<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/NCT04415372</url>
  </required_header>
  <id_info>
    <org_study_id>2020-0310</org_study_id>
    <secondary_id>1R01EB027087-01</secondary_id>
    <secondary_id>A539300</secondary_id>
    <secondary_id>SMPH/RADIOLOGY/RADIOLOGY</secondary_id>
    <secondary_id>Protocol Version 4/29/2021</secondary_id>
    <nct_id>NCT04415372</nct_id>
  </id_info>
  <brief_title>Macromolecular Imaging of White and Gray Matter Pathology in Multiple Sclerosis</brief_title>
  <official_title>Macromolecular Imaging of White and Gray Matter Pathology in Multiple Sclerosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Wisconsin, Madison</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute for Biomedical Imaging and Bioengineering (NIBIB)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Wisconsin, Madison</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The overall purpose of this research is to determine whether new macromolecular measures&#xD;
      optimized for whole brain (gray matter and white matter) magnetic resonance imaging (MRI),&#xD;
      predict neuro-cognitive impairment in multiple sclerosis (MS) patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      MRI is a vital component of a MS work-up, providing noninvasive evidence of MS lesions,&#xD;
      detecting active inflammatory lesions, and measuring brain atrophy to assess&#xD;
      neurodegeneration. Recent years of MRI research have generated strong evidence of gray matter&#xD;
      (GM) involvement in MS, resulting in the reclassification of MS as a whole-brain disease.&#xD;
      Similar to white matter (WM), a primary target of MS pathology in GM is myelin, the&#xD;
      protective sheath insulating the penetrating axons within GM and extending brain connectivity&#xD;
      all the way to the neuronal bodies.&#xD;
&#xD;
      This aim of this research is to examine if the associations between imaging measures of GM&#xD;
      disease and cognitive performance can establish GM-based imaging correlates predicting the&#xD;
      disease course and accurately assessing treatment results.&#xD;
&#xD;
      This observational research will enroll adults diagnosed with MS both with and without&#xD;
      cognitive impairment. Subjects will be asked to complete a single research visit that&#xD;
      includes the administration of a MRI scan and a neuro-cognitive testing session.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 19, 2021</start_date>
  <completion_date type="Anticipated">April 2027</completion_date>
  <primary_completion_date type="Anticipated">April 2025</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>Measurement of macromolecular proton content (MPC) by Magnetic resonance imaging</measure>
    <time_frame>24 hours</time_frame>
    <description>Macromolecular Proton Fraction (MPF) is calculated from several specially acquired MR images and is characterized by high degree of sensitivity and specificity to tissue macromolecules, which are the main target of pathological process in neurodegenerative diseases including multiple sclerosis (MS). These properties of MPF are in contrast with standard MR images, which are primarily sensitive to tissue water molecules.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Neurocognitive performance as measured by Minimal Assessment of Cognitive Function in MS (MACFIMS) battery of neuropsychological (NP) tests</measure>
    <time_frame>24 hours</time_frame>
    <description>The results of Minimal Assessment of Cognitive Function in MS (MACFIMS) battery of neuropsychological (NP) tests will form the secondary outcome measure. The NP scores will be correlated with MPF to study association between macromolecular tissue damage and neurocognitive performance.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neurocognitive performance as measured by the Montreal Cognitive Assessment (MoCA) score</measure>
    <time_frame>24 hours</time_frame>
    <description>Neurocognitive performance will be measured by Montreal Cognitive Assessment. MoCA scores range from 0 to 30, higher values corresponding to better cognitive performances.</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Anticipated">75</enrollment>
  <condition>Multiple Sclerosis</condition>
  <condition>MS</condition>
  <arm_group>
    <arm_group_label>Cognitive Impairment</arm_group_label>
    <description>Adults diagnosed with MS that have evidence of cognitive decline.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No Cognitive Impairment</arm_group_label>
    <description>Adults diagnosed with MS that have no evidence of cognitive decline.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy Controls</arm_group_label>
    <description>Healthy adult volunteers will form a control group matched for age, gender, education, handedness</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>MRI</intervention_name>
    <description>The MRI protocol will include conventional testing for MS lesion detection and functional MR imaging to localize associated neurocognitive domains in each subject.</description>
    <arm_group_label>Cognitive Impairment</arm_group_label>
    <arm_group_label>Healthy Controls</arm_group_label>
    <arm_group_label>No Cognitive Impairment</arm_group_label>
    <other_name>Functional MRI</other_name>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Neuropsychological Testing</intervention_name>
    <description>A comprehensive battery of neuropsychological tests will be administered to assess memory, new learning, spatial processing and higher executive function.</description>
    <arm_group_label>Cognitive Impairment</arm_group_label>
    <arm_group_label>Healthy Controls</arm_group_label>
    <arm_group_label>No Cognitive Impairment</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Adults diagnosed with MS both with and without evidence of cognitive impairment.&#xD;
&#xD;
        Healthy controls will be recruited from the MRI Volunteer Database (2017-0004, PI: Reeder)&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Clinically definite MS&#xD;
&#xD;
          -  Adult age 18 to 60&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Contraindication to MRI&#xD;
&#xD;
          -  Changes in MS therapy in the last 6 months&#xD;
&#xD;
          -  Less than 6 weeks after relapse or corticosteroid use&#xD;
&#xD;
          -  Currently taking medication that may affect cognition (e.g. donepezil, rivastigmine,&#xD;
             adderall)&#xD;
&#xD;
          -  History of significant alcohol or drug abuse&#xD;
&#xD;
          -  Current or recent significant migraines&#xD;
&#xD;
