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

Smoking Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01796951
• Other study ID #: VR5137
• Status: Completed
• Phase: Early Phase 1
• First received: February 14, 2013
• Last updated: March 30, 2017
• Start date: February 2013
• Est. completion date: February 2016

Study information

• Verified date: March 2017
• Source: Vanderbilt University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: February 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 35 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Smoking
• Tobacco Use Disorder

Intervention

Drug:
• Aspirin 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.
• Celecoxib 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.

Locations

Country	Name	City	State
United States	Vanderbilt University	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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