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

H-51973

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.

2024-04-01

2027-01-01

2028-01-01

Not yet recruiting

Early phase I

80

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

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2024-03-18