          -  Confounding neurological or cognitive disorders or deficits (stroke, Parkinson's&#xD;
             disease, Alzheimer's disease, epilepsy)&#xD;
&#xD;
          -  Sensory or physical impairments that might interfere significantly with cognitive&#xD;
             testing&#xD;
&#xD;
          -  History of developmental or learning disability or attention-deficit/hyperactivity&#xD;
             disorder.\&#xD;
&#xD;
        Exclusion Criteria for Healthy Controls:&#xD;
&#xD;
          -  history of alcohol/drug abuse&#xD;
&#xD;
          -  history of migraines&#xD;
&#xD;
          -  developmental or learning disability/attention-deficit/hyperactivity disorder&#xD;
&#xD;
          -  currently pregnant/breastfeeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alexey Samsonov, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UW Madison</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Gemma Gliori, MS</last_name>
    <phone>608-262-7269</phone>
    <email>ggliori@uwhealth.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Suzanne Hanson, BS</last_name>
    <phone>608-263-7421</phone>
    <email>shanson@uwhealth.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of Wisconsin, Madison</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53705</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lacey Lubeley, BS</last_name>
      <phone>608-807-9594</phone>
      <email>Radstudy@uwhealth.org</email>
    </contact>
    <contact_backup>
      <last_name>Gemma Gliori, MS</last_name>
      <phone>608-262-7269</phone>
      <email>ggliori@uwhealth.org</email>
    </contact_backup>
    <investigator>
      <last_name>Alexey Samsonov, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>May 29, 2020</study_first_submitted>
  <study_first_submitted_qc>May 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>April 27, 2023</last_update_submitted>
  <last_update_submitted_qc>April 27, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 28, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Magnetic resonance imaging</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Sclerosis</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/NCT04415372
org study id: 2020-0310
secondary id: 1R01EB027087-01
secondary id: A539300
secondary id: SMPH/RADIOLOGY/RADIOLOGY
secondary id: Protocol Version 4/29/2021
nct id: NCT04415372
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
The overall purpose of this research is to determine whether new macromolecular measures
      optimized for whole brain (gray matter and white matter) magnetic resonance imaging (MRI),
      predict neuro-cognitive impairment in multiple sclerosis (MS) patients.
MRI is a vital component of a MS work-up, providing noninvasive evidence of MS lesions,
      detecting active inflammatory lesions, and measuring brain atrophy to assess
      neurodegeneration. Recent years of MRI research have generated strong evidence of gray matter
      (GM) involvement in MS, resulting in the reclassification of MS as a whole-brain disease.
      Similar to white matter (WM), a primary target of MS pathology in GM is myelin, the
      protective sheath insulating the penetrating axons within GM and extending brain connectivity
      all the way to the neuronal bodies.

      This aim of this research is to examine if the associations between imaging measures of GM
      disease and cognitive performance can establish GM-based imaging correlates predicting the
      disease course and accurately assessing treatment results.

      This observational research will enroll adults diagnosed with MS both with and without
      cognitive impairment. Subjects will be asked to complete a single research visit that
      includes the administration of a MRI scan and a neuro-cognitive testing session.
observational model: Case-Control
time perspective: Prospective
measure: Measurement of macromolecular proton content (MPC) by Magnetic resonance imaging
time frame: 24 hours
description: Macromolecular Proton Fraction (MPF) is calculated from several specially acquired MR images and is characterized by high degree of sensitivity and specificity to tissue macromolecules, which are the main target of pathological process in neurodegenerative diseases including multiple sclerosis (MS). These properties of MPF are in contrast with standard MR images, which are primarily sensitive to tissue water molecules.
measure: Neurocognitive performance as measured by Minimal Assessment of Cognitive Function in MS (MACFIMS) battery of neuropsychological (NP) tests
time frame: 24 hours
description: The results of Minimal Assessment of Cognitive Function in MS (MACFIMS) battery of neuropsychological (NP) tests will form the secondary outcome measure. The NP scores will be correlated with MPF to study association between macromolecular tissue damage and neurocognitive performance.
measure: Neurocognitive performance as measured by the Montreal Cognitive Assessment (MoCA) score
time frame: 24 hours
description: Neurocognitive performance will be measured by Montreal Cognitive Assessment. MoCA scores range from 0 to 30, higher values corresponding to better cognitive performances.
arm group label: Cognitive Impairment
description: Adults diagnosed with MS that have evidence of cognitive decline.
arm group label: No Cognitive Impairment
description: Adults diagnosed with MS that have no evidence of cognitive decline.
arm group label: Healthy Controls
description: Healthy adult volunteers will form a control group matched for age, gender, education, handedness
intervention type: Diagnostic Test
intervention name: MRI
description: The MRI protocol will include conventional testing for MS lesion detection and functional MR imaging to localize associated neurocognitive domains in each subject.
arm group label: Cognitive Impairment
arm group label: Healthy Controls
arm group label: No Cognitive Impairment
other name: Functional MRI
intervention type: Diagnostic Test
intervention name: Neuropsychological Testing
description: A comprehensive battery of neuropsychological tests will be administered to assess memory, new learning, spatial processing and higher executive function.
arm group label: Cognitive Impairment
arm group label: Healthy Controls
arm group label: No Cognitive Impairment
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Alexey Samsonov, PhD
role: Principal Investigator
affiliation: UW Madison
last name: Gemma Gliori, MS
phone: 608-262-7269
email: ggliori@uwhealth.org
last name: Suzanne Hanson, BS
phone: 608-263-7421
email: shanson@uwhealth.org
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Multiple Sclerosis
mesh term: Sclerosis
sharing ipd: No