<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/NCT01726959</url>
  </required_header>
  <id_info>
    <org_study_id>MRS1</org_study_id>
    <nct_id>NCT01726959</nct_id>
  </id_info>
  <brief_title>Prediction of Methotrexate Response - A Pilot Study</brief_title>
  <acronym>MRS</acronym>
  <official_title>Prediction of Methotrexate Response - A Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Wake Forest University Health Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of North Carolina, Chapel Hill</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Wake Forest University Health Sciences</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this study is to identify genetic predictors of individual methotrexate&#xD;
      (MTX) response in patients with rheumatic diseases by determining genetic and metabolomic&#xD;
      factors related to nutrient metabolism and drug transport.&#xD;
&#xD;
      The development of better genetic predictors of individual MTX treatment response would&#xD;
      provide invaluable prognostic information prior to initiating treatment, which would allow&#xD;
      more appropriate choice of therapy, decreased adverse events, and more efficient&#xD;
      dose-escalation of the drug, with ultimate benefits of improved effectiveness and&#xD;
      tolerability rates in patients being treated with MTX for autoimmune diseases.&#xD;
&#xD;
      Despite being the gold-standard therapy for rheumatoid arthritis and other types of chronic&#xD;
      autoimmune diseases since 1951, MTX's efficacy and safety profile limit its use: MTX is&#xD;
      discontinued in greater than 50% of patients secondary to inefficacy or poor tolerability.&#xD;
      Upon initial treatment, discontinuation rates approach 12% because of drug toxicity, despite&#xD;
      prophylactic measures such as the co-administration of folic acid. The causes of primary&#xD;
      failure, secondary failure, and adverse events of MTX may be related to genetic variation of&#xD;
      dihydrofolate reductase (DHFR) and other genes involved in folate metabolism, one-carbon&#xD;
      transfer, and drug transport. The purpose of this study is to identify genetic variations&#xD;
      involved in methotrexate response so that we may better understand the pharmacodynamics of&#xD;
      MTX metabolism in patients with rheumatic diseases.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>December 2011</start_date>
  <completion_date type="Actual">December 2014</completion_date>
  <primary_completion_date type="Actual">December 2014</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>lymphocyte proliferation</measure>
    <time_frame>9 days in culture</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>dihydrofolate reductase expression</measure>
    <time_frame>9 days in culture</time_frame>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">36</enrollment>
  <condition>Rheumatoid Arthritis</condition>
  <condition>Rheumatic Diseases</condition>
  <arm_group>
    <arm_group_label>Methotrexate</arm_group_label>
    <description>Methotrexate for rheumatic diseases, 2.5 - 25 mg weekly</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Patient with rheumatic disease being newly treated with methotrexate, recruited from a&#xD;
        single rheumatology practice&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All adult patients (i.e. &gt;18 years of age) who are enrolled at NorthEast Rheumatology&#xD;
             at the Carolinas Medical Center - NorthEast who will be initiating MTX as standard&#xD;
             treatment for their particular rheumatic disease, which may include (but not be&#xD;
             limited to) conditions such as rheumatoid arthritis, psoriatic arthritis, ankylosing&#xD;
             spondylitis, inflammatory-bowel disease related arthropathies, lupus (systemic lupus&#xD;
             erythematosus, cutaneous lupus erythematosus), Sjogren's syndrome, Behcet's disease,&#xD;
             systemic sclerosis, and vasculitides.&#xD;
&#xD;
          -  No prior enrollment into this study&#xD;
&#xD;
          -  Enrollment and initial blood sample collection prior to first MTX administration&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  NONE&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gordon K. Lam, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Carolinas Medical Center - NorthEast Rheumatology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Carolinas Medical Center - NorthEast</name>
      <address>
        <city>Concord</city>
        <state>North Carolina</state>
        <zip>28025</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2015</verification_date>
  <study_first_submitted>November 12, 2012</study_first_submitted>
  <study_first_submitted_qc>November 14, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 15, 2012</study_first_posted>
  <last_update_submitted>August 31, 2022</last_update_submitted>
  <last_update_submitted_qc>August 31, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>methotrexate</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rheumatic Diseases</mesh_term>
    <mesh_term>Collagen Diseases</mesh_term>
  </condition_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/NCT01726959
org study id: MRS1
nct id: NCT01726959
lead sponsor: 
collaborator: 
has dmc: No
The objective of this study is to identify genetic predictors of individual methotrexate
      (MTX) response in patients with rheumatic diseases by determining genetic and metabolomic
      factors related to nutrient metabolism and drug transport.

      The development of better genetic predictors of individual MTX treatment response would
      provide invaluable prognostic information prior to initiating treatment, which would allow
      more appropriate choice of therapy, decreased adverse events, and more efficient
      dose-escalation of the drug, with ultimate benefits of improved effectiveness and
      tolerability rates in patients being treated with MTX for autoimmune diseases.

      Despite being the gold-standard therapy for rheumatoid arthritis and other types of chronic
      autoimmune diseases since 1951, MTX's efficacy and safety profile limit its use: MTX is
      discontinued in greater than 50% of patients secondary to inefficacy or poor tolerability.
      Upon initial treatment, discontinuation rates approach 12% because of drug toxicity, despite
      prophylactic measures such as the co-administration of folic acid. The causes of primary
      failure, secondary failure, and adverse events of MTX may be related to genetic variation of
      dihydrofolate reductase (DHFR) and other genes involved in folate metabolism, one-carbon
      transfer, and drug transport. The purpose of this study is to identify genetic variations
      involved in methotrexate response so that we may better understand the pharmacodynamics of
      MTX metabolism in patients with rheumatic diseases.
observational model: Cohort
time perspective: Prospective
measure: lymphocyte proliferation
time frame: 9 days in culture
measure: dihydrofolate reductase expression
time frame: 9 days in culture
arm group label: Methotrexate
description: Methotrexate for rheumatic diseases, 2.5 - 25 mg weekly
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gordon K. Lam, MD
role: Principal Investigator
affiliation: Carolinas Medical Center - NorthEast Rheumatology
facility: 
country: United States
responsible party type: Sponsor
mesh term: Rheumatic Diseases
mesh term: Collagen Diseases