<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/NCT03816228</url>
  </required_header>
  <id_info>
    <org_study_id>IND 123119 Protocol Z</org_study_id>
    <nct_id>NCT03816228</nct_id>
  </id_info>
  <brief_title>Imaging of Brain Structural/Functional Connectivity and Amyloid and Tau Lesions in APOE4 Carriers.</brief_title>
  <acronym>Protocol_Z</acronym>
  <official_title>Imaging of Brain Structural/Functional Connectivity and Amyloid and Tau Lesions in APOE4 Carriers. (IND 123119, Protocol Z)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tammie L. S. Benzinger, MD, PhD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Washington University School of Medicine</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To advance current knowledge on the vascular contributions to dementia&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a multi-center study at Washington University (WASH U), University of Southern&#xD;
      California (USC), and Huntington Medical Research Institute (HMRI).The overall goal of both&#xD;
      the AA program and the PPG program is to advance current knowledge on the vascular&#xD;
      contributions to dementia particularly in individuals with the major genetic risk factor for&#xD;
      late-onset AD, i.e., apolipoprotein E-ε4 (APOE4) gene that develop early vascular dysfunction&#xD;
      and significant cerebrovascular pathology compared to non-carriers, and establish whether the&#xD;
      neurovasculature plays a key role in cognitive decline, and therefore is a key new&#xD;
      therapeutic target to treat dementia in APOE4 carriers.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    We will capture subjects under another study&#xD;
  </why_stopped>
  <start_date type="Anticipated">January 2022</start_date>
  <completion_date type="Actual">October 11, 2022</completion_date>
  <primary_completion_date type="Anticipated">October 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>F 18 T807 Standard Uptake Value Ratios</measure>
    <time_frame>5 years</time_frame>
    <description>F 18 T807 Standard Uptake Value Ratios (SUVR) will be correlated with other imaging modalities (MRI, PET amyloid imaging) and cognitive performance.</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">0</enrollment>
  <condition>Alzheimer Disease</condition>
  <arm_group>
    <arm_group_label>Experimental Flortaucipir</arm_group_label>
    <description>Participants will receive a single intravenous bolus injection of flortaucipir along with PET imaging.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>F 18 T807 Flortaucipir</intervention_name>
    <description>Participants will receive a single intravenous bolus injection of approximately 6.5-10mCi (240-370MBq) of F 18 T807. For those who cannot tolerate the full exam, participants will receive single intravenous bolus injection of approximately 6.5-10mCi (240-370MBq) of F 18 T807.</description>
    <arm_group_label>Experimental Flortaucipir</arm_group_label>
    <other_name>18F-AV-1451</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        A total of participants currently enrolled in ongoing projects affiliated with the Knight&#xD;
        ADRC will be recruited. Without disclosing individual genetic risk status, 202 of these&#xD;
        participants will include a mix of APOE4/4 (~7%), APOE3/4 (~30%), and APOE3/3 (~63%)&#xD;
        carriers. In addition, without disclosing individual mutation status, ~40 PSEN1 carriers&#xD;
        and non-carrier family members currently enrolled in the Dominantly Inherited Alzheimer&#xD;
        Network (DIAN) study at Washington University will be recruited.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female, any race&#xD;
&#xD;
          -  Age &gt; 18 years&#xD;
&#xD;
          -  Participation in one of the ongoing projects affiliated with the Knight ADRC at&#xD;
             Washington University and referred by the MAP staff and a Washington University&#xD;
             physician.&#xD;
&#xD;
          -  Normal cognition or early-stage symptomatic AD&#xD;
&#xD;
          -  Females of childbearing potential without documented history of menopause or&#xD;
             hysterectomy who do participate must not be pregnant or breastfeeding at screening&#xD;
&#xD;
          -  (negative urine β-HCG within 24 hours prior to injection), and must agree to avoid&#xD;
             becoming pregnant. Females of childbearing potential who do not agree to use reliable&#xD;
             contraception or refrain from sexual activity for 24 hours following administration of&#xD;
             flortaucipir injection.&#xD;
&#xD;
          -  Enrollment in DCE-MRI study&#xD;
&#xD;
          -  Capacity to give informed consent and follow study procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any illness preventing cooperation with testing or longitudinal participation&#xD;
&#xD;
          -  Exclusion from the Knight ADRC or DIAN referring project&#xD;
&#xD;
          -  Has a high risk for Torsades de Pointes or is taking medications known to prolong or&#xD;
             may prolong QT interval (refer to study attachment &quot;Restricted Medication List&quot;).&#xD;
&#xD;
          -  MRI contraindications (e.g. electronic medical devices, severe claustrophobia,&#xD;
             inability to lie still for long periods) that make it unsafe to participate in an MRI&#xD;
             scan, using standard screening processes implemented by Washington University and&#xD;
             Barnes-Jewish Hospital&#xD;
&#xD;
          -  Currently pregnant or breastfeeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tammie Benzinger, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Washington University School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Akinyemi RO, Mukaetova-Ladinska EB, Attems J, Ihara M, Kalaria RN. Vascular risk factors and neurodegeneration in ageing related dementias: Alzheimer's disease and vascular dementia. Curr Alzheimer Res. 2013 Jul;10(6):642-53. doi: 10.2174/15672050113109990037.</citation>
    <PMID>23627757</PMID>
  </reference>
  <reference>
