<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/NCT03016702</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00078117</org_study_id>
    <secondary_id>P30AG028716-11S1</secondary_id>
    <secondary_id>SPS # 224571</secondary_id>
    <nct_id>NCT03016702</nct_id>
  </id_info>
  <brief_title>The Cognitive Resilience Study</brief_title>
  <acronym>CogRes</acronym>
  <official_title>The Cognitive Resilience Study: Stress Tests for Alzheimer's Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute on Aging (NIA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Bryan Alzheimer's Disease Research Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Duke University Center for the Study of Aging and Human Development</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to test whether two new cognitive &quot;stress tests&quot; may help&#xD;
      distinguish between people at lower or higher genetic risk of Alzheimer's Disease. The&#xD;
      investigators are trying to understand how these cognitive &quot;stress tests&quot; work in people who&#xD;
      have not been diagnosed with Alzheimer's Disease and are not exhibiting symptoms of&#xD;
      Alzheimer's Disease. Study subjects will undergo testing of memory and executive function&#xD;
      during functional magnetic resonance image (fMRI) of the brain and also during a walking&#xD;
      test.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The objective is to establish the feasibility and evaluate the role of two novel tests of&#xD;
      cognitive resilience for use in identification of early Alzheimer's Disease. The&#xD;
      investigators hypothesize that exposure to the controlled stressor of increased cognitive&#xD;
      task demand will evoke measurable phenotypes of poor resilience, which will be associated&#xD;
      with Alzheimer's Disease risk. The study will include 30 volunteer participants from the Duke&#xD;
      Alzheimer's Disease Prevention Registry (ADPR). The ADPR cohort has been characterized&#xD;
      according to genetic risk based on genotype at loci associated with Alzheimer's Disease. The&#xD;
      investigators will recruit a sample from the ADPR that includes 15 people in the &quot;genetic&#xD;
      high risk&quot; group and 15 people, matched by age, in the &quot;genetic low risk&quot; group.&#xD;
      Investigators and experimenters are masked to the genetic profile of all participants. All&#xD;
      participants will undergo two cognitive stress test protocols. Both protocols include memory&#xD;
      and executive function components, one done during functional MRI and one while ambulating on&#xD;
      a force sensor mat. Both cognitive stress tests are minimal risk; the primary risk of this&#xD;
      study is loss of confidentiality. Genetic testing is not performed as part of this protocol;&#xD;
      the sampling strategy will make use of prior genetic testing results, which are not revealed&#xD;
      to the primary investigators. In addition to determining whether scores on the two novel&#xD;
      tests statistically differ by AD risk groups, the project will establish the tests'&#xD;
      feasibility and characteristics for use in future study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 27, 2017</start_date>
  <completion_date type="Actual">August 9, 2017</completion_date>
  <primary_completion_date type="Actual">August 9, 2017</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in reaction time during memory testing during fMRI</measure>
    <time_frame>Measured immediately during one hour fMRI</time_frame>
    <description>The primary dependent variable will be change in reaction time when comparing a neutral memory task to a stress condition. Reaction time will be in ms and will be recorded while the subject is undergoing fMRI.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in reaction time during executive function testing during fMRI</measure>
    <time_frame>Measured immediately during one hour fMRI</time_frame>
    <description>The primary dependent variable will be change in reaction time when comparing a neutral executive function task to a stress condition. Reaction time will be in ms and will be recorded while the subject is undergoing fMRI.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in accuracy during memory testing during gait task</measure>
    <time_frame>Measured immediately during one hour gait session</time_frame>
    <description>The primary dependent variable will be DTEcog = (Dual task [cognitive score] - Single Task [cognitive score] / Single task [cognitive score]. For the memory task, the primary cognitive measure will be the number of correct responses.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in reaction time during executive function testing during gait task</measure>
    <time_frame>Measured immediately during one hour gait session</time_frame>
    <description>The primary dependent variable will be DTEcog = (Dual task [cognitive score] - Single Task [cognitive score] / Single task [cognitive score]. For the executive task, the primary cognitive measure in the DTEcog calculation will be reaction time.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in accuracy during memory testing during fMRI</measure>
    <time_frame>Measured immediately during one hour fMRI</time_frame>
    <description>Secondary dependent variables are accuracy (% correct) when comparing a neutral memory task to a stress condition.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in accuracy during executive function testing during fMRI</measure>
    <time_frame>Measured immediately during one hour fMRI</time_frame>
    <description>Secondary dependent variables are accuracy (% correct) when comparing a neutral memory task to a stress condition.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Brain activation during memory testing during fMRI</measure>
    <time_frame>Measured immediately during one hour fMRI</time_frame>
    <description>Group differences in brain activation provoked by the memory stress condition will be assessed using brain maps that compare block-average BOLD signal for resting vs neutral task, resting vs stress task, neutral vs stress task.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Brain activation during executive function testing during fMRI</measure>
    <time_frame>Measured immediately during one hour fMRI</time_frame>
    <description>Group differences in brain activation provoked by the executive function stress condition will be assessed using brain maps that compare block-average BOLD signal for resting vs neutral task, resting vs stress task, neutral vs stress task.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in gait performance provoked by memory dual tasking</measure>
    <time_frame>Measured immediately during one hour gait session</time_frame>
    <description>The secondary dependent variable will be DTEmob = (Dual task[mobility score] - Single Task[mobility score] / Single task [mobility score]. For both memory and executive tasks, the mobility measure in the DTEmob calculation will be gait speed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in gait performance provoked by executive function dual tasking</measure>
    <time_frame>Measured immediately during one hour gait session</time_frame>
    <description>The secondary dependent variable will be DTEmob = (Dual task[mobility score] - Single Task[mobility score] / Single task [mobility score]. For both memory and executive tasks, the mobility measure in the DTEmob calculation will be gait speed.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">29</enrollment>
  <condition>Alzheimer Disease</condition>
  <arm_group>
    <arm_group_label>High Risk Alzheimer's Disease</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This group includes subjects with APOEe4 homozygotes, the genetic profile associated with the highest risk for late-onset AD and the next highest-risk group, APOE e3/e4 heterozygotes. To target the highest risk among the APOEe3/e4 heterozygotes in ADPR, the study team will consider TOMM40-'523 variant status. Although there is uncertainty about the independent role of TOMM40 in AD risk-stratification (especially across racial/ethnic groups), this study will use TOMM40-'523 to guide heterozygote selection based on findings that among e3/e4 heterozygotes, longer TOMM40-523 polyT sequences are associated with earlier age of onset for late-onset AD.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Low Risk Alzheimer Disease</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This group includes e2/e2 homozygotes (rare) and e2/e3 heterozygotes. the genetic profile associated with low risk for late-onset development of Alzheimer's disease.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Cognitive stress tests during functional MRI</intervention_name>
    <description>Subjects will undergo progressively more complex cognitive stress tests that assess memory and executive function while undergoing fMRI.</description>
    <arm_group_label>High Risk Alzheimer's Disease</arm_group_label>
    <arm_group_label>Low Risk Alzheimer Disease</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Cognitive stress tests during gait task</intervention_name>
    <description>Subjects will undergo progressively more complex cognitive stress tests that assess memory and executive function both in sitting and while ambulating on a force sensor mat.</description>
    <arm_group_label>High Risk Alzheimer's Disease</arm_group_label>
    <arm_group_label>Low Risk Alzheimer Disease</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Able to walk 2 minutes without assistive device or assistance from another person&#xD;
&#xD;
          -  Cognitive function within normal limits&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unable to undergo MRI&#xD;
&#xD;
          -  Left handed&#xD;
&#xD;
          -  Red/Green Color Blind&#xD;
&#xD;
          -  Severe vision impairments&#xD;
&#xD;
          -  Diagnosis of Alzheimer's Disease or other dementia/memory problem&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>58 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Heather Whitson, MD, MHS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University Aging Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>January 9, 2017</study_first_submitted>
  <study_first_submitted_qc>January 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 10, 2017</study_first_posted>
  <last_update_submitted>August 11, 2017</last_update_submitted>
  <last_update_submitted_qc>August 11, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alzheimer Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03016702
org study id: Pro00078117
secondary id: P30AG028716-11S1
secondary id: SPS # 224571
nct id: NCT03016702
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to test whether two new cognitive "stress tests" may help
      distinguish between people at lower or higher genetic risk of Alzheimer's Disease. The
      investigators are trying to understand how these cognitive "stress tests" work in people who
      have not been diagnosed with Alzheimer's Disease and are not exhibiting symptoms of
      Alzheimer's Disease. Study subjects will undergo testing of memory and executive function
      during functional magnetic resonance image (fMRI) of the brain and also during a walking
      test.
The objective is to establish the feasibility and evaluate the role of two novel tests of
      cognitive resilience for use in identification of early Alzheimer's Disease. The
      investigators hypothesize that exposure to the controlled stressor of increased cognitive
      task demand will evoke measurable phenotypes of poor resilience, which will be associated
      with Alzheimer's Disease risk. The study will include 30 volunteer participants from the Duke
      Alzheimer's Disease Prevention Registry (ADPR). The ADPR cohort has been characterized
      according to genetic risk based on genotype at loci associated with Alzheimer's Disease. The
      investigators will recruit a sample from the ADPR that includes 15 people in the "genetic
      high risk" group and 15 people, matched by age, in the "genetic low risk" group.
      Investigators and experimenters are masked to the genetic profile of all participants. All
      participants will undergo two cognitive stress test protocols. Both protocols include memory
      and executive function components, one done during functional MRI and one while ambulating on
      a force sensor mat. Both cognitive stress tests are minimal risk; the primary risk of this
      study is loss of confidentiality. Genetic testing is not performed as part of this protocol;
      the sampling strategy will make use of prior genetic testing results, which are not revealed
      to the primary investigators. In addition to determining whether scores on the two novel
      tests statistically differ by AD risk groups, the project will establish the tests'
      feasibility and characteristics for use in future study.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Change in reaction time during memory testing during fMRI
time frame: Measured immediately during one hour fMRI
description: The primary dependent variable will be change in reaction time when comparing a neutral memory task to a stress condition. Reaction time will be in ms and will be recorded while the subject is undergoing fMRI.
measure: Change in reaction time during executive function testing during fMRI
time frame: Measured immediately during one hour fMRI
description: The primary dependent variable will be change in reaction time when comparing a neutral executive function task to a stress condition. Reaction time will be in ms and will be recorded while the subject is undergoing fMRI.
measure: Change in accuracy during memory testing during gait task
time frame: Measured immediately during one hour gait session
description: The primary dependent variable will be DTEcog = (Dual task [cognitive score] - Single Task [cognitive score] / Single task [cognitive score]. For the memory task, the primary cognitive measure will be the number of correct responses.
measure: Change in reaction time during executive function testing during gait task
time frame: Measured immediately during one hour gait session
description: The primary dependent variable will be DTEcog = (Dual task [cognitive score] - Single Task [cognitive score] / Single task [cognitive score]. For the executive task, the primary cognitive measure in the DTEcog calculation will be reaction time.
measure: Change in accuracy during memory testing during fMRI
time frame: Measured immediately during one hour fMRI
description: Secondary dependent variables are accuracy (% correct) when comparing a neutral memory task to a stress condition.
measure: Change in accuracy during executive function testing during fMRI
time frame: Measured immediately during one hour fMRI
description: Secondary dependent variables are accuracy (% correct) when comparing a neutral memory task to a stress condition.
measure: Brain activation during memory testing during fMRI
time frame: Measured immediately during one hour fMRI
description: Group differences in brain activation provoked by the memory stress condition will be assessed using brain maps that compare block-average BOLD signal for resting vs neutral task, resting vs stress task, neutral vs stress task.
measure: Brain activation during executive function testing during fMRI
time frame: Measured immediately during one hour fMRI
description: Group differences in brain activation provoked by the executive function stress condition will be assessed using brain maps that compare block-average BOLD signal for resting vs neutral task, resting vs stress task, neutral vs stress task.
measure: Change in gait performance provoked by memory dual tasking
time frame: Measured immediately during one hour gait session
description: The secondary dependent variable will be DTEmob = (Dual task[mobility score] - Single Task[mobility score] / Single task [mobility score]. For both memory and executive tasks, the mobility measure in the DTEmob calculation will be gait speed.
measure: Change in gait performance provoked by executive function dual tasking
time frame: Measured immediately during one hour gait session
description: The secondary dependent variable will be DTEmob = (Dual task[mobility score] - Single Task[mobility score] / Single task [mobility score]. For both memory and executive tasks, the mobility measure in the DTEmob calculation will be gait speed.
arm group label: High Risk Alzheimer's Disease
arm group type: Experimental
description: This group includes subjects with APOEe4 homozygotes, the genetic profile associated with the highest risk for late-onset AD and the next highest-risk group, APOE e3/e4 heterozygotes. To target the highest risk among the APOEe3/e4 heterozygotes in ADPR, the study team will consider TOMM40-'523 variant status. Although there is uncertainty about the independent role of TOMM40 in AD risk-stratification (especially across racial/ethnic groups), this study will use TOMM40-'523 to guide heterozygote selection based on findings that among e3/e4 heterozygotes, longer TOMM40-523 polyT sequences are associated with earlier age of onset for late-onset AD.
arm group label: Low Risk Alzheimer Disease
arm group type: Experimental
description: This group includes e2/e2 homozygotes (rare) and e2/e3 heterozygotes. the genetic profile associated with low risk for late-onset development of Alzheimer's disease.
intervention type: Other
intervention name: Cognitive stress tests during functional MRI
description: Subjects will undergo progressively more complex cognitive stress tests that assess memory and executive function while undergoing fMRI.
arm group label: High Risk Alzheimer's Disease
arm group label: Low Risk Alzheimer Disease
intervention type: Other
intervention name: Cognitive stress tests during gait task
description: Subjects will undergo progressively more complex cognitive stress tests that assess memory and executive function both in sitting and while ambulating on a force sensor mat.
arm group label: High Risk Alzheimer's Disease
arm group label: Low Risk Alzheimer Disease
criteria: 
gender: All
minimum age: 58 Years
maximum age: 70 Years
healthy volunteers: No
last name: Heather Whitson, MD, MHS
role: Principal Investigator
affiliation: Duke University Aging Center
facility: 
country: United States
responsible party type: Sponsor
mesh term: Alzheimer Disease
sharing ipd: No