This randomized phase II trial studies the safety and effects of acetylsalicylic acid (aspirin) taken continuously or intermittently on gene expression in the nasal tissue of current smokers. Smokers are at increased risk of developing lung cancer. Acetylsalicylic acid may be useful in preventing lung cancer.
PRIMARY OBJECTIVES: I. To analyze the impact of a 12-week intervention of intermittent and continuous acetylsalicylic acid (ASA) on a smoking-related gene expression signature in the nasal epithelium of current smokers and to analyze any difference between the intermittent and continuous ASA interventions. SECONDARY OBJECTIVES: I. To determine whether the change in the smoking-related gene expression signature of nasal epithelium persists one week off agent intervention. II. To compare the change in urinary prostaglandin E metabolite (PGE-M) and leukotriene E (4) (LTE \[4\]) between the continuous and intermittent dosing arms and to determine whether the change persists one week off agent intervention. III. To analyze the impact of intermittent and continuous ASA on a three lung cancer-related gene signatures (an 80-gene signature, a phosphoinositide 3-kinase \[PI3K\] gene signature, and a nasal epithelium cancer signature) in the nasal epithelium and to analyze any difference between the intermittent and continuous ASA interventions. IV. To determine whether the change, if any, in the lung cancer-related gene expression signatures of nasal epithelium persists one week off agent intervention. V. To compare the safety in current smokers of 12 week exposure to continuous versus intermittent ASA. VI. To evaluate a gender effect in the modulatory effects of intermittent and continuous ASA on smoking-related gene expression signature. VII. To explore in a discovery-driven fashion the effect of ASA intervention on whole-genome gene expression. VIII. To analyze the impact of intermittent and continuous ASA on karyometric analysis of buccal cells and to analyze any difference between intermittent and continuous ASA interventions. OUTLINE: Participants are randomized to 1 of 2 treatment arms. ARM I (CONTINUOUS): Participants receive aspirin orally (PO) once daily (QD) for 12 weeks. ARM II (INTERMITTENT): Participants receive placebo PO QD during weeks 1, 3, 5, 7, 9, and 11 and aspirin PO QD during weeks 2, 4, 6, 8, 10, and 12. After completion of study treatment, participants are followed up for 2 weeks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
54
The University of Arizona Medical Center-University Campus
Tucson, Arizona, United States
Boston University School of Medicine
Boston, Massachusetts, United States
Changes in Smoking-related Gene Expression Signature Score in Nasal Epithelium
Change in nasal smoking-related gene expression signature score derived from prior research was compared between the two study arms. Prior research showed that a higher score was observed in never smokers compared to current smokers. An increased score implicated a more favorable intervention effect. There is no minimum or maximum score.
Time frame: Baseline to 12 weeks (End-of-Intervention)
Changes in Urine Leukotriene E4 (LTE(4)) Levels
Urinary LTE(4) was used as a biomarker 5-lipoxygenase (5-LOX) mediated arachidonic acid metabolism. Decreased LTE4 implicated inhibition of the 5-LOX mediated pathway.
Time frame: Baseline to 12 weeks (End-of-Intervention)
Changes in Urine Prostaglandin E2 Metabolite (PGE-M) Levels
Urinary PGE-M was used as a biomarker of cyclooxygenase (COX) mediated arachidonic acid metabolism. Decreased PGE-M implicated inhibition of COX mediated pathway.
Time frame: Baseline to 12 weeks (End-of-Intervention)
Number of Participants Experiencing Possibly/Probably/Definitely-related Adverse Events
Time frame: Up to 2 weeks post-treatment
Gender Effect on Smoking-related Gene Expression Signature Score
Change in nasal smoking-related gene expression signature score was compared between male and female participants. The gender comparison was not stratified by arm because of the small sample size. Prior research showed that a higher score was observed in never smokers compared to current smokers. An increased score implicated a more favorable intervention effect. There is no minimum or maximum score.
Time frame: Baseline to 12 weeks (End-of-Intervention)
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Changes in Lung Cancer-related Gene Expression Signature Score in the Nasal Epithelium
Change in lung cancer-related gene expression signature score derived from prior research was compared between the two study arms. Prior research showed that the score was higher in lung cancer cases than healthy controls. A decreased score implicated a more favorable intervention effect. There is no minimum or maximum score.
Time frame: Baseline to 12 weeks (End-of-Intervention)
Persistence of the Change in the Lung Cancer-related Gene Expression Signature Score in the Nasal Epithelium One Week Off Agent Intervention
Change in the lung cancer-related gene expression signature score from baseline to one week off agent intervention was compared between the two study arms. Prior research showed that higher scores were observed in lung cancer cases than healthy controls. A decreased score implicated a favorable intervention effect. There is no minimum or maximum score.
Time frame: Baseline to 1 week post-intervention
Persistence of the Change in the Smoking-related Gene Expression Signature Score in the Nasal Epithelium One Week Off Agent Intervention
Change in nasal smoking-related gene expression signature score from baseline to 1 week post-intervention was compared between the two study arms. Prior research showed that a higher score was observed in never smokers compared to current smokers. An increased score implicated a more favorable intervention effect. There is no minimum or maximum score.
Time frame: Baseline to 1 week post-intervention
Whole-genome Gene Expression - Number of Canonical Pathways Differentially Expressed
Gene set enrichment analysis was performed on the MSigDB canonical pathways with the intent to discover differentially expressed genes after aspirin intervention.
Time frame: Baseline to 12 weeks
Change in Buccal Cells Via Karyometric Analysis
Time frame: Baseline to up to one week post-intervention