Gulf War SyndromePhase 1(GWI)NCT05992311
Clinical Evaluation of Montelukast in Veterans With Gulf War Illness
A Phase 1 study testing Montelukast in people with Gulf War Syndrome, run by Baylor College of Medicine at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 50 to 70 years
- Conditions the study is for
- Gulf War Syndrome
- What is being tested?
- Montelukast
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Aug 2025to Aug 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 13Show fewer
- 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
Who cannot join
- 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
Show all 30Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Michael E. DeBakey VA Medical Center
Houston, Texas, 77030
Kandice Motley, BS, 713-440-4445, Kandice.Motley@va.gov
About this study
Official title: Clinical Evaluation of Montelukast on Cognitive and Mood Dysfunction and Neuroinflammation in Veterans With Gulf War Illness (GWI)
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.
Read the 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.
- Conditions
- Gulf War Syndrome
- Being tested
- Montelukast, Placebo
- Keywords
- Montelukast
- Medical subject headings
- Persian Gulf Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MontelukastDrug
Also called Singulair
This group will receive the montelukast treatment.
PlaceboOther
This group will receive a placebo pill instead of montelukast
| Study group | Role | What they receive |
|---|---|---|
| Montelukast Group | Experimental | Montelukast two capsules of 20 mg (40 mg total) taken by mouth once daily for ten weeks Receives: Drug: Montelukast |
| Placebo Group | Placebo comparator | Microcrystalline cellulose two capsules taken by mouth once daily for ten weeks Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Leukotriene concentration
Concentrations in the brain-derived extracellular vesicles collected from the circulating peripheral blood.
Measured: taken at baseline (week 0) and after the intervention (week 10)
Secondary outcomes (2)
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.
Measured: taken at baseline (week 0) and after the intervention (week 10)
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.
Measured: taken at baseline (week 0) and after the intervention (week 10)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2023
- Study start15 Aug 2025
- Primary completionApr 2028 (estimated)
- Study completionAug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gulf War SyndromeStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Double blind, placebo-controlled, randomized clinical trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Michael E. DeBakey VA Medical Center, Texas A&M University
- Responsible party
- Principal investigator, Drew Helmer, Baylor College of Medicine
- Investigators
- Drew A Helmer, MD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05992311
- Sponsor's protocol ID
- H-51973
- Other IDs
- CDMRP-GW210062
- Acronym
- (GWI)
- Status last verified
- Aug 2026
- First submitted
- 28 Jul 2023
- Last updated
- 1 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Evaluation of Montelukast on Cognitive and Mood Dysfunction and Neuroinflammation in Veterans With Gulf War Illness (GWI)
- ClinicalTrials.gov ID
- NCT05992311
- Acronym / sponsor ID
- (GWI) / H-51973
- Conditions
- Gulf War Syndrome
- Keywords
- Montelukast
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Collaborators
- Michael E. DeBakey VA Medical Center, Texas A&M University
- Study start
- 15 Aug 2025 (actual)
- Primary completion
- Apr 2028 (estimated)
- Study completion
- Aug 2028 (estimated)
- First posted
- 15 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Double blind, placebo-controlled, randomized clinical trial
| Arm | Type | Receives |
|---|---|---|
| Montelukast Group | Experimental | Drug: MontelukastMontelukast two capsules of 20 mg (40 mg total) taken by mouth once daily for ten weeks |
| Placebo Group | Placebo comparator | Other: PlaceboMicrocrystalline cellulose two capsules taken by mouth once daily for ten weeks |
Who may qualify
- Ages
- 50 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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:
- 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:
Key exclusion criteria (30 listed)
- Diagnosed by a physician with any chronic condition that may explain their profile of symptoms or prevent their ability to accurately report them including:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MontelukastAlso: SingulairThis group will receive the montelukast treatment. | Drug | Montelukast Group |
| PlaceboThis group will receive a placebo pill instead of montelukast | Other | Placebo Group |
Primary outcome
Leukotriene concentration
Time frame: taken at baseline (week 0) and after the intervention (week 10)
Concentrations in the brain-derived extracellular vesicles collected from the circulating peripheral blood.
2 secondary outcomes
Change in RCAT (Halstead Category Test-Russell Revised Version)
Time frame: taken at baseline (week 0) and after the intervention (week 10)
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)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2026.
- Individual participant dataSharing planned: No
Related trials for Gulf War Syndrome
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Pycnogenol (French Maritime Pine Bark) for the Treatment of Gulf War Illness
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Growth Hormone Replacement in Veterans With GWI and AGHD (GWIT)
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Resistant Potato Starch to Alleviate GWI
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Coenzyme Q10 for Gulf War Illness: A Replication Study
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Drew A Helmer, MD principal investigator
Baylor College of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Montelukast in people with Gulf War Syndrome, run by Baylor College of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 1 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jason K Aguilar, BA (713-440-4633, jason.aguilar@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Leukotriene concentration (time frame: taken at baseline (week 0) and after the intervention (week 10)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2026.