Clinical trial NCT02123849: Intermittent or Continuous Acetylsalicylic Acid and Gene Expression in the Nasal Tissue of Current Smokers
Official title: The Effect of Intermittent Versus Continuous Dose Aspirin (ASA) on Nasal Epithelium Gene Expression in Current Smokers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Carcinoma
Tobacco Use Disorder
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2014-04-28
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Male or female current tobacco smokers with \>= 20 pack years of self-reported smoking exposure and an average use of \>= 10 cigarettes/day
* Karnofsky \>= 70%
* Leukocytes \>= 3,000/microliter
* Absolute neutrophil count \>= 1,500/microliter
* Hematocrit within normal institutional limits
* Platelets within normal institutional limits
* Total bilirubin =\< 1.5 × institutional upper limit of normal (ULN)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 1.5 × institutional ULN
* Creatinine =\< the upper institutional limits
* Prothrombin time (PT)/partial thromboplastin time (PTT) within normal institutional limits
* Fertile subjects must use adequate contraception (abstinence, barrier methods, or birth control pills) prior to study entry and for the duration of study participation
* Participants may have a history of indeterminate pulmonary nodule(s) by chest imaging if nodule follow-up has been completed or the study procedures would not interfere with nodule follow-up
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* History of allergic reaction to aspirin or attributed to compounds of similar chemical or biologic composition to aspirin, including other nonsteroidal anti-inflammatory drugs (NSAIDs)
* Gastric intolerance attributable to ASA or NSAIDs
* History of gastric ulcer within the past 5 years (with or without bleeding)
* Use of ASA or NSAIDs for more than 5 days per month within 3 months of enrollment
* Not willing or are unable to refrain from use of any non-study ASA or NSAIDs during the study period
* Adult asthma
* Chronic, current or recent (within the past three months) use of leukotriene antagonists
* Require chronic anticoagulation or anti-platelet therapy
* History of bleeding disorder or hemorrhagic stroke
* Chronic, current or recent (within the past three months) use of glucocorticoids (systemic, topical and/or nasal sprays)
* History of chronic sinusitis or recent nasal polyps
* Not willing or are unable to limit alcohol consumption to =\< 2 alcoholic beverages a day during the study period
* Pregnant or lactating women; breastfeeding should be discontinued if the mother is treated with aspirin; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
* Participants may not be receiving any other investigational agents
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Have a known history of inability to absorb an oral agent
* Invasive cancer within the past five years except non-melanoma skin cancer
* Urine cotinine level, if collected at screening, does not confirm active smoking status

Primary outcomes:
measure: Changes in Smoking-related Gene Expression Signature Score in Nasal Epithelium
timeFrame: Baseline to 12 weeks (End-of-Intervention)
Secondary outcomes:
measure: Changes in Urine Leukotriene E4 (LTE(4)) Levels
timeFrame: Baseline to 12 weeks (End-of-Intervention)
measure: Changes in Urine Prostaglandin E2 Metabolite (PGE-M) Levels
timeFrame: Baseline to 12 weeks (End-of-Intervention)
measure: Number of Participants Experiencing Possibly/Probably/Definitely-related Adverse Events
timeFrame: Up to 2 weeks post-treatment
measure: Gender Effect on Smoking-related Gene Expression Signature Score
timeFrame: Baseline to 12 weeks (End-of-Intervention)
measure: Changes in Lung Cancer-related Gene Expression Signature Score in the Nasal Epithelium
timeFrame: Baseline to 12 weeks (End-of-Intervention)
measure: Persistence of the Change in the Lung Cancer-related Gene Expression Signature Score in the Nasal Epithelium One Week Off Agent Intervention
timeFrame: Baseline to 1 week post-intervention
measure: Persistence of the Change in the Smoking-related Gene Expression Signature Score in the Nasal Epithelium One Week Off Agent Intervention
timeFrame: Baseline to 1 week post-intervention
measure: Whole-genome Gene Expression - Number of Canonical Pathways Differentially Expressed
timeFrame: Baseline to 12 weeks
measure: Change in Buccal Cells Via Karyometric Analysis
timeFrame: Baseline to up to one week post-intervention
Other outcomes:
Locations:
city: Tucson
country: United States
facility: The University of Arizona Medical Center-University Campus
state: Arizona
city: Boston
country: United States
facility: Boston University School of Medicine
state: Massachusetts
Study officials:
affiliation: The University of Arizona Medical Center-University Campus
name: Linda Garland
role: PRINCIPAL_INVESTIGATOR
References: