<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/NCT01734369</url>
  </required_header>
  <id_info>
    <org_study_id>130015</org_study_id>
    <secondary_id>13-E-0015</secondary_id>
    <nct_id>NCT01734369</nct_id>
  </id_info>
  <brief_title>Environmental Risk Factors for Myositis in Military Personnel</brief_title>
  <official_title>Environmental Risk Factors for the Development of Myositis in Military Personnel</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Environmental Health Sciences (NIEHS)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
        -  Myositis is a rare disease in which the body s immune cells attack the muscle tissue. It&#xD;
           can cause muscle weakness, swelling, and pain. It can develop in people with no history&#xD;
           of muscle problems. Environmental exposures may determine who develops myositis. Genes&#xD;
           may also affect development of the disease.&#xD;
&#xD;
        -  Some people who serve in the military develop myositis. However, other military&#xD;
           personnel do not. Researchers want to compare military personnel with and without&#xD;
           myositis. They will look for common factors that might have led to the disease.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      - To study environmental risk factors for myositis in military personnel.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
        -  Military personnel who developed myositis during their period of service.&#xD;
&#xD;
        -  Healthy military personnel who do not have myositis or another autoimmune disease.&#xD;
&#xD;
      Design:&#xD;
&#xD;
        -  Participants will have a physical exam and medical history.&#xD;
&#xD;
        -  Participants will fill out forms about environmental exposures, particularly while in&#xD;
           the military. The questions will ask about past infections, vaccines and medications,&#xD;
           and personal habits. They will also ask about participants occupations during military&#xD;
           service and their deployments.&#xD;
&#xD;
        -  Participants will also provide blood samples for study.&#xD;
&#xD;
        -  No treatment will be provided as part of this study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Myositis, an autoimmune muscle disease, likely develops as a result of environmental&#xD;
      exposures in genetically susceptible persons. Preliminary data suggest a trend for an&#xD;
      increasing incidence in myositis in military personnel over the last decade for unknown&#xD;
      reasons. Although a few environmental exposures have been preliminarily associated with&#xD;
      myositis in the civilian population, these have not been confirmed. In addition, no study has&#xD;
      assessed exposures that might result in the development of myositis in military personnel.&#xD;
      Military personnel experience a number of intense, unique exposures, often over a relatively&#xD;
      short interval, which include different stresses, novel vaccines, distinct occupational&#xD;
      exposures, battlefield injuries and unique chemicals during field deployment, that differ&#xD;
      from those exposures in non-military populations. Therefore, we propose a protocol that&#xD;
      consists of three complementary approaches to attempt to determine the environmental factors&#xD;
      associated with the development of myositis in active duty military personnel and an initial&#xD;
      understanding of the possible mechanisms involved. In the first approach, we will assess risk&#xD;
      factors in a case-control study of 300 patients who developed myositis while on active duty&#xD;
      by comparing them to 1500 active duty military personnel (randomly selected, but matched 5:1&#xD;
      by gender, race, and age and military service within 10 years) who have not been diagnosed&#xD;
      with an autoimmune disease or chronic muscle disease. For this first approach, we will&#xD;
      analyze existing military databases for information on medications, vaccines, infections,&#xD;
      co-existing medical conditions, military occupations, deployments, and worldwide active duty&#xD;
      locations. In the second case-control approach, we will attempt to define environmental&#xD;
      factors associated with the development of myositis that developed in military personnel&#xD;
      (n=150) by comparing them to 150 similarly matched military personnel who have not been&#xD;
      diagnosed with an autoimmune disease or chronic muscle disease. This second approach will&#xD;
      differ from the first approach, in that subjects will be prospectively enrolled and assessed&#xD;
      during a single clinic visit to confirm diagnoses and examine patient questionnaires on&#xD;
      focused environmental exposures, including those not captured in the military databases. A&#xD;
      third laboratory approach will identify, in an exploratory study, the global DNA methylation&#xD;
      epigenetic changes, microRNA and mRNA profiles in peripheral blood and muscle tissues from 18&#xD;
      subjects (six PM and six DM compared to six non-myositis controls enrolled in the second&#xD;
      approach) and assess the effects of selected environmental exposures on these parameters.&#xD;
      These complementary approaches should enhance the understanding of environmental factors and&#xD;
      possible mechanisms associated with the development of myositis in the military, and provide&#xD;
      insights into environmental risk factors that may also be relevant to the development of&#xD;
      myositis in non-military populations.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 13, 2014</start_date>
  <primary_completion_date type="Actual">October 31, 2021</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>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Military Myositis Questionnaire</measure>
    <time_frame>Assessed once per respondent</time_frame>
    <description>Myositis and control subjects will complete the environmnetal exposure questionnaire, a connective tissue screening questionnaire and the Patient Reported Outcomes Measurement Information System (PROMIS) Quality of Life measure to assess health related quality of life</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">37</enrollment>
  <condition>Dermatomyositis</condition>
  <condition>Adult Polymyositis</condition>
  <condition>Inclusion Body Myositis</condition>
  <condition>Myositis</condition>
  <arm_group>
    <arm_group_label>Healthy Control Subjects</arm_group_label>
    <description>Military service members active duty or no longer in duty, military contractors, and civilians working for the military. Controls should be without a recognized autoimmune or chronic muscle disease.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Myositis Subjects</arm_group_label>
    <description>Diagnosis of myositis during military service or service as a military contractor or civilian working for the military with polymyositis, dermatomyositis, or inclusion body myositis.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Myositis patients include diagnosis of myositis during military service or service as a&#xD;
        military contractor based on criteria for probable or definite PM or DM, or clinically or&#xD;
        pathologically defined or possible IBM. Subjects may be active duty or no longer active&#xD;
        duty personnel. Military contractors include those with at least 1 year of collective&#xD;
        service on a military base or who actively deployed with military units after October 1998&#xD;
        and developed myositis will be eligible for this study. Control subjects include persons&#xD;
        with military experience or having served as a military contractor attending the same&#xD;
        clinic or hospital as the myositis subject to which they are matched, or if not available,&#xD;
        volunteers from the general community (such as other participating military or VA&#xD;
        hospitals, private HCPs, or the NIH healthy volunteer program), matched to the myositis&#xD;
        subject.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        -  ELIGIBILITY CRITERIA:&#xD;
&#xD;
        For Aim 1 of the study:&#xD;
&#xD;
        The inclusion criteria for myositis subjects are:&#xD;
&#xD;
        -Diagnosis of PM, DM or IBM during military service. Subjects may be active duty or no&#xD;
        longer active duty personnel. A matrix diagnosis of myositis will be based on ICD-9 codes,&#xD;
        laboratory tests and medical records in an attempt to match criteria for probable or&#xD;
        definite PM, DM or IBM&#xD;
&#xD;
        The inclusion criteria for matched control subjects are:&#xD;
&#xD;
        -The same gender, race, age within 10 years, and service in the military within 10 years as&#xD;
        the myositis subject.&#xD;
&#xD;
        The exclusion criteria for control subjects are:&#xD;
&#xD;
        -A matrix diagnosis of autoimmune or chronic muscle disease based on ICD-9 codes and&#xD;
        medical records.&#xD;
&#xD;
        For Aims 2 and 3 of the study:&#xD;
&#xD;
        The inclusion criteria for enrollment of myositis subjects are:&#xD;
&#xD;
          -  Diagnosis of myositis during military service or service as a military contractor or&#xD;
             civilian working for the military, based on criteria for probable or definite PM or&#xD;
             DM, or clinically or pathologically defined or possible IBM. Subjects may be active&#xD;
             duty or no longer active duty personnel. Military contractors or civilians working for&#xD;
             the military include those with at least 1 year of collective service on a military&#xD;
             base or who actively deployed with military units after October 1998 and developed&#xD;
             myositis will be eligible for this study.&#xD;
&#xD;
          -  Able and willing to give informed consent, to complete the questionnaires and to&#xD;
             donate blood samples.&#xD;
&#xD;
        The inclusion criteria for matched controls are:&#xD;
&#xD;
          -  Persons with military experience or having served as a military contractor or civilian&#xD;
             working for the military attending the same clinic or hospital as the myositis subject&#xD;
             to which they are matched, or if not available, volunteers from the general community&#xD;
             (such as other participating military or VA hospitals, private HCPs, or the NIH&#xD;
             healthy volunteer program), gender- race- and age- (within 10 years) and military&#xD;
             service period (within 10 years) matched to the myositis subject. Military contractors&#xD;
             include those with at least 1 year of collective service on a military base or who&#xD;
             actively deployed with military units after October 1998.&#xD;
&#xD;
          -  Controls should be without a recognized autoimmune or chronic muscle disease, able and&#xD;
             willing to give informed consent, to complete the questionnaires and to donate blood&#xD;
             samples.&#xD;
&#xD;
        The exclusion criteria for all protocol subjects are:&#xD;
&#xD;
          -  Medical illness that in the judgment of the investigators does not allow safe blood&#xD;
             draws or other clinical evaluations needed for study participation.&#xD;
&#xD;
          -  Chronic muscle diseases other than idiopathic inflammatory myopathy (e.g., infectious,&#xD;
             dystrophic, metabolic, toxic or drug-induced myopathies).&#xD;
&#xD;
          -  Cognitive impairment.&#xD;
&#xD;
          -  Not able or willing to give informed consent.&#xD;
&#xD;
          -  Age &lt;18 years.&#xD;
&#xD;
          -  Current incarceration&#xD;
&#xD;
        There are no gender or ethnic restrictions to enrollment in the study.&#xD;
&#xD;
        HIV is not an exclusion for this study for the two following reasons:&#xD;
&#xD;
          -  It has no impact on study procedures or tests.&#xD;
&#xD;
          -  HIV may be one of the viral risk factors we are investigating.&#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>Adam I Schiffenbauer, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Institute of Environmental Health Sciences (NIEHS)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Walter Reed National Medical Center</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Institutes of Health Clinical Center</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NIEHS Clinical Research Unit (CRU)</name>
      <address>
        <city>Research Triangle Park</city>
        <state>North Carolina</state>
        <zip>27709</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2013-E-0015.html</url>
    <description>NIH Clinical Center Detailed Web Page</description>
  </link>
  <reference>
    <citation>Bacarese-Hamilton T, Mezzasoma L, Ardizzoni A, Bistoni F, Crisanti A. Serodiagnosis of infectious diseases with antigen microarrays. J Appl Microbiol. 2004;96(1):10-7. doi: 10.1046/j.1365-2672.2003.02111.x.</citation>
    <PMID>14678154</PMID>
  </reference>
  <reference>
    <citation>Aggarwal R, Lucas M, Fertig N, Oddis CV, Medsger TA Jr. Anti-U3 RNP autoantibodies in systemic sclerosis. Arthritis Rheum. 2009 Apr;60(4):1112-8. doi: 10.1002/art.24409.</citation>
    <PMID>19333934</PMID>
  </reference>
  <reference>
    <citation>Bach JF. The effect of infections on susceptibility to autoimmune and allergic diseases. N Engl J Med. 2002 Sep 19;347(12):911-20. doi: 10.1056/NEJMra020100. No abstract available.</citation>
    <PMID>12239261</PMID>
  </reference>
  <verification_date>May 22, 2023</verification_date>
  <study_first_submitted>November 22, 2012</study_first_submitted>
  <study_first_submitted_qc>November 22, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 27, 2012</study_first_posted>
  <last_update_submitted>September 2, 2023</last_update_submitted>
  <last_update_submitted_qc>September 2, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Dermatomyositis</keyword>
  <keyword>Inclusion Body Myositis</keyword>
  <keyword>Myositis</keyword>
  <keyword>Polymyositis</keyword>
  <keyword>Military</keyword>
  <keyword>Natural History</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dermatomyositis</mesh_term>
    <mesh_term>Myositis</mesh_term>
    <mesh_term>Polymyositis</mesh_term>
    <mesh_term>Myositis, Inclusion Body</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>.It is not yet known if there will be a plan to make IPD available</ipd_description>
  </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/NCT01734369
org study id: 130015
secondary id: 13-E-0015
nct id: NCT01734369
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Background:

        -  Myositis is a rare disease in which the body s immune cells attack the muscle tissue. It
           can cause muscle weakness, swelling, and pain. It can develop in people with no history
           of muscle problems. Environmental exposures may determine who develops myositis. Genes
           may also affect development of the disease.

        -  Some people who serve in the military develop myositis. However, other military
           personnel do not. Researchers want to compare military personnel with and without
           myositis. They will look for common factors that might have led to the disease.

      Objectives:

      - To study environmental risk factors for myositis in military personnel.

      Eligibility:

        -  Military personnel who developed myositis during their period of service.

        -  Healthy military personnel who do not have myositis or another autoimmune disease.

      Design:

        -  Participants will have a physical exam and medical history.

        -  Participants will fill out forms about environmental exposures, particularly while in
           the military. The questions will ask about past infections, vaccines and medications,
           and personal habits. They will also ask about participants occupations during military
           service and their deployments.

        -  Participants will also provide blood samples for study.

        -  No treatment will be provided as part of this study.
Myositis, an autoimmune muscle disease, likely develops as a result of environmental
      exposures in genetically susceptible persons. Preliminary data suggest a trend for an
      increasing incidence in myositis in military personnel over the last decade for unknown
      reasons. Although a few environmental exposures have been preliminarily associated with
      myositis in the civilian population, these have not been confirmed. In addition, no study has
      assessed exposures that might result in the development of myositis in military personnel.
      Military personnel experience a number of intense, unique exposures, often over a relatively
      short interval, which include different stresses, novel vaccines, distinct occupational
      exposures, battlefield injuries and unique chemicals during field deployment, that differ
      from those exposures in non-military populations. Therefore, we propose a protocol that
      consists of three complementary approaches to attempt to determine the environmental factors
      associated with the development of myositis in active duty military personnel and an initial
      understanding of the possible mechanisms involved. In the first approach, we will assess risk
      factors in a case-control study of 300 patients who developed myositis while on active duty
      by comparing them to 1500 active duty military personnel (randomly selected, but matched 5:1
      by gender, race, and age and military service within 10 years) who have not been diagnosed
      with an autoimmune disease or chronic muscle disease. For this first approach, we will
      analyze existing military databases for information on medications, vaccines, infections,
      co-existing medical conditions, military occupations, deployments, and worldwide active duty
      locations. In the second case-control approach, we will attempt to define environmental
      factors associated with the development of myositis that developed in military personnel
      (n=150) by comparing them to 150 similarly matched military personnel who have not been
      diagnosed with an autoimmune disease or chronic muscle disease. This second approach will
      differ from the first approach, in that subjects will be prospectively enrolled and assessed
      during a single clinic visit to confirm diagnoses and examine patient questionnaires on
      focused environmental exposures, including those not captured in the military databases. A
      third laboratory approach will identify, in an exploratory study, the global DNA methylation
      epigenetic changes, microRNA and mRNA profiles in peripheral blood and muscle tissues from 18
      subjects (six PM and six DM compared to six non-myositis controls enrolled in the second
      approach) and assess the effects of selected environmental exposures on these parameters.
      These complementary approaches should enhance the understanding of environmental factors and
      possible mechanisms associated with the development of myositis in the military, and provide
      insights into environmental risk factors that may also be relevant to the development of
      myositis in non-military populations.
observational model: Case-Control
time perspective: Cross-Sectional
measure: Military Myositis Questionnaire
time frame: Assessed once per respondent
description: Myositis and control subjects will complete the environmnetal exposure questionnaire, a connective tissue screening questionnaire and the Patient Reported Outcomes Measurement Information System (PROMIS) Quality of Life measure to assess health related quality of life
arm group label: Healthy Control Subjects
description: Military service members active duty or no longer in duty, military contractors, and civilians working for the military. Controls should be without a recognized autoimmune or chronic muscle disease.
arm group label: Myositis Subjects
description: Diagnosis of myositis during military service or service as a military contractor or civilian working for the military with polymyositis, dermatomyositis, or inclusion body myositis.
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Adam I Schiffenbauer, M.D.
role: Principal Investigator
affiliation: National Institute of Environmental Health Sciences (NIEHS)
facility: 
facility: 
facility: 
country: United States
url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2013-E-0015.html
description: NIH Clinical Center Detailed Web Page
citation: Bacarese-Hamilton T, Mezzasoma L, Ardizzoni A, Bistoni F, Crisanti A. Serodiagnosis of infectious diseases with antigen microarrays. J Appl Microbiol. 2004;96(1):10-7. doi: 10.1046/j.1365-2672.2003.02111.x.
PMID: 14678154
citation: Aggarwal R, Lucas M, Fertig N, Oddis CV, Medsger TA Jr. Anti-U3 RNP autoantibodies in systemic sclerosis. Arthritis Rheum. 2009 Apr;60(4):1112-8. doi: 10.1002/art.24409.
PMID: 19333934
citation: Bach JF. The effect of infections on susceptibility to autoimmune and allergic diseases. N Engl J Med. 2002 Sep 19;347(12):911-20. doi: 10.1056/NEJMra020100. No abstract available.
PMID: 12239261
responsible party type: Sponsor
mesh term: Dermatomyositis
mesh term: Myositis
mesh term: Polymyositis
mesh term: Myositis, Inclusion Body
sharing ipd: Undecided
ipd description: .It is not yet known if there will be a plan to make IPD available