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Clinical Evaluation of Montelukast in Veterans With Gulf War Illness ((GWI))

Primary Purpose

Gulf War Syndrome

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Montelukast
Placebo
Sponsored by
Baylor College of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gulf War Syndrome focused on measuring Montelukast

Eligibility Criteria

50 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Gulf War Veterans of the U.S. military deployed on military orders to the Persian Gulf Region between August 2, 1990, and December 31, 1991 Diagnosed with GWI according to the CDC and modified Kansas criteria as recommended by the Institute of Medicine (IOM), that is, endorse multiple or moderate-to-severe symptoms, with symptom onset during or after deployment to the Persian Gulf region in 1990-1991, persisting for six months or longer, in at least 3 of 6 domains: fatigue/sleep disturbances neurological/cognitive/mood symptoms somatic pain gastrointestinal problems respiratory symptoms skin symptoms Self-reported cognitive dysfunction based on a T-score of 40 or less on the PROMIS v2.0 Cognitive Function 8a short form Be able to: provide written consent and be able to communicate with the research team in verbal and written English attend the two in-person study encounters have reliable telephone service for the eight weekly telephone encounters Exclusion Criteria: Diagnosed by a physician with any chronic condition that may explain their profile of symptoms or prevent their ability to accurately report them including: chronic autoimmune conditions systemic inflammatory conditions cancer not in remission at least 5 years congestive heart failure anemia multiple sclerosis amyotrophic lateral sclerosis (ALS) poorly controlled diabetes post-chemo or radiation syndromes sickle cell anemia symptomatic Coronary Artery Disease (CAD) chronic liver disease chemical insufficiency morbid obesity (body mass index (BMI) >= 40) human immunodeficiency virus (HIV) alcohol/substance use disorder/stimulant/opioid/other depressant misuse in the past year major mental health condition (e.g., psychosis, suicidal ideations, major depressive disorder) that interferes with their ability to accurately report symptoms hospitalized or undergoing invasive procedures in the past 12 months due to exacerbations of any chronic conditions (such as diabetes, coronary artery disease, hypertension, or emphysema) elevated liver enzymes (2.5 times upper limit of normal) at baseline visit estimated glomerular filtration rate less than 60 ml/min/1.73 sqm at baseline visit hemoglobin less than 10 g/L at baseline visit evidence of poorly controlled chronic conditions listed above, or others that may mimic GWI as per the PI, either by self-report, Veterans Health Administration (VHA) electronic health record information review, laboratory testing or physical examination Changes in medications for chronic conditions in the 3 months preceding enrollment (based on self-report) Suicidal ideation based on their responses on the Columbia Suicide Risk Inventory Prescribed or taking Montelukast in the past 6 months for any reason Taking 2 or more medications with moderate interactions with Montelukast Pregnancy or intention to become pregnant Active homicidal ideation COVID-19 illness (confirmed or suspected) without recovery to pre-COVID health status

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Montelukast Group

    Placebo Group

    Arm Description

    Montelukast two capsules of 20 mg (40 mg total) taken by mouth once daily for ten weeks

    Microcrystalline cellulose two capsules taken by mouth once daily for ten weeks

    Outcomes

    Primary Outcome Measures

    Leukotriene concentration
    Concentrations in the brain-derived extracellular vesicles collected from the circulating peripheral blood.

    Secondary Outcome Measures

    Change in RCAT (Halstead Category Test-Russell Revised Version)
    Instrument designed to measure cognitive function. Scores are reported as T-scores while participant's age, gender, ethnicity, and level of education are controlled. A higher T-score correlates to better executive functioning.
    Change in Veterans Rand-36 Physical Component Summary (VR-36 PCS) score
    Scores reflect physical health-related quality of life. The scores are reported on a scale 0-100 with 0 being the worst possible score and 100 being the best possible score. The mean score of the US population is 50.

    Full Information

    First Posted
    July 28, 2023
    Last Updated
    October 3, 2023
    Sponsor
    Baylor College of Medicine
    Collaborators
    Michael E. DeBakey VA Medical Center, Texas A&M University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05992311
    Brief Title
    Clinical Evaluation of Montelukast in Veterans With Gulf War Illness
    Acronym
    (GWI)
    Official Title
    Clinical Evaluation of Montelukast on Cognitive and Mood Dysfunction and Neuroinflammation in Veterans With Gulf War Illness (GWI)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 2023 (Anticipated)
    Primary Completion Date
    September 2026 (Anticipated)
    Study Completion Date
    September 2027 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Baylor College of Medicine
    Collaborators
    Michael E. DeBakey VA Medical Center, Texas A&M University

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    Yes
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    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.
    Detailed Description
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Gulf War Syndrome
    Keywords
    Montelukast

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Parallel Assignment
    Model Description
    Double blind, placebo-controlled, randomized clinical trial
    Masking
    ParticipantCare ProviderInvestigatorOutcomes 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.
    Allocation
    Randomized
    Enrollment
    80 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Montelukast Group
    Arm Type
    Experimental
    Arm Description
    Montelukast two capsules of 20 mg (40 mg total) taken by mouth once daily for ten weeks
    Arm Title
    Placebo Group
    Arm Type
    Placebo Comparator
    Arm Description
    Microcrystalline cellulose two capsules taken by mouth once daily for ten weeks
    Intervention Type
    Drug
    Intervention Name(s)
    Montelukast
    Other Intervention Name(s)
    Singulair
    Intervention Description
    This group will receive the montelukast treatment.
    Intervention Type
    Other
    Intervention Name(s)
    Placebo
    Intervention Description
    This group will receive a placebo pill instead of montelukast
    Primary Outcome Measure Information:
    Title
    Leukotriene concentration
    Description
    Concentrations in the brain-derived extracellular vesicles collected from the circulating peripheral blood.
    Time Frame
    taken at baseline (week 0) and after the intervention (week 10)
    Secondary Outcome Measure Information:
    Title
    Change in RCAT (Halstead Category Test-Russell Revised Version)
    Description
    Instrument designed to measure cognitive function. Scores are reported as T-scores while participant's age, gender, ethnicity, and level of education are controlled. A higher T-score correlates to better executive functioning.
    Time Frame
    taken at baseline (week 0) and after the intervention (week 10)
    Title
    Change in Veterans Rand-36 Physical Component Summary (VR-36 PCS) score
    Description
    Scores reflect physical health-related quality of life. The scores are reported on a scale 0-100 with 0 being the worst possible score and 100 being the best possible score. The mean score of the US population is 50.
    Time Frame
    taken at baseline (week 0) and after the intervention (week 10)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    50 Years
    Maximum Age & Unit of Time
    70 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Gulf War Veterans of the U.S. military deployed on military orders to the Persian Gulf Region between August 2, 1990, and December 31, 1991 Diagnosed with GWI according to the CDC and modified Kansas criteria as recommended by the Institute of Medicine (IOM), that is, endorse multiple or moderate-to-severe symptoms, with symptom onset during or after deployment to the Persian Gulf region in 1990-1991, persisting for six months or longer, in at least 3 of 6 domains: fatigue/sleep disturbances neurological/cognitive/mood symptoms somatic pain gastrointestinal problems respiratory symptoms skin symptoms Self-reported cognitive dysfunction based on a T-score of 40 or less on the PROMIS v2.0 Cognitive Function 8a short form Be able to: provide written consent and be able to communicate with the research team in verbal and written English attend the two in-person study encounters have reliable telephone service for the eight weekly telephone encounters Exclusion Criteria: Diagnosed by a physician with any chronic condition that may explain their profile of symptoms or prevent their ability to accurately report them including: chronic autoimmune conditions systemic inflammatory conditions cancer not in remission at least 5 years congestive heart failure anemia multiple sclerosis amyotrophic lateral sclerosis (ALS) poorly controlled diabetes post-chemo or radiation syndromes sickle cell anemia symptomatic Coronary Artery Disease (CAD) chronic liver disease chemical insufficiency morbid obesity (body mass index (BMI) >= 40) human immunodeficiency virus (HIV) alcohol/substance use disorder/stimulant/opioid/other depressant misuse in the past year major mental health condition (e.g., psychosis, suicidal ideations, major depressive disorder) that interferes with their ability to accurately report symptoms hospitalized or undergoing invasive procedures in the past 12 months due to exacerbations of any chronic conditions (such as diabetes, coronary artery disease, hypertension, or emphysema) elevated liver enzymes (2.5 times upper limit of normal) at baseline visit estimated glomerular filtration rate less than 60 ml/min/1.73 sqm at baseline visit hemoglobin less than 10 g/L at baseline visit evidence of poorly controlled chronic conditions listed above, or others that may mimic GWI as per the PI, either by self-report, Veterans Health Administration (VHA) electronic health record information review, laboratory testing or physical examination Changes in medications for chronic conditions in the 3 months preceding enrollment (based on self-report) Suicidal ideation based on their responses on the Columbia Suicide Risk Inventory Prescribed or taking Montelukast in the past 6 months for any reason Taking 2 or more medications with moderate interactions with Montelukast Pregnancy or intention to become pregnant Active homicidal ideation COVID-19 illness (confirmed or suspected) without recovery to pre-COVID health status
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Jason K Aguilar, BA
    Phone
    7134404633
    Email
    jason.aguilar@va.gov
    First Name & Middle Initial & Last Name or Official Title & Degree
    Carl J Berghult, BS
    Phone
    (713) 794-8601
    Ext
    10335
    Email
    carl.berghult@bcm.edu
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Drew A Helmer, MD
    Organizational Affiliation
    Baylor College of Medicine
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

    Clinical Evaluation of Montelukast in Veterans With Gulf War Illness

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