Cinimic: In-vivo Effects of E-cigarette Aerosol on Innate Lung Host Defense

• Sponsor: University of North Carolina, Chapel Hill (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03700892
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 19
• Location: 1
• Arms: 3
• Actual Duration (Months): 16.5
• Patients Per Site Per Month: 1.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Smoking; Healthy	Other: Cinnamaldehyde e-liquid; Other: PG/VG e-liquid	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Controls will not be randomized and will not receive the study intervention.Controls will not be randomized and will not receive the study intervention.
• Masking: Double (Participant, Outcomes Assessor)
• Masking Description: The e-liquids will be maintained by an individual not active in the study procedures or analysis.
• Primary Purpose: Basic Science
• Official Title: In-vivo Effects of E-cigarette Aerosol on Innate Lung Host Defense
• Actual Study Start Date: Oct 19, 2018
• Actual Primary Completion Date: Mar 3, 2020
• Actual Study Completion Date: Mar 3, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cinnamaldehyde, then PG/VG Participants will inhale cinnamaldehyde e-liquid in 6, 5-minute paced vaping segments (1 puff/minute) over 1 hour. A 2-3 week washout period will follow. Then participants will inhale Propylene Glycol/Vegetable Glycerin (PG/VG) e-liquid in 6, 5-minute paced vaping segments (1 puff/minute) over 1 hour.	Other: Cinnamaldehyde e-liquid; Participants will inhale an e-liquid that contains cinnamaldehyde from Vapor Shark DNA 250™ e-cigarette device allowing manual control and vapor setting recordings (voltage, wattage, puff volume, and frequency).; Other Names: Cinnamon ; Other: PG/VG e-liquid; Participants will inhale an e-liquid that contains PG/VG from the Vapor Shark DNA 250™ e-cigarette device allowing manual control and vapor setting recordings (voltage, wattage, puff volume, and frequency).; Other Names: Placebo
Experimental: PG/VG, then Cinnamaldehyde Participants will inhale PG/VG e-liquid in 6, 5-minute paced vaping segments (1 puff/minute) over 1 hour. A 2-3 week washout period will follow. Then participants will inhale cinnamaldehyde e-liquid in 6, 5-minute vaping segments (1 puff/minute) over 1 hour.	Other: Cinnamaldehyde e-liquid; Participants will inhale an e-liquid that contains cinnamaldehyde from Vapor Shark DNA 250™ e-cigarette device allowing manual control and vapor setting recordings (voltage, wattage, puff volume, and frequency).; Other Names: Cinnamon ; Other: PG/VG e-liquid; Participants will inhale an e-liquid that contains PG/VG from the Vapor Shark DNA 250™ e-cigarette device allowing manual control and vapor setting recordings (voltage, wattage, puff volume, and frequency).; Other Names: Placebo
No Intervention: Healthy Controls Participants will only undergo the baseline testing and thus serve as a non-exposed/non-vaping control group.

Outcome Measures

Primary Outcome Measures

1. CA-induced Changes in Whole Lung MCC [Through study completion, an average of three months]

   Absolute values of whole lung MCC at baseline compared to after CA vaping session. Absolute repeat values of Whole lung MCC = average % mucus cleared from the whole lung over a 90-minute period.

Secondary Outcome Measures

1. CA-induced Changes in Regional Lung MCC [Through study completion, an average of three months]

   Absolute repeat values of Central and Peripheral lung MCC = average % mucus cleared from the Central and Peripheral lung over a 90-minute period. This will assess clearance rates from the central (C) and peripheral (P) regions as secondary endpoints that may reflect differential effects between a region with relatively more (C) vs. less (P) large bronchial airways.

2. Percent Polymorphonuclear Leukocytes (PMN) in Induced Sputum [Through study completion, an average of three months]

   Percent change of PMNs in vapers from baseline compared to post CA vaping session. Percent change in PMNs in vapers from baseline compared to post PG/VG vaping session are included as an additional comparison.

3. Absolute Values of Whole Lung MCC for Each Group [Start of study, up to three months]

   Baseline Differences in Whole lung MCC clearance rates in Non-smokers/Non-vapers as Compared to E-cigarette Users. Absolute group values of Whole Lung MCC =average % mucus cleared from the whole lung over a 90-minute period.

