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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03700892
Recruitment Status : Recruiting
First Posted : October 9, 2018
Last Update Posted : July 1, 2019
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill

Tracking Information
First Submitted Date  ICMJE October 4, 2018
First Posted Date  ICMJE October 9, 2018
Last Update Posted Date July 1, 2019
Actual Study Start Date  ICMJE October 19, 2018
Estimated Primary Completion Date October 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 5, 2018)
CA-induced changes in MCC [ Time Frame: Through study completion, an average of three months ]
Percent change as compared to baseline measurement
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03700892 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 5, 2018)
  • Regional lung clearance rates. [ Time Frame: Through study completion, an average of three months ]
    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.
  • Differential cell counts in CA-induced changes in IS samples [ Time Frame: Through study completion, an average of three months ]
    Percent change of per cell type as compared to baseline
  • Baseline differences in MCC in non-smokers/non-vapers as compared to e-cigarette users [ Time Frame: Start of study, up to three months ]
    Difference as calculated per MCC clearance rates between non-smokers and non-vapers.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: June 26, 2019)
  • CA-Induced changes in immune cell function [ Time Frame: Through study completion, an average of three months ]
    Percent change from baseline in phagocytosis
  • Peripheral blood mononuclear cell analysis [ Time Frame: Through study completion, an average of three months ]
    Percent change in cell counts as compared to baseline
  • Blood serum analysis of inflammatory mediators [ Time Frame: Through study completion, an average of three months ]
    Percent change of mediator expression as compared to baseline
  • CA-Induced changes in Epithelial Lining Fluid [ Time Frame: Through study completion, an average of three months ]
    Pre-vaping session versus post-vaping session expressed as a percent change
  • CA-Induced changes in Epithelial Lining Fluid 24 hours after vaping session [ Time Frame: Through study completion, an average of three months ]
    Percent change as compared to post-vaping session sample
  • Changes in Epithelial Lining Fluid [ Time Frame: Through study completion, an average of three months ]
    Percent change as compared to baseline
  • Tidal volume subjects own e-cigarette device [ Time Frame: Through study completion, an average of three months ]
    Tidal Volume in milliliters
  • Respiratory rate with subjects own e-cigarette device [ Time Frame: Through study completion, an average of three months ]
    Respiratory Rate in breaths per minute
  • Minute ventilation with subjects own e-cigarette device [ Time Frame: Through study completion, an average of three months ]
    Minute Ventilation in L/min
  • Inspiratory flow with subjects own e-cigarette device [ Time Frame: Through study completion, an average of three months ]
    Inspiratory flow in L/min
  • Expiratory flow with subjects own e-cigarette device [ Time Frame: Through study completion, an average of three months ]
    Expiratory flow in L/min
  • Tidal volume with investigator e-cigarette device [ Time Frame: Through study completion, an average of three months ]
    Tidal Volume in milliliters
  • Respiratory rate with investigator e-cigarette device [ Time Frame: Through study completion, an average of three months ]
    Respiratory Rate in breaths per minute
  • Minute ventilation with investigator e-cigarette device [ Time Frame: Through study completion, an average of three months ]
    Minute Ventilation in L/min
  • Inspiratory flow with investigator e-cigarette device [ Time Frame: Through study completion, an average of three months ]
    Inspiratory flow in L/min
  • Expiratory flow with investigator e-cigarette device [ Time Frame: Through study completion, an average of three months ]
    Expiratory flow in L/min
Original Other Pre-specified Outcome Measures
 (submitted: October 5, 2018)
  • Baseline Fractional Exhaled Nitric Oxide (FeNO) Between Groups [ Time Frame: Start of study, up to three months ]
    Difference in FeNO between cohorts
  • CA-Induced changes in immune cell function [ Time Frame: Through study completion, an average of three months ]
    Percent change from baseline in phagocytosis
  • Peripheral blood mononuclear cell analysis [ Time Frame: Through study completion, an average of three months ]
    Percent change in cell counts as compared to baseline
  • Blood serum analysis of inflammatory mediators [ Time Frame: Through study completion, an average of three months ]
    Percent change of mediator expression as compared to baseline
  • CA-Induced changes in Epithelial Lining Fluid [ Time Frame: Through study completion, an average of three months ]
    Pre-vaping session versus post-vaping session expressed as a percent change
  • CA-Induced changes in Epithelial Lining Fluid 24 hours after vaping session [ Time Frame: Through study completion, an average of three months ]
    Percent change as compared to post-vaping session sample
  • Changes in Epithelial Lining Fluid [ Time Frame: Through study completion, an average of three months ]
    Percent change as compared to baseline
  • Tidal volume subjects own e-cigarette device [ Time Frame: Through study completion, an average of three months ]
    Tidal Volume in milliliters
  • Respiratory rate with subjects own e-cigarette device [ Time Frame: Through study completion, an average of three months ]
    Respiratory Rate in breaths per minute
  • Minute ventilation with subjects own e-cigarette device [ Time Frame: Through study completion, an average of three months ]
    Minute Ventilation in L/min
  • Inspiratory flow with subjects own e-cigarette device [ Time Frame: Through study completion, an average of three months ]
    Inspiratory flow in L/min
  • Expiratory flow with subjects own e-cigarette device [ Time Frame: Through study completion, an average of three months ]
    Expiratory flow in L/min
  • Tidal volume with investigator e-cigarette device [ Time Frame: Through study completion, an average of three months ]
    Tidal Volume in milliliters
  • Respiratory rate with investigator e-cigarette device [ Time Frame: Through study completion, an average of three months ]
    Respiratory Rate in breaths per minute
  • Minute ventilation with investigator e-cigarette device [ Time Frame: Through study completion, an average of three months ]
    Minute Ventilation in L/min
  • Inspiratory flow with investigator e-cigarette device [ Time Frame: Through study completion, an average of three months ]
    Inspiratory flow in L/min
  • Expiratory flow with investigator e-cigarette device [ Time Frame: Through study completion, an average of three months ]
    Expiratory flow in L/min
 
Descriptive Information
Brief Title  ICMJE In-vivo Effects of E-cigarette Aerosol on Innate Lung Host Defense
Official Title  ICMJE In-vivo Effects of E-cigarette Aerosol on Innate Lung Host Defense
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 22 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 30mM 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=22), 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=22 non-vaping control subjects and E-cig cohort of n=22 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 Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:
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
Condition  ICMJE
  • Smoking
  • Healthy
Intervention  ICMJE
  • 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 Name: 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 Name: Placebo
Study Arms  ICMJE
  • 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.
    Interventions:
    • Other: Cinnamaldehyde e-liquid
    • Other: PG/VG e-liquid
  • 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.
    Interventions:
    • Other: Cinnamaldehyde e-liquid
    • Other: PG/VG e-liquid
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 5, 2018)
44
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2022
Estimated Primary Completion Date October 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 40 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Carole Robinette, MS 919-843-8472 Carole_Robinette@med.unc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03700892
Other Study ID Numbers  ICMJE 17-2275
R01HL139369 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
Supporting Materials: Study Protocol
Time Frame: Beginning 9 months and ending 36 months following article publication
Access Criteria:

Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose.

Proposals may be submitted up to 36 months following article publication. After 36 months the data will be available in our University's data warehouse but without investigator support other than deposited metadata

Requests for access to individual participant data should be sent to bring44@email.unc.edu or carole.robinette@med.unc.edu. Access will be granted after a data access agreement has been signed with UNC.

Responsible Party University of North Carolina, Chapel Hill
Study Sponsor  ICMJE University of North Carolina, Chapel Hill
Collaborators  ICMJE National Heart, Lung, and Blood Institute (NHLBI)
Investigators  ICMJE
Principal Investigator: Ilona Jaspers, PhD University of North Carolina
PRS Account University of North Carolina, Chapel Hill
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP