<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/NCT02206620</url>
  </required_header>
  <id_info>
    <org_study_id>9437</org_study_id>
    <nct_id>NCT02206620</nct_id>
  </id_info>
  <brief_title>Effects of Cholinergic Augmentation on Measures of Balance and Gait</brief_title>
  <official_title>Effects of Cholinergic Augmentation on Measures of Balance and Gait</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Oregon Health and Science University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Michael J. Fox Foundation for Parkinson's Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Oregon Health and Science University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will compare the effects of placebo and donepezil, a drug that helps conserve&#xD;
      concentrations of the neurotransmitter, acetylcholine, on measures of balance and gait in&#xD;
      subjects with Parkinson's disease (PD). This study is a double-blind, placebo controlled,&#xD;
      cross-over randomized clinical trial. Short-latency afferent inhibition (SAI), a&#xD;
      physiological index of cholinergic function will be measured to determine if the deficits in&#xD;
      balance and gait correlate with abnormalities of the SAI and if SAI is altered by donepezil&#xD;
      as a measure of drug efficacy. Cognitive tests like the Attention Network Test (ANT) will be&#xD;
      administered to determine if changes in gait and balance are mediated by changes in&#xD;
      attention.&#xD;
&#xD;
      The results of this study will be the most direct test of the hypothesized role of&#xD;
      cholinergic neurons and the neurotransmitter, acetylcholine in terms of gait and balance. The&#xD;
      study is exploratory because it is not known whether donepezil will affect gait, balance or&#xD;
      attention, nor which measures of gait, balance or attention will be sensitive to drug&#xD;
      manipulation. The study's immediate goal is to determine the potential utility of cholinergic&#xD;
      manipulation as a strategy for preventing or treating balance and gait dysfunction in PD. The&#xD;
      findings of this trial are intended to lead to more sharply focused questions about the role&#xD;
      of cholinergic neurons in balance and gait and eventually to Phase II B trials to determine&#xD;
      clinical utility of cholinergic manipulation to prevent falls and improve mobility.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 2014</start_date>
  <completion_date type="Actual">July 2017</completion_date>
  <primary_completion_date type="Actual">July 2017</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Delta Medio-lateral Postural Sway Range (Foam)</measure>
    <time_frame>Six weeks</time_frame>
    <description>Increased body sway while standing may be markers for increased risk of falling in Parkinson's disease. Sway was measured with an inertial sensor attached to the waist. Participants did this task on a foam pad. We reported the delta in the donepezil and placebo phases [post-donepezil - pre-donepezil for the donepezil phase, and post-placebo - pre-placebo for the placebo phase].</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Delta of the Variability of Stride Time While Walking</measure>
    <time_frame>Six weeks</time_frame>
    <description>Variability in stride time time and an increase with dual tasking is another marker for increased fall risk in Parkinson's disease. Stride time variability was measured with inertial sensors attached to both feet. The delta for each phase is reported [post-donepezil - pre-donepezil for the donepezil phase, and post-placebo - pre-placebo for the placebo phase].</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Short-latency Afferent Inhibition is a Marker of Cortical Cholinergic Activity</measure>
    <time_frame>Six weeks</time_frame>
    <description>Short-latency afferent inhibition (SAI) by a peripheral stimulation is a transcranial magnetic stimulation method to evaluate cortical cholinergic activity. Short-latency afferent Inhibition will be used to determine if our subjects with Parkinson's disease have evidence of reduced cholinergic tone which correlates with their measures of postural and gait instability. We report the SAI at the end of each phase (post-placebo phase and post-donepezil phase). SAI is reported in motor-evoked potential (MEP).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Attention Network Test</measure>
    <time_frame>Six weeks</time_frame>
    <description>Attention Network Test (ANT) is 15 minute computerized test or reaction times with various cues and targets designed to assess alerting, orienting and executive control of attention. Deficits of attention are related to fall risk and may be affected by donepezil.&#xD;
The delta of the Orienting Network Efficiency is reported for each phase (pre- and post-donepezil phase and pre- and post-placebo phase).&#xD;
Details: In accordance with Fan et al. (2002), the subtraction method was applied to isolate the efficiency of the three attentional networks as follows: for the alerting network efficiency: mean RT NC trials - mean RT DC trials; for the orienting network efficiency: mean RT CC trials - mean RT SC trials; and for the executive network efficiency: mean RT I trials - mean RT C trials. For both the alerting and orienting effects, higher subtraction scores indicate greater efficiency; by contrast, the more efficient the executive network is, the lower the subtraction score.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">49</enrollment>
