Trial Outcomes & Findings for Aspirin and Zileuton and Biomarker Expression in Nasal Tissue of Current Smokers (NCT NCT02348203)
NCT ID: NCT02348203
Last Updated: 2022-06-02
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
63 participants
Primary outcome timeframe
Baseline to 12 weeks (End-of-intervention)
Results posted on
2022-06-02
Participant Flow
Participant milestones
| Measure |
Arm I (Aspirin, Zileuton)
Patients receive aspirin PO QD and zileuton PO BID for 12 weeks in the absence of unacceptable toxicity.
Aspirin: Given PO
Laboratory Biomarker Analysis: Correlative studies
Zileuton: Given PO
|
Arm II (Double Placebo)
Patients receive aspirin placebo PO QD and zileuton placebo PO BID for 12 weeks.
Laboratory Biomarker Analysis: Correlative studies
Placebo Administration: Given aspirin placebo PO
Placebo Administration: Given zileuton placebo PO
|
|---|---|---|
|
Overall Study
STARTED
|
31
|
32
|
|
Overall Study
COMPLETED
|
21
|
22
|
|
Overall Study
NOT COMPLETED
|
10
|
10
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Aspirin and Zileuton and Biomarker Expression in Nasal Tissue of Current Smokers
Baseline characteristics by cohort
| Measure |
Arm I (Aspirin, Zileuton)
n=31 Participants
Patients receive aspirin PO QD and zileuton PO BID for 12 weeks in the absence of unacceptable toxicity.
Aspirin: Given PO
Laboratory Biomarker Analysis: Correlative studies
Zileuton: Given PO
|
Arm II (Double Placebo)
n=32 Participants
Patients receive aspirin placebo PO QD and zileuton placebo PO BID for 12 weeks.
Laboratory Biomarker Analysis: Correlative studies
Placebo Administration: Given aspirin placebo PO
Placebo Administration: Given zileuton placebo PO
|
Total
n=63 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
49.6 years
STANDARD_DEVIATION 8.6 • n=5 Participants
|
53.5 years
STANDARD_DEVIATION 10.7 • n=7 Participants
|
51.6 years
STANDARD_DEVIATION 9.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
36 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
28 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
56 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
28 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
52 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
31 participants
n=5 Participants
|
32 participants
n=7 Participants
|
63 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to 12 weeks (End-of-intervention)Population: The number of participants analyzed is different from the numbers provided in the Participant Flow Module because gene expression analysis was restricted to samples that met quality metrics.
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.
Outcome measures
| Measure |
Arm I (Aspirin, Zileuton)
n=19 Participants
Patients receive aspirin PO QD and zileuton PO BID for 12 weeks in the absence of unacceptable toxicity.
Aspirin: Given PO
Laboratory Biomarker Analysis: Correlative studies
Zileuton: Given PO
|
Arm II (Double Placebo)
n=21 Participants
Patients receive aspirin placebo PO QD and zileuton placebo PO BID for 12 weeks.
Laboratory Biomarker Analysis: Correlative studies
Placebo Administration: Given aspirin placebo PO
Placebo Administration: Given zileuton placebo PO
|
|---|---|---|
|
Changes in a Smoking-related Gene Expression Signature Score in the Nasal Epithelium of Current Smokers
|
-0.15 score on a scale
Standard Deviation 2.89
|
0.26 score on a scale
Standard Deviation 2.26
|
SECONDARY outcome
Timeframe: Baseline to 12 weeks (End of Intervention)Population: The number of participants analyzed is different from the numbers provided in the Participant Flow Module because gene expression analysis was restricted to samples that met quality metrics.
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.
Outcome measures
| Measure |
Arm I (Aspirin, Zileuton)
n=19 Participants
Patients receive aspirin PO QD and zileuton PO BID for 12 weeks in the absence of unacceptable toxicity.
Aspirin: Given PO
Laboratory Biomarker Analysis: Correlative studies
Zileuton: Given PO
|
Arm II (Double Placebo)
n=21 Participants
Patients receive aspirin placebo PO QD and zileuton placebo PO BID for 12 weeks.
Laboratory Biomarker Analysis: Correlative studies
Placebo Administration: Given aspirin placebo PO
Placebo Administration: Given zileuton placebo PO
|
|---|---|---|
|
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
bronchial smoking signature
|
-1.0 score on a scale
Standard Deviation 2.87
|
-0.43 score on a scale
Standard Deviation 3.37
|
|
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
PI3 pathway gene signature
|
-0.32 score on a scale
Standard Deviation 1.57
|
0.42 score on a scale
Standard Deviation 1.68
|
|
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
nasal diagnostic gene signature
|
1.82 score on a scale
Standard Deviation 8.63
|
2.17 score on a scale
Standard Deviation 11.21
|
SECONDARY outcome
Timeframe: Baseline to 14 days post interventionPopulation: The number of participants analyzed is different from the numbers provided in the Participant Flow Module because gene expression analysis was restricted to samples that met quality metrics.
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.
Outcome measures
| Measure |
Arm I (Aspirin, Zileuton)
n=19 Participants
Patients receive aspirin PO QD and zileuton PO BID for 12 weeks in the absence of unacceptable toxicity.
Aspirin: Given PO
Laboratory Biomarker Analysis: Correlative studies
Zileuton: Given PO
|
Arm II (Double Placebo)
n=21 Participants
Patients receive aspirin placebo PO QD and zileuton placebo PO BID for 12 weeks.
Laboratory Biomarker Analysis: Correlative studies
Placebo Administration: Given aspirin placebo PO
Placebo Administration: Given zileuton placebo PO
|
|---|---|---|
|
Changes in a Smoking-related Gene Expression Signature Score in the Nasal Epithelium of Current Smokers 10-14 Days Post Intervention
|
-0.24 score on a scale
Standard Deviation 3.04
|
-1.16 score on a scale
Standard Deviation 3.55
|
SECONDARY outcome
Timeframe: Baseline to 14 days post interventionPopulation: The number of participants analyzed is different from the numbers provided in the Participant Flow Module because gene expression analysis was restricted to samples that met quality metrics.
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.
Outcome measures
| Measure |
Arm I (Aspirin, Zileuton)
n=19 Participants
Patients receive aspirin PO QD and zileuton PO BID for 12 weeks in the absence of unacceptable toxicity.
Aspirin: Given PO
Laboratory Biomarker Analysis: Correlative studies
Zileuton: Given PO
|
Arm II (Double Placebo)
n=21 Participants
Patients receive aspirin placebo PO QD and zileuton placebo PO BID for 12 weeks.
Laboratory Biomarker Analysis: Correlative studies
Placebo Administration: Given aspirin placebo PO
Placebo Administration: Given zileuton placebo PO
|
|---|---|---|
|
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
bronchial signature
|
-1.37 score on a scale
Standard Deviation 2.69
|
0.88 score on a scale
Standard Deviation 3.71
|
|
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
PI3K pathway gene signature
|
-0.16 score on a scale
Standard Deviation 1.63
|
0.71 score on a scale
Standard Deviation 2.35
|
|
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
nasal diagnostic gene signature
|
2.78 score on a scale
Standard Deviation 6.35
|
-1.98 score on a scale
Standard Deviation 11.58
|
SECONDARY outcome
Timeframe: Baseline to 12 weeks (End-of-intervention)Outcome measures
| Measure |
Arm I (Aspirin, Zileuton)
n=21 Participants
Patients receive aspirin PO QD and zileuton PO BID for 12 weeks in the absence of unacceptable toxicity.
Aspirin: Given PO
Laboratory Biomarker Analysis: Correlative studies
Zileuton: Given PO
|
Arm II (Double Placebo)
n=22 Participants
Patients receive aspirin placebo PO QD and zileuton placebo PO BID for 12 weeks.
Laboratory Biomarker Analysis: Correlative studies
Placebo Administration: Given aspirin placebo PO
Placebo Administration: Given zileuton placebo PO
|
|---|---|---|
|
Change in Urinary PGE-M Levels
|
-5.9 ng/mg creatinine
Standard Deviation 13.9
|
0.71 ng/mg creatinine
Standard Deviation 9.3
|
SECONDARY outcome
Timeframe: Baseline to 12 weeks (End-of-intervention)Outcome measures
| Measure |
Arm I (Aspirin, Zileuton)
n=21 Participants
Patients receive aspirin PO QD and zileuton PO BID for 12 weeks in the absence of unacceptable toxicity.
Aspirin: Given PO
Laboratory Biomarker Analysis: Correlative studies
Zileuton: Given PO
|
Arm II (Double Placebo)
n=22 Participants
Patients receive aspirin placebo PO QD and zileuton placebo PO BID for 12 weeks.
Laboratory Biomarker Analysis: Correlative studies
Placebo Administration: Given aspirin placebo PO
Placebo Administration: Given zileuton placebo PO
|
|---|---|---|
|
Change in Urinary LTE (4) Levels
|
-57.6 pg/mg creatinine
Standard Deviation 65.6
|
35.2 pg/mg creatinine
Standard Deviation 92.7
|
SECONDARY outcome
Timeframe: Up to 2 weeks post-treatmentPopulation: All participants who have received at least one dose of the study agent.
Outcome measures
| Measure |
Arm I (Aspirin, Zileuton)
n=31 Participants
Patients receive aspirin PO QD and zileuton PO BID for 12 weeks in the absence of unacceptable toxicity.
Aspirin: Given PO
Laboratory Biomarker Analysis: Correlative studies
Zileuton: Given PO
|
Arm II (Double Placebo)
n=32 Participants
Patients receive aspirin placebo PO QD and zileuton placebo PO BID for 12 weeks.
Laboratory Biomarker Analysis: Correlative studies
Placebo Administration: Given aspirin placebo PO
Placebo Administration: Given zileuton placebo PO
|
|---|---|---|
|
Number of Participants Experiencing Possibly/Probably/Definitely-related Adverse Events
|
9 Participants
|
8 Participants
|
SECONDARY outcome
Timeframe: Baseline to 12 weeks (End-of-intervention)Population: The number of participants analyzed is different from the numbers provided in the Participant Flow Module because gene expression analysis was restricted to samples that met quality metrics.
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.
Outcome measures
| Measure |
Arm I (Aspirin, Zileuton)
n=19 Participants
Patients receive aspirin PO QD and zileuton PO BID for 12 weeks in the absence of unacceptable toxicity.
Aspirin: Given PO
Laboratory Biomarker Analysis: Correlative studies
Zileuton: Given PO
|
Arm II (Double Placebo)
n=21 Participants
Patients receive aspirin placebo PO QD and zileuton placebo PO BID for 12 weeks.
Laboratory Biomarker Analysis: Correlative studies
Placebo Administration: Given aspirin placebo PO
Placebo Administration: Given zileuton placebo PO
|
|---|---|---|
|
Gender Effect on Smoking-related Gene Expression Signature
Females
|
0.01 score on a scale
Standard Deviation 2.93
|
-0.20 score on a scale
Standard Deviation 2.01
|
|
Gender Effect on Smoking-related Gene Expression Signature
Males
|
-0.27 score on a scale
Standard Deviation 2.99
|
0.76 score on a scale
Standard Deviation 2.51
|
SECONDARY outcome
Timeframe: Baseline to 12 weeks (End-of-intervention)Population: Data were not collected.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 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
Outcome measures
| Measure |
Arm I (Aspirin, Zileuton)
n=19 Participants
Patients receive aspirin PO QD and zileuton PO BID for 12 weeks in the absence of unacceptable toxicity.
Aspirin: Given PO
Laboratory Biomarker Analysis: Correlative studies
Zileuton: Given PO
|
Arm II (Double Placebo)
n=21 Participants
Patients receive aspirin placebo PO QD and zileuton placebo PO BID for 12 weeks.
Laboratory Biomarker Analysis: Correlative studies
Placebo Administration: Given aspirin placebo PO
Placebo Administration: Given zileuton placebo PO
|
|---|---|---|
|
Number of Genes Differentially Expressed After Aspirin and Zileuton Intervention Compared to Placebo
|
83 gene
|
0 gene
|
SECONDARY outcome
Timeframe: Up to week 12Population: Data were not collected.
Outcome measures
Outcome data not reported
Adverse Events
Arm I (Aspirin, Zileuton)
Serious events: 0 serious events
Other events: 25 other events
Deaths: 0 deaths
Arm II (Double Placebo)
Serious events: 0 serious events
Other events: 17 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Arm I (Aspirin, Zileuton)
n=31 participants at risk
Patients receive aspirin PO QD and zileuton PO BID for 12 weeks in the absence of unacceptable toxicity.
Aspirin: Given PO
Laboratory Biomarker Analysis: Correlative studies
Zileuton: Given PO
|
Arm II (Double Placebo)
n=32 participants at risk
Patients receive aspirin placebo PO QD and zileuton placebo PO BID for 12 weeks.
