- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02348203
Aspirin and Zileuton and Biomarker Expression in Nasal Tissue of Current Smokers
Clinical Study of the Effect of Combined Treatment of Aspirin and Zileuton on Biomarkers of Tobacco-Related Carcinogenesis in Current Smokers
Study Overview
Status
Conditions
Detailed Description
PRIMARY OBJECTIVES:
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.
SECONDARY OBJECTIVES:
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[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.
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
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Arizona
-
Tucson, Arizona, United States, 85719
- Banner University Medical Center - Tucson
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02118
- Boston University School of Medicine
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
- 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
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, NSAIDs and leukotriene antagonists 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 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm I (aspirin, zileuton)
Patients receive aspirin PO QD and zileuton PO BID for 12 weeks in the absence of unacceptable toxicity.
|
Correlative studies
Given PO
Other Names:
Given PO
Other Names:
|
Placebo Comparator: Arm II (double placebo)
Patients receive aspirin placebo PO QD and zileuton placebo PO BID for 12 weeks.
|
Correlative studies
Given aspirin placebo PO
Given zileuton placebo PO
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Baseline to 12 weeks (End-of-intervention)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants Experiencing Possibly/Probably/Definitely-related Adverse Events
Time Frame: Up to 2 weeks post-treatment
|
Up to 2 weeks post-treatment
|
|
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)
|
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.
|
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
|
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.
|
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 (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.
|
Baseline to 14 days post intervention
|
Change in Urinary PGE-M Levels
Time Frame: Baseline to 12 weeks (End-of-intervention)
|
Baseline to 12 weeks (End-of-intervention)
|
|
Change in Urinary LTE (4) Levels
Time Frame: Baseline to 12 weeks (End-of-intervention)
|
Baseline to 12 weeks (End-of-intervention)
|
|
Gender Effect on Smoking-related Gene Expression Signature
Time Frame: Baseline to 12 weeks (End-of-intervention)
|
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.
|
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)
|
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.
|
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)
|
Number of genes differentially expressed after aspirin and zileuton intervention compared to placebo using whole-genome gene expression data
|
Baseline to 12 weeks (End-of-intervention)
|
Impact of ASA and Zileuton on Karyometric Analysis of Buccal Cells
Time Frame: Up to week 12
|
Up to week 12
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Linda L Garland, The University of Arizona Medical Center-University Campus
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Chemically-Induced Disorders
- Substance-Related Disorders
- Tobacco Use Disorder
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Fibrinolytic Agents
- Fibrin Modulating Agents
- Platelet Aggregation Inhibitors
- Cyclooxygenase Inhibitors
- Antipyretics
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Leukotriene Antagonists
- Hormone Antagonists
- Lipoxygenase Inhibitors
- Aspirin
- Zileuton
Other Study ID Numbers
- NCI-2015-00061 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- P30CA023074 (U.S. NIH Grant/Contract)
- N01-CN-2012-00031
- N01CN00031 (U.S. NIH Grant/Contract)
- 1403269898 (Other Identifier: Banner University Medical Center - Tucson)
- UAZ2013-02-01 (Other Identifier: DCP)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Tobacco Use Disorder
-
Washington University School of MedicineNational Cancer Institute (NCI); National Institutes of Health (NIH)CompletedSmoking | Smoking Cessation | Tobacco Use | Tobacco Smoking | Tobacco Use Cessation | Nicotine Dependence | Tobacco Dependence | Smoking, Tobacco | Nicotine Use Disorder | Nicotine Dependence, Cigarettes | Smoking, Cigarette | Nicotine Dependence Tobacco Product | Tobacco; Use, Rehabilitation | Smoking (Tobacco) Addiction and other conditionsUnited States
-
Johns Hopkins UniversityNational Institute on Drug Abuse (NIDA)RecruitingTobacco Use | Tobacco Smoking | Tobacco Use Disorder | Tobacco Use Cessation | Tobacco DependenceUnited States
-
Harvard School of Public Health (HSPH)Beacon Communities; The Community BuildersEnrolling by invitationTobacco Use | Tobacco Smoking | Tobacco Use Disorder | Tobacco Use Cessation | Second Hand Tobacco SmokeUnited States
-
University of California, San FranciscoNational Institute on Minority Health and Health Disparities (NIMHD)CompletedSmoking | Smoking Cessation | Tobacco Use | Tobacco Smoking | Tobacco Use Disorder | Tobacco Use Cessation | Tobacco Dependence | Smoking, Tobacco | Smoking, CigaretteUnited States
-
University of California, San FranciscoTobacco Related Disease Research ProgramCompletedSmoking | Smoking Cessation | Tobacco Use | Tobacco Smoking | Tobacco Use Disorder | Tobacco Use Cessation | Tobacco Dependence | Smoking, Tobacco | Smoking, CigaretteUnited States
-
New York State Psychiatric InstituteTerminatedSmoking | Smoking Cessation | Tobacco Use | Tobacco Smoking | Tobacco Use Disorder | Nicotine Dependence | Cigarette Smoking | Tobacco Dependence | Nicotine Use Disorder | Smoking, CigaretteUnited States
-
Rutgers, The State University of New JerseyNational Institute on Drug Abuse (NIDA)CompletedSchizophrenia | Schizoaffective Disorder | Tobacco Use | Tobacco Smoking | Tobacco Use Disorder | Tobacco Use CessationUnited States
-
University of PennsylvaniaFood and Drug Administration (FDA)Completed
-
University of Kansas Medical CenterCompletedTobacco Use Disorder/Cigarette SmokingUnited States
-
Ottawa Hospital Research InstituteCompletedTobacco Use Disorder | Tobacco Use Cessation | Tobacco Dependence
Clinical Trials on Laboratory Biomarker Analysis
-
Children's Oncology GroupNational Cancer Institute (NCI)Completed
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Active, not recruitingLeukemia | Acute Lymphoblastic Leukemia | Acute Promyelocytic LeukemiaUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedUntreated Adult Acute Lymphoblastic Leukemia | Untreated Childhood Acute Lymphoblastic LeukemiaUnited States, Canada, Australia, New Zealand, Puerto Rico, Switzerland
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedChildhood Acute Lymphoblastic Leukemia in Remission | Recurrent Childhood Acute Lymphoblastic LeukemiaUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)CompletedLung CancerUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Completed
-
Children's Oncology GroupNational Cancer Institute (NCI)WithdrawnClear Cell Renal Cell Carcinoma | Rhabdoid Tumor of the Kidney | Congenital Mesoblastic Nephroma | Childhood Kidney NeoplasmUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)WithdrawnBreast Carcinoma | BRCA1 Mutation Carrier | BRCA2 Mutation CarrierUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedWilms Tumor and Other Childhood Kidney TumorsUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedChildhood Acute Monoblastic Leukemia (M5a) | Childhood Acute Monocytic Leukemia (M5b) | Childhood Acute Myeloblastic Leukemia Without Maturation (M1) | Childhood Acute Myelomonocytic Leukemia (M4) | Childhood Acute Myeloid Leukemia/Other Myeloid MalignanciesUnited States