<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/NCT03757910</url>
  </required_header>
  <id_info>
    <org_study_id>AAAS1176</org_study_id>
    <secondary_id>3U01DK048404-25S1</secondary_id>
    <nct_id>NCT03757910</nct_id>
  </id_info>
  <brief_title>Brain Imaging in the Diabetes Prevention Program Outcomes Study</brief_title>
  <acronym>DPPOS-Brain</acronym>
  <official_title>Amyloid Brain Positron Emission Tomography (PET) Imaging With 11C-PIB and Tau PET Imaging With 18F-MK-6240 in the Diabetes Prevention Program Outcomes Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>José A. Luchsinger</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Albert Einstein College of Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>George Washington University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Columbia University</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>
      This is a cross-sectional pilot study of Alzheimer's disease (AD) brain imaging biomarkers in&#xD;
      Diabetes Prevention Program (DPP) outcomes study (DPPOS) participants from the New York City&#xD;
      sites (Columbia and Einstein), comparing 10 persons originally randomized to metformin and 10&#xD;
      persons randomized to placebo in DPP. All study procedures will be conducted at Columbia&#xD;
      University Irving Medical Center. Eligible participants will receive a PET scans and a brain&#xD;
      MRI, which may be conducted in one, two, or three separate visits.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hyperinsulinemia is believed to increase the risk of Alzheimer's dementia through both&#xD;
      cerebrovascular and A related mechanisms, and this hypothesis has prompted testing strategies&#xD;
      related to hyperinsulinemia and diabetes in the prevention and treatment of Alzheimer's&#xD;
      dementia.These strategies usually entail improving insulin sensitivity to lower insulin and&#xD;
      glucose levels, such as lifestyle (diet and exercise) and metformin, which were effective&#xD;
      strategies for preventing diabetes in the DPPOS. There are conflicting data relating&#xD;
      metformin with increased AD risk, and this needs to be clarified in DPPOS. Several laboratory&#xD;
      and human studies have suggested that metformin increases the risk of Alzheimer's dementia,&#xD;
      but this is countered by other studies indicating that it is beneficial. Preliminary data in&#xD;
      humans and animals support the beneficial effects of metformin on Alzheimer's dementia risk.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Enrolling by invitation</last_known_status>
  <start_date type="Actual">October 1, 2019</start_date>
  <completion_date type="Anticipated">January 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">January 31, 2022</primary_completion_date>
  <phase>Early Phase 1</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Brain Amyloid SUVR</measure>
    <time_frame>Up to 1 hour post-injection</time_frame>
    <description>Whole brain amyloid (11C-PIB) standardized uptake volume ratio (SUVR)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Brain Tau SUVR</measure>
    <time_frame>Up to 1 hour post-injection</time_frame>
    <description>Tau (18F-MK-6240) SUVR in medial and inferior temporal lobes</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hippocampal Cortical Thickness</measure>
    <time_frame>Up to 1 hour post-injection</time_frame>
    <description>Thickness in the hippocampal cortex</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>White Matter Hyper Intensity Volume</measure>
    <time_frame>Up to 1 hour post-injection</time_frame>
    <description>Volume of brain white matter hyper-intensities</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Alzheimer Disease</condition>
  <arm_group>
    <arm_group_label>DPPOS Exposed to Metformin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>DPPOS participants with exposure to metformin will be scanned with 18F-MK-6240 and 11C-PIB.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>DPPOS Exposed to Placebo</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>DPPOS participants with no exposure to metformin but only placebo will be scanned with 18F-MK-6240 and 11C-PIB.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>18F-MK-6240</intervention_name>
    <description>This radiotracer will be used to detect Tau.The injected activity will equal 5 millicuries (mCi).</description>
    <arm_group_label>DPPOS Exposed to Metformin</arm_group_label>
    <arm_group_label>DPPOS Exposed to Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>11C-PIB</intervention_name>
    <description>This radiotracer will be used to detect amyloid. Participants will be injected with an intravenous bolus of up to 5-15 mCi.</description>
    <arm_group_label>DPPOS Exposed to Metformin</arm_group_label>
    <arm_group_label>DPPOS Exposed to Placebo</arm_group_label>
    <other_name>11C-Pittsburgh Compound B</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Active participants in the Diabetes Prevention Program Outcomes Study (DPPOS) in New&#xD;
             York City originally randomized to metformin or placebo&#xD;
&#xD;
          -  60 years and older&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known dementia&#xD;
&#xD;
          -  Contraindications to magnetic resonance imaging (MRI)&#xD;
&#xD;
          -  Contraindications to radio-contrast agents.&#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>F. X. Pi-Sunyer, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Columbia University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Columbia University Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Albert Einstein College of Medicine</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10461</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>November 27, 2018</study_first_submitted>
  <study_first_submitted_qc>November 27, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 29, 2018</study_first_posted>
  <last_update_submitted>July 8, 2021</last_update_submitted>
  <last_update_submitted_qc>July 8, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 9, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Columbia University</investigator_affiliation>
    <investigator_full_name>José A. Luchsinger</investigator_full_name>
    <investigator_title>Professor of Medicine and Epidemiology</investigator_title>
  </responsible_party>
  <keyword>Metformin</keyword>
  <keyword>Pre-diabetes</keyword>
  <keyword>Type 2 diabetes</keyword>
  <keyword>DPPOS</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alzheimer Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Corticosterone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03757910
org study id: AAAS1176
secondary id: 3U01DK048404-25S1
nct id: NCT03757910
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a cross-sectional pilot study of Alzheimer's disease (AD) brain imaging biomarkers in
      Diabetes Prevention Program (DPP) outcomes study (DPPOS) participants from the New York City
      sites (Columbia and Einstein), comparing 10 persons originally randomized to metformin and 10
      persons randomized to placebo in DPP. All study procedures will be conducted at Columbia
      University Irving Medical Center. Eligible participants will receive a PET scans and a brain
      MRI, which may be conducted in one, two, or three separate visits.
Hyperinsulinemia is believed to increase the risk of Alzheimer's dementia through both
      cerebrovascular and A related mechanisms, and this hypothesis has prompted testing strategies
      related to hyperinsulinemia and diabetes in the prevention and treatment of Alzheimer's
      dementia.These strategies usually entail improving insulin sensitivity to lower insulin and
      glucose levels, such as lifestyle (diet and exercise) and metformin, which were effective
      strategies for preventing diabetes in the DPPOS. There are conflicting data relating
      metformin with increased AD risk, and this needs to be clarified in DPPOS. Several laboratory
      and human studies have suggested that metformin increases the risk of Alzheimer's dementia,
      but this is countered by other studies indicating that it is beneficial. Preliminary data in
      humans and animals support the beneficial effects of metformin on Alzheimer's dementia risk.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Brain Amyloid SUVR
time frame: Up to 1 hour post-injection
description: Whole brain amyloid (11C-PIB) standardized uptake volume ratio (SUVR)
measure: Brain Tau SUVR
time frame: Up to 1 hour post-injection
description: Tau (18F-MK-6240) SUVR in medial and inferior temporal lobes
measure: Hippocampal Cortical Thickness
time frame: Up to 1 hour post-injection
description: Thickness in the hippocampal cortex
measure: White Matter Hyper Intensity Volume
time frame: Up to 1 hour post-injection
description: Volume of brain white matter hyper-intensities
arm group label: DPPOS Exposed to Metformin
arm group type: Experimental
description: DPPOS participants with exposure to metformin will be scanned with 18F-MK-6240 and 11C-PIB.
arm group label: DPPOS Exposed to Placebo
arm group type: Active Comparator
description: DPPOS participants with no exposure to metformin but only placebo will be scanned with 18F-MK-6240 and 11C-PIB.
intervention type: Drug
intervention name: 18F-MK-6240
description: This radiotracer will be used to detect Tau.The injected activity will equal 5 millicuries (mCi).
arm group label: DPPOS Exposed to Metformin
arm group label: DPPOS Exposed to Placebo
intervention type: Drug
intervention name: 11C-PIB
description: This radiotracer will be used to detect amyloid. Participants will be injected with an intravenous bolus of up to 5-15 mCi.
arm group label: DPPOS Exposed to Metformin
arm group label: DPPOS Exposed to Placebo
other name: 11C-Pittsburgh Compound B
criteria: 
gender: All
minimum age: 60 Years
maximum age: N/A
healthy volunteers: No
last name: F. X. Pi-Sunyer, MD
role: Principal Investigator
affiliation: Columbia University
facility: 
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Columbia University
investigator full name: José A. Luchsinger
investigator title: Professor of Medicine and Epidemiology
mesh term: Alzheimer Disease
mesh term: Corticosterone
sharing ipd: Undecided