<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/NCT02207075</url>
  </required_header>
  <id_info>
    <org_study_id>1309014365</org_study_id>
    <nct_id>NCT02207075</nct_id>
  </id_info>
  <brief_title>Measuring Active Microglia in Progressive Multiple Sclerosis</brief_title>
  <official_title>Measuring Active Microglia in Progressive Multiple Sclerosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Weill Medical College of Cornell University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Genzyme, a Sanofi Company</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Weill Medical College of Cornell 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 pilot study designed to quantifying the innate immune inflammatory burden in a cohort&#xD;
      of secondary progressive multiple sclerosis subjects. Innate immunity is recognized as a&#xD;
      major cause of tissue injury in central nervous system (CNS) disease. Our hypothesis is that&#xD;
      the innate immune response is heightened in SPMS as compared to healthy controls (HC's) and&#xD;
      this activity increases over time and correlates with ongoing neuronal loss and disability.&#xD;
      The investigators will test this hypothesis by using highly specific molecular imaging&#xD;
      techniques, specifically PET, in conjunction with high field MRI. The investigators will&#xD;
      utilize the PET radioligand [11C]PK11195 which will be used as a marker of activated&#xD;
      macrophages/microglia. The investigators will correlate [11C]PK11195 uptake with conventional&#xD;
      measures of inflammation and neuronal integrity on high-resolution MRI.&#xD;
&#xD;
      SPMS subjects will have two baseline [11C]PK-11195 PET scans (separated by 24 to 72 hours,&#xD;
      test-retest) and subsequent scans at 6, 12 and 24 months. SPMS Subjects will have brain MRI's&#xD;
      at baseline, 6, 12 and 24 months.&#xD;
&#xD;
      Healthy Controls will have 2 baseline PET scans and one MRI.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is pilot study designed to determine the baseline and longitudinal regional-specific&#xD;
      change in uptake of [11C]PK-11195 in subjects with secondary progressive multiple sclerosis&#xD;
      (SPMS). Eighteen subjects with SPMS will be enrolled in the two-year study. Given low sample&#xD;
      size, a stable treatment regimen is required to control for potential treatment effect. In&#xD;
      addition, subjects must have been on current therapy for at least 6 months to ensure the&#xD;
      measurement is reflective of true disease activity and not treatment effect. Thirteen&#xD;
      age-matched healthy controls (HC) will be enrolled. The role of HC is to establish the&#xD;
      variability or &quot;noise&quot; associated with the instrument (test-retest), which will ensure that&#xD;
      PK uptake measured at any time point in MS is biologically relevant.&#xD;
&#xD;
      This proposal also includes a sub-study to validate a non-invasive quantification methodology&#xD;
      for PK-PET. The most rigorous method, or gold standard, for quantifying PET data is based&#xD;
      upon measuring the arterial input function. Measuring radioactivity within the arterial&#xD;
      circulation requires arterial cannulation. Arterial cannulation is considered safe; however,&#xD;
      is labor-intensive and often discourages subjects from participation. Image-derived input&#xD;
      function (IDIF) is a method to calculate the input function without cannulation of the artery&#xD;
      using the imaging data. Studies in human research volunteers are still required to compare&#xD;
      the results obtained with classical arterial sampling and the IDIF. The current study will&#xD;
      validate IDIF as a substitute for arterial sampling in this context. All healthy controls&#xD;
      will undergo this validation process, which will include arterial and venous sampling. This&#xD;
      validation is also required within subjects. Subjects will be given the option to participate&#xD;
      in this validation stage.&#xD;
&#xD;
      Absolute Quantification of PK-PET (gold standard arterial sampling): Catheters will be placed&#xD;
      in the radial artery for characterizing the plasma input function. This will make it possible&#xD;
      to use a two tissue reversible plasma input (2T4k) model. Blood sampling will be acquired&#xD;
      using both an online continuous blood sampling device as well as manually at discrete times&#xD;
      (5, 10, 15, 20, 30, 40, 50 and 60 minutes post injection). The continuous sampling will be&#xD;
      used to measure the activity concentrations of the whole blood, while the discrete manual&#xD;
      sampling will be used to calculate the plasma concentration, and estimate the fraction of&#xD;
      radioactive metabolites using HPLC. The total blood loss is estimated to be 8-10 tablespoons&#xD;
      (120-150 mL, or about one third of the amount that volunteers donate to the Red Cross when&#xD;
      giving blood). To generate the plasma input functions, the ratio of the plasma data to whole&#xD;
      blood will be calculated for each manual blood sample and fitted through these points to a&#xD;
      model with a one- or two-exponential function. Metabolite correction will be accomplished by&#xD;
      multiplying the plasma curve with a function obtainable from a fit to the measured parent&#xD;
