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

Early Phase 1
Completed
Conditions
Tobacco Use Disorder
Smoking
Interventions
Registration Number
NCT01796951
Lead Sponsor
Vanderbilt University
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
6
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Celecoxib, aspirin, followed by aspirin/celecoxibAspirin 325 mg dailyCelecoxib 200 mg twice daily x3 days, aspirin 325 mg daily x10 days, celecoxib 200 mb twice daily + aspirin 325 mg daily x 3 days
Celecoxib, aspirin, followed by aspirin/celecoxibCelecoxib 200 mg BIDCelecoxib 200 mg twice daily x3 days, aspirin 325 mg daily x10 days, celecoxib 200 mb twice daily + aspirin 325 mg daily x 3 days
Primary Outcome Measures
NameTimeMethod
Change in COX-2 dependent urinary PGE-M (ng/mg Cr) production after 16 days of aspirin treatment16 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.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Vanderbilt University

🇺🇸

Nashville, Tennessee, United States

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