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/NCT05992311</url>
    </required_header>
    <id_info>
      <org_study_id>H-51973</org_study_id>
      <nct_id>NCT05992311</nct_id>
    </id_info>
    <brief_title>Clinical Evaluation of Montelukast in Veterans With Gulf War Illness</brief_title>
    <acronym>(GWI)</acronym>
    <official_title>Clinical Evaluation of Montelukast on Cognitive and Mood Dysfunction and Neuroinflammation in Veterans With Gulf War Illness (GWI)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Baylor College of Medicine</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Michael E. DeBakey VA Medical Center</agency>
        <agency_class>U.S. Fed</agency_class>
      </collaborator>
      <collaborator>
        <agency>Texas A&amp;M University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Baylor College of Medicine</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>Yes</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        The study addresses the pre-clinical promise of Montelukast (MLK) for improving brain&#xD;
        function in veterans with Gulf War Illness (GWI). MLK, a US Food and Drug administration&#xD;
        (FDA)-approved drug for asthma, has shown efficacy in an animal model of GWI to improve&#xD;
        cognitive and mood function through modulation of leukotriene signaling and suppression of&#xD;
        neuroinflammation.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Background: Approximately 30% of Gulf War Veterans (1990-1991) suffer from Gulf War Illness&#xD;
        (GWI), a chronic condition characterized by disabling symptoms in multiple domains. Animal&#xD;
        models and human data suggest a prominent neuroinflammatory basis for many of the symptoms of&#xD;
        GWI. Preliminary data from an established GWI rat model demonstrates the involvement of&#xD;
        increased leukotriene signaling in the brain and its potential as a marker of&#xD;
        neuroinflammation when detected in neuron- and astrocyte-derived extracellular vesicles&#xD;
        present in the peripheral blood. MLK, an FDA-approved drug for asthma, has shown efficacy in&#xD;
        an animal model of GWI to improve cognitive and mood function through modulation of&#xD;
        leukotriene signaling and suppression of neuroinflammation. MLK has a strong safety record&#xD;
        and has been recognized for its potential as a modulator of neurodegeneration in human&#xD;
        disease and is, therefore, a promising intervention for GWI.&#xD;
  &#xD;
        Hypothesis/Objective: Examine the impact of MLK on cognition, quality of life, and symptoms&#xD;
        of depression and anxiety in Veterans with GWI and test for changes in brain-specific&#xD;
        leukotrienes (markers of neuroinflammation) detectable in the extracellular vesicles&#xD;
        circulating in the peripheral blood.&#xD;
  &#xD;
        Specific Aim 1: To evaluate the effect of MLK on cognitive function, functional status and&#xD;
        mood in veterans with GWI using validated neurocognitive and self-reported measures&#xD;
        consistent with the GWI Common Data Elements.&#xD;
  &#xD;
        Specific Aim 2: To examine the antiinflammatory effects of MLK on the brain. The&#xD;
        investigators will evaluate neuron-derived extracellular vesicles and astrocyte-derived&#xD;
        extracellular vesicles in blood samples from Veterans with GWI receiving MLK or placebo&#xD;
        treatment.&#xD;
  &#xD;
        Study Design: 1:1 randomized, double-blind, placebo controlled trial of 80 Veterans who meet&#xD;
        both the Kansas and Center for Disease Control (CDC) definition of GWI and report cognitive&#xD;
        dysfunction treated with either: 1) two capsules of 20 mg of MLK or 2) two capsules of&#xD;
        matched placebo taken daily for 10 weeks. Participants will be recruited to participate at&#xD;
        Michael E. DeBakey VA Medical Center (MEDVAMC) in Houston, TX, using best practices including&#xD;
        Veteran community outreach and engagement, active recruitment from local and national VA&#xD;
        databases, and a strong social media presence. Participants will be screened for eligibility&#xD;
        by phone and attend only two in-person evaluations (self-reported instruments, blood draw,&#xD;
        and neuropsychology tests) with regular phone contact throughout study enrollment. Blood&#xD;
        specimens will be obtained, and plasma processed at MEDVAMC, and shipped to Texas A&amp;M&#xD;
        University College of Medicine (TAMU-COM) for specialized assays. Data will be maintained,&#xD;
        managed and analyzed by the MEDVAMC team in collaboration with the TAMU team.&#xD;
  &#xD;
        Impact: The findings from the proposed research will advance the understanding of the&#xD;
        pathophysiology, validate the use of extracellular vesicle assays as a biomarker of central&#xD;
        nervous system inflammation, and advance a potential treatment (i.e., MLK) for a specific&#xD;
        putative underlying mechanism of GWI. The short-term impact will be an important validation&#xD;
        of the theory of neuroinflammation as central pathophysiology of GWI through the tested&#xD;
        hypotheses. The longer-term impact of the proposed work includes a relatively short timeline&#xD;
        to the use of MLK as a specific treatment for GWI. Because MLK is already FDA approved and&#xD;
        safe, if findings from this project support the safety, tolerability, and efficacy of MLK in&#xD;
        Veterans with GWI, a definitive randomized controlled trial confirming its efficacy would be&#xD;
        warranted.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">September 2027</completion_date>
    <primary_completion_date type="Anticipated">September 2026</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_model_description>Double blind, placebo-controlled, randomized clinical trial</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
      <masking_description>Study group assignment will be determined by the research pharmacist using a random number generator within blocks of four participants. Participant group assignment will be disclosed only at time of data analysis or in case of emergency.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Leukotriene concentration</measure>
      <time_frame>taken at baseline (week 0) and after the intervention (week 10)</time_frame>
      <description>Concentrations in the brain-derived extracellular vesicles collected from the circulating peripheral blood.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change in RCAT (Halstead Category Test-Russell Revised Version)</measure>
      <time_frame>taken at baseline (week 0) and after the intervention (week 10)</time_frame>
      <description>cognitive function</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Veterans Rand-36 Physical Component Summary (VR-36 PCS) score</measure>
      <time_frame>taken at baseline (week 0) and after the intervention (week 10)</time_frame>
      <description>health-related quality of life</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">80</enrollment>
    <condition>Gulf War Syndrome</condition>
    <arm_group>
      <arm_group_label>Montelukast Group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Montelukast two capsules of 20 mg (40 mg total) taken by mouth once daily for ten weeks</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo Group</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Microcrystalline cellulose two capsules taken by mouth once daily for ten weeks</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Montelukast</intervention_name>
      <description>This group will receive the montelukast treatment.</description>
      <arm_group_label>Montelukast Group</arm_group_label>
      <other_name>Singulair</other_name>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>This group will receive a placebo pill instead of montelukast</description>
      <arm_group_label>Placebo Group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Gulf War Veterans of the U.S. military deployed on military orders to the Persian Gulf&#xD;
               Region between August 2, 1990, and December 31, 1991&#xD;
  &#xD;
            -  Diagnosed with GWI according to the CDC and modified Kansas criteria as recommended by&#xD;
               the Institute of Medicine (IOM), that is, endorse multiple or moderate-to-severe&#xD;
               symptoms, with symptom onset during or after deployment to the Persian Gulf region in&#xD;
               1990-1991, persisting for six months or longer, in at least 3 of 6 domains:&#xD;
  &#xD;
                 1. fatigue/sleep disturbances&#xD;
  &#xD;
                 2. neurological/cognitive/mood symptoms&#xD;
  &#xD;
                 3. somatic pain&#xD;
  &#xD;
                 4. gastrointestinal problems&#xD;
  &#xD;
                 5. respiratory symptoms&#xD;
  &#xD;
                 6. skin symptoms&#xD;
  &#xD;
            -  Self-reported cognitive dysfunction based on a T-score of 40 or less on the PROMIS&#xD;
               v2.0 Cognitive Function 8a short form&#xD;
  &#xD;
            -  Be able to:&#xD;
  &#xD;
                 -  provide written consent and be able to communicate with the research team in&#xD;
                    verbal and written English&#xD;
  &#xD;
                 -  attend the two in-person study encounters&#xD;
  &#xD;
                 -  have reliable telephone service for the eight weekly telephone encounters&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Diagnosed by a physician with any chronic condition that may explain their profile of&#xD;
               symptoms or prevent their ability to accurately report them including:&#xD;
  &#xD;
                 -  chronic autoimmune conditions&#xD;
  &#xD;
                 -  systemic inflammatory conditions&#xD;
  &#xD;
                 -  cancer not in remission at least 5 years&#xD;
  &#xD;
                 -  congestive heart failure&#xD;
  &#xD;
                 -  anemia&#xD;
  &#xD;
                 -  multiple sclerosis&#xD;
  &#xD;
                 -  amyotrophic lateral sclerosis (ALS)&#xD;
  &#xD;
                 -  poorly controlled diabetes&#xD;
  &#xD;
                 -  post-chemo or radiation syndromes&#xD;
  &#xD;
                 -  sickle cell anemia&#xD;
  &#xD;
                 -  symptomatic Coronary Artery Disease (CAD)&#xD;
  &#xD;
                 -  chronic liver disease&#xD;
  &#xD;
                 -  chemical insufficiency&#xD;
  &#xD;
                 -  morbid obesity (body mass index (BMI) &gt;= 40)&#xD;
  &#xD;
                 -  human immunodeficiency virus (HIV)&#xD;
  &#xD;
                 -  alcohol/substance use disorder/stimulant/opioid/other depressant misuse in the&#xD;
                    past year&#xD;
  &#xD;
                 -  major mental health condition (e.g., psychosis, suicidal ideations, major&#xD;
                    depressive disorder) that interferes with their ability to accurately report&#xD;
                    symptoms&#xD;
  &#xD;
                 -  hospitalized or undergoing invasive procedures in the past 12 months due to&#xD;
                    exacerbations of any chronic conditions (such as diabetes, coronary artery&#xD;
                    disease, hypertension, or emphysema)&#xD;
  &#xD;
                 -  elevated liver enzymes (2.5 times upper limit of normal) at baseline visit&#xD;
  &#xD;
                 -  estimated glomerular filtration rate less than 60 ml/min/1.73 sqm at baseline&#xD;
                    visit&#xD;
  &#xD;
                 -  hemoglobin less than 10 g/L at baseline visit&#xD;
  &#xD;
                 -  evidence of poorly controlled chronic conditions listed above, or others that may&#xD;
                    mimic GWI as per the PI, either by self-report, Veterans Health Administration&#xD;
                    (VHA) electronic health record information review, laboratory testing or physical&#xD;
                    examination&#xD;
  &#xD;
            -  Changes in medications for chronic conditions in the 3 months preceding enrollment&#xD;
               (based on self-report)&#xD;
  &#xD;
            -  Suicidal ideation based on their responses on the Columbia Suicide Risk Inventory&#xD;
  &#xD;
            -  Prescribed or taking Montelukast in the past 6 months for any reason&#xD;
  &#xD;
            -  Taking 2 or more medications with moderate interactions with Montelukast&#xD;
  &#xD;
            -  Pregnancy or intention to become pregnant&#xD;
  &#xD;
            -  Active homicidal ideation&#xD;
  &#xD;
            -  COVID-19 illness (confirmed or suspected) without recovery to pre-COVID health status&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>50 Years</minimum_age>
      <maximum_age>70 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Drew A Helmer, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Baylor College of Medicine</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Jason K Aguilar, BA</last_name>
      <phone>7134404633</phone>
      <email>jason.aguilar@va.gov</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Carl J Berghult, BS</last_name>
      <phone>(713) 794-8601</phone>
      <phone_ext>10335</phone_ext>
      <email>carl.berghult@bcm.edu</email>
    </overall_contact_backup>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 28, 2023</study_first_submitted>
    <study_first_submitted_qc>August 7, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 15, 2023</study_first_posted>
    <last_update_submitted>August 7, 2023</last_update_submitted>
    <last_update_submitted_qc>August 7, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Baylor College of Medicine</investigator_affiliation>
      <investigator_full_name>Drew Helmer</investigator_full_name>
      <investigator_title>Professor</investigator_title>
    </responsible_party>
    <keyword>Montelukast</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Persian Gulf Syndrome</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Montelukast</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- 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/NCT05992311
  org study id: H-51973
  nct id: NCT05992311
  lead sponsor: 
  collaborator: 
  collaborator: 
  has dmc: No
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: Yes
  The study addresses the pre-clinical promise of Montelukast (MLK) for improving brain
        function in veterans with Gulf War Illness (GWI). MLK, a US Food and Drug administration
        (FDA)-approved drug for asthma, has shown efficacy in an animal model of GWI to improve
        cognitive and mood function through modulation of leukotriene signaling and suppression of
        neuroinflammation.
  Background: Approximately 30% of Gulf War Veterans (1990-1991) suffer from Gulf War Illness
        (GWI), a chronic condition characterized by disabling symptoms in multiple domains. Animal
        models and human data suggest a prominent neuroinflammatory basis for many of the symptoms of
        GWI. Preliminary data from an established GWI rat model demonstrates the involvement of
        increased leukotriene signaling in the brain and its potential as a marker of
        neuroinflammation when detected in neuron- and astrocyte-derived extracellular vesicles
        present in the peripheral blood. MLK, an FDA-approved drug for asthma, has shown efficacy in
        an animal model of GWI to improve cognitive and mood function through modulation of
        leukotriene signaling and suppression of neuroinflammation. MLK has a strong safety record
        and has been recognized for its potential as a modulator of neurodegeneration in human
        disease and is, therefore, a promising intervention for GWI.
  
        Hypothesis/Objective: Examine the impact of MLK on cognition, quality of life, and symptoms
        of depression and anxiety in Veterans with GWI and test for changes in brain-specific
        leukotrienes (markers of neuroinflammation) detectable in the extracellular vesicles
        circulating in the peripheral blood.
  
        Specific Aim 1: To evaluate the effect of MLK on cognitive function, functional status and
        mood in veterans with GWI using validated neurocognitive and self-reported measures
        consistent with the GWI Common Data Elements.
  
        Specific Aim 2: To examine the antiinflammatory effects of MLK on the brain. The
        investigators will evaluate neuron-derived extracellular vesicles and astrocyte-derived
        extracellular vesicles in blood samples from Veterans with GWI receiving MLK or placebo
        treatment.
  
        Study Design: 1:1 randomized, double-blind, placebo controlled trial of 80 Veterans who meet
        both the Kansas and Center for Disease Control (CDC) definition of GWI and report cognitive
        dysfunction treated with either: 1) two capsules of 20 mg of MLK or 2) two capsules of
        matched placebo taken daily for 10 weeks. Participants will be recruited to participate at
        Michael E. DeBakey VA Medical Center (MEDVAMC) in Houston, TX, using best practices including
        Veteran community outreach and engagement, active recruitment from local and national VA
        databases, and a strong social media presence. Participants will be screened for eligibility
        by phone and attend only two in-person evaluations (self-reported instruments, blood draw,
        and neuropsychology tests) with regular phone contact throughout study enrollment. Blood
        specimens will be obtained, and plasma processed at MEDVAMC, and shipped to Texas A&M
        University College of Medicine (TAMU-COM) for specialized assays. Data will be maintained,
        managed and analyzed by the MEDVAMC team in collaboration with the TAMU team.
  
        Impact: The findings from the proposed research will advance the understanding of the
        pathophysiology, validate the use of extracellular vesicle assays as a biomarker of central
        nervous system inflammation, and advance a potential treatment (i.e., MLK) for a specific
        putative underlying mechanism of GWI. The short-term impact will be an important validation
        of the theory of neuroinflammation as central pathophysiology of GWI through the tested
        hypotheses. The longer-term impact of the proposed work includes a relatively short timeline
        to the use of MLK as a specific treatment for GWI. Because MLK is already FDA approved and
        safe, if findings from this project support the safety, tolerability, and efficacy of MLK in
        Veterans with GWI, a definitive randomized controlled trial confirming its efficacy would be
        warranted.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Double blind, placebo-controlled, randomized clinical trial
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  masking description: Study group assignment will be determined by the research pharmacist using a random number generator within blocks of four participants. Participant group assignment will be disclosed only at time of data analysis or in case of emergency.
  measure: Leukotriene concentration
  time frame: taken at baseline (week 0) and after the intervention (week 10)
  description: Concentrations in the brain-derived extracellular vesicles collected from the circulating peripheral blood.
  measure: Change in RCAT (Halstead Category Test-Russell Revised Version)
  time frame: taken at baseline (week 0) and after the intervention (week 10)
  description: cognitive function
  measure: Change in Veterans Rand-36 Physical Component Summary (VR-36 PCS) score
  time frame: taken at baseline (week 0) and after the intervention (week 10)
  description: health-related quality of life
  arm group label: Montelukast Group
  arm group type: Experimental
  description: Montelukast two capsules of 20 mg (40 mg total) taken by mouth once daily for ten weeks
  arm group label: Placebo Group
  arm group type: Placebo Comparator
  description: Microcrystalline cellulose two capsules taken by mouth once daily for ten weeks
  intervention type: Drug
  intervention name: Montelukast
  description: This group will receive the montelukast treatment.
  arm group label: Montelukast Group
  other name: Singulair
  intervention type: Other
  intervention name: Placebo
  description: This group will receive a placebo pill instead of montelukast
  arm group label: Placebo Group
  criteria: 
  gender: All
  minimum age: 50 Years
  maximum age: 70 Years
  healthy volunteers: No
  last name: Drew A Helmer, MD
  role: Principal Investigator
  affiliation: Baylor College of Medicine
  last name: Jason K Aguilar, BA
  phone: 7134404633
  email: jason.aguilar@va.gov
  last name: Carl J Berghult, BS
  phone: (713) 794-8601
  phone ext: 10335
  email: carl.berghult@bcm.edu
  responsible party type: Principal Investigator
  investigator affiliation: Baylor College of Medicine
  investigator full name: Drew Helmer
  investigator title: Professor
  mesh term: Persian Gulf Syndrome
  mesh term: Montelukast
  sharing ipd: No