<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/NCT02225977</url>
  </required_header>
  <id_info>
    <org_study_id>MSGilenya</org_study_id>
    <nct_id>NCT02225977</nct_id>
  </id_info>
  <brief_title>Assessing Induction of Type II (M2) Monocytes/Macrophages in Patients Receiving Gilenya.</brief_title>
  <official_title>Assessing Induction of Type II (M2) Monocytes/Macrophages in Patients Receiving Gilenya.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Southern California</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Southern California</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this study we wish to test the hypothesis that continuous Gilenya treatment alters immune&#xD;
      homeostasis in favor of an anti-inflammatory type II monocyte and macrophage (M2) phenotype&#xD;
      in the circulation of patients with relapsing-remitting Multiple Sclerosis (MS). In this&#xD;
      study we will determine the change in ratio of M2 (type II, alternatively activated) versus&#xD;
      M1 (type I, classically activated) monocytes and macrophages in a cohort of patients that&#xD;
      have received continuous Gilenya treatment for 0, 1, 3, 6 or 12 months. We will also assess&#xD;
      changes in cell surface expression of the M1 marker CCR7 and the M2 markers CD206 or CD301 by&#xD;
      monocytes and macrophages using FACS analysis of whole blood, and assess the tyrosine&#xD;
      phosphorylation of the signal transducer and activator of transcription STAT-1 (pTyr-STAT1),&#xD;
      which is critical for the activation of M1 myeloid cells. We will assess correlates with&#xD;
      changes in M1 and M2 cytokine expression assessing possible mechanisms of action of Gilenya&#xD;
      on myeloid lineage cells.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 31, 2013</start_date>
  <completion_date type="Actual">April 30, 2017</completion_date>
  <primary_completion_date type="Actual">December 31, 2016</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>Change in ratio of M2 versus M1 monocytes and macrophages.</measure>
    <time_frame>12 months</time_frame>
  </primary_outcome>
  <number_of_groups>5</number_of_groups>
  <enrollment type="Actual">125</enrollment>
  <condition>Multiple Sclerosis</condition>
  <arm_group>
    <arm_group_label>Gilenya treated - 1 month</arm_group_label>
    <description>Patient's taking continuous oral Gilenya at prescribed dose for 1 month.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Gilenya treated - 3 months</arm_group_label>
    <description>Patient's taking continuous oral Gilenya at prescribed dose for 3 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Gilenya treated - 6 months</arm_group_label>
    <description>Patient's taking continuous oral Gilenya at prescribed dose for 6 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Gilenya treated - 12 months</arm_group_label>
    <description>Patient's taking continuous oral Gilenya at prescribed dose for 12 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Gilenya qualified - untreated</arm_group_label>
    <description>Patient's qualifying to start treatment with oral Gilenya at prescribed dose but still as yet untreated.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gilenya</intervention_name>
    <arm_group_label>Gilenya treated - 1 month</arm_group_label>
    <arm_group_label>Gilenya treated - 12 months</arm_group_label>
    <arm_group_label>Gilenya treated - 3 months</arm_group_label>
    <arm_group_label>Gilenya treated - 6 months</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients will be selected from those seen by physicians at the USC Multiple Sclerosis&#xD;
        Comprehensive Care Center.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must qualify to receive treatment with Gilenya, according to the University&#xD;
             of Southern California, Department of Neurology, MS Group, Gilenya Prescribing&#xD;
             Process.&#xD;
&#xD;
          -  Clinically definite Multiple Sclerosis defined by the revised McDonald criteria&#xD;
             (Polman et al., 2005, Polman et al., 2010) of the relapsing-remitting form with an&#xD;
             Expanded Disability Status Scale (EDSS) score of 0 to 5.5.&#xD;
&#xD;
          -  Ability to understand and sign this study-specific institutional review board-approved&#xD;
             informed consent form.&#xD;
&#xD;
          -  Willing to donate ~50mls of blood for immunological testing on up to five occasions.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient does not qualify to receive treatment with Gilenya, according to the USC,&#xD;
             Department of Neurology, MS Group, Gilenya Prescribing Process.&#xD;
&#xD;
          -  Inability to understand nature of the study.&#xD;
&#xD;
          -  Treatment with any of the following within 30 days of commencing treatment with&#xD;
             Gilenya: Avonex, Betaseron, Rebif, Copaxone, Natalizumab, Rituximab, Mitoxantrone,&#xD;
             Cyclophosphamide, Cyclosporine, Azathioprine, Methotrexate or any other&#xD;
             immunomodulatory, immunosuppressant or immune homeostasis altering drug.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Brett T Lund, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Southern California</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Southern California, Department of Neurology</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>August 24, 2014</study_first_submitted>
  <study_first_submitted_qc>August 24, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 26, 2014</study_first_posted>
  <last_update_submitted>August 21, 2018</last_update_submitted>
  <last_update_submitted_qc>August 21, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 22, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Southern California</investigator_affiliation>
    <investigator_full_name>Brett T. Lund</investigator_full_name>
    <investigator_title>Assistant Professor of Neurology</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Sclerosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fingolimod Hydrochloride</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/NCT02225977
org study id: MSGilenya
nct id: NCT02225977
lead sponsor: 
has dmc: No
In this study we wish to test the hypothesis that continuous Gilenya treatment alters immune
      homeostasis in favor of an anti-inflammatory type II monocyte and macrophage (M2) phenotype
      in the circulation of patients with relapsing-remitting Multiple Sclerosis (MS). In this
      study we will determine the change in ratio of M2 (type II, alternatively activated) versus
      M1 (type I, classically activated) monocytes and macrophages in a cohort of patients that
      have received continuous Gilenya treatment for 0, 1, 3, 6 or 12 months. We will also assess
      changes in cell surface expression of the M1 marker CCR7 and the M2 markers CD206 or CD301 by
      monocytes and macrophages using FACS analysis of whole blood, and assess the tyrosine
      phosphorylation of the signal transducer and activator of transcription STAT-1 (pTyr-STAT1),
      which is critical for the activation of M1 myeloid cells. We will assess correlates with
      changes in M1 and M2 cytokine expression assessing possible mechanisms of action of Gilenya
      on myeloid lineage cells.
observational model: Cohort
time perspective: Prospective
measure: Change in ratio of M2 versus M1 monocytes and macrophages.
time frame: 12 months
arm group label: Gilenya treated - 1 month
description: Patient's taking continuous oral Gilenya at prescribed dose for 1 month.
arm group label: Gilenya treated - 3 months
description: Patient's taking continuous oral Gilenya at prescribed dose for 3 months.
arm group label: Gilenya treated - 6 months
description: Patient's taking continuous oral Gilenya at prescribed dose for 6 months.
arm group label: Gilenya treated - 12 months
description: Patient's taking continuous oral Gilenya at prescribed dose for 12 months.
arm group label: Gilenya qualified - untreated
description: Patient's qualifying to start treatment with oral Gilenya at prescribed dose but still as yet untreated.
intervention type: Drug
intervention name: Gilenya
arm group label: Gilenya treated - 1 month
arm group label: Gilenya treated - 12 months
arm group label: Gilenya treated - 3 months
arm group label: Gilenya treated - 6 months
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Brett T Lund, Ph.D.
role: Principal Investigator
affiliation: University of Southern California
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Southern California
investigator full name: Brett T. Lund
investigator title: Assistant Professor of Neurology
mesh term: Multiple Sclerosis
mesh term: Fingolimod Hydrochloride