Trial Outcomes & Findings for Intermittent or Continuous Acetylsalicylic Acid and Gene Expression in the Nasal Tissue of Current Smokers (NCT NCT02123849)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

54 participants

Primary outcome timeframe

Baseline to 12 weeks (End-of-Intervention)

Results posted on

2018-08-29

Participant Flow

Participant milestones

Participant milestones
Measure	Arm I (Continuous Aspirin) Participants receive aspirin PO QD for 12 weeks. Aspirin: Given PO Laboratory Biomarker Analysis: Correlative studies	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. Aspirin: Given PO Laboratory Biomarker Analysis: Correlative studies Placebo: Given PO
Overall Study STARTED	27	27
Overall Study COMPLETED	23	18
Overall Study NOT COMPLETED	4	9

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I (Continuous Aspirin) n=27 Participants Participants receive aspirin PO QD for 12 weeks. Aspirin: Given PO Laboratory Biomarker Analysis: Correlative studies	Arm II (Intermittent Aspirin) n=27 Participants 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. Aspirin: Given PO Laboratory Biomarker Analysis: Correlative studies Placebo: Given PO	Total n=54 Participants Total of all reporting groups
Age, Continuous	52 years STANDARD_DEVIATION 8 • n=5 Participants	52 years STANDARD_DEVIATION 8 • n=7 Participants	52 years STANDARD_DEVIATION 8 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	12 Participants n=7 Participants	24 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	15 Participants n=7 Participants	30 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	21 Participants n=5 Participants	23 Participants n=7 Participants	44 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	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 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	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	24 Participants n=5 Participants	21 Participants n=7 Participants	45 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	2 Participants n=7 Participants	2 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

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 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

Outcome measures
Measure	Arm I (Continuous Aspirin) n=22 Participants Participants receive aspirin PO QD for 12 weeks. Aspirin: Given PO Laboratory Biomarker Analysis: Correlative studies	Arm II (Intermittent Aspirin) n=14 Participants 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. Aspirin: Given PO Laboratory Biomarker Analysis: Correlative studies Placebo: Given PO
Changes in Smoking-related Gene Expression Signature Score in Nasal Epithelium	-1.11 gene expression signature score Standard Deviation 4.05	1.39 gene expression signature score Standard Deviation 4.41

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Arm I (Continuous Aspirin) n=23 Participants Participants receive aspirin PO QD for 12 weeks. Aspirin: Given PO Laboratory Biomarker Analysis: Correlative studies	Arm II (Intermittent Aspirin) n=18 Participants 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. Aspirin: Given PO Laboratory Biomarker Analysis: Correlative studies Placebo: Given PO
Changes in Urine Leukotriene E4 (LTE(4)) Levels	-6.89 pg/mg creatinine Standard Deviation 95.16	-21.90 pg/mg creatinine Standard Deviation 309.8

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Arm I (Continuous Aspirin) n=23 Participants Participants receive aspirin PO QD for 12 weeks. Aspirin: Given PO Laboratory Biomarker Analysis: Correlative studies	Arm II (Intermittent Aspirin) n=18 Participants 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. Aspirin: Given PO Laboratory Biomarker Analysis: Correlative studies Placebo: Given PO
Changes in Urine Prostaglandin E2 Metabolite (PGE-M) Levels	-3.73 ng/mg creatinine Standard Deviation 9.69	-5.59 ng/mg creatinine Standard Deviation 13.74

SECONDARY outcome

Timeframe: Up to 2 weeks post-treatment

Outcome measures

Outcome measures
Measure	Arm I (Continuous Aspirin) n=27 Participants Participants receive aspirin PO QD for 12 weeks. Aspirin: Given PO Laboratory Biomarker Analysis: Correlative studies	Arm II (Intermittent Aspirin) n=27 Participants 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. Aspirin: Given PO Laboratory Biomarker Analysis: Correlative studies Placebo: Given PO
Number of Participants Experiencing Possibly/Probably/Definitely-related Adverse Events	3 Participants	4 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 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.

Outcome measures

Outcome measures
Measure	Arm I (Continuous Aspirin) n=18 Participants Participants receive aspirin PO QD for 12 weeks. Aspirin: Given PO Laboratory Biomarker Analysis: Correlative studies	Arm II (Intermittent Aspirin) n=18 Participants 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. Aspirin: Given PO Laboratory Biomarker Analysis: Correlative studies Placebo: Given PO
Gender Effect on Smoking-related Gene Expression Signature Score	0.45 gene expression signature score Standard Deviation 5.04	-0.72 gene expression signature score Standard Deviation 3.48

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 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.

Outcome measures

Outcome measures
Measure	Arm I (Continuous Aspirin) n=22 Participants Participants receive aspirin PO QD for 12 weeks. Aspirin: Given PO Laboratory Biomarker Analysis: Correlative studies	Arm II (Intermittent Aspirin) n=14 Participants 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. Aspirin: Given PO Laboratory Biomarker Analysis: Correlative studies Placebo: Given PO
Changes in Lung Cancer-related Gene Expression Signature Score in the Nasal Epithelium	-0.03 gene expression signature score Standard Deviation 0.12	0.04 gene expression signature score Standard Deviation 0.11

SECONDARY outcome

Timeframe: Baseline to 1 week post-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 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.

Outcome measures

Outcome measures
Measure	Arm I (Continuous Aspirin) n=21 Participants Participants receive aspirin PO QD for 12 weeks. Aspirin: Given PO Laboratory Biomarker Analysis: Correlative studies	Arm II (Intermittent Aspirin) n=14 Participants 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. Aspirin: Given PO Laboratory Biomarker Analysis: Correlative studies Placebo: Given PO
Persistence of the Change in the Lung Cancer-related Gene Expression Signature Score in the Nasal Epithelium One Week Off Agent Intervention	-0.04 gene expression signature score Standard Deviation 0.09	0.02 gene expression signature score Standard Deviation 0.1

SECONDARY outcome

Timeframe: Baseline to 1 week post-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 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.

Outcome measures

Outcome measures
Measure	Arm I (Continuous Aspirin) n=21 Participants Participants receive aspirin PO QD for 12 weeks. Aspirin: Given PO Laboratory Biomarker Analysis: Correlative studies	Arm II (Intermittent Aspirin) n=14 Participants 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. Aspirin: Given PO Laboratory Biomarker Analysis: Correlative studies Placebo: Given PO
Persistence of the Change in the Smoking-related Gene Expression Signature Score in the Nasal Epithelium One Week Off Agent Intervention	-1.95 gene expression signature score Standard Deviation 3.42	-0.1 gene expression signature score Standard Deviation 3.38

SECONDARY outcome

Timeframe: Baseline to 12 weeks

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.

Gene set enrichment analysis was performed on the MSigDB canonical pathways with the intent to discover differentially expressed genes after aspirin intervention.

Outcome measures

Outcome measures
Measure	Arm I (Continuous Aspirin) n=22 Participants Participants receive aspirin PO QD for 12 weeks. Aspirin: Given PO Laboratory Biomarker Analysis: Correlative studies	Arm II (Intermittent Aspirin) n=14 Participants 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. Aspirin: Given PO Laboratory Biomarker Analysis: Correlative studies Placebo: Given PO
Whole-genome Gene Expression - Number of Canonical Pathways Differentially Expressed	301 canonical pathway	120 canonical pathway

SECONDARY outcome

Timeframe: Baseline to up to one week post-intervention

Population: Data were not collected

Outcome measures

Outcome data not reported

Adverse Events

Arm I (Continuous Aspirin)

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Arm II (Intermittent Aspirin)

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Arm I (Continuous Aspirin) n=27 participants at risk Participants receive aspirin PO QD for 12 weeks. Aspirin: Given PO Laboratory Biomarker Analysis: Correlative studies	Arm II (Intermittent Aspirin) n=27 participants at risk 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. Aspirin: Given PO Laboratory Biomarker Analysis: Correlative studies Placebo: Given PO
Gastrointestinal disorders Dyspepsia	7.4% 2/27 • 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.	7.4% 2/27 • 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.
Injury, poisoning and procedural complications Upper Respiratory Infection	7.4% 2/27 • 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.	14.8% 4/27 • 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 syndromes	3.7% 1/27 • 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.	7.4% 2/27 • 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.
Injury, poisoning and procedural complications Bruising	0.00% 0/27 • 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.	7.4% 2/27 • 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.
Injury, poisoning and procedural complications Fall	3.7% 1/27 • 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.	7.4% 2/27 • 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.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications, others	3.7% 1/27 • 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.	7.4% 2/27 • 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	14.8% 4/27 • 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.	11.1% 3/27 • 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% 0/27 • 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.	18.5% 5/27 • 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	0.00% 0/27 • 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.	7.4% 2/27 • 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.
Pregnancy, puerperium and perinatal conditions Headache	11.1% 3/27 • 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.	11.1% 3/27 • 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 Dehydration	7.4% 2/27 • 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% 0/27 • 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.
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/27 • 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.	7.4% 2/27 • 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.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	7.4% 2/27 • 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% 0/27 • 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	0.00% 0/27 • 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.	7.4% 2/27 • 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

Dr. Sherry Chow

University of Arizona

Phone: 5206263358

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60