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

NCT01796951 | Completed Early Phase 1

• 1 other identifier: VR5137
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Tobacco Use Disorder; Smoking

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

Celecoxib, aspirin, followed by aspirin/celecoxib

EXPERIMENTAL

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; Drug: Celecoxib 200 mg BID

Interventions

Aspirin 325 mg daily DRUG

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, aspirin, followed by aspirin/celecoxib

Celecoxib 200 mg BID DRUG

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, aspirin, followed by aspirin/celecoxib

Eligibility Criteria

• Age: 35 Years - 90 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vanderbilt University: lead

Study Sites (1)

Vanderbilt University

Nashville, Tennessee, 37212, United States

Location

MeSH Terms

Conditions

Tobacco Use Disorder; Smoking

Interventions

Aspirin; Celecoxib; BID protein, human

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Behavior

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzenesulfonamides; Sulfonamides; Amides; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• John A Oates, MD

  Vanderbilt University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Hematology/Oncology Clinical Fellow

Study Record Dates

• First Submitted: February 14, 2013
• First Posted: February 22, 2013
• Study Start: February 1, 2013
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: April 4, 2017

Record last verified: 2017-03

Locations

US (1)