Montelukast for Gulf War Syndrome

((GWI) Trial)

Overseen By Kandice Motley, BS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Baylor College of Medicine

Must not be taking: Montelukast, Moderate interactions

Disqualifiers: Chronic autoimmune, Cancer, Diabetes, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 10 weeks

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Montelukast, a drug typically used for asthma, to determine if it can enhance brain function in veterans with Gulf War Illness (GWI). GWI includes symptoms such as fatigue, mood issues, and cognitive problems. Participants will take either Montelukast or a placebo (a pill with no active drug) daily for ten weeks. Veterans who served in the Gulf War and have experienced GWI symptoms in at least three areas, such as sleep disturbances or mood symptoms, for six months or more, might be suitable for this trial. As a Phase 1 trial, this research aims to understand how Montelukast works in people, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot participate if you've changed medications for chronic conditions in the past 3 months or if you're taking 2 or more medications that interact with Montelukast.

Is there any evidence suggesting that Montelukast is likely to be safe for humans?

Research has shown that the FDA has approved Montelukast for treating asthma, indicating it has been tested for safety in people with that condition. For asthma patients, Montelukast is usually well-tolerated. However, a warning exists about possible mental health side effects, such as mood changes or depression.

Montelukast has also shown promise in animal studies for improving brain function in Gulf War Illness. In these studies, it improved mood and thinking problems. However, it is important to remember that these results are from animals, not humans.

Since this is a Phase 1 study, the main goal is to assess the safety of Montelukast for Gulf War Illness. Researchers aim to determine how well people with this condition tolerate Montelukast. They will closely monitor for any side effects. Montelukast's past use in asthma provides some confidence in its safety, but it is crucial to see how it works specifically for Gulf War Illness. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Gulf War Syndrome?

Most treatments for Gulf War Syndrome focus on alleviating symptoms with therapies like cognitive behavioral therapy, antidepressants, or pain medications. Montelukast is unique because it targets inflammation by blocking leukotrienes, which are chemicals in the body that can trigger inflammation and allergic reactions. This approach is different because it addresses a potential underlying cause of symptoms rather than just managing them. Researchers are excited about Montelukast's potential to offer relief by reducing inflammation, which could provide a new avenue for treatment that current options don't address.

What evidence suggests that Montelukast might be an effective treatment for Gulf War Syndrome?

Research has shown that Montelukast, a medication already used for asthma, may improve brain function in Gulf War Illness (GWI) based on animal studies. In these studies, Montelukast improved thinking and mood by reducing brain inflammation, affecting certain chemicals involved in inflammation. Although these results are promising, they come from animal studies, so human trials are necessary to determine its effectiveness for GWI in people. This trial will compare Montelukast with a placebo to evaluate its effectiveness in treating GWI. ^{1 5 6 7 8}

Who Is on the Research Team?

Drew A Helmer, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for U.S. Gulf War veterans who served between August 2, 1990, and December 31, 1991, and are experiencing symptoms like somatic pain, fatigue or sleep issues, respiratory or skin conditions, cognitive dysfunction with a specific test score threshold, mood disturbances or gastrointestinal problems. Participants must be able to communicate in English and attend two in-person study visits.

Inclusion Criteria

I experience body pain.

I experience fatigue or have trouble sleeping.

I have symptoms affecting my skin.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phone screening

Treatment

Participants receive either Montelukast or placebo for 10 weeks

10 weeks

2 visits (in-person), regular phone contact

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Montelukast

Trial Overview The trial is testing Montelukast (MLK), an FDA-approved asthma drug that may improve brain function by reducing inflammation. It's being compared to a placebo to see if it can help with cognitive and mood issues in veterans with Gulf War Illness.

How Is the Trial Designed?

Group I: Montelukast Group Experimental Treatment 1 Intervention

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

Group II: Placebo Group Placebo Group 1 Intervention

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

Montelukast is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Singulair for:

• Asthma
• Exercise-induced bronchoconstriction
• Allergic rhinitis

Approved in Canada as Singulair for:

• Asthma
• Exercise-induced bronchoconstriction
• Allergic rhinitis

Approved in European Union as Singulair for:

• Asthma
• Exercise-induced bronchoconstriction
• Allergic rhinitis

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Michael E. DeBakey VA Medical Center

Collaborator

Trials

68

Recruited

17,200+

Texas A&M University

Collaborator

Trials

156

Recruited

28,900+

Published Research Related to This Trial

Montelukast sodium is a safe and effective oral medication that acts as a leukotriene-receptor antagonist, specifically targeting the CysLT1 receptor, making it useful for preventing asthma and allergic rhinitis in both adults and children.

