Trial Outcomes & Findings for Bronchoscopy in Determining the Effect of E-Cigarette Smoking on Biomarkers in the Lungs (NCT NCT03691350)
NCT ID: NCT03691350
Last Updated: 2026-04-23
Results Overview
Obtained via bronchoscopy with saline bronchoalveolar lavage (BAL) and bronchial brushings. Descriptive statistics and clustering (e.g., principal components analysis \[PCA\]), will be performed for all biomarker data measured at the different visits. Baseline data (1st bronchoscopy) will then be compared between the four groups (3 conditions and control) using a one-way analysis of variance (ANOVA). The non-parametric Kruskal-Wallis test (continuous or ordinal variables) or the chi-square test (categorical variables) will be applied when the normality assumption of the data is not met. Controls will be compared to complete substitution with the standardized research electronic cigarettes (SREC) (with and without nicotine) or nicotine replacement therapy (NRT. Generalized linear models (GLM) will be employed with measurement (cell count, gene expression, etc.) as the dependent variable, a covariable for baseline measure, and a main effect of arm.
Recruitment status
COMPLETED
Study phase
EARLY_PHASE1
Target enrollment
66 participants
Primary outcome timeframe
Baseline to day 71
Results posted on
2026-04-23
Participant Flow
Subjects were withdrawn from the study post-consent if they did not meet eligibility criteria or chose not to participate.
Participant milestones
| Measure |
Group I (Usual Cigarette Brand)
Participants undergo bronchoscopy over 30-60 minutes at baseline. Participants continue to smoke their usual brand of cigarettes. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Cigarette: Smoke usual brand
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
|
Group II (SREC With Nicotine)
Participants undergo bronchoscopy over 30-60 minutes at baseline. After the baseline bronchoscopy, participants learn to use the SREC with nicotine for 2 weeks and switch completely to the SREC with nicotine starting day 15 for 8 weeks. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Electronic Cigarette: Smoke SREC with nicotine
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
|
Group III (SREC Without Nicotine)
Participants undergo bronchoscopy over 30-60 minutes at baseline. Beginning 1 week after bronchoscopy, participants learn to use the SREC without nicotine for 2 weeks and switch completely to the SREC without nicotine starting day 15 for 8 weeks. Participants will be offered varenicline to aid cessation. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Electronic Cigarette: Smoke SREC without nictoine
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
|
Group IV (Nicotine Replacement Therapy [NRT])
Participants undergo bronchoscopy over 30-60 minutes at baseline. One week before the day 15 quit date, participants stop smoking using NRT comprising either patch, gum, or lozenge for 8 weeks. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Laboratory Biomarker Analysis: Correlative studies
Nicotine Replacement: Receive NRT comprising patch, gum, or lozenge
Questionnaire Administration: Ancillary studies
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
11
|
9
|
10
|
5
|
|
Overall Study
COMPLETED
|
4
|
6
|
5
|
2
|
|
Overall Study
NOT COMPLETED
|
7
|
3
|
5
|
3
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Bronchoscopy in Determining the Effect of E-Cigarette Smoking on Biomarkers in the Lungs
Baseline characteristics by cohort
| Measure |
Group IV (Nicotine Replacement Therapy [NRT])
n=5 Participants
Participants undergo bronchoscopy over 30-60 minutes at baseline. One week before the day 15 quit date, participants stop smoking using NRT comprising either patch, gum, or lozenge for 8 weeks. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Laboratory Biomarker Analysis: Correlative studies
Nicotine Replacement: Receive NRT comprising patch, gum, or lozenge
Questionnaire Administration: Ancillary studies
|
Total
n=35 Participants
Total of all reporting groups
|
Group I (Usual Cigarette Brand)
n=11 Participants
Participants undergo bronchoscopy over 30-60 minutes at baseline. Participants continue to smoke their usual brand of cigarettes. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Cigarette: Smoke usual brand
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
|
Group II (SREC With Nicotine)
n=9 Participants
Participants undergo bronchoscopy over 30-60 minutes at baseline. After the baseline bronchoscopy, participants learn to use the SREC with nicotine for 2 weeks and switch completely to the SREC with nicotine starting day 15 for 8 weeks. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Electronic Cigarette: Smoke SREC with nicotine
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
|
Group III (SREC Without Nicotine)
n=10 Participants
Participants undergo bronchoscopy over 30-60 minutes at baseline. Beginning 1 week after bronchoscopy, participants learn to use the SREC without nicotine for 2 weeks and switch completely to the SREC without nicotine starting day 15 for 8 weeks. Participants will be offered varenicline to aid cessation. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Electronic Cigarette: Smoke SREC without nictoine
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
|
|---|---|---|---|---|---|
|
Age, Continuous
|
34.8 years
STANDARD_DEVIATION 6.9 • n=7 Participants
|
37.9 years
STANDARD_DEVIATION 7.4 • n=3 Participants
|
36.2 years
STANDARD_DEVIATION 8.3 • n=60 Participants
|
39.7 years
STANDARD_DEVIATION 5.4 • n=56 Participants
|
39.6 years
STANDARD_DEVIATION 8.7 • n=116 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=7 Participants
|
18 Participants
n=3 Participants
|
5 Participants
n=60 Participants
|
5 Participants
n=56 Participants
|
5 Participants
n=116 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=7 Participants
|
17 Participants
n=3 Participants
|
6 Participants
n=60 Participants
|
4 Participants
n=56 Participants
|
5 Participants
n=116 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=7 Participants
|
1 Participants
n=3 Participants
|
0 Participants
n=60 Participants
|
0 Participants
n=56 Participants
|
1 Participants
n=116 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
5 Participants
n=7 Participants
|
34 Participants
n=3 Participants
|
11 Participants
n=60 Participants
|
9 Participants
n=56 Participants
|
9 Participants
n=116 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=7 Participants
|
0 Participants
n=3 Participants
|
0 Participants
n=60 Participants
|
0 Participants
n=56 Participants
|
0 Participants
n=116 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=7 Participants
|
1 Participants
n=3 Participants
|
0 Participants
n=60 Participants
|
0 Participants
n=56 Participants
|
1 Participants
n=116 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=7 Participants
|
0 Participants
n=3 Participants
|
0 Participants
n=60 Participants
|
0 Participants
n=56 Participants
|
0 Participants
n=116 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=7 Participants
|
0 Participants
n=3 Participants
|
0 Participants
n=60 Participants
|
0 Participants
n=56 Participants
|
0 Participants
n=116 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=7 Participants
|
3 Participants
n=3 Participants
|
2 Participants
n=60 Participants
|
0 Participants
n=56 Participants
|
1 Participants
n=116 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=7 Participants
|
28 Participants
n=3 Participants
|
8 Participants
n=60 Participants
|
8 Participants
n=56 Participants
|
7 Participants
n=116 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=7 Participants
|
3 Participants
n=3 Participants
|
1 Participants
n=60 Participants
|
1 Participants
n=56 Participants
|
1 Participants
n=116 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=7 Participants
|
0 Participants
n=3 Participants
|
0 Participants
n=60 Participants
|
0 Participants
n=56 Participants
|
0 Participants
n=116 Participants
|
|
Region of Enrollment
United States
|
5 participants
n=7 Participants
|
35 participants
n=3 Participants
|
11 participants
n=60 Participants
|
9 participants
n=56 Participants
|
10 participants
n=116 Participants
|
PRIMARY outcome
Timeframe: Baseline to day 71Population: Descriptive analysis - mean of within subject change
Obtained via bronchoscopy with saline bronchoalveolar lavage (BAL) and bronchial brushings. Descriptive statistics and clustering (e.g., principal components analysis \[PCA\]), will be performed for all biomarker data measured at the different visits. Baseline data (1st bronchoscopy) will then be compared between the four groups (3 conditions and control) using a one-way analysis of variance (ANOVA). The non-parametric Kruskal-Wallis test (continuous or ordinal variables) or the chi-square test (categorical variables) will be applied when the normality assumption of the data is not met. Controls will be compared to complete substitution with the standardized research electronic cigarettes (SREC) (with and without nicotine) or nicotine replacement therapy (NRT. Generalized linear models (GLM) will be employed with measurement (cell count, gene expression, etc.) as the dependent variable, a covariable for baseline measure, and a main effect of arm.
Outcome measures
| Measure |
Group IV (Nicotine Replacement Therapy [NRT])
n=4 Samples
Participants undergo bronchoscopy over 30-60 minutes at baseline. One week before the day 15 quit date, participants stop smoking using NRT comprising either patch, gum, or lozenge for 8 weeks. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Laboratory Biomarker Analysis: Correlative studies
Nicotine Replacement: Receive NRT comprising patch, gum, or lozenge
Questionnaire Administration: Ancillary studies
|
Group I (Usual Cigarette Brand)
n=8 Samples
Participants undergo bronchoscopy over 30-60 minutes at baseline. Participants continue to smoke their usual brand of cigarettes. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Cigarette: Smoke usual brand
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
|
Group II (SREC With Nicotine)
n=12 Samples
Participants undergo bronchoscopy over 30-60 minutes at baseline. After the baseline bronchoscopy, participants learn to use the SREC with nicotine for 2 weeks and switch completely to the SREC with nicotine starting day 15 for 8 weeks. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Electronic Cigarette: Smoke SREC with nicotine
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
|
Group III (SREC Without Nicotine)
n=10 Samples
Participants undergo bronchoscopy over 30-60 minutes at baseline. Beginning 1 week after bronchoscopy, participants learn to use the SREC without nicotine for 2 weeks and switch completely to the SREC without nicotine starting day 15 for 8 weeks. Participants will be offered varenicline to aid cessation. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Electronic Cigarette: Smoke SREC without nictoine
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
|
|---|---|---|---|---|
|
Changes in Cytokines
IL.12p70..pg.ml.
|
0.02638 pg/ml
Standard Deviation 0.0767
|
0.02283 pg/ml
Standard Deviation 0.09368
|
-0.01303 pg/ml
Standard Deviation 0.05229
|
-0.1596 pg/ml
Standard Deviation 0.07308
|
|
Changes in Cytokines
TNF.a..pg.ml.
|
0.07065 pg/ml
Standard Deviation 0.01902
|
0.04016 pg/ml
Standard Deviation 0.1505
|
-0.04686 pg/ml
Standard Deviation 0.1702
|
-0.07742 pg/ml
Standard Deviation 0.2066
|
|
Changes in Cytokines
IL.13..pg.ml.
|
-0.1842 pg/ml
Standard Deviation 0.7568
|
0.2066 pg/ml
Standard Deviation 0.7857
|
-0.1103 pg/ml
Standard Deviation 0.2917
|
-0.8337 pg/ml
Standard Deviation 0.7446
|
|
Changes in Cytokines
IL.1B..pg.ml.
|
-1.05 pg/ml
Standard Deviation 0.5547
|
0.5406 pg/ml
Standard Deviation 3.443
|
-0.7182 pg/ml
Standard Deviation 1.55
|
-0.9908 pg/ml
Standard Deviation 1.737
|
|
Changes in Cytokines
IL.2..pg.ml.
|
0.1856 pg/ml
Standard Deviation 0.2435
|
0.1987 pg/ml
Standard Deviation 0.1069
|
-0.1263 pg/ml
Standard Deviation 0.1346
|
-0.349 pg/ml
Standard Deviation 0.2486
|
|
Changes in Cytokines
IL.4..pg.ml.
|
-0.0005731 pg/ml
Standard Deviation 0.04561
|
0.03686 pg/ml
Standard Deviation 0.02152
|
0.01534 pg/ml
Standard Deviation 0.02481
|
-0.04491 pg/ml
Standard Deviation 0.02173
|
|
Changes in Cytokines
IL.6..pg.ml.
|
-2.371 pg/ml
Standard Deviation 2.574
|
-0.8534 pg/ml
Standard Deviation 2.307
|
-0.041 pg/ml
Standard Deviation 1.871
|
-3.166 pg/ml
Standard Deviation 6.037
|
|
Changes in Cytokines
IL.8..pg.ml.
|
3.302 pg/ml
Standard Deviation 26.65
|
-15.98 pg/ml
Standard Deviation 55.62
|
-7.757 pg/ml
Standard Deviation 38.18
|
-66.47 pg/ml
Standard Deviation 114.9
|
|
Changes in Cytokines
IFN.g..pg.ml.
|
-0.05875 pg/ml
Standard Deviation 0.03597
|
0.2473 pg/ml
Standard Deviation 0.3059
|
-0.04988 pg/ml
Standard Deviation 0.2939
|
-0.1137 pg/ml
Standard Deviation 0.2185
|
|
Changes in Cytokines
IL.10..pg.ml.
|
-0.01876 pg/ml
Standard Deviation 0.01566
|
0.04439 pg/ml
Standard Deviation 0.06116
|
-0.01088 pg/ml
Standard Deviation 0.03202
|
-0.0847 pg/ml
Standard Deviation 0.04652
|
PRIMARY outcome
Timeframe: Baseline to day 71Population: Descriptive analysis - mean of within subject change
Obtained via bronchoscopy with saline bronchoalveolar lavage (BAL) and bronchial brushings. Descriptive statistics and clustering (e.g., principal components analysis \[PCA\]), will be performed for all biomarker data measured at the different visits. Baseline data (1st bronchoscopy) will then be compared between the four groups (3 conditions and control) using a one-way analysis of variance (ANOVA). The non-parametric Kruskal-Wallis test (continuous or ordinal variables) or the chi-square test (categorical variables) will be applied when the normality assumption of the data is not met. Controls will be compared to complete substitution with the standardized research electronic cigarettes (SREC) (with and without nicotine) or nicotine replacement therapy (NRT. Generalized linear models (GLM) will be employed with measurement (cell count, gene expression, etc.) as the dependent variable, a covariable for baseline measure, and a main effect of arm.
Outcome measures
| Measure |
Group IV (Nicotine Replacement Therapy [NRT])
n=4 Samples
Participants undergo bronchoscopy over 30-60 minutes at baseline. One week before the day 15 quit date, participants stop smoking using NRT comprising either patch, gum, or lozenge for 8 weeks. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Laboratory Biomarker Analysis: Correlative studies
Nicotine Replacement: Receive NRT comprising patch, gum, or lozenge
Questionnaire Administration: Ancillary studies
|
Group I (Usual Cigarette Brand)
n=8 Samples
Participants undergo bronchoscopy over 30-60 minutes at baseline. Participants continue to smoke their usual brand of cigarettes. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Cigarette: Smoke usual brand
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
|
Group II (SREC With Nicotine)
n=12 Samples
Participants undergo bronchoscopy over 30-60 minutes at baseline. After the baseline bronchoscopy, participants learn to use the SREC with nicotine for 2 weeks and switch completely to the SREC with nicotine starting day 15 for 8 weeks. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Electronic Cigarette: Smoke SREC with nicotine
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
|
Group III (SREC Without Nicotine)
n=10 Samples
Participants undergo bronchoscopy over 30-60 minutes at baseline. Beginning 1 week after bronchoscopy, participants learn to use the SREC without nicotine for 2 weeks and switch completely to the SREC without nicotine starting day 15 for 8 weeks. Participants will be offered varenicline to aid cessation. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Electronic Cigarette: Smoke SREC without nictoine
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
|
|---|---|---|---|---|
|
Changes in Cell Counts
Cell.concentration..cells.ml.
|
-340625 cells/ml
Standard Deviation 437522
|
367938 cells/ml
Standard Deviation 557773
|
-42479 cells/ml
Standard Deviation 194150
|
-147825 cells/ml
Standard Deviation 517646
|
|
Changes in Cell Counts
Macrophages
|
2.5 cells/ml
Standard Deviation 6.364
|
4.25 cells/ml
Standard Deviation 9.179
|
-4.667 cells/ml
Standard Deviation 10.48
|
-8 cells/ml
Standard Deviation 18.32
|
|
Changes in Cell Counts
Neutrophils
|
-3 cells/ml
Standard Deviation 0
|
0.25 cells/ml
Standard Deviation 1.708
|
1.333 cells/ml
Standard Deviation 5.538
|
-8 cells/ml
Standard Deviation 18.32
|
|
Changes in Cell Counts
Lymphocytes
|
2 cells/ml
Standard Deviation 7.071
|
-4.25 cells/ml
Standard Deviation 7.274
|
3.167 cells/ml
Standard Deviation 6.274
|
8.8 cells/ml
Standard Deviation 16.12
|
|
Changes in Cell Counts
Eosinophils
|
-1.5 cells/ml
Standard Deviation 0.7071
|
-0.25 cells/ml
Standard Deviation 0.5
|
0.1667 cells/ml
Standard Deviation 0.4082
|
0 cells/ml
Standard Deviation 1
|
SECONDARY outcome
Timeframe: Baseline up to day 71Population: Subjects completing two bronchoscopy procedures
FeNO will be measured with the NIOX VERO. Descriptive statistics and clustering (e.g. PCA), will be performed for all biomarker data measured at the different visits. Baseline data (1st bronchoscopy) will then be compared between the four groups (3 conditions and control) using a one-way ANOVA. The non-parametric Kruskal-Wallis test (continuous or ordinal variables) or the chi-square test (categorical variables) will be applied when the normality assumption of the data is not met. Controls will be compared to complete substitution with the SREC (with and without nicotine) or NRT. GLM will be employed with measurement (cell count, gene expression, etc.) as the dependent variable, a covariable for baseline measure, and a main effect of arm.
Outcome measures
| Measure |
Group IV (Nicotine Replacement Therapy [NRT])
n=4 Exhaled breath
Participants undergo bronchoscopy over 30-60 minutes at baseline. One week before the day 15 quit date, participants stop smoking using NRT comprising either patch, gum, or lozenge for 8 weeks. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Laboratory Biomarker Analysis: Correlative studies
Nicotine Replacement: Receive NRT comprising patch, gum, or lozenge
Questionnaire Administration: Ancillary studies
|
Group I (Usual Cigarette Brand)
n=8 Exhaled breath
Participants undergo bronchoscopy over 30-60 minutes at baseline. Participants continue to smoke their usual brand of cigarettes. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Cigarette: Smoke usual brand
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
|
Group II (SREC With Nicotine)
n=12 Exhaled breath
Participants undergo bronchoscopy over 30-60 minutes at baseline. After the baseline bronchoscopy, participants learn to use the SREC with nicotine for 2 weeks and switch completely to the SREC with nicotine starting day 15 for 8 weeks. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Electronic Cigarette: Smoke SREC with nicotine
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
|
Group III (SREC Without Nicotine)
n=10 Exhaled breath
Participants undergo bronchoscopy over 30-60 minutes at baseline. Beginning 1 week after bronchoscopy, participants learn to use the SREC without nicotine for 2 weeks and switch completely to the SREC without nicotine starting day 15 for 8 weeks. Participants will be offered varenicline to aid cessation. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Electronic Cigarette: Smoke SREC without nictoine
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
|
|---|---|---|---|---|
|
Changes in Fractional Exhaled Nitric Oxide (FeNO) Levels
|
-0.5 PPM
Standard Deviation 4.95
|
0 PPM
Standard Deviation 4.08
|
3.5 PPM
Standard Deviation 5.01
|
1.2 PPM
Standard Deviation 6.10
|
SECONDARY outcome
Timeframe: Baseline up to day 71Population: Only a fraction of the anticipated number of samples were collected, preventing completion of testing and analysis. Recruitment was adversely affected by several challenges, including COVID-19 and manufacturer-related product delays. As a result, the target sample size was not achieved, and no further analysis is planned at this time.
Total RNA containing small RNAs will be extracted from bronchial brushing specimens using commercially available kits and used for both gene expression using the Affymetrix GeneChip Human Transcriptome Array and for miRNA expression using the Affymetrix GeneChip miRNA Array. Expression will separately be assessed through RNA sequencing. Total RNA will be extracted from lavage cells and saliva for comprehensive profiling of microbiome using commercially available kits. The ?omics? (miRNA, mRNA, and metabolomics) analysis and visualization of the data will be performed in the R statistical language. Data will be log2-transformed and normalized using either quantile normalization for gene expression (miRNA and mRNA) or normalization for metabolomics. Unsupervised clustering analysis, including PCA and hierarchical clustering will be performed to visualize natural clusters in the dataset and evaluate data quality.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline up to day 71Population: Only a fraction of the anticipated number of samples were collected, preventing completion of testing and analysis. Recruitment was adversely affected by several challenges, including COVID-19 and manufacturer-related product delays. As a result, the target sample size was not achieved, and no further analysis is planned at this time.
Total DNA will be extracted using commercially available kits and used for genome-wide DNA methylation profiling. Total DNA including mitochondrial DNA (mtDNA) will be extracted using commercially available kits and used for mtDNA mutation using Hiseq Next Generation Sequencing (NGS) and for mtDNA contents using quantitative polymerase chain reaction (qPCR). For preliminary identification of patterns in DNA methylation, unsupervised hierarchical clustering among the groups of samples will be performed. The Euclidian distance among the groups of samples will be calculated by the average linkage. In order to assess variance among samples, PCA will be done.
Outcome measures
| Measure |
Group IV (Nicotine Replacement Therapy [NRT])
Participants undergo bronchoscopy over 30-60 minutes at baseline. One week before the day 15 quit date, participants stop smoking using NRT comprising either patch, gum, or lozenge for 8 weeks. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Laboratory Biomarker Analysis: Correlative studies
Nicotine Replacement: Receive NRT comprising patch, gum, or lozenge
Questionnaire Administration: Ancillary studies
|
Group I (Usual Cigarette Brand)
Participants undergo bronchoscopy over 30-60 minutes at baseline. Participants continue to smoke their usual brand of cigarettes. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Cigarette: Smoke usual brand
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
|
Group II (SREC With Nicotine)
Participants undergo bronchoscopy over 30-60 minutes at baseline. After the baseline bronchoscopy, participants learn to use the SREC with nicotine for 2 weeks and switch completely to the SREC with nicotine starting day 15 for 8 weeks. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Electronic Cigarette: Smoke SREC with nicotine
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
|
Group III (SREC Without Nicotine)
Participants undergo bronchoscopy over 30-60 minutes at baseline. Beginning 1 week after bronchoscopy, participants learn to use the SREC without nicotine for 2 weeks and switch completely to the SREC without nicotine starting day 15 for 8 weeks. Participants will be offered varenicline to aid cessation. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Electronic Cigarette: Smoke SREC without nictoine
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
|
|---|---|---|---|---|
|
Changes in Deoxyribonucleic Acid (DNA) Gene Methylation
|
0 Samples
|
0 Samples
|
0 Samples
|
0 Samples
|
SECONDARY outcome
Timeframe: Baseline up to day 71Population: Only a fraction of the anticipated number of samples were collected, preventing completion of testing and analysis. Recruitment was adversely affected by several challenges, including COVID-19 and manufacturer-related product delays. As a result, the target sample size was not achieved, and no further analysis is planned at this time.
Obtained via bronchoscopy with saline BAL and bronchial brushings. Samples will be analyzed to determine their bacterial composition.
Outcome measures
| Measure |
Group IV (Nicotine Replacement Therapy [NRT])
Participants undergo bronchoscopy over 30-60 minutes at baseline. One week before the day 15 quit date, participants stop smoking using NRT comprising either patch, gum, or lozenge for 8 weeks. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Laboratory Biomarker Analysis: Correlative studies
Nicotine Replacement: Receive NRT comprising patch, gum, or lozenge
Questionnaire Administration: Ancillary studies
|
Group I (Usual Cigarette Brand)
Participants undergo bronchoscopy over 30-60 minutes at baseline. Participants continue to smoke their usual brand of cigarettes. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Cigarette: Smoke usual brand
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
|
Group II (SREC With Nicotine)
Participants undergo bronchoscopy over 30-60 minutes at baseline. After the baseline bronchoscopy, participants learn to use the SREC with nicotine for 2 weeks and switch completely to the SREC with nicotine starting day 15 for 8 weeks. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Electronic Cigarette: Smoke SREC with nicotine
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
|
Group III (SREC Without Nicotine)
Participants undergo bronchoscopy over 30-60 minutes at baseline. Beginning 1 week after bronchoscopy, participants learn to use the SREC without nicotine for 2 weeks and switch completely to the SREC without nicotine starting day 15 for 8 weeks. Participants will be offered varenicline to aid cessation. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Electronic Cigarette: Smoke SREC without nictoine
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
|
|---|---|---|---|---|
|
Changes in the Microbiome in BAL Cells and Saliva
|
0 Samples
|
0 Samples
|
0 Samples
|
0 Samples
|
SECONDARY outcome
Timeframe: Baseline up to day 71Population: Only a fraction of the anticipated number of samples were collected, preventing completion of testing and analysis. Recruitment was adversely affected by several challenges, including COVID-19 and manufacturer-related product delays. As a result, the target sample size was not achieved, and no further analysis is planned at this time.
Obtained via bronchoscopy with saline BAL and bronchial brushings. The omics (miRNA, mRNA, and metabolomics) analysis and visualization of the data will be performed in the R statistical language. Data will be log2-transformed and normalized using either quantile normalization for gene expression (miRNA and mRNA) or normalization for metabolomics. Unsupervised clustering analysis, including PCA and hierarchical clustering will be performed to visualize natural clusters in the dataset and evaluate data quality.
Outcome measures
| Measure |
Group IV (Nicotine Replacement Therapy [NRT])
Participants undergo bronchoscopy over 30-60 minutes at baseline. One week before the day 15 quit date, participants stop smoking using NRT comprising either patch, gum, or lozenge for 8 weeks. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Laboratory Biomarker Analysis: Correlative studies
Nicotine Replacement: Receive NRT comprising patch, gum, or lozenge
Questionnaire Administration: Ancillary studies
|
Group I (Usual Cigarette Brand)
Participants undergo bronchoscopy over 30-60 minutes at baseline. Participants continue to smoke their usual brand of cigarettes. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Cigarette: Smoke usual brand
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
|
Group II (SREC With Nicotine)
Participants undergo bronchoscopy over 30-60 minutes at baseline. After the baseline bronchoscopy, participants learn to use the SREC with nicotine for 2 weeks and switch completely to the SREC with nicotine starting day 15 for 8 weeks. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Electronic Cigarette: Smoke SREC with nicotine
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
|
Group III (SREC Without Nicotine)
Participants undergo bronchoscopy over 30-60 minutes at baseline. Beginning 1 week after bronchoscopy, participants learn to use the SREC without nicotine for 2 weeks and switch completely to the SREC without nicotine starting day 15 for 8 weeks. Participants will be offered varenicline to aid cessation. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Electronic Cigarette: Smoke SREC without nictoine
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
|
|---|---|---|---|---|
|
Changes in Untargeted Metabolomics Using Mass Spectrometry
|
0 Samples
|
0 Samples
|
0 Samples
|
0 Samples
|
Adverse Events
Group I (Usual Cigarette Brand)
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Group II (SREC With Nicotine)
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Group III (SREC Without Nicotine)
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Group IV (Nicotine Replacement Therapy [NRT])
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Group I (Usual Cigarette Brand)
n=11 participants at risk
Participants undergo bronchoscopy over 30-60 minutes at baseline. Participants continue to smoke their usual brand of cigarettes. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Cigarette: Smoke usual brand
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
|
Group II (SREC With Nicotine)
n=9 participants at risk
Participants undergo bronchoscopy over 30-60 minutes at baseline. After the baseline bronchoscopy, participants learn to use the SREC with nicotine for 2 weeks and switch completely to the SREC with nicotine starting day 15 for 8 weeks. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Electronic Cigarette: Smoke SREC with nicotine
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
|
Group III (SREC Without Nicotine)
n=10 participants at risk
Participants undergo bronchoscopy over 30-60 minutes at baseline. Beginning 1 week after bronchoscopy, participants learn to use the SREC without nicotine for 2 weeks and switch completely to the SREC without nicotine starting day 15 for 8 weeks. Participants will be offered varenicline to aid cessation. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Electronic Cigarette: Smoke SREC without nictoine
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
|
Group IV (Nicotine Replacement Therapy [NRT])
n=5 participants at risk
Participants undergo bronchoscopy over 30-60 minutes at baseline. One week before the day 15 quit date, participants stop smoking using NRT comprising either patch, gum, or lozenge for 8 weeks. Participants undergo a second bronchoscopy on day 71.
Bronchoscopy with Bronchoalveolar Lavage: Undergo bronchoscopy with bronchoalveolar lavage
Laboratory Biomarker Analysis: Correlative studies
Nicotine Replacement: Receive NRT comprising patch, gum, or lozenge
Questionnaire Administration: Ancillary studies
|
|---|---|---|---|---|
|
Nervous system disorders
Mild headache (non-migraine)
|
0.00%
0/11 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
44.4%
4/9 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
20.0%
2/10 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
20.0%
1/5 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
|
Respiratory, thoracic and mediastinal disorders
Mild throat irritation
|
9.1%
1/11 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
22.2%
2/9 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
20.0%
2/10 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
0.00%
0/5 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
|
Nervous system disorders
Mild irritability (mood)
|
0.00%
0/11 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
22.2%
2/9 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
0.00%
0/10 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
0.00%
0/5 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
|
Respiratory, thoracic and mediastinal disorders
Mild productive cough
|
9.1%
1/11 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
44.4%
4/9 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
0.00%
0/10 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
0.00%
0/5 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
|
Respiratory, thoracic and mediastinal disorders
Mild dry mouth
|
0.00%
0/11 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
22.2%
2/9 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
0.00%
0/10 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
0.00%
0/5 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
|
Respiratory, thoracic and mediastinal disorders
Mild hoarseness of voice
|
9.1%
1/11 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
0.00%
0/9 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
20.0%
2/10 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
60.0%
3/5 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
|
Respiratory, thoracic and mediastinal disorders
Mild phlegm without cough
|
9.1%
1/11 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
33.3%
3/9 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
20.0%
2/10 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
40.0%
2/5 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
|
Respiratory, thoracic and mediastinal disorders
Mild sore throat
|
54.5%
6/11 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
66.7%
6/9 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
50.0%
5/10 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
40.0%
2/5 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
|
Respiratory, thoracic and mediastinal disorders
Mild dry cough
|
54.5%
6/11 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
44.4%
4/9 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
50.0%
5/10 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
100.0%
5/5 • Reported AE's were collected from the first bronchoscopy through the follow-up period (6 months)
|
Additional Information
Dr. Peter G. Shields
Ohio State University Comprehensive Cancer Center
Phone: 614-688-6563
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place