Clinical trial NCT03700892: In-vivo Effects of E-cigarette Aerosol on Innate Lung Host Defense
Official title: In-vivo Effects of E-cigarette Aerosol on Innate Lung Host Defense
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Smoking
Healthy
Keywords: e-cig
E-cigarette
Electronic cigarette
Vaping
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2018-10-09
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Controls will not be randomized and will not receive the study intervention.
Primary purpose: BASIC_SCIENCE

Brief summary: While e-cigs are commonly represented as safer alternatives to tobacco cigarettes, little is known regarding the health effects of their short- or long-term use. The responses and the e-cig components exerting these effects on the airways are largely unknown. This study will identify if specific e-cig flavors modify respiratory immune responses. This study will determine the effects of cinnamaldehyde (CA)-containing e-cigarettes on airway epithelial cell ciliary function (i.e., MCC) in humans. Additionally the study will determine the effects of CA-containing e-cigarettes on airway immune cells obtained through induced sputum (SI) after inhalation of CA-containing e-cig aerosols to determine CA-induced effects on a) immune cell function (e.g., phagocytosis, respiratory burst), b) immune cell surface phenotype, and c) mediator production in humans in vivo.

Detailed description: Investigators will evaluate the acute effect of CA-flavored e-cigs on MCC and IS immune cells in up to 32 healthy, young adults who are current e-cig users with a total of less than 10 pack-years cigarette smoking history. MCC will be measured by gamma scintigraphy at baseline and following controlled vaping of e-liquids with and without cinnamon flavoring. Two different e-liquids (one completely devoid and one containing at least 30 mM CA similar to "Hot Cinnamon Candies" which is commercially available) will be used for two separate randomized vaping sessions.

The randomization scheme for the two different e-liquids (e-liquids with and without CA) will be generated by using the Web site Randomization.com (http://www.randomization.com), assigned treatment Regimen A and B by an assigned study team member, and provided to the study team. This individual will also be responsible for loading the e-cigarette with the appropriate solution for that session prior to the vaping sessions.

Participants will undergo baseline testing during the screening visit, which will occur 2-3 weeks prior to the first controlled vaping session. Investigators will also recruit non-vaping control subjects (n=32), who will only undergo the baseline testing and thus serve as a non-exposed/non-vaping control group. will aim to recruit similar numbers of males and females in both cohorts. While investigators cannot guarantee age-matching and sex-matching in these cohorts, based on our previous studies, investigators do not expect to find significant age and sex differences in the two cohort. In addition, potential confounders, such as age, sex, and BMI will be included as covariates in our multivariate analysis.

Observations obtained from the non-vaping control group will provide necessary information on potential baseline differences in the two cohorts (i.e. current vapers versus non-vaping controls). These data from the non-vaping control group are important to provide a reference for any potential CA-induced changes in the vaping group. Hence, there are two stages of the study:

Stage 1. A cross sectional observational cohort comparison of baseline MCC and IS immune cells in a reference cohort of n=32 non-vaping control subjects and E-cig cohort of n=32 currently vaping subjects (confounding based on other variables such as BMI, sex, age is possible for this stage).

Stage 2. A randomized comparison of changes in MCC and IS immune cells after Regimen A (e-cig us without CA) and Regimen B (e-cig use with CA). The cohort of e-cig users will undergo a randomized 2-treatment, 2-period, 2-sequence crossover study of CA exposure.

For stage 1, baseline measurements of Tc99m-SC clearance will be used to measure each subject's normal baseline MCC and IS immune cell characteristics. For both stages, subjects will be asked to complete a vaping diary to record information on the device and e-liquids (name/vendor/e-liquids/puffs/device settings) used during their normal vaping sessions for the entire duration of the study. In addition, for stage 2, participants will be asked to maintain their current habits for the duration of the study, not to significantly increase or decrease their vaping patterns, including the nicotine concentrations of their e-liquids.

For stage 2, for each e-cig vaping session (Training and MCC Test Days), subjects will be asked to follow a laboratory-based protocol involving 6, 5-minute paced vaping segments (1 puff/minute) over a 1 hour time period, vaping the e-liquid with and without CA provided by us. On each Test Day, participants will undergo the vaping protocol immediately prior to inhalation of the Tc99m-SC (10 min between end of vaping and inhalation of Tc99m-SC). An initial deposition scan of Tc99m-SC will then be obtained followed by dynamic imaging of the lung with subjects seated in front of the gamma camera to determine potential changes in MCC induced by acute exposure to CA-flavored e- cigarettes. Induced sputum samples will be collected at baseline, and after each MCC scan.

24 hours after completion of the MCC scans. The two randomized vaping sessions will be separated by 2-3 weeks. While there are no data providing specific information on the duration needed to washout the effects of CA on MCC, previous studies examining changes in MCC following inhalation of other aerosols have shown that this washout period is sufficient to prevent potential carryover between the two treatments.

Eligibility criteria: Inclusion Criteria:

* An equal number of participants who currently use a vaping device and those who do not use a vaping device
* Age 18-40
* Must have a Forced Vital Capacity (FVC) and Forced Expiratory Volume in 1 second (FEV₁) of at least 80% of predicted. Participants who fall out of the normal range will be offered a copy of the test to share with their personal physician.

Exclusion Criteria:

* Any pre-existing lung disease (asthma, cystic fibrosis, etc.)
* Any significant chronic illness, such as, but not limited to, heart disease, uncontrolled hypertension, diabetes, auto-immune disease
* Any use of tobacco products (other than e-cig) in the past 3 months, or a greater than 10 pack year history of smoking cigarettes
* Pregnant or nursing women
* Participants with a history of radiation exposure in the past year which exceeds annual safe limits.

Primary outcomes:
measure: CA-induced Changes in Whole Lung MCC
timeFrame: Through study completion, an average of three months
Secondary outcomes:
measure: CA-induced Changes in Regional Lung MCC
timeFrame: Through study completion, an average of three months
measure: Percent Polymorphonuclear Leukocytes (PMN) in Induced Sputum
timeFrame: Through study completion, an average of three months
measure: Absolute Values of Whole Lung MCC for Each Group
timeFrame: Start of study, up to three months
Other outcomes:
measure: CA-Induced Changes in Immune Cell Function
timeFrame: Through study completion, an average of three months
measure: Peripheral Blood Mononuclear Cell Analysis
timeFrame: Through study completion, an average of three months
measure: Blood Serum Analysis of Inflammatory Mediators
timeFrame: Through study completion, an average of three months
measure: CA-Induced Changes in Epithelial Lining Fluid
timeFrame: Through study completion, an average of three months
measure: CA-Induced Changes in Epithelial Lining Fluid 24 Hours After Vaping Session
timeFrame: Through study completion, an average of three months
measure: Changes in Epithelial Lining Fluid
timeFrame: Through study completion, an average of three months
measure: Tidal Volume Subjects Own E-cigarette Device
timeFrame: Through study completion, an average of three months
measure: Respiratory Rate With Subjects Own E-cigarette Device
timeFrame: Through study completion, an average of three months
measure: Minute Ventilation With Subjects Own E-cigarette Device
timeFrame: Through study completion, an average of three months
measure: Inspiratory Flow With Subjects Own E-cigarette Device
timeFrame: Through study completion, an average of three months
measure: Expiratory Flow With Subjects Own E-cigarette Device
timeFrame: Through study completion, an average of three months
measure: Tidal Volume With Investigator E-cigarette Device
timeFrame: Through study completion, an average of three months
measure: Respiratory Rate With Investigator E-cigarette Device
timeFrame: Through study completion, an average of three months
measure: Minute Ventilation With Investigator E-cigarette Device
timeFrame: Through study completion, an average of three months
measure: Inspiratory Flow With Investigator E-cigarette Device
timeFrame: Through study completion, an average of three months
measure: Expiratory Flow With Investigator E-cigarette Device
timeFrame: Through study completion, an average of three months
Locations:
city: Chapel Hill
country: United States
facility: UNC Center for Environmental Medicine, Asthma and Lung Biology
state: North Carolina
Study officials:
affiliation: University of North Carolina
name: Ilona Jaspers, PhD
role: PRINCIPAL_INVESTIGATOR
References: