Clinical trial NCT02596685: Effects of Electronic Cigarette Use on the Lungs
Official title: Effects of Electronic Cigarette Use on the Human Lung
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Current Smoker
Never Smoker
Tobacco Use Disorder
Former Smoker
E-cig User
Lead sponsor: Ohio State University Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2015-11-04
Enrollment: 142
Sex: ALL
Minimum age (years): 21
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: This randomized pilot clinical trial studies the effects of electronic cigarettes on the lungs. Studying the effects of electronic cigarettes on the lungs may provide the Food and Drug Administration (FDA) and other government regulators with important information, which may help in developing future regulations to make electronic cigarettes safer.

Detailed description: PRIMARY OBJECTIVES:

1) To conduct a pilot cross-sectional study of e-cig users (n=16), never-smokers (n=8 - completed under an earlier version of the protocol before never-smokers were used for Aim 2), (newly added n=15), former smokers who have quit smoking and are currently not using e-cigs (n=15), former smokers who switched to e-cigs (n=15) and smokers (n=16) \[total n=85), to better determine the influence of e-cig and smoking use (i.e., power) between never smokers and e-cig users, and to compare former smokers with e-cig use, and assessing use patterns and biomarkers by bronchoscopies using bronchioalveolar lavage (cell counts, inflammatory cytokines, untargeted metabolomics, and microbiome assessment), bronchial brushings (miRNA and mRNA expression, DNA methylation, acrolein DNA adducts, and mitochondrial DNA mutations and copy number variation), blood and urine to assess exposure to the e-cigs ingredients, saliva for oral microbiome assessment, and nasal brushing and nasal lavages for the lung toxicity as examined in this study as surrogate markers for the lung. We will also measure fractional exhaled nitric oxide (FeNO) as a marker of lower airway inflammation; and,

1a) Conduct a supplemental contamination study to measure if bacteria from oral cavity, nasal cavity or oropharynx may contaminate BAL fluid recovered during the bronchoscopy (n=30). Contamination analyses will measure if bacterial species found in oral cavity, nasal cavity and oropharynx are recovered in BAL. Contamination analyses will not examine differences between groups.

2) To conduct a 4 week pilot clinical trial of nicotine-free and flavor-free e-cig use in never-smokers (n=30), randomized to e-cig use (n=15) or control (no e-cig use) (n=15), and assess biomarkers as in Aim 1 by bronchoscopy at baseline and at 4 weeks while on product (week 5 of trial).

OUTLINE:

PART I: Patients are randomized to 1 of 2 arms.

ARM I: Patients undergo bronchoscopy of the left lung over 30-60 minutes.

ARM II: Patients undergo bronchoscopy of the right lung over 30-60 minutes.

PART II: Patients who are never-smokers are then randomized to 1 of 2 arms.

ARM A: Patients receive nicotine-free and flavor-free electronic cigarettes and instructed to use them twice daily (BID) over a 2 hour period for 4 weeks.

ARM B: Patients receive no intervention.

In both arms, patients undergo a second bronchoscopy during week 5.

Eligibility criteria: Inclusion Criteria:

* Aim 1 only: 1) smokers who smoke at least 10 cigarettes per day with a stable smoking pattern of at least 6 months and no prior e-cig use within one year. Smoking status will be confirmed by salivary cotinine; subjects with at least 10 ng/ml cotinine in their saliva being considered smokers \[150\]. 2) e-cig users who report using e-cigs daily for 3 months with at least one nicotine-containing cartridge/day or 1 ml of liquid/day. They should have not smoked a cigarette for at least one year. 3) former smokers currently using nicotine-containing e-cigs who have completely switched to e-cigs 1-5 years earlier, and previously smoked \>10 cigs/day for \>1 year. 4) former-smokers who have quit smoking 1-5 years previously, and who previously smoked \>10 cigs/day for \>1 year and no e-cig use for a year and \<10 days in their lifetime. 5) never-smokers who have smoked less than 100 cigarettes in their lifetime and not for at least 1 year, and not have used an e-cig for at least 1 year. Lack of regular smoking will be confirmed by NicAlert.
* Aim 2 only: Non-smokers who have smoked less than 100 cigarettes in their lifetime and not for at least 1 year, and not have used an e-cig for at least 1 year. Lack of regular smoking will be confirmed by salivary cotinine. Participants should be in good physical and mental health, particularly those randomized to the control condition;
* No unstable and significant medical conditions as determined by medical history (see exclusion criteria below) 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; and
* Subject has provided written informed consent to participate in the study.

Exclusion Criteria:

* Immune system disorders, pulmonary diseases (e.g., asthma within the prior 5 years, acute bronchitis within 1 year, COPD, chronic bronchitis, and restrictive lung disease), clinically diagnosed kidney or liver diseases, or any other medical disorders that will increase the risk from bronchoscopy, affect biomarker data, or increase risk of an adverse effect from e-cig use. All subjects are screened by a pulmonologist obtaining a medical history and a physical examination (heart, lungs and oral cavity) to ensure no increased risk from bronchoscopy or e-cig use;
* General anesthesia within one year;
* Use of inhalant medications in the last 3 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
* Bronchoscopy or any other lung procedure for any reason within the previous year;
* Current or recent (within three months) alcohol or drug abuse problems, including marijuana use within the last 30 days. Subjects with a positive Tetrahydrocannabinol (THC) strip test at any visit will be excluded;
* Other tobacco use (e.g., combustible products, vapors, etc.) within the last 3 months;
* Other tobacco use within the past year for 7 consecutive days or 14 times.
* Currently using nicotine replacement or other tobacco cessation products (to minimize confounding effects of another product) or intention to quit in next three months;
* BMI \> 40 (risk of unstable airway)
* Pregnant or breastfeeding in prior 3 months - If the subject is female, the investigator will provide a urine pregnancy test at no cost to the subject. The subject will take the pregnancy test before each bronchoscopy; and,
* Unable to read for comprehension or completion of study documents.

Primary outcomes:
measure: Biomarker expression analysis to include cell counts
timeFrame: Up to week 5
measure: Biomarker expression analysis to include inflammatory cytokines (Part I)
timeFrame: Up to week 5
measure: Biomarker expression analysis to include untargeted metabolomics (Part I)
timeFrame: Up to week 5
measure: Biomarker expression analysis to include gene expression (Part I)
timeFrame: Up to week 5
measure: Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment (Part II)
timeFrame: Baseline to 5 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Ohio State University Comprehensive Cancer Center
name: Peter Shields, MD
role: PRINCIPAL_INVESTIGATOR
References: