Aspirin and Zileuton and Biomarker Expression in 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: NCT02348203|
Recruitment Status : Active, not recruiting
First Posted : January 28, 2015
Results First Posted : March 23, 2020
Last Update Posted : October 19, 2020
|Condition or disease||Intervention/treatment||Phase|
|Tobacco Use Disorder||Drug: Aspirin Other: Laboratory Biomarker Analysis Other: Placebo Administration Drug: Zileuton||Phase 2|
I. 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.
I. 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) levels in current smokers after ASA and zileuton.
IV. To assess the safety in current smokers of 12 week exposure to ASA and zileuton.
V. 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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||63 participants|
|Intervention Model:||Parallel Assignment|
|Official Title:||Clinical Study of the Effect of Combined Treatment of Aspirin and Zileuton on Biomarkers of Tobacco-Related Carcinogenesis in Current Smokers|
|Actual Study Start Date :||January 13, 2016|
|Actual Primary Completion Date :||February 22, 2019|
Experimental: Arm I (aspirin, zileuton)
Patients receive aspirin PO QD and zileuton PO BID for 12 weeks in the absence of unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Other Name: Zyflo
Placebo Comparator: Arm II (double placebo)
Patients receive aspirin placebo PO QD and zileuton placebo PO BID for 12 weeks.
Other: Laboratory Biomarker Analysis
Other: Placebo Administration
Given aspirin placebo PO
Other: Placebo Administration
Given zileuton placebo PO
- Changes in a Smoking-related Gene Expression Signature Score in the Nasal Epithelium of Current Smokers After Acetylsalicylic Acid (ASA) and Zileuton Intervention [ 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.
- Impact of ASA and Zileuton on Three Lung Cancer Gene Signatures (an 80-gene Bronchial Signature, a PI3K Pathway Gene Signature and a Nasal Diagnostic Gene Signature) [ Time Frame: Up to week 12 ]Analysis of variance will be performed to evaluate whether ASA and zileuton has significantly different impact on changes in the three lung cancer gene signatures and the changes are significantly different from the placebo group.
- Change in the Smoking-related Gene Expression Signature [ Time Frame: Baseline to 14 days post intervention ]
- Change in the Three Lung Cancer Gene Signatures of Nasal Epithelium [ Time Frame: Baseline to 14 days post intervention ]
- Change in Urinary PGE-M Levels [ Time Frame: Baseline up to week 12 ]Two sample t tests will be performed to evaluate whether or not there are significant differences in changes in PGE-M between the treatment and placebo groups.
- Change in Urinary LTE (4) Levels [ Time Frame: Baseline up to week 12 ]Two sample t tests will be performed to evaluate whether or not there are significant differences in changes in LTE(4) between the treatment and placebo groups.
- Incidence of Adverse Events Graded Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 [ Time Frame: Up to 2 weeks post-treatment ]Descriptive statistics of the type and frequency of all adverse events will be generated, including 95% confidence intervals. For each type of the adverse events, a Fisher's exact test will be performed to compare the frequency of the adverse event between the two groups.
- Gender Effect on Smoking-related Gene Expression Signature [ Time Frame: Up to week 12 ]Exploratory analyses will be performed to evaluate whether the effect of ASA and zileuton on smoking-related gene expression signature is modulated by gender.
- Changes in the Metabolomics Profile of the Arachidonic Acid Pathway [ Time Frame: Baseline to week 12 ]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.
- Whole-genome Gene Expression [ Time Frame: Up to week 12 ]Pair-wise comparisons based on two-sample t tests will be performed to whole-genome gene expression data to identify the genes for which ASA and zileuton has a significantly different expression level from the placebo group. Multivariate statistical techniques such as principle component analysis (PCA) will be used to reduce complexity of the whole-genome expression data.
- Impact of ASA and Zileuton on Karyometric Analysis of Buccal Cells [ Time Frame: Up to week 12 ]
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): NCT02348203
|United States, Arizona|
|Banner University Medical Center - Tucson|
|Tucson, Arizona, United States, 85719|
|United States, Massachusetts|
|Boston University School of Medicine|
|Boston, Massachusetts, United States, 02118|
|Principal Investigator:||Linda L Garland||The University of Arizona Medical Center-University Campus|