<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/NCT01727622</url>
  </required_header>
  <id_info>
    <org_study_id>815471</org_study_id>
    <secondary_id>5R01AG040271</secondary_id>
    <nct_id>NCT01727622</nct_id>
  </id_info>
  <brief_title>Arterial Spin Labeling (ASL) MRI for Cognitive Decline</brief_title>
  <official_title>Optimized Arterial Spin Labeling MRI for Cognitive Decline</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pennsylvania</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute on Aging (NIA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pennsylvania</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine the value of Arterial Spin Labeling (ASL) MRI, a&#xD;
      measure of blood flow to the brain, in Mild Cognitive Impairment (MCI) and compare it to&#xD;
      existing measures. In particular, the investigators will compare ASL MRI to Positron Emission&#xD;
      Tomography (PET/CT), which measures brain metabolism reflecting how well cells in a patient's&#xD;
      brain are functioning. In addition, the investigators will assess the relationship of these&#xD;
      measures to specific protein levels associated with Alzheimer's Disease in the patient's&#xD;
      cerebrospinal fluid (the fluid that surrounds the brain and spinal cord) obtained by lumbar&#xD;
      puncture. By comparing the information that is available from these procedures to the&#xD;
      patient's performance on cognitive tests, the investigators hope to learn which procedures&#xD;
      most accurately reflect and assist in determination of the potential causes of cognitive&#xD;
      difficulties that arise with MCI, and thus, which are most useful in the clinical setting. In&#xD;
      particular, PET scans have been found to be very useful in diagnosis of MCI and Alzheimer's&#xD;
      Disease, but the investigators want to find out if they can get the same, or better,&#xD;
      information from an ASL MRI scan, which is less expensive and easier to acquire.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">May 31, 2018</completion_date>
  <primary_completion_date type="Actual">May 11, 2018</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>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Composite region of interest (ROI) measure of cerebral blood flow (CBF) measured by ASL MRI versus composite ROI measure of cerebral metabolism measured by FDG PET</measure>
    <time_frame>2 weeks</time_frame>
    <description>Our primary aim is to determine if the diagnostic accuracy of 'state-of-the art' Arterial Spin Labeling (ASL) MRI is as good as (i.e., noninferior to) the diagnostic accuracy of FDG-PET/CT in comparison of MCI patients to cognitively normal adults. To test if ASL in noninferior to FDG-PET, we will use an asymptotic z test statistic for equivalent studies described in an equation of Zhou et al. (2002). The test statistic compares the AUCs from ASL and FDG-PET/CT by appropriately accounting for the correlation between them.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Prediction of longitudinal change in hippocampal volume</measure>
    <time_frame>1 year</time_frame>
    <description>Investigators will compare ASL MRI versus FDG PET in their ability to predict disease progression based on change in hippocampal volume. Investigators will define patients as 'progressors' if they display an atrophy rate greater than one standard deviation above the mean rate for healthy controls. Investigators will again use the composite ROI for ASL sequences and FDG-PET data to determine the best single or combination of predictors of progression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prediction of longitudinal change in clinical status (i.e. progression to Alzheimer's Disease)</measure>
    <time_frame>2 years</time_frame>
    <description>Investigators will compare ASL MRI versus FDG PET in their ability to predict disease progression based on conversion to clinical Alzheimer's Disease. Investigators will determine which measure best predicts conversion to clinical Alzheimer's Disease.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">102</enrollment>
  <condition>Mild Cognitive Impairment</condition>
  <condition>Alzheimer's Disease</condition>
  <arm_group>
    <arm_group_label>Controls</arm_group_label>
    <description>ASL-MRI and FDG-PET will be compared for ability to discriminate between Control subjects and adults with Mild Cognitive Impairment (prodromal AD). A lumbar puncture will be obtained in a proportion of the participants.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Mild Cognitive Impairment</arm_group_label>
    <description>ASL-MRI and FDG-PET will be compared for ability to discriminate between Control subjects and adults with Mild Cognitive Impairment (prodromal AD). A lumbar puncture will be obtained in a proportion of the participants.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FDG-PET</intervention_name>
    <description>Diagnostic: FDG-PET imaging to examine neuronal health</description>
    <arm_group_label>Controls</arm_group_label>
    <arm_group_label>Mild Cognitive Impairment</arm_group_label>
    <other_name>fluorodeoxyglucose</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>ASL-MRI</intervention_name>
    <description>Arterial-Spin Labeled MRI to examine cerebral blood flow</description>
    <arm_group_label>Controls</arm_group_label>
    <arm_group_label>Mild Cognitive Impairment</arm_group_label>
    <other_name>Arterial Spin Labeling</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Lumbar Puncture</intervention_name>
    <description>Lumbar puncture to acquire a small amount of cerebrospinal fluid for protein level analyses. Note that this will not be required in all participants.</description>
    <arm_group_label>Controls</arm_group_label>
    <arm_group_label>Mild Cognitive Impairment</arm_group_label>
    <other_name>Spinal Tap</other_name>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      cerebrospinal fluid&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        This project will focus on a population enriched in individuals with incipient AD (i.e.&#xD;
        MCI). These subjects, as well as age-matched controls, will be recruited from the&#xD;
        Alzheimer's Disease Center at the University of Pennsylania.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males and females between the ages of 55 and 89.&#xD;
&#xD;
          -  Fluent in English&#xD;
&#xD;
          -  Part of the longitudinal cohort of the PMC/ADCC (must already be or agree to become a&#xD;
             part of the Penn Memory Center cohort so baseline neuropsychological testing is&#xD;
             available before study participation begins)&#xD;
&#xD;
          -  Adequate visual and auditory acuity to allow for neuropsychological testing&#xD;
&#xD;
          -  Women: post-menopausal or surgically sterile&#xD;
&#xD;
          -  Willing and able to complete all required study procedures&#xD;
&#xD;
          -  Completed 6 grades of education&#xD;
&#xD;
          -  Geriatric Depression scale less than 6 (assessed within 3 months)&#xD;
&#xD;
        PATIENTS ONLY:&#xD;
&#xD;
          -  Diagnosis of MCI&#xD;
&#xD;
          -  MMSE between 24 and 30&#xD;
&#xD;
          -  Has a study partner&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any contraindication to MRI (i.e. presence of pacemaker, ferrous metal in the eye,&#xD;
             severe claustrophobia that would preclude subject from completing the MRI, etc.).&#xD;
&#xD;
          -  Major depression, bipolar disorder, history of schizophrenia&#xD;
&#xD;
          -  History of substance abuse or dependence within the past 2 years.&#xD;
&#xD;
          -  Any medical or neurological condition that, in the opinion of the investigator, would&#xD;
             compromise the subject's safety, successful participation in, or integrity of the&#xD;
             study.&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Recent history of poorly controlled diabetes (e.g. multiple blood glucose reports of ≥&#xD;
             180 mg/dl.)&#xD;
&#xD;
          -  Currently receiving medical or drug treatment contraindicating protocol participation&#xD;
             e.g. anticoagulants such as Coumadin/Warfarin&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>55 Years</minimum_age>
    <maximum_age>89 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David A Wolk, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pennsylvania</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Penn Memory Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>October 22, 2012</study_first_submitted>
  <study_first_submitted_qc>November 12, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 16, 2012</study_first_posted>
  <last_update_submitted>September 25, 2020</last_update_submitted>
  <last_update_submitted_qc>September 25, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 28, 2020</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>
    <mesh_term>Cognitive Dysfunction</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fluorodeoxyglucose F18</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/NCT01727622
org study id: 815471
secondary id: 5R01AG040271
nct id: NCT01727622
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of this study is to determine the value of Arterial Spin Labeling (ASL) MRI, a
      measure of blood flow to the brain, in Mild Cognitive Impairment (MCI) and compare it to
      existing measures. In particular, the investigators will compare ASL MRI to Positron Emission
      Tomography (PET/CT), which measures brain metabolism reflecting how well cells in a patient's
      brain are functioning. In addition, the investigators will assess the relationship of these
      measures to specific protein levels associated with Alzheimer's Disease in the patient's
      cerebrospinal fluid (the fluid that surrounds the brain and spinal cord) obtained by lumbar
      puncture. By comparing the information that is available from these procedures to the
      patient's performance on cognitive tests, the investigators hope to learn which procedures
      most accurately reflect and assist in determination of the potential causes of cognitive
      difficulties that arise with MCI, and thus, which are most useful in the clinical setting. In
      particular, PET scans have been found to be very useful in diagnosis of MCI and Alzheimer's
      Disease, but the investigators want to find out if they can get the same, or better,
      information from an ASL MRI scan, which is less expensive and easier to acquire.
observational model: Case-Control
time perspective: Prospective
measure: Composite region of interest (ROI) measure of cerebral blood flow (CBF) measured by ASL MRI versus composite ROI measure of cerebral metabolism measured by FDG PET
time frame: 2 weeks
description: Our primary aim is to determine if the diagnostic accuracy of 'state-of-the art' Arterial Spin Labeling (ASL) MRI is as good as (i.e., noninferior to) the diagnostic accuracy of FDG-PET/CT in comparison of MCI patients to cognitively normal adults. To test if ASL in noninferior to FDG-PET, we will use an asymptotic z test statistic for equivalent studies described in an equation of Zhou et al. (2002). The test statistic compares the AUCs from ASL and FDG-PET/CT by appropriately accounting for the correlation between them.
measure: Prediction of longitudinal change in hippocampal volume
time frame: 1 year
description: Investigators will compare ASL MRI versus FDG PET in their ability to predict disease progression based on change in hippocampal volume. Investigators will define patients as 'progressors' if they display an atrophy rate greater than one standard deviation above the mean rate for healthy controls. Investigators will again use the composite ROI for ASL sequences and FDG-PET data to determine the best single or combination of predictors of progression.
measure: Prediction of longitudinal change in clinical status (i.e. progression to Alzheimer's Disease)
time frame: 2 years
description: Investigators will compare ASL MRI versus FDG PET in their ability to predict disease progression based on conversion to clinical Alzheimer's Disease. Investigators will determine which measure best predicts conversion to clinical Alzheimer's Disease.
arm group label: Controls
description: ASL-MRI and FDG-PET will be compared for ability to discriminate between Control subjects and adults with Mild Cognitive Impairment (prodromal AD). A lumbar puncture will be obtained in a proportion of the participants.
arm group label: Mild Cognitive Impairment
description: ASL-MRI and FDG-PET will be compared for ability to discriminate between Control subjects and adults with Mild Cognitive Impairment (prodromal AD). A lumbar puncture will be obtained in a proportion of the participants.
intervention type: Drug
intervention name: FDG-PET
description: Diagnostic: FDG-PET imaging to examine neuronal health
arm group label: Controls
arm group label: Mild Cognitive Impairment
other name: fluorodeoxyglucose
intervention type: Other
intervention name: ASL-MRI
description: Arterial-Spin Labeled MRI to examine cerebral blood flow
arm group label: Controls
arm group label: Mild Cognitive Impairment
other name: Arterial Spin Labeling
intervention type: Procedure
intervention name: Lumbar Puncture
description: Lumbar puncture to acquire a small amount of cerebrospinal fluid for protein level analyses. Note that this will not be required in all participants.
arm group label: Controls
arm group label: Mild Cognitive Impairment
other name: Spinal Tap
cerebrospinal fluid
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 55 Years
maximum age: 89 Years
healthy volunteers: Accepts Healthy Volunteers
last name: David A Wolk, MD
role: Principal Investigator
affiliation: University of Pennsylvania
facility: 
country: United States
responsible party type: Sponsor
mesh term: Alzheimer Disease
mesh term: Cognitive Dysfunction
mesh term: Fluorodeoxyglucose F18