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

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.

Study Overview

• Status: Completed
• Conditions: Smoking; Tobacco Use Disorder
• Intervention / Treatment: Drug: Aspirin 325 mg daily; Drug: Celecoxib 200 mg BID

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Celecoxib, aspirin, followed by aspirin/celecoxib; 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; 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.; Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Vanderbilt University
• Investigators: Study Director: John A Oates, MD, Vanderbilt University

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 1, 2013
• Primary Completion (ACTUAL): February 1, 2016
• Study Completion (ACTUAL): February 1, 2016

Study Registration Dates

• First Submitted: February 14, 2013
• First Submitted That Met QC Criteria: February 19, 2013
• First Posted (ESTIMATE): February 22, 2013

Study Record Updates

• Last Update Posted (ACTUAL): April 4, 2017
• Last Update Submitted That Met QC Criteria: March 30, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Tobacco Use Disorder; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Cyclooxygenase 2 Inhibitors; Aspirin; Celecoxib
• Other Study ID Numbers: VR5137

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No