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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02123849
Recruitment Status : Completed
First Posted : April 28, 2014
Results First Posted : August 29, 2018
Last Update Posted : August 29, 2018
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

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.

Condition or disease Intervention/treatment Phase
Lung Carcinoma Tobacco Use Disorder Drug: Aspirin Other: Laboratory Biomarker Analysis Other: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 54 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: The Effect of Intermittent Versus Continuous Dose Aspirin (ASA) on Nasal Epithelium Gene Expression in Current Smokers
Study Start Date : June 2014
Actual Primary Completion Date : September 2016
Actual Study Completion Date : February 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Aspirin

Arm Intervention/treatment
Experimental: Arm I (continuous aspirin)
Participants receive aspirin PO QD for 12 weeks.
Drug: Aspirin
Given PO
Other Names:
  • Acetylsalicylic Acid
  • ASA
  • Aspergum
  • Ecotrin
  • Empirin
  • Entericin
  • Extren
  • Measurin

Other: Laboratory Biomarker Analysis
Correlative studies

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
Given PO
Other Names:
  • Acetylsalicylic Acid
  • ASA
  • Aspergum
  • Ecotrin
  • Empirin
  • Entericin
  • Extren
  • Measurin

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Placebo
Given PO
Other Names:
  • placebo therapy
  • PLCB
  • sham therapy




Primary Outcome Measures :
  1. Changes in Smoking-related Gene Expression Signature Score in Nasal Epithelium [ Time Frame: Baseline to 12 weeks (End-of-Intervention) ]
    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.


Secondary Outcome Measures :
  1. Changes in Urine Leukotriene E4 (LTE(4)) Levels [ Time Frame: Baseline to 12 weeks (End-of-Intervention) ]
    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.

  2. Changes in Urine Prostaglandin E2 Metabolite (PGE-M) Levels [ Time Frame: Baseline to 12 weeks (End-of-Intervention) ]
    Urinary PGE-M was used as a biomarker of cyclooxygenase (COX) mediated arachidonic acid metabolism. Decreased PGE-M implicated inhibition of COX mediated pathway.

  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 [ Time Frame: Baseline to 12 weeks (End-of-Intervention) ]
    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.

  5. Changes in Lung Cancer-related Gene Expression Signature Score in the Nasal Epithelium [ Time Frame: Baseline to 12 weeks (End-of-Intervention) ]
    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.

  6. Persistence of the Change in the Lung Cancer-related Gene Expression Signature Score in the Nasal Epithelium One Week Off Agent Intervention [ Time Frame: Baseline to 1 week post-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.

  7. Persistence of the Change in the Smoking-related Gene Expression Signature Score in the Nasal Epithelium One Week Off Agent Intervention [ Time Frame: Baseline to 1 week post-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.

  8. Whole-genome Gene Expression - Number of Canonical Pathways Differentially Expressed [ Time Frame: Baseline to 12 weeks ]
    Gene set enrichment analysis was performed on the MSigDB canonical pathways with the intent to discover differentially expressed genes after aspirin intervention.

  9. Change in Buccal Cells Via Karyometric Analysis [ Time Frame: Baseline to up to one week post-intervention ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02123849


Locations
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United States, Arizona
The University of Arizona Medical Center-University Campus
Tucson, Arizona, United States, 85724
United States, Massachusetts
Boston University School of Medicine
Boston, Massachusetts, United States, 02118
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Linda Garland The University of Arizona Medical Center-University Campus
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02123849    
Other Study ID Numbers: NCI-2014-01006
NCI-2014-01006 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
N01-CN-2012-00031
HHSN2612012000311
1300000502 ( Other Identifier: The University of Arizona Medical Center-University Campus )
UAZ2013-01-01 ( Other Identifier: DCP )
N01CN00031 ( U.S. NIH Grant/Contract )
P30CA023074 ( U.S. NIH Grant/Contract )
First Posted: April 28, 2014    Key Record Dates
Results First Posted: August 29, 2018
Last Update Posted: August 29, 2018
Last Verified: July 2018
Additional relevant MeSH terms:
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Tobacco Use Disorder
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Aspirin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics