia or appendicular apraxia, which may differentiate&#xD;
             them from idiopathic PD. The use of the UKPDSBRC clinical diagnostic criteria for PD&#xD;
             will mitigate the inclusion of subjects with atypical parkinsonism and all&#xD;
             participants will undergo [11-Carbon]dihydrotetrabenazine PET to confirm striatal&#xD;
             dopaminergic denervation.&#xD;
&#xD;
          2. Subjects on neuroleptic, anticholinergic (trihexphenidyl, benztropine), or&#xD;
             cholinesterase inhibitor drugs.&#xD;
&#xD;
          3. Current or previous (within last 6 months) use of any product or medication containing&#xD;
             nicotinic agents,including use of tobacco products such as cigarettes, cigars, pipes,&#xD;
             chewing tobacco, etc., electronic cigarettes, over-the-counter nicotine patches,&#xD;
             chewing gum containing nicotine, or varenicline.&#xD;
&#xD;
          4. Evidence of a stroke or mass lesion on structural brain imaging (MRI).&#xD;
&#xD;
          5. Participants in whom magnetic resonance imaging (MRI) is contraindicated including,&#xD;
             but not limited to, those with a pacemaker, presence of metallic fragments near the&#xD;
             eyes or spinal cord, or cochlear implant.&#xD;
&#xD;
          6. Severe claustrophobia precluding MR or PET imaging&#xD;
&#xD;
          7. Subjects limited by participation in research procedures involving ionizing radiation.&#xD;
&#xD;
          8. Pregnancy (test within 48 hours of each PET session) or breastfeeding.&#xD;
&#xD;
          9. Significant risk of cardiovascular event.&#xD;
&#xD;
         10. Active, significant mood disorder.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>45 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Roger L Albin, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Michigan</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Mancini M, Carlson-Kuhta P, Zampieri C, Nutt JG, Chiari L, Horak FB. Postural sway as a marker of progression in Parkinson's disease: a pilot longitudinal study. Gait Posture. 2012 Jul;36(3):471-6. doi: 10.1016/j.gaitpost.2012.04.010. Epub 2012 Jun 29.</citation>
    <PMID>22750016</PMID>
  </results_reference>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>May 21, 2020</study_first_submitted>
  <study_first_submitted_qc>May 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 27, 2020</study_first_posted>
  <results_first_submitted>December 21, 2020</results_first_submitted>
  <results_first_submitted_qc>January 25, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">January 27, 2021</results_first_posted>
  <disposition_first_submitted>May 27, 2020</disposition_first_submitted>
  <disposition_first_submitted_qc>January 25, 2021</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">January 27, 2021</disposition_first_posted>
  <last_update_submitted>January 25, 2021</last_update_submitted>
  <last_update_submitted_qc>January 25, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 27, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Michigan</investigator_affiliation>
    <investigator_full_name>Roger L. Albin</investigator_full_name>
    <investigator_title>Professor of Neurology</investigator_title>
  </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>Varenicline</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 1, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/99/NCT04403399/SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>April 17, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/99/NCT04403399/Prot_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Varenicline Then Placebo</title>
          <description>Patients will take varenicline initially for 3 weeks, then after a 3 week washout period, they will switch to placebo for 3 weeks.</description>
        </group>
        <group group_id="P2">
          <title>Placebo Then Varenicline</title>
          <description>Patients will take placebo initially for 3 weeks, then after a 3 week washout period they will switch to varenicline for 3 weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Period 1</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Period 2</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Varenicline Then Placebo</title>
          <description>Patients will take varenicline initially for 3 weeks, then after a 3 week washout period, they will switch to placebo for 3 weeks.</description>
        </group>
        <group group_id="B2">
          <title>Placebo Then Varenicline</title>
          <description>Patients will take placebo initially for 3 weeks, then after a 3 week washout period, they will switch to varenicline for 3 weeks.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="18"/>
            <count group_id="B2" value="16"/>
            <count group_id="B3" value="34"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="68.1" spread="5.7"/>
                    <measurement group_id="B2" value="64.2" spread="5.3"/>
                    <measurement group_id="B3" value="66.3" spread="5.78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age at Diagnosis of Parkinson's Disease</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61.3" spread="6.66"/>
                    <measurement group_id="B2" value="57.7" spread="7.22"/>
                    <measurement group_id="B3" value="59.6" spread="7.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>MDS-UPDRS III</title>
          <description>Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III (motor examination) includes 18 items (33 scores). Each item scores from 0 (normal) to 4 (severe) and total score is obtained from the sum of the corresponding item scores. The minimum is 0, maximum is 132, with higher scores indicating more disability.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="33.2" spread="13.92"/>
                    <measurement group_id="B2" value="30.7" spread="12.4"/>
