<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/NCT02248636</url>
  </required_header>
  <id_info>
    <org_study_id>CLIN-014-13F</org_study_id>
    <nct_id>NCT02248636</nct_id>
  </id_info>
  <brief_title>Cholinesterase Inhibitor Discontinuation</brief_title>
  <acronym>CID</acronym>
  <official_title>Cholinesterase Inhibitor Discontinuation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>VA Office of Research and Development</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>VA Office of Research and Development</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study tries to determine if stopping certain medications that are used to treat dementia&#xD;
      will cause worsening from the patient and family perspective.&#xD;
&#xD;
      All of the participants will take pills that look identical, and that may contain active drug&#xD;
      or an inactive pill (a placebo). Half of the group will receive the same treatment they were&#xD;
      taking before the study -- this is called the &quot;sham discontinuation&quot; arm. The other half will&#xD;
      receive a reduced dose of their medication, and then an inactive pill (placebo) -- this is&#xD;
      called the &quot;real discontinuation&quot; arm.&#xD;
&#xD;
      Participants will be able to return to their previous dose of medication at any time during&#xD;
      the study. The percentage of people who return will be measured and compared. Other medical&#xD;
      events and factors such as behaviors, thinking, and caregiver distress, will be measured and&#xD;
      compared between the groups.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There are no reliable findings from controlled trials about discontinuation of cholinesterase&#xD;
      inhibitors from a patient and family perspective. It is unknown at what point these&#xD;
      medications do not have effects, and how they can safely be discontinued.&#xD;
&#xD;
      The investigators will identify Veterans who have been taking a cholinesterase inhibitor (CI)&#xD;
      (donepezil or galantamine) for at least one year. After informed consent, the investigators&#xD;
      will randomize them to Real Taper (half-dose of the CI they had taken for 3 weeks, then&#xD;
      placebo for 3 weeks), or Sham Taper (continued full dose of the CI they had taken for 6&#xD;
      weeks). The pills will be blinded by over-encapsulating of the drug or placebo.&#xD;
&#xD;
      An intake interview will ascertain history and measure behaviors, cognitive symptoms, and&#xD;
      mood, as well as caregiver burden. Phone calls will assess treatment use and adverse events&#xD;
      at week 2 and week 4. An exit interview at week 6 will measure the same variables as at&#xD;
      baseline. Participants will be unblinded at that point so they will know which treatment had&#xD;
      been used. A follow-up call at 12 weeks will ascertain ongoing treatment and any further&#xD;
      adverse events.&#xD;
&#xD;
      At any point in the study, participants and caregivers will be able to return to their&#xD;
      pre-study dose of medication.&#xD;
&#xD;
      The primary outcome is the percentage of participants who successfully complete a 6-week&#xD;
      discontinuation. This will be compared between arms. Other outcomes related to medical events&#xD;
      (e.g. hospitalizations, falls), symptoms (e.g. cognition, behaviors), and caregiver distress&#xD;
      will be measured and compared.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 22, 2015</start_date>
  <completion_date type="Actual">October 1, 2019</completion_date>
  <primary_completion_date type="Actual">October 1, 2019</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Successful Completion</measure>
    <time_frame>6 weeks</time_frame>
    <description>Participants can return to their pre-study dose of medication at any time. If they complete 6 weeks of either real discontinuation or sham discontinuation, they are considered to have successfully completed treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Caregiver Burden</measure>
    <time_frame>6 weeks</time_frame>
    <description>The Zarit Caregiver Burden Interview contains 22 items, each on a 5-point scale, for a maximum score of 110. The minimum score is 0. A higher score indicates worse subjective burden.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Veteran Cognition</measure>
    <time_frame>6 weeks</time_frame>
    <description>Six-Item Screener is a telephone-based assessment of cognitive status. The score ranges from 0 to 6. A higher score indicates better cognition.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Veteran Functioning</measure>
    <time_frame>6 weeks</time_frame>
    <description>The Alzheimer's Disease Cooperative Study ADL Scale (ADCS-ADL) is a 23-item scale divided into activities of daily living and independent activities of daily living. Scores range from 0-78. A lower score indicates worse functional ability.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Behavioral Symptoms</measure>
    <time_frame>6 weeks</time_frame>
    <description>The Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) is a 25-item instrument. Scores range from 0-75, with a higher number indicating worse behavioral symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-study Treatment Choice</measure>
    <time_frame>12 weeks</time_frame>
    <description>Veteran and caregiver decision to continue, or to have restarted, the pre-study medication at 12 weeks. The participants were unblinded at 6 weeks, and were requested to make their own decision about restarting.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">72</enrollment>
  <condition>Dementia</condition>
  <arm_group>
    <arm_group_label>Real discontinuation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This group is tapered off their previous cholinesterase inhibitor medication.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham discontinuation</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>This group receives their previous cholinesterase inhibitor medication, but in in placebo form.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cholinesterase inhibitor</intervention_name>
    <description>This group receives a half-dose of their previous cholinesterase inhibitor medication (in overencapsulated form) for two weeks, then receives placebo.</description>
    <arm_group_label>Real discontinuation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sham discontinuation</intervention_name>
    <description>This group receives their previous dose of cholinesterase inhibitor medication, but in overencapsulated form</description>
    <arm_group_label>Sham discontinuation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males and females ages 60 and older.&#xD;
&#xD;
          -  Taking stable dose of donepezil 10mg or greater per day, or galantamine 8mg or greater&#xD;
             per day, for at least 1 year.&#xD;
&#xD;
          -  Presence of a primary caregiver who can assume responsibility for medication&#xD;
             compliance, OR residence in a nursing home with a staff member who can provide&#xD;
             information.&#xD;
&#xD;
          -  Primary care visit within last 12 months.&#xD;
&#xD;
          -  Willing to have the CI medication discontinued.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Terminal medical condition for which life expectancy would be less than 6 months.&#xD;
&#xD;
          -  Parkinson's Disease&#xD;
&#xD;
          -  Presence of any uncontrolled systemic illness that would interfere with participation&#xD;
             in the study.&#xD;
&#xD;
          -  Unstable medical condition.&#xD;
&#xD;
          -  Receiving services from hospice.&#xD;
&#xD;
          -  Current prescription with more than one CI&#xD;
&#xD;
          -  Receiving medication in an investigational drug study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Stephen M Thielke, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>VA Puget Sound Health Care System Seattle Division, Seattle, WA</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Central Arkansas VHS John L. McClellan Memorial Veterans Hospital, Little Rock, AR</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72205-5484</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boise VA Medical Center, Boise, ID</name>
      <address>
        <city>Boise</city>
        <state>Idaho</state>
        <zip>83702</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Edith Nourse Rogers Memorial Veterans Hospital, Bedford, MA</name>
      <address>
        <city>Bedford</city>
        <state>Massachusetts</state>
        <zip>01730</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Puget Sound Health Care System Seattle Division, Seattle, WA</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>September 22, 2014</study_first_submitted>
  <study_first_submitted_qc>September 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <results_first_submitted>September 29, 2020</results_first_submitted>
  <results_first_submitted_qc>September 29, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">October 23, 2020</results_first_posted>
  <last_update_submitted>September 29, 2020</last_update_submitted>
  <last_update_submitted_qc>September 29, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 23, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Alzheimer's disease</keyword>
  <keyword>Cholinesterase inhibitor</keyword>
  <keyword>Discontinuation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dementia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cholinesterase Inhibitors</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <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>May 2, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/36/NCT02248636/Prot_000.pdf</document_url>
    </provided_document>
    <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>May 8, 2014</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/36/NCT02248636/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Veterans who have received a prescription for a cholinesterase inhibitor for one year or greater.</recruitment_details>
      <pre_assignment_details>72 people were enrolled and consented, but only 61 were randomized.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Real Discontinuation</title>
          <description>This group is tapered off their previous cholinesterase inhibitor medication.&#xD;
Cholinesterase inhibitor: This group receives a half-dose of their previous cholinesterase inhibitor medication (in overencapsulated form) for two weeks, then receives placebo.</description>
        </group>
        <group group_id="P2">
          <title>Sham Discontinuation</title>
          <description>This group receives their previous cholinesterase inhibitor medication, but in in placebo form.&#xD;
Sham discontinuation: This group receives their previous dose of cholinesterase inhibitor medication, but in overencapsulated form</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
                <participants group_id="P2" count="35"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="32"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Real Discontinuation</title>
          <description>This group is tapered off their previous cholinesterase inhibitor medication.&#xD;
Cholinesterase inhibitor: This group receives a half-dose of their previous cholinesterase inhibitor medication (in overencapsulated form) for two weeks, then receives placebo.</description>
        </group>
        <group group_id="B2">
          <title>Sham Discontinuation</title>
          <description>This group receives their previous cholinesterase inhibitor medication, but in in placebo form.&#xD;
Sham discontinuation: This group receives their previous dose of cholinesterase inhibitor medication, but in overencapsulated form.</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="26"/>
            <count group_id="B2" value="35"/>
            <count group_id="B3" value="61"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</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>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="33"/>
                    <measurement group_id="B3" value="56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="77.34" spread="10.48"/>
                    <measurement group_id="B2" value="77.94" spread="9.72"/>
                    <measurement group_id="B3" value="77.69" spread="9.97"/>
                  </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="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="35"/>
                    <measurement group_id="B3" value="60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</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>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="34"/>
                    <measurement group_id="B3" value="60"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </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="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </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="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="54"/>
                  </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="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Successful Completion</title>
        <description>Participants can return to their pre-study dose of medication at any time. If they complete 6 weeks of either real discontinuation or sham discontinuation, they are considered to have successfully completed treatment.</description>
        <time_frame>6 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Real Discontinuation</title>
            <description>This group is tapered off their previous cholinesterase inhibitor medication.&#xD;
Cholinesterase inhibitor: This group receives a half-dose of their previous cholinesterase inhibitor medication (in overencapsulated form) for two weeks, then receives placebo.</description>
          </group>
          <group group_id="O2">
            <title>Sham Discontinuation</title>
            <description>This group receives their previous cholinesterase inhibitor medication, but in in placebo form.&#xD;
Sham discontinuation: This group receives their previous dose of cholinesterase inhibitor medication, but in overencapsulated form</description>
          </group>
        </group_list>
        <measure>
          <title>Successful Completion</title>
          <description>Participants can return to their pre-study dose of medication at any time. If they complete 6 weeks of either real discontinuation or sham discontinuation, they are considered to have successfully completed treatment.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Caregiver Burden</title>
        <description>The Zarit Caregiver Burden Interview contains 22 items, each on a 5-point scale, for a maximum score of 110. The minimum score is 0. A higher score indicates worse subjective burden.</description>
        <time_frame>6 weeks</time_frame>
        <population>Not all of the caregivers completed the instrument. Some were unavailable after study enrollment. Some had a change in caregiver. Some refused to respond to all of the questions, since the instrument is rather lengthy.</population>
        <group_list>
          <group group_id="O1">
            <title>Real Discontinuation</title>
            <description>This group is tapered off their previous cholinesterase inhibitor medication.&#xD;
Cholinesterase inhibitor: This group receives a half-dose of their previous cholinesterase inhibitor medication (in overencapsulated form) for two weeks, then receives placebo.</description>
          </group>
          <group group_id="O2">
            <title>Sham Discontinuation</title>
            <description>This group receives their previous cholinesterase inhibitor medication, but in in placebo form.&#xD;
Sham discontinuation: This group receives their previous dose of cholinesterase inhibitor medication, but in overencapsulated form</description>
          </group>
        </group_list>
        <measure>
          <title>Caregiver Burden</title>
