<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/NCT04505735</url>
  </required_header>
  <id_info>
    <org_study_id>16-2064</org_study_id>
    <nct_id>NCT04505735</nct_id>
  </id_info>
  <brief_title>Amyloid Imaging With 11C-PiB in Healthy Aging and Mild Cognitive Impairment</brief_title>
  <official_title>Amyloid Imaging With 11C-PiB in Healthy Aging and Mild Cognitive Impairment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Colorado, Denver</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Colorado, Denver</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>
      The purpose of this study is to measure the amount of amyloid in the brain. Amyloid is a&#xD;
      protein found in the brain of patients with Alzheimer's disease and can be detected using a&#xD;
      Positron Emission Tomography (PET) scan. This study is interested in how amyloid levels in&#xD;
      the brain relate to memory and thinking abilities.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The overarching goal of this study is to use 11C-PiB, a commonly used tracer that binds to&#xD;
      amyloid plaques in the brain, as a biological marker of Alzheimer's disease (AD) related&#xD;
      brain changes. Data from this PET-only study will be compared to and analyzed with data from&#xD;
      the Investigators' longitudinal biomarker studies, COMIRB #15-1774 and COMIRB #18-2607. This&#xD;
      enables investigators to examine how deposition of the amyloid protein relates to cognitive&#xD;
      aging in both symptomatic and asymptomatic older adults. It will assist investigators in&#xD;
      comparing rates of change in memory and thinking ability in healthy subjects who are amyloid&#xD;
      positive versus amyloid negative, as well as in comparing rates of conversion to a higher&#xD;
      level of impairment (e.g. such as Mild Cognitive Impairment converting to Alzheimer's&#xD;
      Disease) based on the quantitative analysis of amyloid burden. Moreover, by capitalizing on&#xD;
      data across the two studies, the investigators will be able to better understand the&#xD;
      relationship between amyloid deposition (as assessed by PET; current proposal) and other&#xD;
      biomarkers (as assessed in COMIRB #15-1774, COMIRB #18-2607), which ultimately may help the&#xD;
      investigators better predict the onset and progression of clinical AD symptoms. Participants&#xD;
      will be recruited solely from the longitudinal study (COMIRB # 15-1774) in order to provide&#xD;
      data comparison on an individual and group basis.&#xD;
&#xD;
      The goals of this study are as follows:&#xD;
&#xD;
        1. Evaluate the relationship between amyloid burden, as assessed by 11C-PiB, with both&#xD;
           cross-sectional and longitudinal biomarkers (e.g. blood; nasal biopsy; CSF; MRI; DNA)&#xD;
           obtained in the longitudinal study (COMIRB # 15-1774, COMIRB #18-2607).&#xD;
&#xD;
        2. Compare rates of change in memory and other cognitive abilities (obtained in COMIRB #&#xD;
           15-1774, COMIRB #18-2607) in healthy subjects who show elevated amyloid deposition with&#xD;
           those who are &quot;amyloid negative&quot;.&#xD;
&#xD;
        3. Evaluate the relationship between amyloid burden and health history, informant report of&#xD;
           subjective cognitive and psychiatric difficulties, and participant-reported psychiatric&#xD;
           symptoms.&#xD;
&#xD;
        4. Investigate predictive utility of amyloid burden in identifying individuals most at risk&#xD;
           for conversion (e.g. healthy controls to MCI, and MCI to AD).&#xD;
&#xD;
        5. Identify why a subset of &quot;amyloid positive&quot; individuals do not show symptoms of clinical&#xD;
           AD or delay conversion to MCI or AD.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Issues with local production of 11-cPiB radiotracer&#xD;
  </why_stopped>
  <start_date type="Actual">November 22, 2016</start_date>
  <completion_date type="Actual">September 23, 2022</completion_date>
  <primary_completion_date type="Actual">September 23, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Amyloid burden</measure>
    <time_frame>Single visit PET scan (Day 0)</time_frame>
    <description>Amyloid burden will be calculated using the standardized uptake volume ratio (SUVr) to do a centiloid analysis. This is assessed on a 100-point scale, the &quot;Centiloid&quot; (CL), where the data is scaled so that an average value of zero is amyloid-negative subjects and an average value of 100 is a typical Alzheimer's Disease patient (with negative numbers and numbers above 100 being possible). The site will scale the data along this 0-100 scale to determine amyloid burden in relation to Alzheimer's disease and compare to data from COMIRB #15-1774 or COMIRB #18-2607</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">25</enrollment>
  <condition>Alzheimer Disease</condition>
  <condition>Healthy Aging</condition>
  <arm_group>
    <arm_group_label>Normal Control</arm_group_label>
    <description>Adults with no history of memory complaints, diagnosis of MCI, or dementia from a physician</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Adults with Mild Cognitive Impairment</arm_group_label>
    <description>Adults with cognitive decline verified by a study partner or cognitive impairment verified by the study physician. The cognitive decline has had limited impact on functional activities; general cognition and functional performance are sufficiently preserved such that a diagnosis of dementia cannot be made by the enrolling physician</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>11C-PiB</intervention_name>
    <description>Pittsburgh Compound-B (11C-PiB) is a diagnostic imaging agent that binds to beta-amyloid plaques and allows them to be viewed using positron emission tomography (PET) imaging.</description>
    <arm_group_label>Adults with Mild Cognitive Impairment</arm_group_label>
    <arm_group_label>Normal Control</arm_group_label>
    <other_name>Pittsburgh compound B</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Participants will be recruited from the Rocky Mountain Alzheimer's Disease Center at the&#xD;
        University of Colorado School of Medicine (RMADC at UCSOM) Longitudinal Biomarker and&#xD;
        Clinical Phenotyping Study (Bio-AD; COMIRB #15-1774) and/or Longitudinal Innate Immunity&#xD;
        and Aging study (LIIA; COMIRB #18-2607).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patients may be enrolled in the Normal Control group if the following criteria are met:&#xD;
&#xD;
          1. Males or nonpregnant females ≥ 50 years of age;&#xD;
&#xD;
          2. Have no history of memory complaints;&#xD;
&#xD;
          3. Have no diagnosis of MCI or dementia from a physician&#xD;
&#xD;
          4. Currently enrolled in the Rocky Mountain Alzheimer's Disease Center at the University&#xD;
             of Colorado School of Medicine (RMADC at UCSOM) Longitudinal Biomarker and Clinical&#xD;
             Phenotyping Study (COMIRB #15-1774) or Longitudinal Innate Immunity and Aging study&#xD;
             (LIIA; COMIRB #18-2607)&#xD;
&#xD;
          5. Willing to have clinical research information from the Longitudinal Biomarker and&#xD;
             Clinical Phenotyping Study (COMIRB #15-1774) and/or LIIA (COMIRB #18-2607) study&#xD;
             shared/combined with the current study.&#xD;
&#xD;
          6. Participated in the MRI procedure for COMIRB #15-1774 or COMIRB #18-2607.&#xD;
&#xD;
        Patients may be enrolled in the Mild Cognitive Impairment (not demented) group if the&#xD;
        following criteria are met:&#xD;
&#xD;
          1. Males or nonpregnant females ≥ 50 years of age;&#xD;
&#xD;
          2. Have cognitive decline verified by a study partner or cognitive impairment verified by&#xD;
             the study physician. The cognitive decline has had limited impact on functional&#xD;
             activities; general cognition and functional performance are sufficiently preserved&#xD;
             such that a diagnosis of dementia cannot be made by the enrolling physician&#xD;
&#xD;
          3. Have a Clinical Dementia Rating score of 0.5*&#xD;
&#xD;
          4. Can tolerate a 70-minute PET scan. The Principal Investigator and Co-PI will carefully&#xD;
             assess each patient and use sound judgment to determine whether the patient can&#xD;
             tolerate the PET scan procedure;&#xD;
&#xD;
          5. Ability to provide informed consent for study procedures (If the patient is ineligible&#xD;
             to give informed consent, based on local standards, the patient's legally authorized&#xD;
             representative may consent on behalf of the patient but the patient must still confirm&#xD;
             assent. This person may serve as the study partner as well).&#xD;
&#xD;
          6. Concurrently enrolled in the Rocky Mountain Alzheimer's Disease Center at the&#xD;
             University of Colorado School of Medicine (RMADC at UCSOM) Longitudinal Biomarker and&#xD;
             Clinical Phenotyping Study (Bio-AD; COMIRB #15-1774) or Longitudinal Innate Immunity&#xD;
             and Aging study (LIIA; COMIRB #18-2607)&#xD;
&#xD;
          7. Participated in the MRI procedure for COMIRB #15-1774 or COMIRB #18-2607.&#xD;
&#xD;
          8. Willing to have clinical research information from the Longitudinal Biomarker and&#xD;
             Clinical Phenotyping Study (COMIRB #15-1774) and/or LIIA (COMIRB #18-2607) study&#xD;
             shared/combined with the current study.&#xD;
&#xD;
               -  For aging adults with atypical phenotypes (e.g., early onset Alzheimer's Disease;&#xD;
                  Posterior Cortical Atrophy; Logopenic variant primary progressive aphasia), a CDR&#xD;
                  of 1 will be accepted if the study team determines that their severity is mild.&#xD;
                  The reason for this caveat is that these phenotypes often reach a CDR of 1&#xD;
                  quickly due to cortical symptoms (e.g., loss of visual perception); in these&#xD;
                  cases, the CDR may overestimate their true severity level.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Patients will be excluded from enrollment if they:&#xD;
&#xD;
          1. Have a current serious or unstable illness that in the enrolling physician's opinion,&#xD;
             could interfere with completion of the safety or efficacy evaluations included in this&#xD;
             study.&#xD;
&#xD;
          2. Have a known brain lesion, pathology or alternative diagnosis that strongly explains&#xD;
             the patient's clinical presentation;&#xD;
&#xD;
          3. Are receiving any investigational medications, or have participated in a trial with&#xD;
             investigational medications within the last 30 days;&#xD;
&#xD;
          4. Have had a clinical radiopharmaceutical imaging or treatment procedure within 7 days&#xD;
             prior to the study imaging session; have had a research radiopharmaceutical imaging&#xD;
             study done within 12 months or have one planned in the next 12 months.&#xD;
&#xD;
          5. Exposed to radiation in the work place during the previous year&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Brianne M Bettcher, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Colorado, Denver</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Colorado, Denver</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>July 29, 2020</study_first_submitted>
  <study_first_submitted_qc>August 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2020</study_first_posted>
  <last_update_submitted>April 5, 2023</last_update_submitted>
  <last_update_submitted_qc>April 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 7, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Healthy Older Adults</keyword>
  <keyword>Mild Cognitve Impairment</keyword>
  <keyword>Imaging</keyword>
  <keyword>C-PiB</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alzheimer Disease</mesh_term>
    <mesh_term>Cognitive Dysfunction</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>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/NCT04505735
org study id: 16-2064
nct id: NCT04505735
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to measure the amount of amyloid in the brain. Amyloid is a
      protein found in the brain of patients with Alzheimer's disease and can be detected using a
      Positron Emission Tomography (PET) scan. This study is interested in how amyloid levels in
      the brain relate to memory and thinking abilities.
The overarching goal of this study is to use 11C-PiB, a commonly used tracer that binds to
      amyloid plaques in the brain, as a biological marker of Alzheimer's disease (AD) related
      brain changes. Data from this PET-only study will be compared to and analyzed with data from
      the Investigators' longitudinal biomarker studies, COMIRB #15-1774 and COMIRB #18-2607. This
      enables investigators to examine how deposition of the amyloid protein relates to cognitive
      aging in both symptomatic and asymptomatic older adults. It will assist investigators in
      comparing rates of change in memory and thinking ability in healthy subjects who are amyloid
      positive versus amyloid negative, as well as in comparing rates of conversion to a higher
      level of impairment (e.g. such as Mild Cognitive Impairment converting to Alzheimer's
      Disease) based on the quantitative analysis of amyloid burden. Moreover, by capitalizing on
      data across the two studies, the investigators will be able to better understand the
      relationship between amyloid deposition (as assessed by PET; current proposal) and other
      biomarkers (as assessed in COMIRB #15-1774, COMIRB #18-2607), which ultimately may help the
      investigators better predict the onset and progression of clinical AD symptoms. Participants
      will be recruited solely from the longitudinal study (COMIRB # 15-1774) in order to provide
      data comparison on an individual and group basis.

      The goals of this study are as follows:

        1. Evaluate the relationship between amyloid burden, as assessed by 11C-PiB, with both
           cross-sectional and longitudinal biomarkers (e.g. blood; nasal biopsy; CSF; MRI; DNA)
           obtained in the longitudinal study (COMIRB # 15-1774, COMIRB #18-2607).

        2. Compare rates of change in memory and other cognitive abilities (obtained in COMIRB #
           15-1774, COMIRB #18-2607) in healthy subjects who show elevated amyloid deposition with
           those who are "amyloid negative".

        3. Evaluate the relationship between amyloid burden and health history, informant report of
           subjective cognitive and psychiatric difficulties, and participant-reported psychiatric
           symptoms.

        4. Investigate predictive utility of amyloid burden in identifying individuals most at risk
           for conversion (e.g. healthy controls to MCI, and MCI to AD).

        5. Identify why a subset of "amyloid positive" individuals do not show symptoms of clinical
           AD or delay conversion to MCI or AD.
observational model: Case-Control
time perspective: Cross-Sectional
measure: Amyloid burden
time frame: Single visit PET scan (Day 0)
description: Amyloid burden will be calculated using the standardized uptake volume ratio (SUVr) to do a centiloid analysis. This is assessed on a 100-point scale, the "Centiloid" (CL), where the data is scaled so that an average value of zero is amyloid-negative subjects and an average value of 100 is a typical Alzheimer's Disease patient (with negative numbers and numbers above 100 being possible). The site will scale the data along this 0-100 scale to determine amyloid burden in relation to Alzheimer's disease and compare to data from COMIRB #15-1774 or COMIRB #18-2607
arm group label: Normal Control
description: Adults with no history of memory complaints, diagnosis of MCI, or dementia from a physician
arm group label: Adults with Mild Cognitive Impairment
description: Adults with cognitive decline verified by a study partner or cognitive impairment verified by the study physician. The cognitive decline has had limited impact on functional activities; general cognition and functional performance are sufficiently preserved such that a diagnosis of dementia cannot be made by the enrolling physician
intervention type: Drug
intervention name: 11C-PiB
description: Pittsburgh Compound-B (11C-PiB) is a diagnostic imaging agent that binds to beta-amyloid plaques and allows them to be viewed using positron emission tomography (PET) imaging.
arm group label: Adults with Mild Cognitive Impairment
arm group label: Normal Control
other name: Pittsburgh compound B
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Brianne M Bettcher, Ph.D.
role: Principal Investigator
affiliation: University of Colorado, Denver
facility: 
country: United States
responsible party type: Sponsor
mesh term: Alzheimer Disease
mesh term: Cognitive Dysfunction
mesh term: Corticosterone
sharing ipd: No