Clinical Evaluation of Montelukast on Cognitive and Mood Dysfunction and Neuroinflammation in Veterans with Gulf War Illness (GWI)
Abstract
Overarching Challenge: Our research seeks to learn more about Gulf War Illness (GWI) and find better treatments – revolutionize treatment as stated in the Gulf War Illness Research Program strategic challenges. In this study, we plan to test whether montelukast, a commonly used asthma drug, can improve mood and cognitive ability in Veterans suffering from GWI. Objective and Rationale: Almost 30% of Gulf War Veterans (1990–1991) suffer from GWI. The disease is thought to be caused by an excessive and misdirected attack by the immune system on the brain. This is called brain inflammation. Leukotrienes are an important type of chemical made during inflammation, and researchers can use the levels of certain types of leukotrienes to see when and where inflammation is happening in the body. For this project, we look for specific leukotrienes in extracellular vesicles that the brain cells shed into the bloodstream. Taking blood samples from the arm allows us to perform a liquid brain biopsy to detect and measure the leukotrienes from the brain to gauge the extent of brain inflammation. Montelukast, a drug commonly prescribed to patients with asthma, works by decreasing the harmful effects of leukotrienes in the lungs, thereby reducing inflammation. The research team has demonstrated that montelukast crosses into the brain in an animal model of GWI and reduces the negative effects of leukotrienes in the brains of these animals and actually improves their ability to perform on certain brain function tasks. Montelukast has been shown to be safe for many years and is readily available in the United States. We plan to test whether montelukast can improve thinking, mood, and quality of life in Veterans with GWI in this study. We will enroll 60 Veterans with GWI and assign them using a process like a coin flip to either receive montelukast capsules or a matching placebo (sugar pill) for 10 weeks. Veterans will be evaluated at baseline and at 10 weeks with self-reported surveys, tests of thinking ability, and blood draws. They will be contacted by telephone every 2 weeks in between to assess for side effects and ability to take the capsules. We will analyze the data to look for differences between the two groups in brain inflammation, symptoms, quality of life, and thinking ability. Applicability: Findings from the study will help us learn more about the underlying mechanisms of GWI. What isn’t working properly? We will test whether leukotrienes are really contributing to brain inflammation in Veterans with GWI. Second, we will improve our ability to detect brain inflammation with the liquid brain biopsy approach using the markers in the blood. Third, we will have preliminary data informing the potential for montelukast as a treatment for Veterans with GWI. The risk to subjects in this study is low; montelukast is a commonly used medication with a very safe profile of effects. This trial will take place over 10 weeks and provide important validation to our first and second goals during that time. If the study subjects respond well to the treatment, we plan to follow up this trial with a larger randomized controlled trial to confirm montelukast’s benefit.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210413
Entities
People
- Drew Helmer
Organizations
- Michael E. DeBakey VA Medical Center
- United States Army