          <description>The Zarit Caregiver Burden Interview contains 22 items, each on a 5-point scale, for a maximum score of 110. The minimum score is 0. A higher score indicates worse subjective burden.</description>
          <population>Not all of the caregivers completed the instrument. Some were unavailable after study enrollment. Some had a change in caregiver. Some refused to respond to all of the questions, since the instrument is rather lengthy.</population>
          <units>Change in Zarit score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.58" spread="11.13"/>
                    <measurement group_id="O2" value="1.66" spread="17.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Veteran Cognition</title>
        <description>Six-Item Screener is a telephone-based assessment of cognitive status. The score ranges from 0 to 6. A higher score indicates better cognition.</description>
        <time_frame>6 weeks</time_frame>
        <population>Some of the participants refused to complete the cognitive instrument over the phone.</population>
        <group_list>
          <group group_id="O1">
            <title>Real Discontinuation</title>
            <description>This group is tapered off their previous cholinesterase inhibitor medication.&#xD;
Cholinesterase inhibitor: This group receives a half-dose of their previous cholinesterase inhibitor medication (in overencapsulated form) for two weeks, then receives placebo.</description>
          </group>
          <group group_id="O2">
            <title>Sham Discontinuation</title>
            <description>This group receives their previous cholinesterase inhibitor medication, but in in placebo form.&#xD;
Sham discontinuation: This group receives their previous dose of cholinesterase inhibitor medication, but in overencapsulated form</description>
          </group>
        </group_list>
        <measure>
          <title>Veteran Cognition</title>
          <description>Six-Item Screener is a telephone-based assessment of cognitive status. The score ranges from 0 to 6. A higher score indicates better cognition.</description>
          <population>Some of the participants refused to complete the cognitive instrument over the phone.</population>
          <units>Change in Six-Item Screener Score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.15" spread="2.13"/>
                    <measurement group_id="O2" value="0.13" spread="0.90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Veteran Functioning</title>
        <description>The Alzheimer's Disease Cooperative Study ADL Scale (ADCS-ADL) is a 23-item scale divided into activities of daily living and independent activities of daily living. Scores range from 0-78. A lower score indicates worse functional ability.</description>
        <time_frame>6 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Real Discontinuation</title>
            <description>This group is tapered off their previous cholinesterase inhibitor medication.&#xD;
Cholinesterase inhibitor: This group receives a half-dose of their previous cholinesterase inhibitor medication (in overencapsulated form) for two weeks, then receives placebo.</description>
          </group>
          <group group_id="O2">
            <title>Sham Discontinuation</title>
            <description>This group receives their previous cholinesterase inhibitor medication, but in in placebo form.&#xD;
Sham discontinuation: This group receives their previous dose of cholinesterase inhibitor medication, but in overencapsulated form</description>
          </group>
        </group_list>
        <measure>
          <title>Veteran Functioning</title>
          <description>The Alzheimer's Disease Cooperative Study ADL Scale (ADCS-ADL) is a 23-item scale divided into activities of daily living and independent activities of daily living. Scores range from 0-78. A lower score indicates worse functional ability.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.44" spread="11.87"/>
                    <measurement group_id="O2" value="-0.59" spread="6.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Behavioral Symptoms</title>
        <description>The Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) is a 25-item instrument. Scores range from 0-75, with a higher number indicating worse behavioral symptoms.</description>
        <time_frame>6 weeks</time_frame>
        <population>Not all caregivers were willing to respond to all the items.</population>
        <group_list>
          <group group_id="O1">
            <title>Real Discontinuation</title>
            <description>This group is tapered off their previous cholinesterase inhibitor medication.&#xD;
Cholinesterase inhibitor: This group receives a half-dose of their previous cholinesterase inhibitor medication (in overencapsulated form) for two weeks, then receives placebo.</description>
          </group>
          <group group_id="O2">
            <title>Sham Discontinuation</title>
            <description>This group receives their previous cholinesterase inhibitor medication, but in in placebo form.&#xD;
Sham discontinuation: This group receives their previous dose of cholinesterase inhibitor medication, but in overencapsulated form</description>
          </group>
        </group_list>
        <measure>
          <title>Behavioral Symptoms</title>
          <description>The Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) is a 25-item instrument. Scores range from 0-75, with a higher number indicating worse behavioral symptoms.</description>
          <population>Not all caregivers were willing to respond to all the items.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.63" spread="6.26"/>
                    <measurement group_id="O2" value="-1.23" spread="3.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Post-study Treatment Choice</title>
        <description>Veteran and caregiver decision to continue, or to have restarted, the pre-study medication at 12 weeks. The participants were unblinded at 6 weeks, and were requested to make their own decision about restarting.</description>
        <time_frame>12 weeks</time_frame>
        <population>We were unable to reach some participants at 12 weeks.</population>
        <group_list>
          <group group_id="O1">
            <title>Real Discontinuation</title>
            <description>This group is tapered off their previous cholinesterase inhibitor medication.&#xD;
Cholinesterase inhibitor: This group receives a half-dose of their previous cholinesterase inhibitor medication (in overencapsulated form) for two weeks, then receives placebo.</description>
          </group>
          <group group_id="O2">
            <title>Sham Discontinuation</title>
            <description>This group receives their previous cholinesterase inhibitor medication, but in in placebo form.&#xD;
Sham discontinuation: This group receives their previous dose of cholinesterase inhibitor medication, but in overencapsulated form</description>
          </group>
        </group_list>
        <measure>
          <title>Post-study Treatment Choice</title>
          <description>Veteran and caregiver decision to continue, or to have restarted, the pre-study medication at 12 weeks. The participants were unblinded at 6 weeks, and were requested to make their own decision about restarting.</description>
          <population>We were unable to reach some participants at 12 weeks.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="32"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Participants taking pre-study medication</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants not taking pre-study medication</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Six weeks.</time_frame>
      <desc>Dementia patients have a variety of behavioral and health events, which may fluctuate over time. We considered adverse events to be novel medical events differing from baseline.</desc>
      <group_list>
        <group group_id="E1">
          <title>Real Discontinuation</title>
          <description>This group is tapered off their previous cholinesterase inhibitor medication.&#xD;
Cholinesterase inhibitor: This group receives a half-dose of their previous cholinesterase inhibitor medication (in overencapsulated form) for two weeks, then receives placebo.</description>
        </group>
        <group group_id="E2">
          <title>Sham Discontinuation</title>
          <description>This group receives their previous cholinesterase inhibitor medication, but in in placebo form.&#xD;
Sham discontinuation: This group receives their previous dose of cholinesterase inhibitor medication, but in overencapsulated form</description>
        </group>
      </group_list>
      <serious_events>
        <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="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="35"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-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="9" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Behavior</sub_title>
                <description>Behavior changed significantly</description>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="26"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="35"/>
              </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>
    <limitations_and_caveats>The study was designed to allow participants to stop the study medication at any time, and for any reason. This is different than administrative withdrawal.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>William Banks, Associate Chief of Staff for Research</name_or_title>
      <organization>Puget Sound VA</organization>
      <phone>206 764-2701</phone>
      <email>william.banks4@va.gov</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/NCT02248636
org study id: CLIN-014-13F
nct id: NCT02248636
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This study tries to determine if stopping certain medications that are used to treat dementia
      will cause worsening from the patient and family perspective.

      All of the participants will take pills that look identical, and that may contain active drug
      or an inactive pill (a placebo). Half of the group will receive the same treatment they were
      taking before the study -- this is called the "sham discontinuation" arm. The other half will
      receive a reduced dose of their medication, and then an inactive pill (placebo) -- this is
      called the "real discontinuation" arm.

      Participants will be able to return to their previous dose of medication at any time during
      the study. The percentage of people who return will be measured and compared. Other medical
      events and factors such as behaviors, thinking, and caregiver distress, will be measured and
      compared between the groups.
There are no reliable findings from controlled trials about discontinuation of cholinesterase
      inhibitors from a patient and family perspective. It is unknown at what point these
      medications do not have effects, and how they can safely be discontinued.

      The investigators will identify Veterans who have been taking a cholinesterase inhibitor (CI)
      (donepezil or galantamine) for at least one year. After informed consent, the investigators
      will randomize them to Real Taper (half-dose of the CI they had taken for 3 weeks, then
      placebo for 3 weeks), or Sham Taper (continued full dose of the CI they had taken for 6
      weeks). The pills will be blinded by over-encapsulating of the drug or placebo.

      An intake interview will ascertain history and measure behaviors, cognitive symptoms, and
      mood, as well as caregiver burden. Phone calls will assess treatment use and adverse events
      at week 2 and week 4. An exit interview at week 6 will measure the same variables as at
      baseline. Participants will be unblinded at that point so they will know which treatment had
      been used. A follow-up call at 12 weeks will ascertain ongoing treatment and any further
      adverse events.

      At any point in the study, participants and caregivers will be able to return to their
      pre-study dose of medication.

      The primary outcome is the percentage of participants who successfully complete a 6-week
      discontinuation. This will be compared between arms. Other outcomes related to medical events
      (e.g. hospitalizations, falls), symptoms (e.g. cognition, behaviors), and caregiver distress
      will be measured and compared.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Successful Completion
time frame: 6 weeks
description: Participants can return to their pre-study dose of medication at any time. If they complete 6 weeks of either real discontinuation or sham discontinuation, they are considered to have successfully completed treatment.
measure: Caregiver Burden
time frame: 6 weeks
description: The Zarit Caregiver Burden Interview contains 22 items, each on a 5-point scale, for a maximum score of 110. The minimum score is 0. A higher score indicates worse subjective burden.
measure: Veteran Cognition
time frame: 6 weeks
description: Six-Item Screener is a telephone-based assessment of cognitive status. The score ranges from 0 to 6. A higher score indicates better cognition.
measure: Veteran Functioning
time frame: 6 weeks
description: The Alzheimer's Disease Cooperative Study ADL Scale (ADCS-ADL) is a 23-item scale divided into activities of daily living and independent activities of daily living. Scores range from 0-78. A lower score indicates worse functional ability.
measure: Behavioral Symptoms
time frame: 6 weeks
description: The Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) is a 25-item instrument. Scores range from 0-75, with a higher number indicating worse behavioral symptoms.
measure: Post-study Treatment Choice
time frame: 12 weeks
description: Veteran and caregiver decision to continue, or to have restarted, the pre-study medication at 12 weeks. The participants were unblinded at 6 weeks, and were requested to make their own decision about restarting.
arm group label: Real discontinuation
arm group type: Experimental
description: This group is tapered off their previous cholinesterase inhibitor medication.
arm group label: Sham discontinuation
arm group type: Sham Comparator
description: This group receives their previous cholinesterase inhibitor medication, but in in placebo form.
intervention type: Drug
intervention name: Cholinesterase inhibitor
description: This group receives a half-dose of their previous cholinesterase inhibitor medication (in overencapsulated form) for two weeks, then receives placebo.
arm group label: Real discontinuation
intervention type: Drug
intervention name: Sham discontinuation
description: This group receives their previous dose of cholinesterase inhibitor medication, but in overencapsulated form
arm group label: Sham discontinuation
criteria: 
gender: All
minimum age: 60 Years
maximum age: N/A
healthy volunteers: No
last name: Stephen M Thielke, MD
role: Principal Investigator
affiliation: VA Puget Sound Health Care System Seattle Division, Seattle, WA
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Dementia
mesh term: Cholinesterase Inhibitors
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The study was designed to allow participants to stop the study medication at any time, and for any reason. This is different than administrative withdrawal.
point of contact: 