Low Dose Aspirin Inhibition of COX-2 Derived PGE2 in Male Smokers

Study Overview
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Brief Summary
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Regular aspirin use has been associated with a reduction in the development of a number of different malignancies including lung cancer. The mechanism of aspirin's cancer prevention is not known. This study will evaluate whether once daily aspirin use can reduce the production of a protein named prostaglandin E2 (PGE-2), which is known to promote cancer. Specifically, this study will evaluate if aspirin can inhibit the production of PGE-2 by blocking an enzyme named cycloxygenase-2 (COX-2). To accomplish these goals, participants will take either aspirin 325 mg daily, celecoxib 200 mg twice daily, or the combination of both during various days of this 16-day study. Urine be collected to evaluate for PGE-2 production at 4 timepoints in this 16-day study.

Official Title
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Low Dose Aspirin Inhibition of COX-2 Derived PGE2 in Male Smokers

Conditions
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Tobacco Use Disorder, Smoking

Intervention / Treatment
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* Drug: Aspirin 325 mg daily
* Drug: Celecoxib 200 mg BID


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male gender Age ≥35 Current smoker of at least 10 cigarettes per day with history of ≥10 pack-years (py) Former smoker, quit no more than 15 years ago with a history of at least 25 py Ability to comply with the design of the study Capacity to freeze urine sample at participant's residence if this participant desires to store the urine specimens in this manner Baseline urine PGE-M > 13 ng/mg creatinine Serum thromboxane > 150 μg/L Exclusion Criteria: History of aspirin use 1-14 days prior to screening NSAID (ibuprofen, naprosyn, meloxicam, etc) use 1-7 days prior to screening Inhaled glucocorticoid use 1-7 days prior to screening Systemic glucocorticoid use 1-14 days prior to screening History of peptic ulcer disease Current or recent clinically significant bleeding Allergy, intolerance or contraindication to aspirin or NSAID use Thrombocytopenia (platelet count < 100,000) in 30 days prior to screening visit Severe hepatic insufficiency GFR < 30 mL/min/1.73 m2 in 30 days prior to screening visit History of aspirin or celecoxib allergy Elevated INR (>1.5) in 30 days prior to screening visit Current diagnosis of malignancy or history of non-skin malignancy in last 5 years Current use of systemic anticoagulants (e.g., warfarin (Coumadin), enoxaparin (Lovenox), Fondaparinux (Arixtra), dabigatran (Pradaxa)) Diagnosis of COPD Intake of > 250 mg of fish oil supplementation daily

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Celecoxib, aspirin, followed by aspirin/celecoxib<br>Celecoxib 200 mg twice daily x3 days, aspirin 325 mg daily x10 days, celecoxib 200 mb twice daily + aspirin 325 mg daily x 3 days | Drug: Aspirin 325 mg daily<br>* In this single-arm trial, participants will take celecoxib 200 mg BID for 5 doses, followed by aspirin 325 mg daily for 10 days, followed by combination of celecoxib 200 mg BID for 5 doses and aspirin 325 mg daily for 3 days.<br>Drug: Celecoxib 200 mg BID<br>* In this single-arm trial, participants will take celecoxib 200 mg BID for 5 doses, followed by aspirin 325 mg daily for 10 days, followed by combination of celecoxib 200 mg BID for 5 doses and aspirin 325 mg daily for 3 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in COX-2 dependent urinary PGE-M (ng/mg Cr) production after 16 days of aspirin treatment | Baseline urinary PGE-2 metabolite (PGE-M) will be measured. Then after 3 days of COX-2 blockade with celecoxib, it will again be measured. Participants will then undergo 10 days of treatment with aspirin and urinary PGE-M will be measured. Finally, participants will be treated with combined aspirin and celecoxib for 3 days and urinary PGE-M will be measured one last time. Using these values, the degree of aspirin inhibition of COX-2 specific urinary PGE-M production can be calculated. | 16 days |