                    <measurement group_id="B3" value="32.0" spread="13.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Geriatric Depression Scale</title>
          <description>Geriatric Depression Scale (GDS) is a 30-item questionnaire (long form) to measure depression in the older population. Participants are asked to respond yes or no to how they felt over the past week. Scores range from 0 to 30, with higher scores indicating more severe depression.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2.4" spread="2.06"/>
                    <measurement group_id="B2" value="4.3" spread="4.19"/>
                    <measurement group_id="B3" value="3.3" spread="3.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Montreal Cognitive Assessment</title>
          <description>Montreal Cognitive Assessment (MoCA) is a questionnaire assessing cognitive dysfunction. It assesses attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. The score ranges from 0 to 30, with higher scores indicating more severe cognitive impairment.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27.2" spread="2.37"/>
                    <measurement group_id="B2" value="26.8" spread="1.97"/>
                    <measurement group_id="B3" value="27.0" spread="2.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Gait Speed</title>
        <description>Gait speed, how fast a person can walk down a corridor, at normal pace with no distractors (i.e., no dual task).</description>
        <time_frame>end of each period: 22 and 64 days</time_frame>
        <population>All randomized participants were included in the mixed effects model. One participant randomized to the placebo then varenicline group was withdrawn by the physician early in period 2; 1 participant randomized to the varenicline then placebo group did not complete the gait assessment in period 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Varenicline</title>
            <description>0.5 mg PO BID varenicline for 3 weeks (beginning with a 0.25 mg dose and escalated over the next 2 days)</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>placebo given PO BID for 3 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Gait Speed</title>
          <description>Gait speed, how fast a person can walk down a corridor, at normal pace with no distractors (i.e., no dual task).</description>
          <population>All randomized participants were included in the mixed effects model. One participant randomized to the placebo then varenicline group was withdrawn by the physician early in period 2; 1 participant randomized to the varenicline then placebo group did not complete the gait assessment in period 2.</population>
          <units>cm/s</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="121.27" spread="1.36"/>
                    <measurement group_id="O2" value="124.89" spread="1.36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.003</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-3.62</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>JERK</title>
        <description>JERK is the time based derivative of spontaneous lower trunk accelerations during standing. It was assessed with the Ambulatory Parkinson's Disease Monitoring (APDM) wearable sensor system (APDM Wearable Technologies, Inc.) using the iSWAY protocol, with participants standing on a foam pad with eyes closed. JERK was calculated using the manufacturer's software (Mobility Lab Version 1).</description>
        <time_frame>end of each period: 22 and 64 days</time_frame>
        <population>All randomized participants were included in the mixed effects model. One participant randomized to the placebo then varenicline group was withdrawn by the physician early in period 2; two participants randomized to the varenicline then placebo group did not complete the iSWAY protocol in period 2.</population>
        <group_list>
          <group group_id="O1">
            <title>Varenicline</title>
            <description>0.5 mg PO BID varenicline for 3 weeks (beginning with a 0.25 mg dose and escalated over the next 2 days)</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>placebo given PO BID for 3 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>JERK</title>
          <description>JERK is the time based derivative of spontaneous lower trunk accelerations during standing. It was assessed with the Ambulatory Parkinson's Disease Monitoring (APDM) wearable sensor system (APDM Wearable Technologies, Inc.) using the iSWAY protocol, with participants standing on a foam pad with eyes closed. JERK was calculated using the manufacturer's software (Mobility Lab Version 1).</description>
          <population>All randomized participants were included in the mixed effects model. One participant randomized to the placebo then varenicline group was withdrawn by the physician early in period 2; two participants randomized to the varenicline then placebo group did not complete the iSWAY protocol in period 2.</population>
          <units>m^2/sec^5</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="33"/>
                <count group_id="O2" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.97" spread="0.20"/>
                    <measurement group_id="O2" value="1.04" spread="0.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.73</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.07</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Attention</title>
        <description>Attention function will be measured with a standard computer test, the Sustained Attention Test (SAT), without a distractor condition. Results are reported as the vigilance index, a measure that corrects estimates of accurate detection with penalties for false detection and not confounded by errors of omission. (Frey PW, Colliver JA. Sensitivity and responsivity measures for discrimination learning. Learn Motiv 1973; 4:327-342.) The minimum score is -1.00 (indicating that all recorded responses were misses or false alarms) and maximum is +1 (indicating that all recorded responses were hits or correct rejections). Higher values indicate better attentional performance.</description>
        <time_frame>end of period: days 22 and 64</time_frame>
        <population>All randomized participants with at least one post-treatment value were included in the mixed effects model. Six participants (1 in the placebo then varenicline, 6 in the varenicline then placebo) were unable to pass practice trials due to delayed response time (task not completed at all visits). Technical errors resulted in missing data for 2 placebo and 1 varenicline participants; 3 varenicline participants requested skipping task due to physical ailments.</population>
        <group_list>
          <group group_id="O1">
            <title>Varenicline</title>
            <description>0.5 mg PO BID varenicline for 3 weeks (beginning with a 0.25 mg dose and escalated over the next 2 days)</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>placebo given PO BID for 3 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Attention</title>
          <description>Attention function will be measured with a standard computer test, the Sustained Attention Test (SAT), without a distractor condition. Results are reported as the vigilance index, a measure that corrects estimates of accurate detection with penalties for false detection and not confounded by errors of omission. (Frey PW, Colliver JA. Sensitivity and responsivity measures for discrimination learning. Learn Motiv 1973; 4:327-342.) The minimum score is -1.00 (indicating that all recorded responses were misses or false alarms) and maximum is +1 (indicating that all recorded responses were hits or correct rejections). Higher values indicate better attentional performance.</description>
          <population>All randomized participants with at least one post-treatment value were included in the mixed effects model. Six participants (1 in the placebo then varenicline, 6 in the varenicline then placebo) were unable to pass practice trials due to delayed response time (task not completed at all visits). Technical errors resulted in missing data for 2 placebo and 1 varenicline participants; 3 varenicline participants requested skipping task due to physical ailments.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.73" spread="0.06"/>
                    <measurement group_id="O2" value="0.66" spread="0.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.03</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.08</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>9 weeks (3 weeks in period 1, 3 weeks in washout, 3 weeks in period 2)</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Varenicline</title>
          <description>0.5 mg PO BID varenicline for 3 weeks (beginning with a 0.25 mg dose and escalated over the next 2 days)</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>placebo given PO BID for 3 weeks</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Syncope, unspecified</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cellulitus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="34"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Systolic ejection murmur</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ringing in ears</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Tiredness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Increase in appetite</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Cramping in left leg</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Decreased reflexes in distal lower extremities</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Difficulty walking</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Hammer toes</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Increase stiffness in hands</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Increased tremors</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Pain in shoulder, pelvic</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Tendon tear</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Lightheadedness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Foggy/Forgetfulness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Increase in PD medication &quot;off&quot; time</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Involuntary movements</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>New onset of perception difficulty</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Vasovagal syncope</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depressed mood</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Inability to sleep</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="34"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Vivid dreams</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="34"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Cathie Spino, Research Professor of Biostatistics</name_or_title>
      <organization>U of Michigan</organization>
      <phone>7346155469</phone>
      <email>spino@umich.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT04403399
org study id: HUM00093188-a
nct id: NCT04403399
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
With an appropriate oral dose of Varenicline (VCN) identified from experiments 1 & 2 of the
      study (see NCT02933372), the investigators will administer VCN to Parkinson Disease (PD)
      participants to determine if VCN improves walking speed and measures of balance. PD
      participants will receive VCN or a placebo (fake drug) for 3 weeks to assess the effects of
      VCN administration on gait speed and balance. Participants will undergo examinations to
      assess the intensity of their Parkinsonism and asked questions to assess their mood and
      thinking.
To demonstrate that α4β2* nAChRs are appropriate therapeutic targets in Parkinson's Disease
      (PD), it is necessary to study key pharmacokinetic-pharmacodynamic features of α4β2* nAChR in
      the context of the PD brain with loss of nerve cells that produce the neurotransmitter
      acetylcholine, a pathologic environment in which they may exhibit unique features. This
      personalized medicine approach focuses our studies on the subgroup of PD subjects with loss
      of nerve cells that produce the neurotransmitter acetylcholine identified by Project II and
      the Clinical Resource Core. The investigators will assess α4β2* nAChR features using PET
      imaging with the α4β2* nAChR ligand [18-Fluorine]flubatine, subacute administration of the
      α4β2* nAChR partial agonist Varenicline (VCN), and laboratory measures of gait, balance, and
      attention. The investigators will use [18-Fluorine] flubatine PET to assess VCN occupancy of
      brain α4β2* nAChRs (experiments 1 & 2). VCN will be administered to both PD participants
      (experiment 1) and healthy controls (experiment 2) and both populations will undergo a
      flubatine PET scan to assess VCN occupancy. Using this PET data to select an appropriate VCN
      dose, the investigators will perform a pharmacodynamic study (experiment 3) with subacute VCN
      administration to determine if α4β2* nAChR stimulation improves laboratory measures of gait
      function, postural control, and attentional function in PD subjects with loss of nerve cells
      that produce the neurotransmitter acetylcholine.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Gait Speed
time frame: end of each period: 22 and 64 days
description: Gait speed, how fast a person can walk down a corridor, at normal pace with no distractors (i.e., no dual task).
measure: JERK
time frame: end of each period: 22 and 64 days
description: JERK is the time based derivative of spontaneous lower trunk accelerations during standing. It was assessed with the Ambulatory Parkinson's Disease Monitoring (APDM) wearable sensor system (APDM Wearable Technologies, Inc.) using the iSWAY protocol, with participants standing on a foam pad with eyes closed. JERK was calculated using the manufacturer's software (Mobility Lab Version 1).
measure: Attention
time frame: end of period: days 22 and 64
description: Attention function will be measured with a standard computer test, the Sustained Attention Test (SAT), without a distractor condition. Results are reported as the vigilance index, a measure that corrects estimates of accurate detection with penalties for false detection and not confounded by errors of omission. (Frey PW, Colliver JA. Sensitivity and responsivity measures for discrimination learning. Learn Motiv 1973; 4:327-342.) The minimum score is -1.00 (indicating that all recorded responses were misses or false alarms) and maximum is +1 (indicating that all recorded responses were hits or correct rejections). Higher values indicate better attentional performance.
arm group label: Varenicline then Placebo
arm group type: Experimental
description: Varenicline 0.5 mg BID orally for 3 weeks, followed by a 3-week washout period, then placebo BID orally for 3 weeks
arm group label: Placebo then Varenicline
arm group type: Experimental
description: Placebo BID orally for 3 weeks, followed by a 3-week washout period, then Varenicline 0.5 mg BID orally for 3 weeks
intervention type: Drug
intervention name: Varenicline
description: Initial 0.25 mg oral dose of varenicline administered with monitoring over 4 hours, then total daily dose escalated over the next 2 days until final 0.5 mg BID oral varenicline administered for the remaining 3 weeks.
arm group label: Placebo then Varenicline
arm group label: Varenicline then Placebo
other name: Chantix
intervention type: Drug
intervention name: Placebo
description: Initial placebo oral dose administered with monitoring over 4 hours, then total daily dose escalated over the next 2 days until final placebo BID dosing administered orally for the remaining 3 weeks.
arm group label: Placebo then Varenicline
arm group label: Varenicline then Placebo
criteria: 
gender: All
minimum age: 45 Years
maximum age: N/A
healthy volunteers: No
last name: Roger L Albin, MD
role: Principal Investigator
affiliation: University of Michigan
facility: 
country: United States
citation: Mancini M, Carlson-Kuhta P, Zampieri C, Nutt JG, Chiari L, Horak FB. Postural sway as a marker of progression in Parkinson's disease: a pilot longitudinal study. Gait Posture. 2012 Jul;36(3):471-6. doi: 10.1016/j.gaitpost.2012.04.010. Epub 2012 Jun 29.
PMID: 22750016
responsible party type: Principal Investigator
investigator affiliation: University of Michigan
investigator full name: Roger L. Albin
investigator title: Professor of Neurology
mesh term: Parkinson Disease
mesh term: Varenicline
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 