<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/NCT02206490</url>
  </required_header>
  <id_info>
    <org_study_id>090562</org_study_id>
    <nct_id>NCT02206490</nct_id>
  </id_info>
  <brief_title>Trial of Naltrexone and Dextromethorphan for Gulf War Illness</brief_title>
  <acronym>GWI Treatment</acronym>
  <official_title>Trial of Naltrexone and Dextromethorphan for Gulf War Veterans Illnesses</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>East Carolina University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>East Carolina University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Veterans of the 1991 Gulf War who developed Gulf War Illness are being studied. Treatments&#xD;
      with FDA approved generic drugs are being administered to see if they help with the symptoms&#xD;
      of Gulf War Illness, such as chronic fatigue; difficulty with memory, concentration, and&#xD;
      thinking; widespread chronic pain; and autonimic dysfunction. Drugs to be tested are&#xD;
      dextromethorphan and naltrexone.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Gulf war veterans' illnesses comprise distinct clusters of symptom-defined illnesses for&#xD;
      which there are neither diagnostic tests nor effective treatments. Gulf war veterans had&#xD;
      variable exposures to a number of chemicals, including organophosphate insecticides,&#xD;
      pyrethrum-related insecticides, DEET, Pyridostigmine bromide, smoke from oil well fires, and&#xD;
      Sarin gas. Gulf war veterans' illnesses may reflect an inflammatory cycle involving the brain&#xD;
      which may be a common mechanism of many neurological conditions, whether initiated by toxic&#xD;
      exposures, infection, or trauma. In this theory, central nervous system inflammation&#xD;
      initiated by toxic exposures and sometimes exacerbated by subsequent exposures is a component&#xD;
      of illness hypothesized to explain the neurological manifestations. Substance P release at&#xD;
      sensory nerve endings is an explanation for the peripheral pain manifestations of illness.&#xD;
&#xD;
      This theory suggests that novel anti-inflammatory drugs may be of benefit in symptom-defined&#xD;
      illnesses related to a cycle of inflammation. Dr. J. S. Hong's laboratory at the National&#xD;
      Institute of Environmental Health Sciences has demonstrated that Morphine-related analogs,&#xD;
      including Naltrexone and Dextromethorphan, have great potency in anti-inflammation and&#xD;
      neuroprotective effects. Naltrexone is a safe and readily available generic medication.&#xD;
      Dextromethorphan is also a safe and readily available generic medication that is available&#xD;
      without a prescription as a cough medication. Results from several clinical trials showed&#xD;
      that Naltrexone is effective in several inflammation-related diseases, such as neurogenic&#xD;
      pain, movement disorders, etc. In addition, there were no obvious side effects in patients&#xD;
      taking this drug for six months. This project will conduct randomized double-blinded studies&#xD;
      for treating ill Gulf war veterans with Naltrexone and Dextromethorphan. Laboratory tests for&#xD;
      markers of inflammation including neurogenic inflammation will be performed pre- and&#xD;
      post-treatment, to see if these markers are elevated and if so, to see if treatment modulates&#xD;
      these markers.&#xD;
&#xD;
      Ill Gulf veterans will be recruited through the media, veterans groups, and individual&#xD;
      veteran activists. A screening telephone interview will be performed to determine if the&#xD;
      veterans meet a modified Kansas case definition for inclusion. Those veterans who meet study&#xD;
      criteria will be invited to participate. Eligible veterans will be invited for an initial&#xD;
      visit that will consist of obtaining written informed consent, a medical history, physical&#xD;
      examination, and laboratory testing. Institutional review board approval of the study will be&#xD;
      in place. The pharmacy staff at the institution will prepare the medications and placebo in&#xD;
      identical capsules.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2012</start_date>
  <completion_date type="Actual">January 2016</completion_date>
  <primary_completion_date type="Actual">January 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Symptoms Scores</measure>
    <time_frame>28 weeks approximately</time_frame>
    <description>Symptoms of Gulf War Illness will be scored by participants using a ten center meter scale.&#xD;
Scores will be collected at the end of 12 weeks/16 weeks/28weeks</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>SF-36</measure>
    <time_frame>28 weeks approximately</time_frame>
    <description>Subjects will complete a standard health assessment tool, the SF-36, at the end of each course of therapy.&#xD;
Scores will be collected at 12 weeks/16 weeks/28 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Connors Continuous Performance Test</measure>
    <time_frame>28 weeks approximately</time_frame>
    <description>Subjects will take the Connors Continuous Performance Test at the end of each course of study drug or placebo.&#xD;
Scores will be collected at 12 weeks/16 weeks/28 weeks</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Gulf War Illness</condition>
  <arm_group>
    <arm_group_label>Naltrexone Study Drug</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects will take naltrexone 4.5 mg daily for three months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Naltrexone placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects will take a 3 month course of a placebo pill identical in appearance to the naltrexone study drug.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>dextromethrophan study drug</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>subjects will take a sustained release dextromethorphan pill twice a day.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>dextromethoprhan placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects will take a 3 month course of a placebo pill identical in appearance to the dextromethorphan study drug.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>naltrexone</intervention_name>
    <description>Randomized controlled trial of naltrexone for Gulf War Illness.</description>
    <arm_group_label>Naltrexone Study Drug</arm_group_label>
    <arm_group_label>Naltrexone placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dextromethorphan</intervention_name>
    <description>Randomized controlled trial of dextromethorphan for Gulf War Illness</description>
    <arm_group_label>dextromethoprhan placebo</arm_group_label>
    <arm_group_label>dextromethrophan study drug</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Served in the Gulf War and developed the symptoms of Gulf War Illness as described by&#xD;
             the modified Kansas Case Definition&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant women, nursing mothers, individuals requiring medications that have drug&#xD;
             interactions with dextromethorphan or naltrexone, cancer not in remission, chronic&#xD;
             infectious disease, liver disease, lupus, multiple sclerosis, stroke, under current&#xD;
             treatment for schizophrenia, bipolar disorder/manic depression, and depression.&#xD;
&#xD;
          -  Those with a history of current illicit drug use will be excluded. Individuals who&#xD;
             have had recent surgery will not be enrolled until they have completely recovered from&#xD;
             the surgery.&#xD;
&#xD;
          -  Subjects participating in other clinical trials will be excluded.&#xD;
&#xD;
          -  Those enrolled recently in a clinical trial will be enrolled after a washout period of&#xD;
             one month.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Brody School of Medicine a East Carolina Univesity</name>
      <address>
        <city>Greenville</city>
        <state>North Carolina</state>
        <zip>27834</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2016</verification_date>
  <study_first_submitted>August 24, 2012</study_first_submitted>
  <study_first_submitted_qc>July 31, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 1, 2014</study_first_posted>
  <last_update_submitted>March 2, 2016</last_update_submitted>
  <last_update_submitted_qc>March 2, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 3, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>East Carolina University</investigator_affiliation>
    <investigator_full_name>William J. Meggs</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Gulf War Illness</keyword>
  <keyword>treatment</keyword>
  <keyword>dextromethorphan</keyword>
  <keyword>naltrexone</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Naltrexone</mesh_term>
    <mesh_term>Dextromethorphan</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/NCT02206490
org study id: 090562
nct id: NCT02206490
lead sponsor: 
has dmc: No
Veterans of the 1991 Gulf War who developed Gulf War Illness are being studied. Treatments
      with FDA approved generic drugs are being administered to see if they help with the symptoms
      of Gulf War Illness, such as chronic fatigue; difficulty with memory, concentration, and
      thinking; widespread chronic pain; and autonimic dysfunction. Drugs to be tested are
      dextromethorphan and naltrexone.
Gulf war veterans' illnesses comprise distinct clusters of symptom-defined illnesses for
      which there are neither diagnostic tests nor effective treatments. Gulf war veterans had
      variable exposures to a number of chemicals, including organophosphate insecticides,
      pyrethrum-related insecticides, DEET, Pyridostigmine bromide, smoke from oil well fires, and
      Sarin gas. Gulf war veterans' illnesses may reflect an inflammatory cycle involving the brain
      which may be a common mechanism of many neurological conditions, whether initiated by toxic
      exposures, infection, or trauma. In this theory, central nervous system inflammation
      initiated by toxic exposures and sometimes exacerbated by subsequent exposures is a component
      of illness hypothesized to explain the neurological manifestations. Substance P release at
      sensory nerve endings is an explanation for the peripheral pain manifestations of illness.

      This theory suggests that novel anti-inflammatory drugs may be of benefit in symptom-defined
      illnesses related to a cycle of inflammation. Dr. J. S. Hong's laboratory at the National
      Institute of Environmental Health Sciences has demonstrated that Morphine-related analogs,
      including Naltrexone and Dextromethorphan, have great potency in anti-inflammation and
      neuroprotective effects. Naltrexone is a safe and readily available generic medication.
      Dextromethorphan is also a safe and readily available generic medication that is available
      without a prescription as a cough medication. Results from several clinical trials showed
      that Naltrexone is effective in several inflammation-related diseases, such as neurogenic
      pain, movement disorders, etc. In addition, there were no obvious side effects in patients
      taking this drug for six months. This project will conduct randomized double-blinded studies
      for treating ill Gulf war veterans with Naltrexone and Dextromethorphan. Laboratory tests for
      markers of inflammation including neurogenic inflammation will be performed pre- and
      post-treatment, to see if these markers are elevated and if so, to see if treatment modulates
      these markers.

      Ill Gulf veterans will be recruited through the media, veterans groups, and individual
      veteran activists. A screening telephone interview will be performed to determine if the
      veterans meet a modified Kansas case definition for inclusion. Those veterans who meet study
      criteria will be invited to participate. Eligible veterans will be invited for an initial
      visit that will consist of obtaining written informed consent, a medical history, physical
      examination, and laboratory testing. Institutional review board approval of the study will be
      in place. The pharmacy staff at the institution will prepare the medications and placebo in
      identical capsules.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Symptoms Scores
time frame: 28 weeks approximately
description: Symptoms of Gulf War Illness will be scored by participants using a ten center meter scale.
Scores will be collected at the end of 12 weeks/16 weeks/28weeks
measure: SF-36
time frame: 28 weeks approximately
description: Subjects will complete a standard health assessment tool, the SF-36, at the end of each course of therapy.
Scores will be collected at 12 weeks/16 weeks/28 weeks
measure: Connors Continuous Performance Test
time frame: 28 weeks approximately
description: Subjects will take the Connors Continuous Performance Test at the end of each course of study drug or placebo.
Scores will be collected at 12 weeks/16 weeks/28 weeks
arm group label: Naltrexone Study Drug
arm group type: Active Comparator
description: Subjects will take naltrexone 4.5 mg daily for three months.
arm group label: Naltrexone placebo
arm group type: Placebo Comparator
description: Subjects will take a 3 month course of a placebo pill identical in appearance to the naltrexone study drug.
arm group label: dextromethrophan study drug
arm group type: Active Comparator
description: subjects will take a sustained release dextromethorphan pill twice a day.
arm group label: dextromethoprhan placebo
arm group type: Placebo Comparator
description: Subjects will take a 3 month course of a placebo pill identical in appearance to the dextromethorphan study drug.
intervention type: Drug
intervention name: naltrexone
description: Randomized controlled trial of naltrexone for Gulf War Illness.
arm group label: Naltrexone Study Drug
arm group label: Naltrexone placebo
intervention type: Drug
intervention name: Dextromethorphan
description: Randomized controlled trial of dextromethorphan for Gulf War Illness
arm group label: dextromethoprhan placebo
arm group label: dextromethrophan study drug
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: East Carolina University
investigator full name: William J. Meggs
investigator title: Professor
mesh term: Naltrexone
mesh term: Dextromethorphan