Bronchoscopy in Determining the Effect of E-Cigarette Smoking on Biomarkers in the Lungs

NCT03691350 | Completed Early Phase 1 Results DMC FDA Drug

• 3 other identifiers: OSU-18044NCI-2018-00283U01DA045530
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

This trial studies biomarkers obtained by bronchoscopy (bronchoalveolar lavage and lung brushings) to determine the effect of smoking e-cigarettes on the lungs. Studying samples of lung cells from participants who smoke e-cigarettes may help doctors learn more about changes that occur in deoxyribonucleic acid and identify biomarkers related to cancer.

Conditions

Cigarette Smoker; Current Every Day Smoker

Outcome Measures

Primary Outcomes (2)

• Changes in Cytokines

  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.

  Baseline to day 71

• Changes in Cell Counts

  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.

  Baseline to day 71

Secondary Outcomes (5)

• Changes in Fractional Exhaled Nitric Oxide (FeNO) Levels

  Baseline up to day 71

• Changes in Messenger (m) Ribonucleic Acid (RNA) and microRNA (miRNA) Gene Expression Analyzed Using Sequencing

  Baseline up to day 71

• Changes in Deoxyribonucleic Acid (DNA) Gene Methylation

  Baseline up to day 71

• Changes in the Microbiome in BAL Cells and Saliva

  Baseline up to day 71

• Changes in Untargeted Metabolomics Using Mass Spectrometry

  Baseline up to day 71

Study Arms (4)

Group I (usual cigarette brand)

ACTIVE COMPARATOR

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.

Procedure: Bronchoscopy with Bronchoalveolar Lavage; Drug: Cigarette; Other: Laboratory Biomarker Analysis; Other: Questionnaire Administration

Group II (SREC with nicotine)

EXPERIMENTAL

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.

Procedure: Bronchoscopy with Bronchoalveolar Lavage; Other: Electronic Cigarette; Other: Laboratory Biomarker Analysis; Other: Questionnaire Administration

Group III (SREC without nicotine)

EXPERIMENTAL

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.

Procedure: Bronchoscopy with Bronchoalveolar Lavage; Other: Electronic Cigarette; Other: Laboratory Biomarker Analysis; Other: Questionnaire Administration

Group IV (Nicotine Replacement Therapy [NRT])

EXPERIMENTAL

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.

Procedure: Bronchoscopy with Bronchoalveolar Lavage; Other: Laboratory Biomarker Analysis; Drug: Nicotine Replacement; Other: Questionnaire Administration

Interventions

Bronchoscopy with Bronchoalveolar Lavage PROCEDURE

Undergo bronchoscopy with bronchoalveolar lavage

Also known as: bronchial washing, Bronchoscopy/Lavage

Group I (usual cigarette brand); Group II (SREC with nicotine); Group III (SREC without nicotine); Group IV (Nicotine Replacement Therapy [NRT])

Cigarette DRUG

Smoke usual brand

Group I (usual cigarette brand)

Electronic Cigarette OTHER

Smoke SREC with nicotine

Also known as: e-Cigarette, Electronic Nicotine Delivery System

Group II (SREC with nicotine)

Laboratory Biomarker Analysis OTHER

Correlative studies

Group I (usual cigarette brand); Group II (SREC with nicotine); Group III (SREC without nicotine); Group IV (Nicotine Replacement Therapy [NRT])

Nicotine Replacement DRUG

Receive NRT comprising patch, gum, or lozenge

Also known as: Nicotine Replacement Therapy, NRT

Group IV (Nicotine Replacement Therapy [NRT])

Questionnaire Administration OTHER

Ancillary studies

Group I (usual cigarette brand); Group II (SREC with nicotine); Group III (SREC without nicotine); Group IV (Nicotine Replacement Therapy [NRT])

Eligibility Criteria

• Age: 21 Years - 52 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Smokers who smoke \>= 5 filtered cigarettes/day for \>= 1 year
• No unstable or significant medical conditions as determined by medical history to ensure safety of the subject, to minimize the effects of poor health on biomarker measures and to maximize compliance to study procedures
• Able to read adequately to complete the survey and related study documents or give consent
• Subject has provided written informed consent to participate in the study

You may not qualify if:

• Regular consumption of roll your own cigarettes
• Immune system disorders requiring medication
• Prior diagnosis of chronic pulmonary disease (e.g., asthma with regular use of medications, chronic obstructive pulmonary disease \[COPD\], chronic bronchitis, and restrictive lung disease)
• Acute bronchitis or pneumonia within 1 year
• Reported history of diagnosed kidney or liver disease
• Any medical disorder that will increase the risk from bronchoscopy, affect biomarker data, or increase risk of an adverse effect from e-cig use
• General anesthesia within 1 year
• Regular use of inhalant medications in the last 2 months
• Use of antibiotics in prior 30 days
• Use of steroids, including corticosteroids, in prior 30 days
• Allergies to study medications, such as, lidocaine, Versed, fentanyl or Cetacaine
• Allergies to propylene glycol/glycerin or flavors
• History of hypersensitivity to varenicline
• Bronchoscopy or any other lung procedure for any reason within the previous 6 months
• Current or recent (within three months) alcohol or drug abuse problems

Sponsors & Collaborators

• National Institute on Drug Abuse (NIDA): collaborator
• Ohio State University Comprehensive Cancer Center: lead

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Links

• The Jamesline

MeSH Terms

Interventions

Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid; Tobacco Products; Electronic Nicotine Delivery Systems; Nicotine Replacement Therapy

Intervention Hierarchy (Ancestors)

Therapeutic Irrigation; Investigative Techniques; Smoking Devices; Manufactured Materials; Technology, Industry, and Agriculture; Drug Therapy; Therapeutics

Limitations and Caveats

Unfortunately, the study encountered several challenges that impacted recruitment (e.g., COVID-19 and product delays from the manufacturer). The target sample size was not met. Therefore, samples were not analyzed, and we were unable to report analyze data for several outcomes (i.e., changes in mRNA and miRNA gene expression, DNA methylation, microbiome in BAL cells and saliva, and untargeted metabolomics). No future analyses are planned at this time.

Results Point of Contact

• Title: Dr. Peter G. Shields
• Organization: Ohio State University Comprehensive Cancer Center

peter.shields@osumc.edu

614-688-6563

Study Officials

• Peter Shields, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 25, 2018
• First Posted: October 1, 2018
• Study Start: September 17, 2018
• Primary Completion: October 23, 2023
• Study Completion: March 10, 2024
• Last Updated: April 23, 2026
• Results First Posted: April 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)