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

31 juli 2018 bijgewerkt door: National Cancer Institute (NCI)

The Effect of Intermittent Versus Continuous Dose Aspirin (ASA) on Nasal Epithelium Gene Expression in Current Smokers

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.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

54

Fase

  • Fase 2

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Verenigde Staten
    • Arizona
      • Tucson, Arizona, Verenigde Staten, 85724
        • The University of Arizona Medical Center-University Campus
    • Massachusetts
      • Boston, Massachusetts, Verenigde Staten, 02118
        • Boston University School of Medicine

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

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

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Preventie
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Dubbele

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Arm I (continuous aspirin)
Participants receive aspirin PO QD for 12 weeks.
Ander: Laboratorium Biomarker Analyse
Correlatieve studies
Geneesmiddel: Aspirine
Gegeven PO
Andere namen:
  • Acetylsalicylzuur
  • ALS EEN
  • Aspergum
  • Ecotrine
  • Empirin
  • Entericine
  • Extren
  • Meten
Experimenteel: 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.
Ander: Laboratorium Biomarker Analyse
Correlatieve studies
Geneesmiddel: Aspirine
Gegeven PO
Andere namen:
  • Acetylsalicylzuur
  • ALS EEN
  • Aspergum
  • Ecotrine
  • Empirin
  • Entericine
  • Extren
  • Meten
Ander: Placebo
Gegeven PO
Andere namen:
  • placebo therapie
  • PLCB
  • schijntherapie

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Changes in Smoking-related Gene Expression Signature Score in Nasal Epithelium
Tijdsspanne: 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.
Baseline to 12 weeks (End-of-Intervention)

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Changes in Urine Leukotriene E4 (LTE(4)) Levels
Tijdsspanne: 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.
Baseline to 12 weeks (End-of-Intervention)
Changes in Urine Prostaglandin E2 Metabolite (PGE-M) Levels
Tijdsspanne: 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.
Baseline to 12 weeks (End-of-Intervention)
Aantal deelnemers dat mogelijk/waarschijnlijk/zeker-gerelateerde bijwerkingen ervaart
Tijdsspanne: Tot 2 weken na de behandeling
Tot 2 weken na de behandeling
Gender Effect on Smoking-related Gene Expression Signature Score
Tijdsspanne: 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.
Baseline to 12 weeks (End-of-Intervention)
Changes in Lung Cancer-related Gene Expression Signature Score in the Nasal Epithelium
Tijdsspanne: 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.
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
Tijdsspanne: 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.
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
Tijdsspanne: 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.
Baseline to 1 week post-intervention
Whole-genome Gene Expression - Number of Canonical Pathways Differentially Expressed
Tijdsspanne: 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.
Baseline to 12 weeks
Change in Buccal Cells Via Karyometric Analysis
Tijdsspanne: Baseline to up to one week post-intervention
Baseline to up to one week post-intervention

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

National Cancer Institute (NCI)

Onderzoekers

  • Hoofdonderzoeker: Linda Garland, The University of Arizona Medical Center-University Campus

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 juni 2014

Primaire voltooiing (Werkelijk)

1 september 2016

Studie voltooiing (Werkelijk)

1 februari 2018

Studieregistratiedata

Eerst ingediend

24 april 2014

Eerst ingediend dat voldeed aan de QC-criteria

24 april 2014

Eerst geplaatst (Schatting)

28 april 2014

Updates van studierecords

Laatste update geplaatst (Werkelijk)

29 augustus 2018

Laatste update ingediend die voldeed aan QC-criteria

31 juli 2018

Laatst geverifieerd

1 juli 2018

Meer informatie

Termen gerelateerd aan deze studie

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • NCI-2014-01006 (Register-ID: CTRP (Clinical Trial Reporting Program))
  • P30CA023074 (Subsidie/contract van de Amerikaanse NIH)
  • HHSN2612012000311
  • N01-CN-2012-00031
  • N01CN00031 (Subsidie/contract van de Amerikaanse NIH)
  • 1300000502 (Andere identificatie: The University of Arizona Medical Center-University Campus)
  • UAZ2013-01-01 (Andere identificatie: DCP)

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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