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CompletedNCT02123849Updated Aug 29, 2018Results posted

Intermittent or Continuous Acetylsalicylic Acid and Gene Expression in the Nasal Tissue of Current Smokers

A Phase 2 interventional study of Aspirin and Laboratory Biomarker Analysis in Lung Carcinoma and Tobacco Use Disorder, sponsored by National Cancer Institute (NCI). Completed at 2 sites in United States. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-08-29.

Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Prevention

Phase
Phase 2
Study type
Interventional
Enrollment
54
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Lung Carcinoma
  • Tobacco Use Disorder
03

In context

Lung Neoplasms

7,333 studies on the registry are indexed under Lung Neoplasms; 1,554 are open to participants now.

This study's enrollment of 54 is close to the median of 60 across 5,345 interventional studies indexed under Lung Neoplasms.

Browse Lung Neoplasms studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,554 studies on the registry; 334 are open to participants now.

Of its 407 completed or terminated interventional studies of FDA-regulated products, 370 (91%) have results posted.

Browse National Cancer Institute (NCI) studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
Yes

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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
05

Study design

Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
54 participants (actual)

Study arms

  • Experimental
    Arm I (continuous aspirin)

    Participants receive aspirin PO QD for 12 weeks.

    Drug: Aspirin · Other: Laboratory Biomarker Analysis

  • Experimental
    Arm II (intermittent aspirin)

    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.

    Drug: Aspirin · Other: Laboratory Biomarker Analysis · Other: Placebo

Interventions

  • DrugAspirin

    Given PO

    Also known as: Acetylsalicylic Acid, ASA, Aspergum, Ecotrin, Empirin, Entericin, Extren, Measurin

  • OtherLaboratory Biomarker Analysis

    Correlative studies

  • OtherPlacebo

    Given PO

    Also known as: placebo therapy, PLCB, sham therapy

06

What researchers measure

Primary outcomes

  1. 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)

Secondary outcomes

  1. 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)

  2. 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)

  3. Number of Participants Experiencing Possibly/Probably/Definitely-related Adverse Events

    Time frame: Up to 2 weeks post-treatment

  4. 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)

  5. 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)

  6. 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

  7. 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

  8. 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

  9. Change in Buccal Cells Via Karyometric Analysis

    Time frame: Baseline to up to one week post-intervention

07

Results

Posted Aug 29, 2018

Participant flow

Participant flow — Overall Study
MilestoneArm I (Continuous Aspirin)Arm II (Intermittent Aspirin)
Started2727
Completed2318
Not completed49

Outcome measures

PrimaryChanges 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)
Reported as:
Mean · gene expression signature score
Changes in Smoking-related Gene Expression Signature Score in Nasal Epithelium
gene expression signature scoreArm I (Continuous Aspirin)Arm II (Intermittent Aspirin)
Changes in Smoking-related Gene Expression Signature Score in Nasal Epithelium-1.11 ± 4.051.39 ± 4.41
Statistical analysis
  • Arm I (Continuous Aspirin) vs Arm II (Intermittent Aspirin) · t-test, 1 sided · p = 0.04
SecondaryChanges 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)
Reported as:
Mean · pg/mg creatinine
Changes in Urine Leukotriene E4 (LTE(4)) Levels
pg/mg creatinineArm I (Continuous Aspirin)Arm II (Intermittent Aspirin)
Changes in Urine Leukotriene E4 (LTE(4)) Levels-6.89 ± 95.16-21.90 ± 309.8
Statistical analysis
  • Arm I (Continuous Aspirin) vs Arm II (Intermittent Aspirin) · t-test, 2 sided · p = 0.84
SecondaryChanges 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)
Reported as:
Mean · ng/mg creatinine
Changes in Urine Prostaglandin E2 Metabolite (PGE-M) Levels
ng/mg creatinineArm I (Continuous Aspirin)Arm II (Intermittent Aspirin)
Changes in Urine Prostaglandin E2 Metabolite (PGE-M) Levels-3.73 ± 9.69-5.59 ± 13.74
Statistical analysis
  • Arm I (Continuous Aspirin) vs Arm II (Intermittent Aspirin) · t-test, 2 sided · p = 0.61
SecondaryNumber of Participants Experiencing Possibly/Probably/Definitely-related Adverse Events
Time frame:
Up to 2 weeks post-treatment
Reported as:
Count of participants · Participants
Number of Participants Experiencing Possibly/Probably/Definitely-related Adverse Events
ParticipantsArm I (Continuous Aspirin)Arm II (Intermittent Aspirin)
Number of Participants Experiencing Possibly/Probably/Definitely-related Adverse Events34
Statistical analysis
  • Arm I (Continuous Aspirin) vs Arm II (Intermittent Aspirin) · Fisher Exact · p = 1.00
SecondaryGender 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)
Reported as:
Mean · gene expression signature score
Gender Effect on Smoking-related Gene Expression Signature Score
gene expression signature scoreMales (Overall)Females (Overall)
Gender Effect on Smoking-related Gene Expression Signature Score0.45 ± 5.04-0.72 ± 3.48
Statistical analysis
  • Males (Overall) vs Females (Overall) · t-test, 2 sided · p = 0.42
SecondaryChanges 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)
Reported as:
Mean · gene expression signature score
Changes in Lung Cancer-related Gene Expression Signature Score in the Nasal Epithelium
gene expression signature scoreArm I (Continuous Aspirin)Arm II (Intermittent Aspirin)
Changes in Lung Cancer-related Gene Expression Signature Score in the Nasal Epithelium-0.03 ± 0.120.04 ± 0.11
Statistical analysis
  • Arm I (Continuous Aspirin) vs Arm II (Intermittent Aspirin) · t-test, 1 sided · p = 0.97
SecondaryPersistence 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
Reported as:
Mean · gene expression signature score
Persistence of the Change in the Lung Cancer-related Gene Expression Signature Score in the Nasal Epithelium One Week Off Agent Intervention
gene expression signature scoreArm I (Continuous Aspirin)Arm II (Intermittent Aspirin)
Persistence of the Change in the Lung Cancer-related Gene Expression Signature Score in the Nasal Epithelium One Week Off Agent Intervention-0.04 ± 0.090.02 ± 0.1
Statistical analysis
  • Arm I (Continuous Aspirin) vs Arm II (Intermittent Aspirin) · t-test, 1 sided · p = 0.97
SecondaryPersistence 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
Reported as:
Mean · gene expression signature score
Persistence of the Change in the Smoking-related Gene Expression Signature Score in the Nasal Epithelium One Week Off Agent Intervention
gene expression signature scoreArm I (Continuous Aspirin)Arm II (Intermittent Aspirin)
Persistence of the Change in the Smoking-related Gene Expression Signature Score in the Nasal Epithelium One Week Off Agent Intervention-1.95 ± 3.42-0.1 ± 3.38
Statistical analysis
  • Arm I (Continuous Aspirin) vs Arm II (Intermittent Aspirin) · t-test, 1 sided · p = 0.06
SecondaryWhole-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
Reported as:
Number · canonical pathway
Whole-genome Gene Expression - Number of Canonical Pathways Differentially Expressed
canonical pathwayArm I (Continuous Aspirin)Arm II (Intermittent Aspirin)
Whole-genome Gene Expression - Number of Canonical Pathways Differentially Expressed301120
SecondaryChange in Buccal Cells Via Karyometric Analysis
Time frame:
Baseline to up to one week post-intervention

No measurements were reported for this outcome.

Adverse events

Collected over Adverse event data were collected from the time that the first dose of study drug was taken until 2 weeks after participants come off the 12-week agent intervention.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Arm I (Continuous Aspirin)0/27 (0%)0/27 (0%)14/27 (51.9%)
Arm II (Intermittent Aspirin)0/27 (0%)0/27 (0%)21/27 (77.8%)
Most frequent other events
Showing 10 of 14
Most frequent other events
EventArm I (Continuous Aspirin)Arm II (Intermittent Aspirin)
Weight lossInvestigations0/275/27
Upper Respiratory InfectionInjury, poisoning and procedural complications2/274/27
Weight gainInvestigations4/273/27
HeadachePregnancy, puerperium and perinatal conditions3/273/27
DyspepsiaGastrointestinal disorders2/272/27
Flu like syndromesGeneral disorders1/272/27
BruisingInjury, poisoning and procedural complications0/272/27
FallInjury, poisoning and procedural complications1/272/27
Injury, poisoning and procedural complications, othersInjury, poisoning and procedural complications1/272/27
DizzinessNervous system disorders0/272/27

Baseline characteristics

Age, Continuous
Age, Continuous(years)Arm I (Continuous Aspirin)Arm II (Intermittent Aspirin)Total
Mean52 ± 852 ± 852 ± 8
Sex: Female, Male
Sex: Female, Male(Participants)Arm I (Continuous Aspirin)Arm II (Intermittent Aspirin)Total
Female121224
Male151530
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Arm I (Continuous Aspirin)Arm II (Intermittent Aspirin)Total
Hispanic or Latino6410
Not Hispanic or Latino212344
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Arm I (Continuous Aspirin)Arm II (Intermittent Aspirin)Total
American Indian or Alaska Native011
Asian101
Native Hawaiian or Other Pacific Islander000
Black or African American235
White242145
More than one race022
Unknown or Not Reported000
08

Study locations

2 sites
  • The University of Arizona Medical Center-University Campus
    Tucson, Arizona 85724, United States
  • Boston University School of Medicine
    Boston, Massachusetts 02118, United States
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 29, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT02123849
Lead sponsor
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Apr 28, 2014
Start date
Jun 2014
Primary completion
Sep 2016
Completion
Feb 2018
Results posted
Aug 29, 2018
Last update
Aug 29, 2018

Study contacts

Linda Garland
principal investigator · The University of Arizona Medical Center-University Campus

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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