Laboratory Biomarker Analysis: Correlative studies
Placebo Administration: Given aspirin placebo PO
Placebo Administration: Given zileuton placebo PO
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhea
|
6.5%
2/31 • Adverse event data were collected from the time that the first dose of study drug was taken until 2 weeks after participants come off the 12-week agent intervention.
|
3.1%
1/32 • Adverse event data were collected from the time that the first dose of study drug was taken until 2 weeks after participants come off the 12-week agent intervention.
|
|
Gastrointestinal disorders
Dyspepsia
|
16.1%
5/31 • Adverse event data were collected from the time that the first dose of study drug was taken until 2 weeks after participants come off the 12-week agent intervention.
|
12.5%
4/32 • Adverse event data were collected from the time that the first dose of study drug was taken until 2 weeks after participants come off the 12-week agent intervention.
|
|
Gastrointestinal disorders
Nausea
|
6.5%
2/31 • Adverse event data were collected from the time that the first dose of study drug was taken until 2 weeks after participants come off the 12-week agent intervention.
|
0.00%
0/32 • Adverse event data were collected from the time that the first dose of study drug was taken until 2 weeks after participants come off the 12-week agent intervention.
|
|
Gastrointestinal disorders
Vomiting
|
6.5%
2/31 • Adverse event data were collected from the time that the first dose of study drug was taken until 2 weeks after participants come off the 12-week agent intervention.
|
0.00%
0/32 • Adverse event data were collected from the time that the first dose of study drug was taken until 2 weeks after participants come off the 12-week agent intervention.
|
|
Investigations
Weight gain
|
9.7%
3/31 • Adverse event data were collected from the time that the first dose of study drug was taken until 2 weeks after participants come off the 12-week agent intervention.
|
3.1%
1/32 • Adverse event data were collected from the time that the first dose of study drug was taken until 2 weeks after participants come off the 12-week agent intervention.
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
6.5%
2/31 • Adverse event data were collected from the time that the first dose of study drug was taken until 2 weeks after participants come off the 12-week agent intervention.
|
0.00%
0/32 • Adverse event data were collected from the time that the first dose of study drug was taken until 2 weeks after participants come off the 12-week agent intervention.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
9.7%
3/31 • Adverse event data were collected from the time that the first dose of study drug was taken until 2 weeks after participants come off the 12-week agent intervention.
|
9.4%
3/32 • Adverse event data were collected from the time that the first dose of study drug was taken until 2 weeks after participants come off the 12-week agent intervention.
|
|
Nervous system disorders
Dizziness
|
6.5%
2/31 • Adverse event data were collected from the time that the first dose of study drug was taken until 2 weeks after participants come off the 12-week agent intervention.
|
3.1%
1/32 • Adverse event data were collected from the time that the first dose of study drug was taken until 2 weeks after participants come off the 12-week agent intervention.
|
|
Nervous system disorders
Headache
|
12.9%
4/31 • Adverse event data were collected from the time that the first dose of study drug was taken until 2 weeks after participants come off the 12-week agent intervention.
|
6.2%
2/32 • Adverse event data were collected from the time that the first dose of study drug was taken until 2 weeks after participants come off the 12-week agent intervention.
|
|
General disorders
Flu like symptoms
|
0.00%
0/31 • Adverse event data were collected from the time that the first dose of study drug was taken until 2 weeks after participants come off the 12-week agent intervention.
|
6.2%
2/32 • Adverse event data were collected from the time that the first dose of study drug was taken until 2 weeks after participants come off the 12-week agent intervention.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/31 • Adverse event data were collected from the time that the first dose of study drug was taken until 2 weeks after participants come off the 12-week agent intervention.
|
6.2%
2/32 • Adverse event data were collected from the time that the first dose of study drug was taken until 2 weeks after participants come off the 12-week agent intervention.
|
|
Investigations
Weight loss
|
0.00%
0/31 • Adverse event data were collected from the time that the first dose of study drug was taken until 2 weeks after participants come off the 12-week agent intervention.
|
6.2%
2/32 • Adverse event data were collected from the time that the first dose of study drug was taken until 2 weeks after participants come off the 12-week agent intervention.
|
|
Vascular disorders
Hypertension
|
0.00%
0/31 • Adverse event data were collected from the time that the first dose of study drug was taken until 2 weeks after participants come off the 12-week agent intervention.
|
6.2%
2/32 • Adverse event data were collected from the time that the first dose of study drug was taken until 2 weeks after participants come off the 12-week agent intervention.
|
|
Infections and infestations
Upper respiratory infection
|
0.00%
0/31 • Adverse event data were collected from the time that the first dose of study drug was taken until 2 weeks after participants come off the 12-week agent intervention.
|
6.2%
2/32 • Adverse event data were collected from the time that the first dose of study drug was taken until 2 weeks after participants come off the 12-week agent intervention.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60