      fraction. Venous blood will be similarly obtained for IDIF metabolic correction and utilized&#xD;
      for validation against classic arterial sampling. The investigators will acquire up to 6&#xD;
      venous samples of 3 mL each with a 2 mL purge prior to each sample, for a total blood loss of&#xD;
      30 mL (one fluid ounce, or about 6.67% of the amount that volunteers donate to the Red Cross&#xD;
      when giving blood).&#xD;
&#xD;
      Dynamic PET acquisition and processing: The data will be acquired in list mode to facilitate&#xD;
      processing at any dynamic framing rate.&#xD;
&#xD;
      Innate immunity is recognized as a major cause of tissue injury in central nervous system&#xD;
      (CNS) disease. In this study the investigators will specifically quantify the innate immune&#xD;
      inflammatory burden in a cohort of secondary progressive multiple sclerosis (SPMS) subjects.&#xD;
      Our hypothesis is that the innate immune response is heightened in SPMS as compared to&#xD;
      healthy controls (HC's) and this activity increases over time and correlates with ongoing&#xD;
      neuronal loss and disability. The investigators will test this hypothesis by using highly&#xD;
      specific molecular imaging techniques, specifically PET, in conjunction with high field MRI.&#xD;
      The investigators will utilize the PET radioligand [11C]1533; PK11195 which binds to the&#xD;
      translocator protein 18 kDa (TSPO) on activated macrophages/microglia. The investigators will&#xD;
      correlate [11C]PK11195 uptake with conventional measures of inflammation and neuronal&#xD;
      integrity on high-resolution MRI.&#xD;
&#xD;
      MS is a chronic inflammatory disease of central nervous system characterized by focal T cell&#xD;
      and macrophage infiltrates associated with demyelination. The primary innate immune cells in&#xD;
      MS consist of infiltrating macrophages/monocytes and resident microglia. Cells of the innate&#xD;
      immune system are effector cells that function to cause CNS injury both through direct&#xD;
      effects on neighboring cells, such as oligodendrocytes, and through generation of soluble&#xD;
      proinflammatory mediators that have distant effects on cells, such as neurons. The innate&#xD;
      immune inflammatory is thus sufficient to explain focal injury and diffuse injury. In the&#xD;
      majority of subjects, MS begins as a relapsing-remitting course but eventually evolves to a&#xD;
      state of progressive decline in disability. Focal inflammatory demyelinating lesions are the&#xD;
      predominant pathological findings in the subjects with relapsing disease whereas diffuse&#xD;
      axonal injury with microglial activation has been found to be the hallmark of progressive&#xD;
      disease.1 Microglial activation itself occurs either as a response to CNS injury for example&#xD;
      as in Wallerian degeneration, or in response to signals from other inflammatory cells&#xD;
      including macrophages and lymphocytes.&#xD;
&#xD;
      Activated microglia and infiltrating macrophages express TSPO (previously referred to as the&#xD;
      peripheral benzodiazepine receptor) which can be detected with radioligand [11C]PK-111952.&#xD;
&#xD;
      Determination of the significance of any [11C]PK-11195 uptake within a cohort of MS subjects&#xD;
      would require a correlation with HC¿s to ensure the observation is a valid measurement of&#xD;
      disease activity.&#xD;
&#xD;
      The MS subjects will also have two baseline [11C]PK-11195 PET scans (separated by 24 to 72&#xD;
      hours, test-retest) to measure disease related intra-individual variability and will have&#xD;
      subsequent scans at 6, 12 and 24 months. Baseline test-retest [11C]PK-11195 PET uptake&#xD;
      between MS subjects and HC's will be compared to ensure minimal disease-related variability&#xD;
      and to ensure our baseline and subsequent longitudinal measurements in MS subjects have met a&#xD;
      level of biological significance. One baseline brain MRI is required for HC and MS subjects.&#xD;
      Subjects will have brain MRI's at 6, 12 and 24 months.&#xD;
&#xD;
      Objective: Aim 1: To quantify level of activity and dynamic change in the innate immune&#xD;
      inflammatory burden over the course of two years in a cohort of SPMS subjects.&#xD;
&#xD;
      Primary objective: Measure the level of baseline and change of whole brain uptake of&#xD;
      [11C]PK-11195 at 6, 12 and 24 months in SPMS subjects.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
        -  To correlate the change in T2-hyperintense lesion volume at 6,12 and 24 months of with&#xD;
           whole brain uptake of [11C]PK-11195 on PET (at the 6,12 and 24 months) in SPMS subjects.&#xD;
&#xD;
        -  To correlate the change of conventional MRI measures of neuronal integrity (Gray Matter&#xD;
           Fraction, White Matter Fraction, whole brain volume, T1-hypointense lesion volume) at&#xD;
           6,12 and 24 months with whole brain PET uptake of [11C]PK-11195 (at the 6,12 and 24&#xD;
           months) in SPMS subjects.&#xD;
&#xD;
        -  To correlate the change in whole brain PET uptake of [11C]PK-11195 (at the 6,12 and 24&#xD;
           months) and level in disability, as measured by a change in EDSS at 6, 12, and 24 months&#xD;
           in SPMS subjects.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">December 2020</completion_date>
  <primary_completion_date type="Actual">December 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Measure the level of baseline and change of whole brain uptake of [11C]PK-11195 at 6, 12 and 24 months in SPMS subjects.</measure>
    <time_frame>24 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>To correlate the change in T2-hyperintense lesion volume at 6,12 and 24 months of with whole brain uptake of [11C]PK-11195 on PET (at the 6,12 and 24 months) in SPMS subjects.</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To correlate the change of conventional MRI measures of neuronal integrity (Gray Matter Fraction, White Matter Fraction, whole brain volume, T1-hypointense lesion volume) at 6,12 and 24 months with whole brain PET uptake of [11C]PK-11195 (at the 6,12 and</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To correlate the change in whole brain PET uptake of [11C]PK-11195 (at the 6,12 and 24 months) and level in disability, as measured by a change in EDSS at 6, 12, and 24 months in SPMS subjects.</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">50</enrollment>
  <condition>Secondary Progressive Multiple Sclerosis</condition>
  <arm_group>
    <arm_group_label>Subjects with SPMS</arm_group_label>
    <description>Secondary progressive MS Subjects either untreated or on consistent treatment for six months prior to enrollment.&#xD;
SPMS subjects will have two baseline [11C]PK-11195 PET scans (separated by 24 to 72 hours, test-retest) and subsequent scans at 6, 12 and 24 months. SPMS Subjects will have brain MRI's at baseline, 6, 12 and 24 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Normal Control Subjects</arm_group_label>
    <description>Healthy Controls will have 2 baseline [C11]PK-1195 PET scans and 1 MRI.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>[C11]PK-1195 PET scan</intervention_name>
    <description>PET scan with tracer [C11]PK-1195</description>
    <arm_group_label>Normal Control Subjects</arm_group_label>
    <arm_group_label>Subjects with SPMS</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Approximately 36 subjects (with SPMS and controls) including screen failures will be&#xD;
        enrolled regardless of gender&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects age 18-80&#xD;
&#xD;
          -  Secondary progressive MS subjects either untreated or on consistent treatment for&#xD;
             six-months prior to enrollment&#xD;
&#xD;
          -  Norman Controls&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects pregnant or woman of child-bearing age not utilizing effective birth control&#xD;
&#xD;
          -  Primary progressive MS subjects&#xD;
&#xD;
          -  Relapsing remitting MS subjects&#xD;
&#xD;
          -  Unstable SPMS subject for which treatment change within the 24 months is likely&#xD;
&#xD;
        Age-Healthy controls will be excluded if have any of the following medical conditions:&#xD;
&#xD;
          -  Any central nervous system disorder&#xD;
&#xD;
          -  Any systemic auto-immune disorder&#xD;
&#xD;
          -  Pregnant or woman of child-bearing age not utilizing effective birth control&#xD;
&#xD;
        Subjects will be withdrawn from the study if treatment is changed during the 24-month study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Susan Gauthier, DO</last_name>
    <role>Principal Investigator</role>
    <affiliation>Weill Medical College of Cornell University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Weill Cornell Medical College</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>July 30, 2014</study_first_submitted>
  <study_first_submitted_qc>July 30, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 1, 2014</study_first_posted>
  <last_update_submitted>January 14, 2022</last_update_submitted>
  <last_update_submitted_qc>January 14, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 18, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>SPMS</keyword>
  <keyword>Myelin Water Fraction</keyword>
  <keyword>activated microglia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Sclerosis</mesh_term>
    <mesh_term>Multiple Sclerosis, Chronic Progressive</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
  </condition_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/NCT02207075
org study id: 1309014365
nct id: NCT02207075
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is pilot study designed to quantifying the innate immune inflammatory burden in a cohort
      of secondary progressive multiple sclerosis subjects. Innate immunity is recognized as a
      major cause of tissue injury in central nervous system (CNS) disease. Our hypothesis is that
      the innate immune response is heightened in SPMS as compared to healthy controls (HC's) and
      this activity increases over time and correlates with ongoing neuronal loss and disability.
      The investigators will test this hypothesis by using highly specific molecular imaging
      techniques, specifically PET, in conjunction with high field MRI. The investigators will
      utilize the PET radioligand [11C]PK11195 which will be used as a marker of activated
      macrophages/microglia. The investigators will correlate [11C]PK11195 uptake with conventional
      measures of inflammation and neuronal integrity on high-resolution MRI.

      SPMS subjects will have two baseline [11C]PK-11195 PET scans (separated by 24 to 72 hours,
      test-retest) and subsequent scans at 6, 12 and 24 months. SPMS Subjects will have brain MRI's
      at baseline, 6, 12 and 24 months.

      Healthy Controls will have 2 baseline PET scans and one MRI.
This is pilot study designed to determine the baseline and longitudinal regional-specific
      change in uptake of [11C]PK-11195 in subjects with secondary progressive multiple sclerosis
      (SPMS). Eighteen subjects with SPMS will be enrolled in the two-year study. Given low sample
      size, a stable treatment regimen is required to control for potential treatment effect. In
      addition, subjects must have been on current therapy for at least 6 months to ensure the
      measurement is reflective of true disease activity and not treatment effect. Thirteen
      age-matched healthy controls (HC) will be enrolled. The role of HC is to establish the
      variability or "noise" associated with the instrument (test-retest), which will ensure that
      PK uptake measured at any time point in MS is biologically relevant.

      This proposal also includes a sub-study to validate a non-invasive quantification methodology
      for PK-PET. The most rigorous method, or gold standard, for quantifying PET data is based
      upon measuring the arterial input function. Measuring radioactivity within the arterial
      circulation requires arterial cannulation. Arterial cannulation is considered safe; however,
      is labor-intensive and often discourages subjects from participation. Image-derived input
      function (IDIF) is a method to calculate the input function without cannulation of the artery
      using the imaging data. Studies in human research volunteers are still required to compare
      the results obtained with classical arterial sampling and the IDIF. The current study will
      validate IDIF as a substitute for arterial sampling in this context. All healthy controls
      will undergo this validation process, which will include arterial and venous sampling. This
      validation is also required within subjects. Subjects will be given the option to participate
      in this validation stage.

      Absolute Quantification of PK-PET (gold standard arterial sampling): Catheters will be placed
      in the radial artery for characterizing the plasma input function. This will make it possible
      to use a two tissue reversible plasma input (2T4k) model. Blood sampling will be acquired
      using both an online continuous blood sampling device as well as manually at discrete times
      (5, 10, 15, 20, 30, 40, 50 and 60 minutes post injection). The continuous sampling will be
      used to measure the activity concentrations of the whole blood, while the discrete manual
      sampling will be used to calculate the plasma concentration, and estimate the fraction of
      radioactive metabolites using HPLC. The total blood loss is estimated to be 8-10 tablespoons
      (120-150 mL, or about one third of the amount that volunteers donate to the Red Cross when
      giving blood). To generate the plasma input functions, the ratio of the plasma data to whole
      blood will be calculated for each manual blood sample and fitted through these points to a
      model with a one- or two-exponential function. Metabolite correction will be accomplished by
      multiplying the plasma curve with a function obtainable from a fit to the measured parent
      fraction. Venous blood will be similarly obtained for IDIF metabolic correction and utilized
      for validation against classic arterial sampling. The investigators will acquire up to 6
      venous samples of 3 mL each with a 2 mL purge prior to each sample, for a total blood loss of
      30 mL (one fluid ounce, or about 6.67% of the amount that volunteers donate to the Red Cross
      when giving blood).

      Dynamic PET acquisition and processing: The data will be acquired in list mode to facilitate
      processing at any dynamic framing rate.

      Innate immunity is recognized as a major cause of tissue injury in central nervous system
      (CNS) disease. In this study the investigators will specifically quantify the innate immune
      inflammatory burden in a cohort of secondary progressive multiple sclerosis (SPMS) subjects.
      Our hypothesis is that the innate immune response is heightened in SPMS as compared to
      healthy controls (HC's) and this activity increases over time and correlates with ongoing
      neuronal loss and disability. The investigators will test this hypothesis by using highly
      specific molecular imaging techniques, specifically PET, in conjunction with high field MRI.
      The investigators will utilize the PET radioligand [11C]1533; PK11195 which binds to the
      translocator protein 18 kDa (TSPO) on activated macrophages/microglia. The investigators will
      correlate [11C]PK11195 uptake with conventional measures of inflammation and neuronal
      integrity on high-resolution MRI.

      MS is a chronic inflammatory disease of central nervous system characterized by focal T cell
      and macrophage infiltrates associated with demyelination. The primary innate immune cells in
      MS consist of infiltrating macrophages/monocytes and resident microglia. Cells of the innate
      immune system are effector cells that function to cause CNS injury both through direct
      effects on neighboring cells, such as oligodendrocytes, and through generation of soluble
      proinflammatory mediators that have distant effects on cells, such as neurons. The innate
      immune inflammatory is thus sufficient to explain focal injury and diffuse injury. In the
      majority of subjects, MS begins as a relapsing-remitting course but eventually evolves to a
      state of progressive decline in disability. Focal inflammatory demyelinating lesions are the
      predominant pathological findings in the subjects with relapsing disease whereas diffuse
      axonal injury with microglial activation has been found to be the hallmark of progressive
      disease.1 Microglial activation itself occurs either as a response to CNS injury for example
      as in Wallerian degeneration, or in response to signals from other inflammatory cells
      including macrophages and lymphocytes.

      Activated microglia and infiltrating macrophages express TSPO (previously referred to as the
      peripheral benzodiazepine receptor) which can be detected with radioligand [11C]PK-111952.

      Determination of the significance of any [11C]PK-11195 uptake within a cohort of MS subjects
      would require a correlation with HC¿s to ensure the observation is a valid measurement of
      disease activity.

      The MS subjects will also have two baseline [11C]PK-11195 PET scans (separated by 24 to 72
      hours, test-retest) to measure disease related intra-individual variability and will have
      subsequent scans at 6, 12 and 24 months. Baseline test-retest [11C]PK-11195 PET uptake
      between MS subjects and HC's will be compared to ensure minimal disease-related variability
      and to ensure our baseline and subsequent longitudinal measurements in MS subjects have met a
      level of biological significance. One baseline brain MRI is required for HC and MS subjects.
      Subjects will have brain MRI's at 6, 12 and 24 months.

      Objective: Aim 1: To quantify level of activity and dynamic change in the innate immune
      inflammatory burden over the course of two years in a cohort of SPMS subjects.

      Primary objective: Measure the level of baseline and change of whole brain uptake of
      [11C]PK-11195 at 6, 12 and 24 months in SPMS subjects.

      Objectives:

        -  To correlate the change in T2-hyperintense lesion volume at 6,12 and 24 months of with
           whole brain uptake of [11C]PK-11195 on PET (at the 6,12 and 24 months) in SPMS subjects.

        -  To correlate the change of conventional MRI measures of neuronal integrity (Gray Matter
           Fraction, White Matter Fraction, whole brain volume, T1-hypointense lesion volume) at
           6,12 and 24 months with whole brain PET uptake of [11C]PK-11195 (at the 6,12 and 24
           months) in SPMS subjects.

        -  To correlate the change in whole brain PET uptake of [11C]PK-11195 (at the 6,12 and 24
           months) and level in disability, as measured by a change in EDSS at 6, 12, and 24 months
           in SPMS subjects.
observational model: Cohort
time perspective: Prospective
measure: Measure the level of baseline and change of whole brain uptake of [11C]PK-11195 at 6, 12 and 24 months in SPMS subjects.
time frame: 24 months
measure: To correlate the change in T2-hyperintense lesion volume at 6,12 and 24 months of with whole brain uptake of [11C]PK-11195 on PET (at the 6,12 and 24 months) in SPMS subjects.
time frame: 24 months
measure: To correlate the change of conventional MRI measures of neuronal integrity (Gray Matter Fraction, White Matter Fraction, whole brain volume, T1-hypointense lesion volume) at 6,12 and 24 months with whole brain PET uptake of [11C]PK-11195 (at the 6,12 and
time frame: 24 months
measure: To correlate the change in whole brain PET uptake of [11C]PK-11195 (at the 6,12 and 24 months) and level in disability, as measured by a change in EDSS at 6, 12, and 24 months in SPMS subjects.
time frame: 24 months
arm group label: Subjects with SPMS
description: Secondary progressive MS Subjects either untreated or on consistent treatment for six months prior to enrollment.
SPMS subjects will have two baseline [11C]PK-11195 PET scans (separated by 24 to 72 hours, test-retest) and subsequent scans at 6, 12 and 24 months. SPMS Subjects will have brain MRI's at baseline, 6, 12 and 24 months.
arm group label: Normal Control Subjects
description: Healthy Controls will have 2 baseline [C11]PK-1195 PET scans and 1 MRI.
intervention type: Drug
intervention name: [C11]PK-1195 PET scan
description: PET scan with tracer [C11]PK-1195
arm group label: Normal Control Subjects
arm group label: Subjects with SPMS
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Susan Gauthier, DO
role: Principal Investigator
affiliation: Weill Medical College of Cornell University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Multiple Sclerosis
mesh term: Multiple Sclerosis, Chronic Progressive
mesh term: Sclerosis
sharing ipd: No