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SmokingCinimicNCT03700892

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

A study testing Cinnamaldehyde e-liquid and PG/VG e-liquid in people with Smoking and Healthy, run by University of North Carolina, Chapel Hill at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 40 yearsHealthy volunteers can take part
Conditions the study is for
Smoking, Healthy
What is being tested?
Cinnamaldehyde e-liquid and PG/VG e-liquid
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
1 siteUnited States
Study dates
19 Oct 2018to 3 Mar 2020
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 40 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • UNC Center for Environmental Medicine, Asthma and Lung Biology

    Chapel Hill, North Carolina, 27599-7310

Other trials in United States

About this study

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.

Read the 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.

Conditions
Smoking, Healthy
Being tested
Cinnamaldehyde e-liquid, PG/VG e-liquid
Keywords
e-cig, E-cigarette, Electronic cigarette, Vaping
Medical subject headings
Smoking, Vaping

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cinnamaldehyde e-liquidOther

    Also called Cinnamon

    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-liquidOther

    Also called Placebo

    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).

Study groups in NCT03700892
Study groupRoleWhat they receive
Cinnamaldehyde, then PG/VGExperimentalParticipants 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.
Receives: Other: Cinnamaldehyde e-liquid; Other: PG/VG e-liquid
PG/VG, then CinnamaldehydeExperimentalParticipants 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.
Receives: Other: Cinnamaldehyde e-liquid; Other: PG/VG e-liquid
Healthy ControlsNo interventionParticipants will only undergo the baseline testing and thus serve as a non-exposed/non-vaping control group.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. CA-induced Changes in Whole Lung MCC

    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.

    Measured: Through study completion, an average of three months

Secondary outcomes (3)
  1. CA-induced Changes in Regional Lung MCC

    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.

    Measured: Through study completion, an average of three months

  2. Percent Polymorphonuclear Leukocytes (PMN) in Induced Sputum

    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.

    Measured: Through study completion, an average of three months

  3. Absolute Values of Whole Lung MCC for Each Group

    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.

    Measured: Start of study, up to three months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Oct 2018
  2. Study start19 Oct 2018
  3. Primary completion3 Mar 2020
  4. Study completion3 Mar 2020

Why it stopped: Covid-19 has been shown to increase risk associated with vaping. To increase participant safety and use real world vaping habits, the investigators plan to continue studying vaping effects on the airways in an observational format.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Crossover
Model description
Controls will not be randomized and will not receive the study intervention.
Masking
Double blind
Who is masked
Participant, Outcomes assessor
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03700892
Sponsor's protocol ID
17-2275
Other IDs
R01HL139369
Acronym
Cinimic
Status last verified
Mar 2021
First submitted
4 Oct 2018
Last updated
10 Jun 2021
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).

Publications

  • Bennett WD, Clapp PW, Zeman KL, Wu J, Ring B, Jaspers I. Acute Effect of E-Cigarette Inhalation on Mucociliary Clearance in E-Cigarette Users. J Aerosol Med Pulm Drug Deliv. 2024 Aug;37(4):167-170. doi: 10.1089/jamp.2023.0027. Epub 2024 Apr 22.

    PubMed 38687136

Questions about this trial

What is this clinical trial studying?

A study testing Cinnamaldehyde e-liquid and PG/VG e-liquid in people with Smoking and Healthy, run by University of North Carolina, Chapel Hill at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 10 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

CA-induced Changes in Whole Lung MCC (time frame: Through study completion, an average of three months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03700892, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2021.

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