Montelukast for cognitive and mood symptoms in Gulf War veterans

Clinical Evaluation of Montelukast on Cognitive and Mood Dysfunction and Neuroinflammation in Veterans With Gulf War Illness (GWI)

This trial tests whether montelukast, an FDA-approved asthma medicine, can improve thinking, mood, and daily function in veterans with Gulf War Illness.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 50 Years to 70 Years
• Sex: All
• Sponsor: Baylor College of Medicine (other)
• Drugs / interventions: radiation
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT05992311 on ClinicalTrials.gov

What this trial studies

This Phase 1 interventional trial gives veterans with Gulf War Illness either montelukast or a matching placebo and measures cognitive performance, mood, and functional status using validated tests and self-reported measures. The study also measures brain-specific leukotrienes in neuron- and astrocyte-derived extracellular vesicles from peripheral blood as a biomarker of neuroinflammation. Participants attend two in-person visits at the Michael E. DeBakey VA Medical Center in Houston for clinical, cognitive, and blood biomarker assessments. Safety and tolerability are monitored given montelukast’s established clinical use.

Who should consider this trial

Good fit: U.S. veterans deployed to the Persian Gulf between Aug 2, 1990 and Dec 31, 1991 who meet CDC/modified Kansas criteria for GWI, report cognitive difficulties (PROMIS T-score ≤40), can communicate in English, and can attend two in-person visits in Houston.

Not a fit: Patients whose symptoms are not driven by neuroinflammation, who do not meet the GWI diagnostic criteria, who cannot travel to the study site, or who have contraindications to montelukast are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, montelukast could reduce neuroinflammation and improve cognition, mood, and daily functioning for veterans with GWI.

How similar studies have performed: Animal models have shown montelukast can improve cognition and mood via reduced leukotriene signaling, but human data in GWI are limited and this application is relatively novel.

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:

  1. fatigue/sleep disturbances
  2. neurological/cognitive/mood symptoms
  3. somatic pain
  4. gastrointestinal problems
  5. respiratory symptoms
  6. 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

Where this trial is running

Houston, Texas

• Michael E. DeBakey VA Medical Center — Houston, Texas, United States (RECRUITING)

Study contacts

• Principal investigator: Drew A Helmer, MD — Baylor College of Medicine
• Study coordinator: Jason K Aguilar, BA

Conditions: Gulf War Syndrome, Montelukast