Other Outcome Measures

1. CA-Induced Changes in Immune Cell Function [Through study completion, an average of three months]

   Percent change from baseline in phagocytosis

2. Peripheral Blood Mononuclear Cell Analysis [Through study completion, an average of three months]

   Percent change in cell counts as compared to baseline

3. Blood Serum Analysis of Inflammatory Mediators [Through study completion, an average of three months]

   Percent change of mediator expression as compared to baseline

4. CA-Induced Changes in Epithelial Lining Fluid [Through study completion, an average of three months]

   Pre-vaping session versus post-vaping session expressed as a percent change

5. CA-Induced Changes in Epithelial Lining Fluid 24 Hours After Vaping Session [Through study completion, an average of three months]

   Percent change as compared to post-vaping session sample

6. Changes in Epithelial Lining Fluid [Through study completion, an average of three months]

   Percent change as compared to baseline

7. Tidal Volume Subjects Own E-cigarette Device [Through study completion, an average of three months]

   Tidal Volume in milliliters

8. Respiratory Rate With Subjects Own E-cigarette Device [Through study completion, an average of three months]

   Respiratory Rate in breaths per minute

9. Minute Ventilation With Subjects Own E-cigarette Device [Through study completion, an average of three months]

   Minute Ventilation in L/min

10. Inspiratory Flow With Subjects Own E-cigarette Device [Through study completion, an average of three months]

    Inspiratory flow in L/min

11. Expiratory Flow With Subjects Own E-cigarette Device [Through study completion, an average of three months]

    Expiratory flow in L/min

12. Tidal Volume With Investigator E-cigarette Device [Through study completion, an average of three months]

    Tidal Volume in milliliters

13. Respiratory Rate With Investigator E-cigarette Device [Through study completion, an average of three months]

    Respiratory Rate in breaths per minute

14. Minute Ventilation With Investigator E-cigarette Device [Through study completion, an average of three months]

    Minute Ventilation in L/min

15. Inspiratory Flow With Investigator E-cigarette Device [Through study completion, an average of three months]

    Inspiratory flow in L/min

16. Expiratory Flow With Investigator E-cigarette Device [Through study completion, an average of three months]

    Expiratory flow in L/min

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 40 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UNC Center for Environmental Medicine, Asthma and Lung Biology	Chapel Hill	North Carolina	United States	27599-7310

Sponsors and Collaborators

• University of North Carolina, Chapel Hill
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Ilona Jaspers, PhD, University of North Carolina

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 15, 2018

More Information

Publications

None provided.

• Responsible Party: University of North Carolina, Chapel Hill
• ClinicalTrials.gov Identifier: NCT03700892
• Other Study ID Numbers: 17-2275; R01HL139369
• First Posted: Oct 9, 2018
• Last Update Posted: Jun 10, 2021
• Last Verified: Mar 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of North Carolina, Chapel Hill: e-cig; E-cigarette; Electronic cigarette; Vaping
• Additional relevant MeSH terms: Cinnamaldehyde

Study Results

Participant Flow

Pre-assignment Detail	After qualifying, all participants move to the baseline day in which an mucociliary clearance (MCC) scan and sputum are collected for baseline measurements. The vaping participants continue on to the crossover design for CA and PG/VG sessions followed by MCC scans and sputum collections for post exposure measurements.

Arm/Group Title	Cinnamaldehyde, Then PG/VG	PG/VG, Then Cinnamaldehyde	Healthy Controls
Arm/Group Description	Participants will inhale cinnamaldehyde(CA) e-liquid in 6, 5-minute paced vaping segments (1 puff/minute) over 1 hour. A 2-3 week washout period will follow. Then participants will inhale Propylene Glycol/Vegetable Glycerin (PG/VG) e-liquid in 6, 5-minute paced vaping segments (1 puff/minute) over 1 hour. Cinnamaldehyde e-liquid: Participants will inhale an e-liquid that contains cinnamaldehyde from Vapor Shark DNA 250™ e-cigarette device allowing manual control and vapor setting recordings (voltage, wattage, puff volume, and frequency). PG/VG e-liquid: Participants will inhale an e-liquid that contains PG/VG from the Vapor Shark DNA 250™ e-cigarette device allowing manual control and vapor setting recordings (voltage, wattage, puff volume, and frequency).	Participants will inhale PG/VG e-liquid in 6, 5-minute paced vaping segments (1 puff/minute) over 1 hour. A 2-3 week washout period will follow. Then participants will inhale cinnamaldehyde e-liquid in 6, 5-minute vaping segments (1 puff/minute) over 1 hour. Cinnamaldehyde e-liquid: Participants will inhale an e-liquid that contains cinnamaldehyde from Vapor Shark DNA 250™ e-cigarette device allowing manual control and vapor setting recordings (voltage, wattage, puff volume, and frequency). PG/VG e-liquid: Participants will inhale an e-liquid that contains PG/VG from the Vapor Shark DNA 250™ e-cigarette device allowing manual control and vapor setting recordings (voltage, wattage, puff volume, and frequency).	Participants will only undergo the baseline testing and thus serve as a non-exposed/non-vaping control group.
Period Title: Baseline
STARTED	15	0	4
COMPLETED	15	0	4
NOT COMPLETED	0	0	0
Period Title: Baseline
STARTED	1	4	0
COMPLETED	1	4	0
NOT COMPLETED	0	0	0
Period Title: Baseline
STARTED	1	4	0
COMPLETED	1	4	0
NOT COMPLETED	0	0	0
Period Title: Baseline
STARTED	1	4	0
Received Intervention	1	3	0
COMPLETED	1	3	0
NOT COMPLETED	0	1	0

Baseline Characteristics

Arm/Group Title	All Treated Participants	Healthy Controls	Total
Arm/Group Description	All participants inhaled cinnamaldehyde e-liquid or Propylene Glycol/Vegetable Glycerin (PG/VG) e-liquid in either Period 1 or Period 2 as per randomization schedule. Cinnamaldehyde e-liquid: Participants will inhale an e-liquid that contains cinnamaldehyde from Vapor Shark DNA 250™ e-cigarette device allowing manual control and vapor setting recordings (voltage, wattage, puff volume, and frequency). PG/VG e-liquid: Participants will inhale an e-liquid that contains PG/VG from the Vapor Shark DNA 250™ e-cigarette device allowing manual control and vapor setting recordings (voltage, wattage, puff volume, and frequency).	Participants will only undergo the baseline testing and thus serve as a non-exposed/non-vaping control group.	Total of all reporting groups
Overall Participants	15	4	19
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	15 100%	4 100%	19 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	3 20%	3 75%	6 31.6%
Male	12 80%	1 25%	13 68.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 13.3%	0 0%	2 10.5%
Not Hispanic or Latino	13 86.7%	4 100%	17 89.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	3 20%	0 0%	3 15.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 6.7%	0 0%	1 5.3%
White	11 73.3%	4 100%	15 78.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	15 100%	4 100%	19 100%

Outcome Measures

1. Primary Outcome

Title	CA-induced Changes in Whole Lung MCC
Description	Absolute values of whole lung MCC at baseline compared to after CA vaping session. Absolute repeat values of Whole lung MCC = average % mucus cleared from the whole lung over a 90-minute period.
Time Frame	Through study completion, an average of three months

Outcome Measure Data

Analysis Population Description

The healthy control participants only undergo the baseline testing and thus serve as a non-exposed/non-vaping control group. This Primary outcome does not apply to the healthy control group as they did not receive the intervention and only baseline data was collected.

Arm/Group Title	Cinnamaldehyde	PG/VG
Arm/Group Description	Participants will inhale cinnamaldehyde e-liquid in 6, 5-minute paced vaping segments (1 puff/minute) over 1 hour. A 2-3 week washout period will follow. Cinnamaldehyde e-liquid: Participants will inhale an e-liquid that contains cinnamaldehyde from Vapor Shark DNA 250™ e-cigarette device allowing manual control and vapor setting recordings (voltage, wattage, puff volume, and frequency).	Participants will inhale PG/VG e-liquid in 6, 5-minute paced vaping segments (1 puff/minute) over 1 hour. A 2-3 week washout period will follow. PG/VG e-liquid: Participants will inhale an e-liquid that contains PG/VG from the Vapor Shark DNA 250™ e-cigarette device allowing manual control and vapor setting recordings (voltage, wattage, puff volume, and frequency).
Measure Participants	4	5
Mean (Standard Deviation) [percent clearance]	41 (5)	27 (17)

2. Secondary Outcome

Title	CA-induced Changes in Regional Lung MCC
Description	Absolute repeat values of Central and Peripheral lung MCC = average % mucus cleared from the Central and Peripheral lung over a 90-minute period. This will assess clearance rates from the central (C) and peripheral (P) regions as secondary endpoints that may reflect differential effects between a region with relatively more (C) vs. less (P) large bronchial airways.
Time Frame	Through study completion, an average of three months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cinnamaldehyde	PG/VG
Arm/Group Description	Participants will inhale cinnamaldehyde e-liquid in 6, 5-minute paced vaping segments (1 puff/minute) over 1 hour. A 2-3 week washout period will follow. Cinnamaldehyde e-liquid: Participants will inhale an e-liquid that contains cinnamaldehyde from Vapor Shark DNA 250™ e-cigarette device allowing manual control and vapor setting recordings (voltage, wattage, puff volume, and frequency).	Participants will inhale PG/VG e-liquid in 6, 5-minute paced vaping segments (1 puff/minute) over 1 hour. A 2-3 week washout period will follow. PG/VG e-liquid: Participants will inhale an e-liquid that contains PG/VG from the Vapor Shark DNA 250™ e-cigarette device allowing manual control and vapor setting recordings (voltage, wattage, puff volume, and frequency).
Measure Participants	4	5
Central Lung	43 (12)	25 (32)
Peripheral Lung	33 (3)	24 (6)

3. Secondary Outcome

Title	Percent Polymorphonuclear Leukocytes (PMN) in Induced Sputum
Description	Percent change of PMNs in vapers from baseline compared to post CA vaping session. Percent change in PMNs in vapers from baseline compared to post PG/VG vaping session are included as an additional comparison.
Time Frame	Through study completion, an average of three months

Outcome Measure Data

Analysis Population Description

The healthy control participants only undergo the baseline testing and thus serve as a non-exposed/non-vaping control group. This outcome does not apply to the healthy control group as they did not receive the intervention and only baseline data was collected.

Arm/Group Title	Cinnamaldehyde	PG/VG
Arm/Group Description	Participants will inhale cinnamaldehyde e-liquid in 6, 5-minute paced vaping segments (1 puff/minute) over 1 hour. A 2-3 week washout period will follow. Cinnamaldehyde e-liquid: Participants will inhale an e-liquid that contains cinnamaldehyde from Vapor Shark DNA 250™ e-cigarette device allowing manual control and vapor setting recordings (voltage, wattage, puff volume, and frequency).	Participants will inhale PG/VG e-liquid in 6, 5-minute paced vaping segments (1 puff/minute) over 1 hour. A 2-3 week washout period will follow. PG/VG e-liquid: Participants will inhale an e-liquid that contains PG/VG from the Vapor Shark DNA 250™ e-cigarette device allowing manual control and vapor setting recordings (voltage, wattage, puff volume, and frequency).
Measure Participants	4	5
Mean (Standard Error) [percent PMN]	3.6 (7.2)	89.4 (5.8)

4. Secondary Outcome

Title	Absolute Values of Whole Lung MCC for Each Group
Description	Baseline Differences in Whole lung MCC clearance rates in Non-smokers/Non-vapers as Compared to E-cigarette Users. Absolute group values of Whole Lung MCC =average % mucus cleared from the whole lung over a 90-minute period.
Time Frame	Start of study, up to three months

Outcome Measure Data

Analysis Population Description

Includes all participants who completed the baseline MCC scan.

Arm/Group Title	E-cigarette Users	Non-smoker/Non-vaper Healthy Controls
Arm/Group Description	Baseline MCC scans and sputum collection performed prior to randomization.	Baseline MCC scans and sputum collection.
Measure Participants	15	4
Mean (Standard Deviation) [percent clearance]	17 (8)	14 (6)

5. Other Pre-specified Outcome

Title	CA-Induced Changes in Immune Cell Function
Description	Percent change from baseline in phagocytosis
Time Frame	Through study completion, an average of three months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Other Pre-specified Outcome

Title	Peripheral Blood Mononuclear Cell Analysis
Description	Percent change in cell counts as compared to baseline
Time Frame	Through study completion, an average of three months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Other Pre-specified Outcome

Title	Blood Serum Analysis of Inflammatory Mediators
Description	Percent change of mediator expression as compared to baseline
Time Frame	Through study completion, an average of three months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Other Pre-specified Outcome

Title	CA-Induced Changes in Epithelial Lining Fluid
Description	Pre-vaping session versus post-vaping session expressed as a percent change
Time Frame	Through study completion, an average of three months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Other Pre-specified Outcome

Title	CA-Induced Changes in Epithelial Lining Fluid 24 Hours After Vaping Session
Description	Percent change as compared to post-vaping session sample
Time Frame	Through study completion, an average of three months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Other Pre-specified Outcome

Title	Changes in Epithelial Lining Fluid
Description	Percent change as compared to baseline
Time Frame	Through study completion, an average of three months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

11. Other Pre-specified Outcome

Title	Tidal Volume Subjects Own E-cigarette Device
Description	Tidal Volume in milliliters
Time Frame	Through study completion, an average of three months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

12. Other Pre-specified Outcome

Title	Respiratory Rate With Subjects Own E-cigarette Device
Description	Respiratory Rate in breaths per minute
Time Frame	Through study completion, an average of three months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

13. Other Pre-specified Outcome

Title	Minute Ventilation With Subjects Own E-cigarette Device
Description	Minute Ventilation in L/min
Time Frame	Through study completion, an average of three months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

14. Other Pre-specified Outcome

Title	Inspiratory Flow With Subjects Own E-cigarette Device
Description	Inspiratory flow in L/min
Time Frame	Through study completion, an average of three months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

15. Other Pre-specified Outcome

Title	Expiratory Flow With Subjects Own E-cigarette Device
Description	Expiratory flow in L/min
Time Frame	Through study completion, an average of three months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

16. Other Pre-specified Outcome

Title	Tidal Volume With Investigator E-cigarette Device
Description	Tidal Volume in milliliters
Time Frame	Through study completion, an average of three months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

17. Other Pre-specified Outcome

Title	Respiratory Rate With Investigator E-cigarette Device
Description	Respiratory Rate in breaths per minute
Time Frame	Through study completion, an average of three months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

18. Other Pre-specified Outcome

Title	Minute Ventilation With Investigator E-cigarette Device
Description	Minute Ventilation in L/min
Time Frame	Through study completion, an average of three months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

19. Other Pre-specified Outcome

Title	Inspiratory Flow With Investigator E-cigarette Device
Description	Inspiratory flow in L/min
Time Frame	Through study completion, an average of three months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

20. Other Pre-specified Outcome

Title	Expiratory Flow With Investigator E-cigarette Device
Description	Expiratory flow in L/min
Time Frame	Through study completion, an average of three months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	From the time a participant signed consent through completion of the second intervention, a total of up to 3 months.
Adverse Event Reporting Description	Adverse event data included all participants who received at least one dose of Cinnamaldehyde (CA) or Propylene Glycol/Vegetable Glycerin (PG/VG).
Arm/Group Title	Cinnamaldehyde		PG/VG		Healthy Controls
Arm/Group Description	Participants who inhaled cinnamaldehyde e-liquid in either Period 1 or Period 2 as per randomization schedule. Cinnamaldehyde e-liquid: Participants will inhale an e-liquid that contains cinnamaldehyde from Vapor Shark DNA 250™ e-cigarette device allowing manual control and vapor setting recordings (voltage, wattage, puff volume, and frequency).		Participants who inhaled Propylene Glycol/Vegetable Glycerin (PG/VG) e-liquid in either Period 1 or Period 2 as per randomization schedule. PG/VG e-liquid: Participants will inhale an e-liquid that contains PG/VG from the Vapor Shark DNA 250™ e-cigarette device allowing manual control and vapor setting recordings (voltage, wattage, puff volume, and frequency).		Participants will only undergo the baseline testing and thus serve as a non-exposed/non-vaping control group.
All Cause Mortality
	Cinnamaldehyde		PG/VG		Healthy Controls
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/5 (0%)		0/4 (0%)
Serious Adverse Events
	Cinnamaldehyde		PG/VG		Healthy Controls
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/5 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	Cinnamaldehyde		PG/VG		Healthy Controls
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/5 (0%)		0/4 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.