Smoking, Tobacco Use Disorder
Conditions
Brief summary
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.
Interventions
DRUGAspirin 325 mg daily
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.
DRUGCelecoxib 200 mg BID
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.
Sponsors
Vanderbilt University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
35 Years to 90 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in COX-2 dependent urinary PGE-M (ng/mg Cr) production after 16 days of aspirin treatment | 16 days | 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. |
Countries
United States
Outcome results
None listed