Clinical trials have demonstrated that montelukast effectively reduces inflammation and symptoms associated with asthma and allergic rhinitis, highlighting its role in managing these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of montelukast in the treatment of asthma and allergic rhinitis. Nayak, A.[2021]

Montelukast is an effective treatment for asthma, providing bronchoprotective, bronchodilating, and anti-inflammatory effects, and is recommended for patients whose asthma is not adequately controlled by inhaled corticosteroids.

The drug is well tolerated, does not require serum monitoring, and can be used alongside inhaled corticosteroids to improve symptoms and lung function in both adults and children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharma-clinics. Medication of the month. Montelukast (Singulair)]. Louis, R.[2021]

A study involving 40 healthy male volunteers demonstrated that Sandoz generic montelukast 4 mg oral granules are bioequivalent to Singulair(®) 4 mg mini oral granules, meaning they have similar absorption and effectiveness in the body.

Both formulations showed a comparable safety profile, with only two mild adverse events reported, indicating that they can be used interchangeably in treating asthma and allergic rhinitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioequivalence of two formulations of montelukast sodium 4 mg oral granules in healthy adults. Fey, C., Thyroff-Friesinger, U., Jones, S.[2021]

A retrospective analysis of 14,670 reports found that montelukast is associated with a significant number of psychiatric disorders in children and adolescents, with 2630 cases specifically linked to these age groups.

The study revealed that suicidal behavior was notably over-represented among children and adolescents taking montelukast, indicating a need for increased awareness and monitoring of neuropsychiatric side effects in young patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychiatric Disorders and Montelukast in Children: A Disproportionality Analysis of the VigiBase(®). Aldea Perona, A., García-Sáiz, M., Sanz Álvarez, E.[2021]

Montelukast is effective in improving clinical scores and respiratory function in patients with chronic asthma and in preventing effort-induced asthma, based on several placebo-controlled trials.

While montelukast has not been directly compared to all standard treatments for asthma, it may be superior to salmeterol for effort-induced asthma, and it generally has a similar side effect profile to placebo, though rare cases of Churg-Strauss syndrome have been reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Montelukast. No current use for asthma. [2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05992311

Clinical Evaluation of Montelukast in Veterans With Gulf ... The study addresses the pre-clinical promise of Montelukast (MLK) for improving brain function in veterans with Gulf War Illness (GWI).

2. withpower.com withpower.com/trial/phase-1-persian-gulf-syndrome-9-2023-d8c40

Montelukast for Gulf War Syndrome ((GWI) Trial) The study addresses the pre-clinical promise of Montelukast (MLK) for improving brain function in veterans with Gulf War Illness (GWI).

3. apps.dtic.mil apps.dtic.mil/sti/html/trecms/AD1218525/index.html

Clinical Evaluation of Montelukast on Cognitive and ... - DTIC This project will examine the pre-clinical promise of Montelukast (MLK) for improving neuroinflammation in veterans with GWI by assessing change in a novel ...

4. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT05992311/

Trial | NCT05992311 The study addresses the pre-clinical promise of Montelukast (MLK) for improving brain function in veterans with Gulf War Illness (GWI).

5. apps.dtic.mil apps.dtic.mil/sti/trecms/pdf/AD1218525.pdf

Clinical Evaluation of Montelukast on Cognitive and Mood ... This project examines the pre-clinical promise of Montelukast (MLK) for improving neuroinflammation in veterans with Gulf War Illness (GWI) by assessing change ...

6. fda.gov fda.gov/drugs/drug-safety-and-availability/fda-requires-boxed-warning-about-serious-mental-health-side-effects-asthma-and-allergy-drug

Boxed Warning about mental health side effects for Singulair Exposure to montelukast was significantly associated with a decreased risk of treated outpatient depressive disorder (overall hazard ratio [HR] ...

7. go.drugbank.com go.drugbank.com/drugs/DB00471

Montelukast: Uses, Interactions, Mechanism of Action Montelukast is indicated for: (a) the prophylaxis and chronic treatment of asthma in adults and pediatric patients who are 12 months of age and older.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9099214/

Brain-Specific Increase in Leukotriene Signaling ... This study investigated changes in LT signaling in the brain of rats displaying significant cognitive impairments six months after exposure to GWI-related ...