Clinical trial NCT03691350: Bronchoscopy in Determining the Effect of E-Cigarette Smoking on Biomarkers in the Lungs
Official title: The Effects of a Standardized Research E-Cigarette on the Human Lung: A Clinical Trial With Bronchoscopic Biomarkers
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Cigarette Smoker
Current Every Day Smoker
Lead sponsor: Ohio State University Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2018-10-01
Enrollment: 239
Sex: ALL
Minimum age (years): 21
Maximum age (years): 52
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Detailed description: PRIMARY OBJECTIVES:

I. To assess inflammatory changes over 10 weeks for lung and urine biomarkers in smokers who undergo serial bronchoscopy. The randomized trial includes four conditions: continued use (n=32), complete switching to the nicotine standardized research electronic cigarettes (e-cig) (SREC) (n=32), complete switching to the placebo (nicotine free) SREC (n=32), and complete switching to nicotine replacement therapy (NRT)(n=32).

OUTLINE: Participants are randomized to 1 of 4 groups.

GROUP I: 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.

GROUP II: 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 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.

GROUP III: Participants undergo bronchoscopy over 30-60 minutes at baseline. After the baseline 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.

GROUP IV: Participants undergo bronchoscopy over 30-60 minutes at baseline. Beginning 1 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.

After completion of study, participants are followed up at 3 months.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* Regularly smoked marijuana within the prior 3 months
* Use of an e-cigarette or other combustible tobacco products in the prior 3 months
* Currently using nicotine replacement or other tobacco cessation products (to minimize confounding effects of another product) or intention to quit in next three months
* Adverse reaction to previous e-cig use
* Body mass index (BMI) \> 40 (risk of unstable airway)
* Pregnant or breastfeeding - if the subject is female, a urine pregnancy test at no cost to the subject will be done on the day of bronchoscopy
* Unable to read for comprehension or completion of study documents

Primary outcomes:
measure: Changes in cell counts and cytokines
timeFrame: Baseline to day 71
Secondary outcomes:
measure: Changes in fractional exhaled nitric oxide (FeNO) levels
timeFrame: Baseline up to day 71
measure: Changes in messenger (m) ribonucleic acid (RNA) and microRNA (miRNA) gene expression analyzed using sequencing
timeFrame: Baseline up to day 71
measure: Changes in deoxyribonucleic acid (DNA) gene methylation
timeFrame: Baseline up to day 71
measure: Changes in the microbiome in BAL cells and saliva
timeFrame: Baseline up to day 71
measure: Changes in untargeted metabolomics using mass spectrometry
timeFrame: Baseline up to day 71
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: