<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/NCT01723553</url>
  </required_header>
  <id_info>
    <org_study_id>12-007139</org_study_id>
    <nct_id>NCT01723553</nct_id>
  </id_info>
  <brief_title>Amyloid-related Imaging Abnormalities (Microbleeds) in Atypical AD</brief_title>
  <official_title>Amyloid-related Imaging Abnormalities (Microbleeds) in Atypical AD</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mayo Clinic</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study is designed to assess the demographic, clinical and imaging associations with the&#xD;
      presence of microbleeds in atypical Alzheimer's disease. The primary hypothesis is that&#xD;
      cognitive and functional performance will be poorer in atypical Alzheimer's subjects with&#xD;
      microbleeds compared to those without microbleeds.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Alzheimer's disease (AD) is associated with amyloid-related imaging abnormalities (ARIA).&#xD;
      Microbleeds (MBs) represent part of the spectrum of ARIA and can be identified as small&#xD;
      hypointense lesions on gradient-recalled echo (GRE) T2*-weighted MRI. They are thought to&#xD;
      represent hemosiderin deposits (and hence have been classified as ARIA-H1) and occur as a&#xD;
      consequence of leakage of blood products out of vessels that have been damaged by deposition&#xD;
      of the protein β-amyloid in cerebral vessels; cerebral amyloid angiopathy (CAA). However, it&#xD;
      is also possible that cerebrovascular disease could contribute to the presence of MBs in AD.&#xD;
      Subjects with MBs are at a greater risk of bleeds which could impact the use of&#xD;
      anti-coagulation treatment approaches.&#xD;
&#xD;
      The presence of CAA has been particularly associated with AD and studies have demonstrated&#xD;
      that MBs occur in 12-33% of subjects with typical Alzheimer's dementia, with a large&#xD;
      proportion of subjects showing multiple MBs. The presence of MBs has been associated with&#xD;
      older age and a greater degree of white matter hyperintensities (WMH) in Alzheimer's&#xD;
      dementia. The association between MBs and WMH, a marker of cerebrovascular disease, suggests&#xD;
      cerebrovascular disease may also play a role in the etiology of MBs in AD. However,&#xD;
      approximately 16% of AD subjects do not present with episodic memory loss, but instead&#xD;
      display language problems such as poor naming and impaired sentence repetition, or&#xD;
      visuospatial and visual perceptual deficits, and are referred to as atypical AD. Since AD is&#xD;
      associated with CAA, one would assume that CAA and hence MBs, would also occur in atypical&#xD;
      AD, although no studies have assessed MBs in atypical AD.&#xD;
&#xD;
      Amyloid-binding ligands, such as Pittsburgh Compound B (PiB), that can be detected using PET&#xD;
      scanning have now been developed and provide an invaluable biomarker to infer the presence of&#xD;
      β-amyloid. The presence of CAA has been shown to be associated with elevated PiB uptake, and&#xD;
      hence the assessment of PiB-PET in subjects with MBs will provide important information on&#xD;
      the association of MBs and β-amyloid deposition in AD.&#xD;
&#xD;
      The goal of the study is to assess the associations between MBs and demographic/clinical&#xD;
      features, assess the associations between MBs and imaging features as well as a possible&#xD;
      correlate to the number of MBs a subject has in atypical AD.&#xD;
&#xD;
      Patients found to be eligible and willing to enroll in this study will be asked to undergo a&#xD;
      Neurologic Examination, Neuropsychometric testing, an MRI scan, and a PiB PET scan of the&#xD;
      brain. This will be done over a period of two days at the Mayo Clinic in Rochester,&#xD;
      Minnesota.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">March 2015</completion_date>
  <primary_completion_date type="Actual">March 2015</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of subjects with and without microbleeds</measure>
    <time_frame>up to day 2 of study</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of white matter hyperintensity burden on MRI and ratio of amyloid burden on PiB PET scan</measure>
    <time_frame>Study entry, approximately day 1 or day 2 of study</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of microbleeds per subject</measure>
    <time_frame>Study entry, approximately day 1 or day 2 of study</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">27</enrollment>
  <condition>Atypical Alzheimers Disease</condition>
  <condition>Logopenic Variant of Primary Progressive Aphasia (LPA)</condition>
  <condition>Posterior Cortical Atrophy (PCA)</condition>
  <arm_group>
    <arm_group_label>PiB positron emission tomography (PET)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All subjects will receive PET imaging with C-11 PiB on approximately day 1 or day 2 of study to determine if they have beta-amyloid deposits in their brains.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>C-11 PiB</intervention_name>
    <description>One time intravenous administration of ~740 megabecquerel (MBq) of [N-methyl-C-11]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole (PiB) (range 370 - 740 MBq).</description>
    <arm_group_label>PiB positron emission tomography (PET)</arm_group_label>
    <other_name>Pittsburgh Compound B</other_name>
    <other_name>PiB</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  over the age of 21&#xD;
&#xD;
          -  will have an informant/study partner who will be able to provide independent&#xD;
             evaluation of functioning&#xD;
&#xD;
          -  must fulfill clinical diagnostic criteria for atypical AD, and hence should either&#xD;
             have a chief complaint of difficulty with language and fulfill criteria for logopenic&#xD;
             variant of primary progressive aphasia, or present with visuospatial/perceptual&#xD;
             deficits and fulfill criteria for posterior cortical atrophy&#xD;
&#xD;
          -  speaks English as their primary language (including bilingual patients whose primary&#xD;
             language is English)&#xD;
&#xD;
          -  agrees to and is eligible to undergo MRI and PET scanning&#xD;
&#xD;
          -  if woman of child bearing age, must agree to pregnancy test no more than 48 hours&#xD;
             before the PET scans&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  subjects with concurrent illnesses that could account for the presenting syndrome,&#xD;
             such as traumatic brain injury, strokes or developmental syndromes&#xD;
&#xD;
          -  subjects meeting criteria for another neurodegenerative disease, particularly typical&#xD;
             Alzheimer's dementia&#xD;
&#xD;
          -  women that are pregnant or post-partum and breast-feeding&#xD;
&#xD;
          -  subjects will also be excluded if MRI is contraindicated (metal in head, cardiac pace&#xD;
             maker, e.t.c.), if there is severe claustrophobia, and if there are conditions that&#xD;
             may confound brain imaging studies (e.g. structural abnormalities, including subdural&#xD;
             hematoma or intracranial neoplasm)&#xD;
&#xD;
          -  subjects will also be excluded if they do not have an informant, do not consent to&#xD;
             research or do not complete all components of the study (neurological exam,&#xD;
             neuropsychometric tests, MRI, PiB PET)&#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>Jennifer Whitwell, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://clinicaltrials.mayo.edu</url>
    <description>Mayo Clinic Clinical Trials</description>
  </link>
  <verification_date>December 2015</verification_date>
  <study_first_submitted>November 6, 2012</study_first_submitted>
  <study_first_submitted_qc>November 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 8, 2012</study_first_posted>
  <last_update_submitted>December 18, 2015</last_update_submitted>
  <last_update_submitted_qc>December 18, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 21, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>Jennifer Whitwell</investigator_full_name>
    <investigator_title>PI</investigator_title>
  </responsible_party>
  <keyword>aphasia</keyword>
  <keyword>logopenic</keyword>
  <keyword>PCA</keyword>
  <keyword>LPA</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alzheimer Disease</mesh_term>
    <mesh_term>Aphasia</mesh_term>
    <mesh_term>Aphasia, Primary Progressive</mesh_term>
    <mesh_term>Pick Disease of the Brain</mesh_term>
    <mesh_term>Frontotemporal Dementia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Corticosterone</mesh_term>
  </intervention_browse>
  <!-- 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/NCT01723553
org study id: 12-007139
nct id: NCT01723553
lead sponsor: 
has dmc: Yes
The study is designed to assess the demographic, clinical and imaging associations with the
      presence of microbleeds in atypical Alzheimer's disease. The primary hypothesis is that
      cognitive and functional performance will be poorer in atypical Alzheimer's subjects with
      microbleeds compared to those without microbleeds.
Alzheimer's disease (AD) is associated with amyloid-related imaging abnormalities (ARIA).
      Microbleeds (MBs) represent part of the spectrum of ARIA and can be identified as small
      hypointense lesions on gradient-recalled echo (GRE) T2*-weighted MRI. They are thought to
      represent hemosiderin deposits (and hence have been classified as ARIA-H1) and occur as a
      consequence of leakage of blood products out of vessels that have been damaged by deposition
      of the protein β-amyloid in cerebral vessels; cerebral amyloid angiopathy (CAA). However, it
      is also possible that cerebrovascular disease could contribute to the presence of MBs in AD.
      Subjects with MBs are at a greater risk of bleeds which could impact the use of
      anti-coagulation treatment approaches.

      The presence of CAA has been particularly associated with AD and studies have demonstrated
      that MBs occur in 12-33% of subjects with typical Alzheimer's dementia, with a large
      proportion of subjects showing multiple MBs. The presence of MBs has been associated with
      older age and a greater degree of white matter hyperintensities (WMH) in Alzheimer's
      dementia. The association between MBs and WMH, a marker of cerebrovascular disease, suggests
      cerebrovascular disease may also play a role in the etiology of MBs in AD. However,
      approximately 16% of AD subjects do not present with episodic memory loss, but instead
      display language problems such as poor naming and impaired sentence repetition, or
      visuospatial and visual perceptual deficits, and are referred to as atypical AD. Since AD is
      associated with CAA, one would assume that CAA and hence MBs, would also occur in atypical
      AD, although no studies have assessed MBs in atypical AD.

      Amyloid-binding ligands, such as Pittsburgh Compound B (PiB), that can be detected using PET
      scanning have now been developed and provide an invaluable biomarker to infer the presence of
      β-amyloid. The presence of CAA has been shown to be associated with elevated PiB uptake, and
      hence the assessment of PiB-PET in subjects with MBs will provide important information on
      the association of MBs and β-amyloid deposition in AD.

      The goal of the study is to assess the associations between MBs and demographic/clinical
      features, assess the associations between MBs and imaging features as well as a possible
      correlate to the number of MBs a subject has in atypical AD.

      Patients found to be eligible and willing to enroll in this study will be asked to undergo a
      Neurologic Examination, Neuropsychometric testing, an MRI scan, and a PiB PET scan of the
      brain. This will be done over a period of two days at the Mayo Clinic in Rochester,
      Minnesota.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Proportion of subjects with and without microbleeds
time frame: up to day 2 of study
measure: Percentage of white matter hyperintensity burden on MRI and ratio of amyloid burden on PiB PET scan
time frame: Study entry, approximately day 1 or day 2 of study
measure: Number of microbleeds per subject
time frame: Study entry, approximately day 1 or day 2 of study
arm group label: PiB positron emission tomography (PET)
arm group type: Experimental
description: All subjects will receive PET imaging with C-11 PiB on approximately day 1 or day 2 of study to determine if they have beta-amyloid deposits in their brains.
intervention type: Drug
intervention name: C-11 PiB
description: One time intravenous administration of ~740 megabecquerel (MBq) of [N-methyl-C-11]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole (PiB) (range 370 - 740 MBq).
arm group label: PiB positron emission tomography (PET)
other name: Pittsburgh Compound B
other name: PiB
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jennifer Whitwell, PhD
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
country: United States
url: http://clinicaltrials.mayo.edu
description: Mayo Clinic Clinical Trials
responsible party type: Principal Investigator
investigator affiliation: Mayo Clinic
investigator full name: Jennifer Whitwell
investigator title: PI
mesh term: Alzheimer Disease
mesh term: Aphasia
mesh term: Aphasia, Primary Progressive
mesh term: Pick Disease of the Brain
mesh term: Frontotemporal Dementia
mesh term: Corticosterone