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

• Status: Completed
• Trial end date: 2016-02-01
• Target enrollment: 0
• Participant gender: Male

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.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Vanderbilt University
• Treatments: Aspirin; Celecoxib

Criteria

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