    <citation>Fleisher A, Grundman M, Jack CR Jr, Petersen RC, Taylor C, Kim HT, Schiller DH, Bagwell V, Sencakova D, Weiner MF, DeCarli C, DeKosky ST, van Dyck CH, Thal LJ; Alzheimer's Disease Cooperative Study. Sex, apolipoprotein E epsilon 4 status, and hippocampal volume in mild cognitive impairment. Arch Neurol. 2005 Jun;62(6):953-7. doi: 10.1001/archneur.62.6.953.</citation>
    <PMID>15956166</PMID>
  </reference>
  <reference>
    <citation>Petersen RC, Doody R, Kurz A, Mohs RC, Morris JC, Rabins PV, Ritchie K, Rossor M, Thal L, Winblad B. Current concepts in mild cognitive impairment. Arch Neurol. 2001 Dec;58(12):1985-92. doi: 10.1001/archneur.58.12.1985.</citation>
    <PMID>11735772</PMID>
  </reference>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>January 22, 2019</study_first_submitted>
  <study_first_submitted_qc>January 22, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 25, 2019</study_first_posted>
  <last_update_submitted>May 5, 2023</last_update_submitted>
  <last_update_submitted_qc>May 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Washington University School of Medicine</investigator_affiliation>
    <investigator_full_name>Tammie L. S. Benzinger, MD, PhD</investigator_full_name>
    <investigator_title>Professor of Radiology &amp; Neurological Surgery</investigator_title>
  </responsible_party>
  <keyword>Dementia</keyword>
  <keyword>Taupathies</keyword>
  <keyword>Brain Disease</keyword>
  <keyword>Mild Cognitive Impairment</keyword>
  <keyword>Neurodegenerative Disease</keyword>
  <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>
    <ipd_description>We will share the data with other researchers. They may be doing research in areas similar to this research or in other unrelated areas. These researchers may be at Washington University, at other research centers and institutions, or industry sponsors of research. We may also share the research data with large data repositories (a repository is a database of information) for broad sharing with the research community. The participant&quot;s individual research data is placed in one of these repositories only qualified researchers, who have received prior approval from individuals that monitor the use of the data, will be able to look at this information.</ipd_description>
  </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/NCT03816228
org study id: IND 123119 Protocol Z
nct id: NCT03816228
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
To advance current knowledge on the vascular contributions to dementia
This is a multi-center study at Washington University (WASH U), University of Southern
      California (USC), and Huntington Medical Research Institute (HMRI).The overall goal of both
      the AA program and the PPG program is to advance current knowledge on the vascular
      contributions to dementia particularly in individuals with the major genetic risk factor for
      late-onset AD, i.e., apolipoprotein E-ε4 (APOE4) gene that develop early vascular dysfunction
      and significant cerebrovascular pathology compared to non-carriers, and establish whether the
      neurovasculature plays a key role in cognitive decline, and therefore is a key new
      therapeutic target to treat dementia in APOE4 carriers.
observational model: Other
time perspective: Prospective
measure: F 18 T807 Standard Uptake Value Ratios
time frame: 5 years
description: F 18 T807 Standard Uptake Value Ratios (SUVR) will be correlated with other imaging modalities (MRI, PET amyloid imaging) and cognitive performance.
arm group label: Experimental Flortaucipir
description: Participants will receive a single intravenous bolus injection of flortaucipir along with PET imaging.
intervention type: Drug
intervention name: F 18 T807 Flortaucipir
description: Participants will receive a single intravenous bolus injection of approximately 6.5-10mCi (240-370MBq) of F 18 T807. For those who cannot tolerate the full exam, participants will receive single intravenous bolus injection of approximately 6.5-10mCi (240-370MBq) of F 18 T807.
arm group label: Experimental Flortaucipir
other name: 18F-AV-1451
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Tammie Benzinger, MD, PhD
role: Principal Investigator
affiliation: Washington University School of Medicine
facility: 
country: United States
citation: Akinyemi RO, Mukaetova-Ladinska EB, Attems J, Ihara M, Kalaria RN. Vascular risk factors and neurodegeneration in ageing related dementias: Alzheimer's disease and vascular dementia. Curr Alzheimer Res. 2013 Jul;10(6):642-53. doi: 10.2174/15672050113109990037.
PMID: 23627757
citation: Fleisher A, Grundman M, Jack CR Jr, Petersen RC, Taylor C, Kim HT, Schiller DH, Bagwell V, Sencakova D, Weiner MF, DeCarli C, DeKosky ST, van Dyck CH, Thal LJ; Alzheimer's Disease Cooperative Study. Sex, apolipoprotein E epsilon 4 status, and hippocampal volume in mild cognitive impairment. Arch Neurol. 2005 Jun;62(6):953-7. doi: 10.1001/archneur.62.6.953.
PMID: 15956166
citation: Petersen RC, Doody R, Kurz A, Mohs RC, Morris JC, Rabins PV, Ritchie K, Rossor M, Thal L, Winblad B. Current concepts in mild cognitive impairment. Arch Neurol. 2001 Dec;58(12):1985-92. doi: 10.1001/archneur.58.12.1985.
PMID: 11735772
responsible party type: Sponsor-Investigator
investigator affiliation: Washington University School of Medicine
investigator full name: Tammie L. S. Benzinger, MD, PhD
investigator title: Professor of Radiology & Neurological Surgery
mesh term: Alzheimer Disease
sharing ipd: No
ipd description: We will share the data with other researchers. They may be doing research in areas similar to this research or in other unrelated areas. These researchers may be at Washington University, at other research centers and institutions, or industry sponsors of research. We may also share the research data with large data repositories (a repository is a database of information) for broad sharing with the research community. The participant"s individual research data is placed in one of these repositories only qualified researchers, who have received prior approval from individuals that monitor the use of the data, will be able to look at this information.