Tobacco Use DisorderPhase 2NCT02348203
Aspirin and Zileuton and Biomarker Expression in Nasal Tissue of Current Smokers
A Phase 2 study testing Aspirin, Laboratory Biomarker Analysis and Zileuton in people with Tobacco Use Disorder, run by National Cancer Institute (NCI) at 2 sites in United States.
Trial summary
This randomized phase II trial studies the effects of aspirin and zileuton on genes related to tobacco use in current smokers. Aspirin and zileuton may interfere with genes related to tobacco use and may be useful in preventing lung cancer in current smokers. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Tobacco Use Disorder
- What is being tested?
- Aspirin, Laboratory Biomarker Analysis and Zileuton
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 63 participants
- Where
- 2 sitesUnited States
- Study dates
- 13 Jan 2016to 9 Mar 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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 >= the lower institutional limit
- Platelets >= the lower institutional limits
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- Total bilirubin within normal institutional limits
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) within normal institutional limits
- 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; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
- 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
Who cannot join
- 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, NSAIDs and leukotriene antagonists during the study period
- Adult asthma
Show all 21Show fewer
- 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 or steroid topical creams to large body surface area); use of steroid topical creams for small body areas (=< 10% body surface) during study intervention is allowed
- History of chronic sinusitis or recent nasal polyps
- History of, or current, active or chronic liver disease even if transaminases have normalized
- History of allergic reaction to zileuton or attributed to compounds of similar chemical or biologic composition to zileuton
- Are taking drugs known to interact with zileuton, including theophylline, warfarin, and propranolol
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Boston University School of Medicine
Boston, Massachusetts, 02118
Banner University Medical Center - Tucson
Tucson, Arizona, 85719
About this study
Official title: Clinical Study of the Effect of Combined Treatment of Aspirin and Zileuton on Biomarkers of Tobacco-Related Carcinogenesis in Current Smokers
This randomized phase II trial studies the effects of aspirin and zileuton on genes related to tobacco use in current smokers. Aspirin and zileuton may interfere with genes related to tobacco use and may be useful in preventing lung cancer in current smokers.
Read the detailed description
PRIMARY OBJECTIVES:
- To analyze the impact of combined treatment of acetylsalicylic acid (ASA) (aspirin) and zileuton on smoking-related gene expression signature in the nasal epithelium in current smokers and to analyze any difference between the ASA and zileuton intervention and placebo control.
SECONDARY OBJECTIVES:
- To assess the impact of ASA and zileuton on three lung cancer gene signatures (an 80-gene bronchial signature, a phosphatidylinositol 3-kinase [PI3K] pathway gene signature and a nasal diagnostic gene signature) and to compare this to placebo control.
II. To determine whether the change in the smoking-related gene expression signature and the three lung cancer gene signatures of nasal epithelium persists 10-14 days off agent intervention.
III. To measure urinary prostaglandin E metabolite (PGE-M) and leukotriene E(4) (LTE[4]) levels in current smokers after ASA and zileuton.
IV. To assess the safety in current smokers of 12 week exposure to ASA and zileuton.
- To evaluate a gender effect in the modulatory effects of ASA and zileuton on smoking related-gene expression signature.
VI. To explore the effect of ASA and zileuton on the metabolomics profile of the arachidonic acid pathway.
VII. To explore, in a discovery-driven fashion, the effect of ASA and zileuton on whole-genome gene expression.
VIII. To analyze the impact of ASA and zileuton on karyometric analysis of buccal cells.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive aspirin orally (PO) once daily (QD) and zileuton PO twice daily (BID) for 12 weeks in the absence of unacceptable toxicity.
ARM II: Patients receive aspirin placebo PO QD and zileuton placebo PO BID for 12 weeks.
After completion of study treatment, patients are followed up for 2 weeks.
- Conditions
- Tobacco Use Disorder
- Being tested
- Aspirin, Laboratory Biomarker Analysis, Placebo Administration, Zileuton
- Medical subject headings
- Tobacco Use Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AspirinDrug
Also called Acetylsalicylic Acid, ASA, Aspergum, Ecotrin
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
Placebo AdministrationOther
Given aspirin placebo PO
Placebo AdministrationOther
Given zileuton placebo PO
ZileutonDrug
Also called Zyflo
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Arm I (aspirin, zileuton) | Experimental | Patients receive aspirin PO QD and zileuton PO BID for 12 weeks in the absence of unacceptable toxicity. Receives: Drug: Aspirin; Other: Laboratory Biomarker Analysis; Drug: Zileuton |
| Arm II (double placebo) | Placebo comparator | Patients receive aspirin placebo PO QD and zileuton placebo PO BID for 12 weeks. Receives: Other: Laboratory Biomarker Analysis; Other: Placebo Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in a Smoking-related Gene Expression Signature Score in the Nasal Epithelium of Current Smokers
Change in a 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.