  <condition>Parkinson's Disease</condition>
  <arm_group>
    <arm_group_label>Donepezil</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Donepezil 5 mg per day for week 1-3 or 12-14. 10 mg/day for weeks 4-6 or 14-18, if tolerated.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo 5 mg per day for week 1-3 or 12-14. 10 mg/day for weeks 4-6 or 14-18, if tolerated.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Donepezil</intervention_name>
    <arm_group_label>Donepezil</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Aricept</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  30 years old or older&#xD;
&#xD;
          -  Diagnosis of idiopathic Parkinson's disease&#xD;
&#xD;
          -  Stand unassisted (without use of an assistance device) and walk continuously for at&#xD;
             least 2 minutes.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  musculoskeletal disorders that affect standing and walking&#xD;
&#xD;
          -  Uncorrected vision disturbance&#xD;
&#xD;
          -  Vestibular problems&#xD;
&#xD;
          -  Major depression&#xD;
&#xD;
          -  Hallucinations or other psychiatric disturbances&#xD;
&#xD;
          -  Tachycardia&#xD;
&#xD;
          -  Bradycardia&#xD;
&#xD;
          -  Arrhythmias&#xD;
&#xD;
          -  Peptic ulcer disease&#xD;
&#xD;
          -  Use of anticholinergics&#xD;
&#xD;
          -  Use of cholinesterase inhibitors&#xD;
&#xD;
          -  Use of bladder antispasmodics&#xD;
&#xD;
          -  Use of tricyclic antidepressants&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>John Nutt, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Oregon Health and Science University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Oregon Health &amp; Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239-3098</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://foxtrialfinder.michaeljfox.org/trial/3851/</url>
    <description>The Michael J. Fox Foundation &quot;Fox Trial Finder&quot; Study Listing</description>
  </link>
  <verification_date>November 2019</verification_date>
  <study_first_submitted>July 29, 2014</study_first_submitted>
  <study_first_submitted_qc>July 31, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 1, 2014</study_first_posted>
  <results_first_submitted>March 13, 2019</results_first_submitted>
  <results_first_submitted_qc>November 11, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">November 14, 2019</results_first_posted>
  <last_update_submitted>November 11, 2019</last_update_submitted>
  <last_update_submitted_qc>November 11, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 14, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Oregon Health and Science University</investigator_affiliation>
    <investigator_full_name>John G. Nutt</investigator_full_name>
    <investigator_title>M.D.</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>Donepezil</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 15, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/20/NCT02206620/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Donepezil, Then Placebo</title>
          <description>Donepezil 5 mg per day for weeks 1-3. 10 mg/day for weeks 4-6. Then 6 week washout followed by 6 weeks of placebo. Placebo (identical appearing capsules), two capsules per day for 2 weeks and four capsules per day for the following 2 weeks.</description>
        </group>
        <group group_id="P2">
          <title>Placebo, Then Donepezil</title>
          <description>Placebo (identical appearing capsules), two capsules per day for weeks 1-3 and four capsules per day for 4-6 weeks followed by washout for 6 weeks and then crossover to donepezil for six weeks. Donepezil 5 mg per day for 2 weeks, then 10 mg/day for the following 2 weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Phase I - First Intervention (6 Weeks)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="27"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="26"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Washout (6 Weeks)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="26"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="26"/>
              </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>Phase II - Second Intervention (6 Weeks)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="26"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>All Study Participants</title>
          <description>Donepezil was taken for 3 weeks at 5mg/day (1 tablet/day) and then increased to 10mg/day (2 tablets/day) for another 3 weeks. The same was done for the placebo (1 tablet for the first 3 weeks, then 2 tablets for the following 3 weeks). There was a washout period of 6 weeks between the interventions. Participants were randomized to start with donepezil or placebo.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="49"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="49"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="69" spread="7"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="49"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Disease Duration</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="49"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7" spread="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>MoCA</title>
          <description>Montreal Cognitive Assessment: overall cognition. Scale from 0 to 30. 30 represents intact cognitive status</description>
          <units>scores on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="49"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26" spread="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>MDS-UPDRS Part III</title>
          <description>Unified Parkinson's Disease Rating Scale (UPDRS), Movement Disorders Society (MDS) revised. Participants are rated on a variety of motor functions in a series of subscales. Subscale scores range from 0 to 4. The sub scales are summed to get the total score. The total score minimum score is 0 and the maximum score is 132. Higher values represent further disease progression.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="49"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="43" spread="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Delta Medio-lateral Postural Sway Range (Foam)</title>
        <description>Increased body sway while standing may be markers for increased risk of falling in Parkinson's disease. Sway was measured with an inertial sensor attached to the waist. Participants did this task on a foam pad. We reported the delta in the donepezil and placebo phases [post-donepezil - pre-donepezil for the donepezil phase, and post-placebo - pre-placebo for the placebo phase].</description>
        <time_frame>Six weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Donepezil</title>
            <description>Donepezil 5 mg per day for week 1-3 or 12-14. 10 mg/day for weeks 4-6 or 14-18, if tolerated.&#xD;
Donepezil</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo 5 mg per day for week 1-3 or 12-14. 10 mg/day for weeks 4-6 or 14-18, if tolerated.&#xD;
Donepezil</description>
          </group>
        </group_list>
        <measure>
          <title>Delta Medio-lateral Postural Sway Range (Foam)</title>
          <description>Increased body sway while standing may be markers for increased risk of falling in Parkinson's disease. Sway was measured with an inertial sensor attached to the waist. Participants did this task on a foam pad. We reported the delta in the donepezil and placebo phases [post-donepezil - pre-donepezil for the donepezil phase, and post-placebo - pre-placebo for the placebo phase].</description>
          <units>m/s^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="49"/>
                <count group_id="O2" value="49"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.007" spread="0.045"/>
                    <measurement group_id="O2" value="-0.004" spread="0.028"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Delta of the Variability of Stride Time While Walking</title>
        <description>Variability in stride time time and an increase with dual tasking is another marker for increased fall risk in Parkinson's disease. Stride time variability was measured with inertial sensors attached to both feet. The delta for each phase is reported [post-donepezil - pre-donepezil for the donepezil phase, and post-placebo - pre-placebo for the placebo phase].</description>
        <time_frame>Six weeks</time_frame>
        <population>Variability of stride time was calculated from the stride time time-series as the coefficient of variation (CV, 100 multiplied by the SD of the stride times divided by the mean of each subject's stride times)</population>
        <group_list>
          <group group_id="O1">
            <title>Donepezil</title>
            <description>Donepezil 5 mg per day for week 1-3. 10 mg/day for weeks 4-6. Then 6 week washout followed by 6 weeks of placebo.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo (identical appearing capsules), two capsules per day for week 1-3 and four capsules per day for 4-6 weeks followed by washout for 6 weeks and then crossover to donepezil for six weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Delta of the Variability of Stride Time While Walking</title>
          <description>Variability in stride time time and an increase with dual tasking is another marker for increased fall risk in Parkinson's disease. Stride time variability was measured with inertial sensors attached to both feet. The delta for each phase is reported [post-donepezil - pre-donepezil for the donepezil phase, and post-placebo - pre-placebo for the placebo phase].</description>
          <population>Variability of stride time was calculated from the stride time time-series as the coefficient of variation (CV, 100 multiplied by the SD of the stride times divided by the mean of each subject's stride times)</population>
          <units>percentage of gait cycle time</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="49"/>
                <count group_id="O2" value="49"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.32" spread="4.07"/>
                    <measurement group_id="O2" value="-0.038" spread="3.98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Short-latency Afferent Inhibition is a Marker of Cortical Cholinergic Activity</title>
        <description>Short-latency afferent inhibition (SAI) by a peripheral stimulation is a transcranial magnetic stimulation method to evaluate cortical cholinergic activity. Short-latency afferent Inhibition will be used to determine if our subjects with Parkinson's disease have evidence of reduced cholinergic tone which correlates with their measures of postural and gait instability. We report the SAI at the end of each phase (post-placebo phase and post-donepezil phase). SAI is reported in motor-evoked potential (MEP).</description>
        <time_frame>Six weeks</time_frame>
        <population>The average and standard deviation (SD) of the SAI at the end of each treatment is reported</population>
        <group_list>
          <group group_id="O1">
            <title>Donepezil</title>
            <description>Donepezil 5 mg per day for week 1-3. 10 mg/day for weeks 4-6. Then 6 week washout followed by 6 weeks of placebo.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo (identical appearing capsules), two capsules per day for week 1-3 and four capsules per day for 4-6 weeks followed by washout for 6 weeks and then crossover to donepezil for six weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Short-latency Afferent Inhibition is a Marker of Cortical Cholinergic Activity</title>
          <description>Short-latency afferent inhibition (SAI) by a peripheral stimulation is a transcranial magnetic stimulation method to evaluate cortical cholinergic activity. Short-latency afferent Inhibition will be used to determine if our subjects with Parkinson's disease have evidence of reduced cholinergic tone which correlates with their measures of postural and gait instability. We report the SAI at the end of each phase (post-placebo phase and post-donepezil phase). SAI is reported in motor-evoked potential (MEP).</description>
          <population>The average and standard deviation (SD) of the SAI at the end of each treatment is reported</population>
          <units>percentage of the unconditioned MEP</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="49"/>
                <count group_id="O2" value="49"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="72.5" spread="26.9"/>
                    <measurement group_id="O2" value="74.3" spread="23.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Attention Network Test</title>
        <description>Attention Network Test (ANT) is 15 minute computerized test or reaction times with various cues and targets designed to assess alerting, orienting and executive control of attention. Deficits of attention are related to fall risk and may be affected by donepezil.&#xD;
The delta of the Orienting Network Efficiency is reported for each phase (pre- and post-donepezil phase and pre- and post-placebo phase).&#xD;
Details: In accordance with Fan et al. (2002), the subtraction method was applied to isolate the efficiency of the three attentional networks as follows: for the alerting network efficiency: mean RT NC trials - mean RT DC trials; for the orienting network efficiency: mean RT CC trials - mean RT SC trials; and for the executive network efficiency: mean RT I trials - mean RT C trials. For both the alerting and orienting effects, higher subtraction scores indicate greater efficiency; by contrast, the more efficient the executive network is, the lower the subtraction score.</description>
        <time_frame>Six weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Donepezil</title>
            <description>Donepezil 5 mg per day for week 1-3. 10 mg/day for weeks 4-6. Then 6 week washout followed by 6 weeks of placebo.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo (identical appearing capsules), two capsules per day for week 1-3 and four capsules per day for 4-6 weeks followed by washout for 6 weeks and then crossover to donepezil for six weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Attention Network Test</title>
          <description>Attention Network Test (ANT) is 15 minute computerized test or reaction times with various cues and targets designed to assess alerting, orienting and executive control of attention. Deficits of attention are related to fall risk and may be affected by donepezil.&#xD;
The delta of the Orienting Network Efficiency is reported for each phase (pre- and post-donepezil phase and pre- and post-placebo phase).&#xD;
Details: In accordance with Fan et al. (2002), the subtraction method was applied to isolate the efficiency of the three attentional networks as follows: for the alerting network efficiency: mean RT NC trials - mean RT DC trials; for the orienting network efficiency: mean RT CC trials - mean RT SC trials; and for the executive network efficiency: mean RT I trials - mean RT C trials. For both the alerting and orienting effects, higher subtraction scores indicate greater efficiency; by contrast, the more efficient the executive network is, the lower the subtraction score.</description>
          <units>ms</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="49"/>
                <count group_id="O2" value="49"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-19.5" spread="16.3"/>
                    <measurement group_id="O2" value="-5.1" spread="5.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse Events were collected through study completion, an average of 18 weeks.</time_frame>
      <desc>Adverse Events were systematically collected by phone call every week. Study clinicians recorded adverse events and reported to the IRB unexpected or serious adverse events. An independent neurologist reviewed the reported adverse events each six months and made recommendations to the trial leadership as well as the IRB about advisability of continuation of the trial.&#xD;
The adverse events are reported below per intervention for each Arm/Group of the study.</desc>
      <group_list>
        <group group_id="E1">
          <title>Donepezil, Then Placebo (Phase I)</title>
          <description>Participants took a donepezil 5mg tablet each day for 3 weeks, then increased the dose to 10mg (2 tablets each day) for 3 weeks. (This was followed by 6 weeks of a washout period and then taking the placebo in the same format -- 3 weeks of one tablet, followed by 3 weeks of 2 tablets to replicate the dosage increase.)</description>
        </group>
        <group group_id="E2">
          <title>Placebo, Then Donepezil (Phase I)</title>
          <description>Participants took the placebo at one tablet each day for 3 weeks, then increased the dosage to 2 tablets each day for 3 weeks. (This was followed by 6 weeks of a washout period and then taking donepezil in the same format -- donepezil 5mg tablet each day for 3 weeks, followed by 3 weeks of an increased dose of 10mg (2 tablets each day).)</description>
        </group>
        <group group_id="E3">
          <title>Donepezil, Then Placebo (Washout)</title>
          <description>There were 6 weeks of a washout period after participants had taken donepezil for 6 weeks.</description>
        </group>
        <group group_id="E4">
          <title>Placebo, Then Donepezil (Washout)</title>
          <description>There were 6 weeks of a washout period after participants had taken the placebo for 6 weeks.</description>
        </group>
        <group group_id="E5">
          <title>Donepezil, Then Placebo (Phase II)</title>
          <description>After the washout period, participants took the placebo in the same format as the donepezil -- 3 weeks of one tablet, followed by 3 weeks of 2 tablets to replicate the dosage increase.</description>
        </group>
        <group group_id="E6">
          <title>Placebo, Then Donepezil (Phase II)</title>
          <description>Then participants took donepezil in the same formats the placebo -- the donepezil 5mg tablet each day for 3 weeks, followed by 3 weeks of an increased dose of 10mg (2 tablets each day).</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-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="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pulmonary Embolus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</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="18" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="27"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="8" subjects_at_risk="26"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="21"/>
                <counts group_id="E6" subjects_affected="26" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="27"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E6" subjects_affected="8" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E6" subjects_affected="3" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="27"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="27"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E6" subjects_affected="6" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Vivid Dreams</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="27"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Light Headedness</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="27"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E6" subjects_affected="3" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Hallucinations</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Memory Disturbances</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="27"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Increased Saliva</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Decreased Saliva</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="27"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Other</sub_title>
                <description>other adverse events consisting of Irregular Heartbeat, Pain, Weakness, Anxiety, Excessive Sweating, Trouble Swallowing, Infection, Rash, Food Poisoning, Impulse Control, Increased Freezing of Gait, etc</description>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="27"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E6" subjects_affected="7" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E6" subjects_affected="3" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Muscle Cramps</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="27"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E6" subjects_affected="5" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary Frequency</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="27"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E6" subjects_affected="4" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Upper Respiratory Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="27"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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. Martina Mancini</name_or_title>
      <organization>Oregon Health &amp; Science University</organization>
      <phone>5034182602</phone>
      <email>mancinim@ohsu.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/NCT02206620
org study id: 9437
nct id: NCT02206620
lead sponsor: 
collaborator: 
has dmc: No
This study will compare the effects of placebo and donepezil, a drug that helps conserve
      concentrations of the neurotransmitter, acetylcholine, on measures of balance and gait in
      subjects with Parkinson's disease (PD). This study is a double-blind, placebo controlled,
      cross-over randomized clinical trial. Short-latency afferent inhibition (SAI), a
      physiological index of cholinergic function will be measured to determine if the deficits in
      balance and gait correlate with abnormalities of the SAI and if SAI is altered by donepezil
      as a measure of drug efficacy. Cognitive tests like the Attention Network Test (ANT) will be
      administered to determine if changes in gait and balance are mediated by changes in
      attention.

      The results of this study will be the most direct test of the hypothesized role of
      cholinergic neurons and the neurotransmitter, acetylcholine in terms of gait and balance. The
      study is exploratory because it is not known whether donepezil will affect gait, balance or
      attention, nor which measures of gait, balance or attention will be sensitive to drug
      manipulation. The study's immediate goal is to determine the potential utility of cholinergic
      manipulation as a strategy for preventing or treating balance and gait dysfunction in PD. The
      findings of this trial are intended to lead to more sharply focused questions about the role
      of cholinergic neurons in balance and gait and eventually to Phase II B trials to determine
      clinical utility of cholinergic manipulation to prevent falls and improve mobility.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Delta Medio-lateral Postural Sway Range (Foam)
time frame: Six weeks
description: Increased body sway while standing may be markers for increased risk of falling in Parkinson's disease. Sway was measured with an inertial sensor attached to the waist. Participants did this task on a foam pad. We reported the delta in the donepezil and placebo phases [post-donepezil - pre-donepezil for the donepezil phase, and post-placebo - pre-placebo for the placebo phase].
measure: Delta of the Variability of Stride Time While Walking
time frame: Six weeks
description: Variability in stride time time and an increase with dual tasking is another marker for increased fall risk in Parkinson's disease. Stride time variability was measured with inertial sensors attached to both feet. The delta for each phase is reported [post-donepezil - pre-donepezil for the donepezil phase, and post-placebo - pre-placebo for the placebo phase].
measure: Short-latency Afferent Inhibition is a Marker of Cortical Cholinergic Activity
time frame: Six weeks
description: Short-latency afferent inhibition (SAI) by a peripheral stimulation is a transcranial magnetic stimulation method to evaluate cortical cholinergic activity. Short-latency afferent Inhibition will be used to determine if our subjects with Parkinson's disease have evidence of reduced cholinergic tone which correlates with their measures of postural and gait instability. We report the SAI at the end of each phase (post-placebo phase and post-donepezil phase). SAI is reported in motor-evoked potential (MEP).
measure: Attention Network Test
time frame: Six weeks
description: Attention Network Test (ANT) is 15 minute computerized test or reaction times with various cues and targets designed to assess alerting, orienting and executive control of attention. Deficits of attention are related to fall risk and may be affected by donepezil.
The delta of the Orienting Network Efficiency is reported for each phase (pre- and post-donepezil phase and pre- and post-placebo phase).
Details: In accordance with Fan et al. (2002), the subtraction method was applied to isolate the efficiency of the three attentional networks as follows: for the alerting network efficiency: mean RT NC trials - mean RT DC trials; for the orienting network efficiency: mean RT CC trials - mean RT SC trials; and for the executive network efficiency: mean RT I trials - mean RT C trials. For both the alerting and orienting effects, higher subtraction scores indicate greater efficiency; by contrast, the more efficient the executive network is, the lower the subtraction score.
arm group label: Donepezil
arm group type: Experimental
description: Donepezil 5 mg per day for week 1-3 or 12-14. 10 mg/day for weeks 4-6 or 14-18, if tolerated.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo 5 mg per day for week 1-3 or 12-14. 10 mg/day for weeks 4-6 or 14-18, if tolerated.
intervention type: Drug
intervention name: Donepezil
arm group label: Donepezil
arm group label: Placebo
other name: Aricept
criteria: 
gender: All
minimum age: 30 Years
maximum age: N/A
healthy volunteers: No
last name: John Nutt, M.D.
role: Principal Investigator
affiliation: Oregon Health and Science University
facility: 
country: United States
url: https://foxtrialfinder.michaeljfox.org/trial/3851/
description: The Michael J. Fox Foundation "Fox Trial Finder" Study Listing
responsible party type: Principal Investigator
investigator affiliation: Oregon Health and Science University
investigator full name: John G. Nutt
investigator title: M.D.
mesh term: Parkinson Disease
mesh term: Donepezil
sharing ipd: Undecided
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 