xml: <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/NCT06023160</url>
    </required_header>
    <id_info>
      <org_study_id>NEOSII</org_study_id>
      <nct_id>NCT06023160</nct_id>
    </id_info>
    <brief_title>Predicting Functional Outcome and Response to Therapy of Anti-NMDAR Encephalitis at Diagnosis</brief_title>
    <acronym>NEOSII</acronym>
    <official_title>Predicting Functional Outcome and Response to Therapy of Anti-NMDAR Encephalitis at Diagnosis: The NEOSII Score</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Erasmus Medical Center</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Erasmus Medical Center</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The goal of this international cohort study is to develop a prediction model for long-term&#xD;
        outcome and response to first-line immunotherapy of anti-NMDAR Encephalitis, already at the&#xD;
        moment of diagnosis.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Anti-NMDARE is a severe, but treatable neurological condition, with considerable and variable&#xD;
        long-term disability. The previously developed anti-NMDAR Encephalitis One-Year Functional&#xD;
        Status (NEOS) score predicts outcome a month into treatment. To predict outcome and response&#xD;
        to immunotherapy at the time of diagnosis would be a serious improvement. This would timely&#xD;
        identify patients in need for aggressive treatment and avoid harmful side-effects in those&#xD;
        with good outcome. International data from five anti-NMDAR encephalitis cohorts will be&#xD;
        combined to attain these goals.&#xD;
  &#xD;
        The investigators strive to have less than 10% missing data on all variables and will impute&#xD;
        data were needed. The datasets will then be split - with equal distributions of cohorts and&#xD;
        good/poor outcome - to develop (70%) and validate (30%) the NEOS2 model. The primary outcome&#xD;
        is functioning one year after diagnosis. A secondary analysis is targeted to predict the&#xD;
        effect of first-line therapy. Potentially relevant predictive variables are identified with a&#xD;
        univariable analysis on the original data, confirmed with backwards selection on the imputed&#xD;
        datasets. After checking for multicollinearity and linearity of the variables, identified&#xD;
        variables are added to a mixed effects logistic regression model on the original and imputed&#xD;
        datasets, to identify the final set of predictive variables. To make the models opportune for&#xD;
        daily medical practice, the investigators will assign points to (categories of) the included&#xD;
        variables, based on the coefficients.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Active, not recruiting</overall_status>
    <start_date type="Actual">December 1, 2020</start_date>
    <completion_date type="Anticipated">November 1, 2023</completion_date>
    <primary_completion_date type="Actual">July 1, 2023</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>Retrospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Functional status one year after diagnosis, on the modified Rankin Scale.</measure>
      <time_frame>One year after diagnosis</time_frame>
      <description>The score on the modified Rankin Scale will be applied as the original ordinal scale as well as dichotomized, where scores 0-2 represent &quot;independent functioning&quot; (without or with symptoms) and scores 3-6 increasing levels of depencency</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Response to first-line immunotherapy</measure>
      <time_frame>Two weeks after administration of first-line immunotherapy</time_frame>
      <description>One point improvement (one point lower than at diagnosis) on the modified Rankin Scale (ranging from 0 - no symptoms - to 6 - deceased - as the most severe category) within two weeks from therapy commencement.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Return to school or work</measure>
      <time_frame>Throughout follow-up time after diagnosis (different per patient, depending on date of diagnosis). Average 3 years (min 0 - max 22 years)</time_frame>
      <description>Time-to-event analysis on the ability to return to school or work during follow-up, including timing of resumption of work after diagnosis.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Relapse rate</measure>
      <time_frame>Throughout follow-up time after diagnosis (different per patient, depending on date of diagnosis). Average 3 years (min 0 - max 22 years)</time_frame>
      <description>Time-to-event analysis on relapses during total available follow-up time, including time of relapse after diagnosis.</description>
    </secondary_outcome>
    <number_of_groups>5</number_of_groups>
    <enrollment type="Actual">714</enrollment>
    <condition>Anti-NMDA (N-Methyl D-Aspartate) Receptor Encephalitis</condition>
    <arm_group>
      <arm_group_label>Dutch National anti-NMDAR Encephalitis Cohort</arm_group_label>
      <description>Dutch National anti-NMDAR Encephalitis Cohort</description>
    </arm_group>
    <arm_group>
      <arm_group_label>German anti-NMDAR Encephalitis Cohort (GENERATE)</arm_group_label>
      <description>German anti-NMDAR Encephalitis Cohort (GENERATE)</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Spanish anti-NMDAR Encephalitis Cohort</arm_group_label>
      <description>Spanish anti-NMDAR Encephalitis Cohort</description>
    </arm_group>
    <arm_group>
      <arm_group_label>French anti-NMDAR Encephalitis Cohort</arm_group_label>
      <description>French anti-NMDAR Encephalitis Cohort</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Japanese anti-NMDAR Encephalitis Cohort</arm_group_label>
      <description>Japanese anti-NMDAR Encephalitis Cohort</description>
    </arm_group>
    <eligibility>
      <study_pop>
        <textblock>
          Retrospective data of five (inter)national anti-NMDAR encephalitis cohorts.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Diagnosed with anti-NMDAR encephalitis (according to the Graus criteria)&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Preceding Herpes Simplex encephalitis&#xD;
  &#xD;
            -  Premorbid dependency (modified Rankin Scale &gt; 2)&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>N/A</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Maarten J. Titulaer, Assoc. Porf.</last_name>
      <role>Principal Investigator</role>
      <affiliation>Erasmus Medical Center</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>Erasmus Medical Center</name>
        <address>
          <city>Rotterdam</city>
          <country>Netherlands</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Netherlands</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 19, 2023</study_first_submitted>
    <study_first_submitted_qc>August 28, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 5, 2023</study_first_posted>
    <last_update_submitted>September 4, 2023</last_update_submitted>
    <last_update_submitted_qc>September 4, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 7, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Erasmus Medical Center</investigator_affiliation>
      <investigator_full_name>Dr. Maarten J. Titulaer. MD, PhD</investigator_full_name>
      <investigator_title>Associate professor, Dr.</investigator_title>
    </responsible_party>
    <keyword>Prognosis</keyword>
    <keyword>Immunotherapy</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Anti-N-Methyl-D-Aspartate Receptor Encephalitis</mesh_term>
      <mesh_term>Encephalitis</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06023160
  org study id: NEOSII
  nct id: NCT06023160
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The goal of this international cohort study is to develop a prediction model for long-term
        outcome and response to first-line immunotherapy of anti-NMDAR Encephalitis, already at the
        moment of diagnosis.
  Anti-NMDARE is a severe, but treatable neurological condition, with considerable and variable
        long-term disability. The previously developed anti-NMDAR Encephalitis One-Year Functional
        Status (NEOS) score predicts outcome a month into treatment. To predict outcome and response
        to immunotherapy at the time of diagnosis would be a serious improvement. This would timely
        identify patients in need for aggressive treatment and avoid harmful side-effects in those
        with good outcome. International data from five anti-NMDAR encephalitis cohorts will be
        combined to attain these goals.
  
        The investigators strive to have less than 10% missing data on all variables and will impute
        data were needed. The datasets will then be split - with equal distributions of cohorts and
        good/poor outcome - to develop (70%) and validate (30%) the NEOS2 model. The primary outcome
        is functioning one year after diagnosis. A secondary analysis is targeted to predict the
        effect of first-line therapy. Potentially relevant predictive variables are identified with a
        univariable analysis on the original data, confirmed with backwards selection on the imputed
        datasets. After checking for multicollinearity and linearity of the variables, identified
        variables are added to a mixed effects logistic regression model on the original and imputed
        datasets, to identify the final set of predictive variables. To make the models opportune for
        daily medical practice, the investigators will assign points to (categories of) the included
        variables, based on the coefficients.
  observational model: Cohort
  time perspective: Retrospective
  measure: Functional status one year after diagnosis, on the modified Rankin Scale.
  time frame: One year after diagnosis
  description: The score on the modified Rankin Scale will be applied as the original ordinal scale as well as dichotomized, where scores 0-2 represent "independent functioning" (without or with symptoms) and scores 3-6 increasing levels of depencency
  measure: Response to first-line immunotherapy
  time frame: Two weeks after administration of first-line immunotherapy
  description: One point improvement (one point lower than at diagnosis) on the modified Rankin Scale (ranging from 0 - no symptoms - to 6 - deceased - as the most severe category) within two weeks from therapy commencement.
  measure: Return to school or work
  time frame: Throughout follow-up time after diagnosis (different per patient, depending on date of diagnosis). Average 3 years (min 0 - max 22 years)
  description: Time-to-event analysis on the ability to return to school or work during follow-up, including timing of resumption of work after diagnosis.
  measure: Relapse rate
  time frame: Throughout follow-up time after diagnosis (different per patient, depending on date of diagnosis). Average 3 years (min 0 - max 22 years)
  description: Time-to-event analysis on relapses during total available follow-up time, including time of relapse after diagnosis.
  arm group label: Dutch National anti-NMDAR Encephalitis Cohort
  description: Dutch National anti-NMDAR Encephalitis Cohort
  arm group label: German anti-NMDAR Encephalitis Cohort (GENERATE)
  description: German anti-NMDAR Encephalitis Cohort (GENERATE)
  arm group label: Spanish anti-NMDAR Encephalitis Cohort
  description: Spanish anti-NMDAR Encephalitis Cohort
  arm group label: French anti-NMDAR Encephalitis Cohort
  description: French anti-NMDAR Encephalitis Cohort
  arm group label: Japanese anti-NMDAR Encephalitis Cohort
  description: Japanese anti-NMDAR Encephalitis Cohort
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: N/A
  maximum age: N/A
  healthy volunteers: No
  last name: Maarten J. Titulaer, Assoc. Porf.
  role: Principal Investigator
  affiliation: Erasmus Medical Center
  facility: 
  country: Netherlands
  responsible party type: Principal Investigator
  investigator affiliation: Erasmus Medical Center
  investigator full name: Dr. Maarten J. Titulaer. MD, PhD
  investigator title: Associate professor, Dr.
  mesh term: Anti-N-Methyl-D-Aspartate Receptor Encephalitis
  mesh term: Encephalitis