Measured: Baseline to 12 weeks (End-of-intervention)
Secondary outcomes (10)
Changes in Three Lung Cancer Gene Signatures (an 80-gene Bronchial Signature, a PI3K Pathway Gene Signature and a Nasal Diagnostic Gene Signature) in the Nasal Epithelium of Current Smokers
Change in three lung cancer gene signatures (an 80-gene bronchial signature, a PI3K pathway gene signature and a nasal diagnostic gene signature) derived from prior research was compared between the two study arms. A decreased signature score implicated a more favorable intervention effect. There is no minimum or maximum score.
Measured: Baseline to 12 weeks (End of Intervention)
Changes in a Smoking-related Gene Expression Signature Score in the Nasal Epithelium of Current Smokers 10-14 Days Post Intervention
Change (from baseline to 10-14 days off intervention) in a 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.
Measured: Baseline to 14 days post intervention
Changes in Three Lung Cancer Gene Signatures (an 80-gene Bronchial Signature, a PI3K Pathway Gene Signature and a Nasal Diagnostic Gene Signature) in the Nasal Epithelium of Current Smokers 10-14 Days Post Intervention
Change (from baseline to 10-14 days off intervention) in three lung cancer gene signatures (an 80-gene bronchial signature, a PI3K pathway gene signature and a nasal diagnostic gene signature) derived from prior research was compared between the two study arms. A decreased signature score implicated a more favorable intervention effect. There is no minimum or maximum score.
Measured: Baseline to 14 days post intervention
Change in Urinary PGE-M Levels
Measured: Baseline to 12 weeks (End-of-intervention)
Change in Urinary LTE (4) Levels
Measured: Baseline to 12 weeks (End-of-intervention)
Number of Participants Experiencing Possibly/Probably/Definitely-related Adverse Events
Measured: Up to 2 weeks post-treatment
Gender Effect on Smoking-related Gene Expression Signature
Change in a nasal smoking-related gene expression signature score derived from prior research was analyzed by gender. 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.
Measured: Baseline to 12 weeks (End-of-intervention)
Changes in the Metabolomics Profile of the Arachidonic Acid Pathway
Two sample t tests will be performed to evaluate whether or not there are significant differences in changes in oxylipin metabolome between the treatment and placebo groups. In addition, system biology methods will also be used to analyze the oxylipin metabolome data.
Measured: Baseline to 12 weeks (End-of-intervention)
Number of Genes Differentially Expressed After Aspirin and Zileuton Intervention Compared to Placebo
Number of genes differentially expressed after aspirin and zileuton intervention compared to placebo using whole-genome gene expression data
Measured: Baseline to 12 weeks (End-of-intervention)
Impact of ASA and Zileuton on Karyometric Analysis of Buccal Cells
Measured: Up to week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2015 (estimated)
- Study start13 Jan 2016
- Primary completion22 Feb 2019
- Study completion9 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Tobacco Use DisorderStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Linda L Garland, Principal investigator, The University of Arizona Medical Center-University Campus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02348203
- Sponsor's protocol ID
- NCI-2015-00061
- Other IDs
- NCI-2015-00061, N01-CN-2012-00031, 1403269898, UAZ2013-02-01, N01CN00031, P30CA023074
- Status last verified
- Jun 2022
- First submitted
- 27 Jan 2015
- Last updated
- 2 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Study of the Effect of Combined Treatment of Aspirin and Zileuton on Biomarkers of Tobacco-Related Carcinogenesis in Current Smokers
- ClinicalTrials.gov ID
- NCT02348203
- Acronym / sponsor ID
- NCI-2015-00061
- Conditions
- Tobacco Use Disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 13 Jan 2016 (actual)
- Primary completion
- 22 Feb 2019 (actual)
- Study completion
- 9 Mar 2021 (actual)
- First posted
- 28 Jan 2015 (estimated)
- Results
- Posted 23 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized phase II trial studies the effects of aspirin and zileuton on genes related to tobacco use in current smokers. Aspirin and zileuton may interfere with genes related to tobacco use and may be useful in preventing lung cancer in current smokers.
Detailed description
PRIMARY OBJECTIVES:
- To analyze the impact of combined treatment of acetylsalicylic acid (ASA) (aspirin) and zileuton on smoking-related gene expression signature in the nasal epithelium in current smokers and to analyze any difference between the ASA and zileuton intervention and placebo control.
SECONDARY OBJECTIVES:
- To assess the impact of ASA and zileuton on three lung cancer gene signatures (an 80-gene bronchial signature, a phosphatidylinositol 3-kinase [PI3K] pathway gene signature and a nasal diagnostic gene signature) and to compare this to placebo control.
II. To determine whether the change in the smoking-related gene expression signature and the three lung cancer gene signatures of nasal epithelium persists 10-14 days off agent intervention.
III. To measure urinary prostaglandin E metabolite (PGE-M) and leukotriene E(4) (LTE[4]) levels in current smokers after ASA and zileuton.
IV. To assess the safety in current smokers of 12 week exposure to ASA and zileuton.
- To evaluate a gender effect in the modulatory effects of ASA and zileuton on smoking related-gene expression signature.
VI. To explore the effect of ASA and zileuton on the metabolomics profile of the arachidonic acid pathway.
VII. To explore, in a discovery-driven fashion, the effect of ASA and zileuton on whole-genome gene expression.
VIII. To analyze the impact of ASA and zileuton on karyometric analysis of buccal cells.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive aspirin orally (PO) once daily (QD) and zileuton PO twice daily (BID) for 12 weeks in the absence of unacceptable toxicity.
ARM II: Patients receive aspirin placebo PO QD and zileuton placebo PO BID for 12 weeks.
After completion of study treatment, patients are followed up for 2 weeks.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (aspirin, zileuton) | Experimental | Drug: Aspirin, Other: Laboratory Biomarker Analysis, Drug: ZileutonPatients receive aspirin PO QD and zileuton PO BID for 12 weeks in the absence of unacceptable toxicity. |
| Arm II (double placebo) | Placebo comparator | Other: Laboratory Biomarker Analysis, Other: Placebo AdministrationPatients receive aspirin placebo PO QD and zileuton placebo PO BID for 12 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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 >= the lower institutional limit
Key exclusion criteria (21 listed)
- 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, NSAIDs and leukotriene antagonists during the study period
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AspirinAlso: Acetylsalicylic Acid, ASA, Aspergum, EcotrinGiven PO | Drug | Arm I (aspirin, zileuton) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Arm I (aspirin, zileuton), Arm II (double placebo) |
| Placebo AdministrationGiven aspirin placebo PO | Other | Arm II (double placebo) |
| Placebo AdministrationGiven zileuton placebo PO | Other | Arm II (double placebo) |
| ZileutonAlso: ZyfloGiven PO | Drug | Arm I (aspirin, zileuton) |
Primary outcome
Changes in a Smoking-related Gene Expression Signature Score in the Nasal Epithelium of Current Smokers
Time frame: Baseline to 12 weeks (End-of-intervention)
Change in a 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.
10 secondary outcomes
Changes in Three Lung Cancer Gene Signatures (an 80-gene Bronchial Signature, a PI3K Pathway Gene Signature and a Nasal Diagnostic Gene Signature) in the Nasal Epithelium of Current Smokers
Time frame: Baseline to 12 weeks (End of Intervention)
Changes in a Smoking-related Gene Expression Signature Score in the Nasal Epithelium of Current Smokers 10-14 Days Post Intervention
Time frame: Baseline to 14 days post intervention
Changes in Three Lung Cancer Gene Signatures (an 80-gene Bronchial Signature, a PI3K Pathway Gene Signature and a Nasal Diagnostic Gene Signature) in the Nasal Epithelium of Current Smokers 10-14 Days Post Intervention
Time frame: Baseline to 14 days post intervention
Change in Urinary PGE-M Levels
Time frame: Baseline to 12 weeks (End-of-intervention)
Change in Urinary LTE (4) Levels
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
Time frame: Baseline to 12 weeks (End-of-intervention)
Changes in the Metabolomics Profile of the Arachidonic Acid Pathway
Time frame: Baseline to 12 weeks (End-of-intervention)
Number of Genes Differentially Expressed After Aspirin and Zileuton Intervention Compared to Placebo
Time frame: Baseline to 12 weeks (End-of-intervention)
Impact of ASA and Zileuton on Karyometric Analysis of Buccal Cells
Time frame: Up to week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Linda L Garland principal investigator
The University of Arizona Medical Center-University Campus
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Aspirin, Laboratory Biomarker Analysis and Zileuton in people with Tobacco Use Disorder, run by National Cancer Institute (NCI) at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in a Smoking-related Gene Expression Signature Score in the Nasal Epithelium of Current Smokers (time frame: Baseline to 12 weeks (End-of-intervention)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2022.