Pulmonary Disease, Chronic ObstructiveEarly Phase 1VaPE-ToxNCT02783768
Ventilation and Pulmonary Endothelium Toxicities of E-cigarettes: A Randomized Crossover Pilot Study
A Early Phase 1 study testing E-cigarette, Hyperpolarized 3-Helium and Gadolinium in people with Pulmonary Disease, Chronic Obstructive and E-cigarettes, run by Columbia University at 1 site in United States.
Trial summary
Determination of the acute pulmonary toxicities of e-cigarettes in young adults is of major public health importance, as e-cigarette vapor contains established toxicants that as hypothesized cause acute damage to the airways and the pulmonary microvasculature that may promote the development of CLD, for which there… Read more about this study
- Who is it for?
- Ages 21 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Pulmonary Disease, Chronic Obstructive, E-cigarettes
- What is being tested?
- E-cigarette, Hyperpolarized 3-Helium and Gadolinium
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2017to 24 Jul 2018
- Phase
- Early Phase 1
- 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 21 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- current use of e-cigarettes (>1x/month but <4 days/week)
Who cannot join
- any chronic medical or major psychiatric problems including current asthma
- self-reported heavy snoring/sleep apnea
- pre-bronchodilator FEV1 or FVC <80% predicted or FEV1/FVC < lower limit of normal
- MRI exclusions (pregnancy, claustrophobia, metal in body, gadolinium allergy, eGFR <60 mL/min/1.73m2)
- MRI scan with contrast within the last 12 months or planned MRI with contrast in the next 6 months
- use of any of the following in the prior 30 days: any conventional cigarettes, marijuana >10 days, any illicit drugs, any medication or inhalers (excluding hormonal contraceptives)
- binge drinking (≥5 alcoholic beverages over 2 hours) over the prior two weeks
- adverse symptomatic response to the study e-cigarette exposure (e.g., palpitations, shortness of breath, chest pain, headache, dizziness)
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Irving Medical Center
New York, New York, 10032
About this study
Official title: Ventilation and Pulmonary Endothelium Toxicities (VaPE-Tox) of E-cigarettes: A Randomized Crossover Pilot Study
Determination of the acute pulmonary toxicities of e-cigarettes in young adults is of major public health importance, as e-cigarette vapor contains established toxicants that as hypothesized cause acute damage to the airways and the pulmonary microvasculature that may promote the development of CLD, for which there remain few effective therapies.
The study therefore propose a pilot study using a randomized crossover design in ten healthy young adults to test the acute effects of a standardized e-cigarette exposure on two sensitive, safe, non-invasive imaging measures: (1) ventilation defects on hyperpolarized helium-enhanced magnetic resonance imaging, and (2) pulmonary microvascular blood flow on gadolinium-enhanced pulmonary magnetic resonance angiography.
Read the detailed description
Magnetic resonance imaging (MRI) and angiography (MRA) measures are promising approaches to detecting and characterizing the anticipated acute pulmonary toxicities of e-cigarettes. Hyperpolarized helium (3He)-enhanced MRI may be more sensitive than spirometry, a global lung function measure, for determination of airway toxicities. 3He-enhanced MRI has been used to demonstrate the extent of ventilation defects in healthy persons with normal spirometry; to measure ventilation changes in asthmatics pre- and post-challenge with bronchodilators and methacholine; and to predict pulmonary hospitalizations in persons with COPD. Meanwhile, until recently, non-invasive measures of pulmonary vascular toxicities were lacking. The investigators have developed an innovative measure of pulmonary microvascular blood flow on gadolinium (Gd)-enhanced MRA, which the investigators found to be markedly abnormal in early chronic obstructive pulmonary disease (COPD) and emphysema, and to be associated with increased endothelial microparticles, a marker of endothelial dysfunction. Nonetheless, neither of these sensitive, non-invasive, repeatable, and reproducible measures has ever been used to assess e-cigarette toxicities.
It is hypothesized that e-cigarette vapor inhalation will result in an acute increase in global and regional ventilation defects and an acute decrease in global and regional pulmonary microvascular perfusion.
This pilot work will provide the experience and data to support subsequent funding applications powered to definitively establish the acute toxicities of e-cigarette vapor of various compositions (e.g., with and without nicotine, with and without flavoring) in persons with and without chronic lung diseases (e.g., asthma) on pulmonary ventilation and microvascular perfusion. Furthermore, confirmation of the hypotheses in this sample would provide important preliminary evidence of e-cigarette pulmonary toxicities to inform interim regulatory decisions, as well as potentially generating vivid images of e-cigarette harms that may be meaningful to the general public and therefore suitable for use in public education campaigns.
- Being tested
- E-cigarette, Sham, Hyperpolarized 3-Helium, Gadolinium
- Keywords
- E-cigarettes, COPD
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Vaping
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
E-cigaretteDevice
The study e-cigarette exposure will be 10 puffs with 30-second inter-puff intervals, as directly observed by a trained research assistant, using a standardized e-cigarette. Cartomizers, batteries, and e-liquids will be obtained from commercial suppliers. The e-cigarette device will be loaded with 1 mL of flavorless e-liquid with a ratio of PG to vegetable glycerin of 70:30 and 1.8 mg/dL of nicotine.
ShamOther
The "unexposed" condition will be breathing from the study e-cigarette (10 puffs with 30-second inter-puff intervals) with the battery off.
Hyperpolarized 3-HeliumDrug
Also called 3-He
Hyperpolarized 3-Helium will be used as an experimental contrast agent for the Ventilation MRIs performed twice per participant in both experimental arms. Approximately 250-600 mL of hyperpolarized 3He mixed with 300-750 mL nitrogen will be inhaled through a one-way valve in one inhalation starting approximately at residual volume.
GadoliniumDrug
Also called Gd
Gadolinium contrast will be injected into the antecubital vein through an 18-20 gauge IV. The type of gadolinium will be 0.03 mmol/kg bodyweight of dotarem (gadoterate meglumine).
| Study group | Role | What they receive |
|---|---|---|
| E-cigarette first | Experimental | Participants will undergo the e-cigarette exposure prior to the first two MRI measures, and then they will undergo the sham exposure prior to the last two MRI measures. The two MRIs performed under both experimental exposures (e-cigarette and sham) will be enhanced by (1) gadolinium and then (2) hyperpolarized 3-helium. Receives: Device: E-cigarette; Other: Sham; Drug: Hyperpolarized 3-Helium; Drug: Gadolinium |
| Sham first | Experimental | Participants will undergo the sham exposure prior to the first two MRI measures, and then they will undergo the e-cigarette exposure prior to the last two MRI measures. The two MRIs performed under both experimental exposures (e-cigarette and sham) will be enhanced by (1) gadolinium and then (2) hyperpolarized 3-helium. Receives: Device: E-cigarette; Other: Sham; Drug: Hyperpolarized 3-Helium; Drug: Gadolinium |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pulmonary Microvascular Blood Flow (PMBF), Measured on Gadolinium-enhanced MRI, Between E-cigarette Exposed and Unexposed Conditions
PMBF will be measured on gadolinium-enhanced MRI after e-cigarette and sham exposures. There were four days between the measurements of PMBF (e-cigarette) and PMBF (sham). PMBF is measured in mL(blood)/min/mL(lung volume). Lower PMBF has been observed in adults with COPD and emphysema.
Measured: After exposure (approximately 30 seconds)
Ventilation Defect Percentage (VDP), Measured on Hyperpolarized 3-helium Enhanced MRI
VDP will be measured on hyperpolarized 3Helium-enhanced MRI after e-cigarette and sham exposures. Due to limitations of prior qualitative/visual assessments of MRI, we developed and validated a new deep learning approach to the precise measurement of ventilation defects and report the percent non-fully ventilated lung using this method.
Measured: After exposure (approximately 30 seconds)
Secondary outcomes (5)
Regional PMBF, Measured on Gadolinium-enhanced MRI
Regional PMBF (ie, in the right versus left, upper versus lower lobes) will be measured on gadolinium-enhanced MRI after e-cigarette and sham exposures.
Measured: After exposure (approximately 30 seconds)
Regional VDP, Measured on Hyperpolarized 3-helium Enhanced MRI
Regional VDP in the lower lung was measured on hyperpolarized 3Helium-enhanced MRI after e-cigarette and sham exposures.
Measured: After exposure (approximately 30 seconds)
Lung Function, Measured on Spirometry
Lung function will be measured on spirometry. Two participants had only one valid FEV1 measure, and one participant had no valid FEV1 measures. Hence, 3 participants (2 in "E-cigarette first" and 1 in "Sham first") were not analyzed. The analysis combines the groups in order to separate the effects of randomization group (order) and exposure.
Measured: After exposure (approximately 30 seconds)
Diffusing Capacity of the Lung for Carbon Monoxide (DLCO)
DLCO will be measured. There was a malfunction of the machine used to measure the DLCO. Hence, only one participant had paired DLCO values and 3 had unpaired measures.
Measured: After exposure (approximately 30 seconds)
Cardiac Output, Measured on Cardiac MRI
Cardiac output will be measured on cardiac MRI. In the "E-cigarette first" arm, 2 participants did not have 2 valid measures of CO (one pair was missing, one was invalid). In the "Sham first" arm, 3 participants had one invalid measure of CO. The analysis combines the groups in order to separate the effects of randomization group (order) and exposure.
Measured: After exposure (approximately 30 seconds)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2016 (estimated)
- Study start1 Mar 2017
- Primary completion24 Jul 2018
- Study completion24 Jul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Pulmonary Disease, Chronic ObstructiveStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Elizabeth Oelsner, Columbia University
- Investigators
- Elizabeth Oelsner, MD, MPH, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02783768
- Sponsor's protocol ID
- AAAQ8089
- Acronym
- VaPE-Tox
- Status last verified
- Sep 2020
- First submitted
- 24 May 2016
- Last updated
- 22 Oct 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ventilation and Pulmonary Endothelium Toxicities (VaPE-Tox) of E-cigarettes: A Randomized Crossover Pilot Study
- ClinicalTrials.gov ID
- NCT02783768
- Acronym / sponsor ID
- VaPE-Tox / AAAQ8089
- Keywords
- E-cigarettes, COPD
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Study start
- 1 Mar 2017 (actual)
- Primary completion
- 24 Jul 2018 (actual)
- Study completion
- 24 Jul 2018 (actual)
- First posted
- 26 May 2016 (estimated)
- Results
- Posted 22 Oct 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Determination of the acute pulmonary toxicities of e-cigarettes in young adults is of major public health importance, as e-cigarette vapor contains established toxicants that as hypothesized cause acute damage to the airways and the pulmonary microvasculature that may promote the development of CLD, for which there remain few effective therapies.
The study therefore propose a pilot study using a randomized crossover design in ten healthy young adults to test the acute effects of a standardized e-cigarette exposure on two sensitive, safe, non-invasive imaging measures: (1) ventilation defects on hyperpolarized helium-enhanced magnetic resonance imaging, and (2) pulmonary microvascular blood flow on gadolinium-enhanced pulmonary magnetic resonance angiography.
Detailed description
Magnetic resonance imaging (MRI) and angiography (MRA) measures are promising approaches to detecting and characterizing the anticipated acute pulmonary toxicities of e-cigarettes. Hyperpolarized helium (3He)-enhanced MRI may be more sensitive than spirometry, a global lung function measure, for determination of airway toxicities. 3He-enhanced MRI has been used to demonstrate the extent of ventilation defects in healthy persons with normal spirometry; to measure ventilation changes in asthmatics pre- and post-challenge with bronchodilators and methacholine; and to predict pulmonary hospitalizations in persons with COPD. Meanwhile, until recently, non-invasive measures of pulmonary vascular toxicities were lacking. The investigators have developed an innovative measure of pulmonary microvascular blood flow on gadolinium (Gd)-enhanced MRA, which the investigators found to be markedly abnormal in early chronic obstructive pulmonary disease (COPD) and emphysema, and to be associated with increased endothelial microparticles, a marker of endothelial dysfunction. Nonetheless, neither of these sensitive, non-invasive, repeatable, and reproducible measures has ever been used to assess e-cigarette toxicities.
It is hypothesized that e-cigarette vapor inhalation will result in an acute increase in global and regional ventilation defects and an acute decrease in global and regional pulmonary microvascular perfusion.
This pilot work will provide the experience and data to support subsequent funding applications powered to definitively establish the acute toxicities of e-cigarette vapor of various compositions (e.g., with and without nicotine, with and without flavoring) in persons with and without chronic lung diseases (e.g., asthma) on pulmonary ventilation and microvascular perfusion. Furthermore, confirmation of the hypotheses in this sample would provide important preliminary evidence of e-cigarette pulmonary toxicities to inform interim regulatory decisions, as well as potentially generating vivid images of e-cigarette harms that may be meaningful to the general public and therefore suitable for use in public education campaigns.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| E-cigarette first | Experimental | Device: E-cigarette, Other: Sham, Drug: Hyperpolarized 3-Helium, Drug: GadoliniumParticipants will undergo the e-cigarette exposure prior to the first two MRI measures, and then they will undergo the sham exposure prior to the last two MRI measures. The two MRIs performed under both experimental exposures (e-cigarette and sham) will be enhanced by (1) gadolinium and then (2) hyperpolarized 3-helium. |
| Sham first | Experimental | Device: E-cigarette, Other: Sham, Drug: Hyperpolarized 3-Helium, Drug: GadoliniumParticipants will undergo the sham exposure prior to the first two MRI measures, and then they will undergo the e-cigarette exposure prior to the last two MRI measures. The two MRIs performed under both experimental exposures (e-cigarette and sham) will be enhanced by (1) gadolinium and then (2) hyperpolarized 3-helium. |
Who may qualify
- Ages
- 21 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- current use of e-cigarettes (>1x/month but <4 days/week)
Key exclusion criteria (8 listed)
- any chronic medical or major psychiatric problems including current asthma
- self-reported heavy snoring/sleep apnea
- pre-bronchodilator FEV1 or FVC <80% predicted or FEV1/FVC < lower limit of normal
- MRI exclusions (pregnancy, claustrophobia, metal in body, gadolinium allergy, eGFR <60 mL/min/1.73m2)
- MRI scan with contrast within the last 12 months or planned MRI with contrast in the next 6 months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| E-cigaretteThe study e-cigarette exposure will be 10 puffs with 30-second inter-puff intervals, as directly observed by a trained research assistant, using a standardized e-cigarette. Cartomizers, batteries, and e-liquids will be obtained from commercial suppliers. The e-cigarette device will be loaded with 1 mL of flavorless e-liquid with a ratio of PG to vegetable glycerin of 70:30 and 1.8 mg/dL of nicotine. | Device | E-cigarette first, Sham first |
| ShamThe "unexposed" condition will be breathing from the study e-cigarette (10 puffs with 30-second inter-puff intervals) with the battery off. | Other | E-cigarette first, Sham first |
| Hyperpolarized 3-HeliumAlso: 3-HeHyperpolarized 3-Helium will be used as an experimental contrast agent for the Ventilation MRIs performed twice per participant in both experimental arms. Approximately 250-600 mL of hyperpolarized 3He mixed with 300-750 mL nitrogen will be inhaled through a one-way valve in one inhalation starting approximately at residual volume. | Drug | E-cigarette first, Sham first |
| GadoliniumAlso: GdGadolinium contrast will be injected into the antecubital vein through an 18-20 gauge IV. The type of gadolinium will be 0.03 mmol/kg bodyweight of dotarem (gadoterate meglumine). | Drug | E-cigarette first, Sham first |
Primary outcome
Pulmonary Microvascular Blood Flow (PMBF), Measured on Gadolinium-enhanced MRI, Between E-cigarette Exposed and Unexposed Conditions
Time frame: After exposure (approximately 30 seconds)
PMBF will be measured on gadolinium-enhanced MRI after e-cigarette and sham exposures. There were four days between the measurements of PMBF (e-cigarette) and PMBF (sham). PMBF is measured in mL(blood)/min/mL(lung volume). Lower PMBF has been observed in adults with COPD and emphysema.
Ventilation Defect Percentage (VDP), Measured on Hyperpolarized 3-helium Enhanced MRI
Time frame: After exposure (approximately 30 seconds)
VDP will be measured on hyperpolarized 3Helium-enhanced MRI after e-cigarette and sham exposures. Due to limitations of prior qualitative/visual assessments of MRI, we developed and validated a new deep learning approach to the precise measurement of ventilation defects and report the percent non-fully ventilated lung using this method.
5 secondary outcomes
Regional PMBF, Measured on Gadolinium-enhanced MRI
Time frame: After exposure (approximately 30 seconds)
Regional VDP, Measured on Hyperpolarized 3-helium Enhanced MRI
Time frame: After exposure (approximately 30 seconds)
Lung Function, Measured on Spirometry
Time frame: After exposure (approximately 30 seconds)
Diffusing Capacity of the Lung for Carbon Monoxide (DLCO)
Time frame: After exposure (approximately 30 seconds)
Cardiac Output, Measured on Cardiac MRI
Time frame: After exposure (approximately 30 seconds)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Pulmonary Disease, Chronic Obstructive
Active, not recruiting
Symptoms and Functions in Patients With COPD and Chronic Bronchitis Switching From CIG to THS
COPD, Smoking
Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Not yet recruiting
The Aim of the Study is to Decipher the Alterations in Signalling Pathways of Skeletal Muscle Stem Cells (Satellite Cells (SCs)) in Individuals With COPD, as Well as to Examine the Effect of Exercise Training on SCs.
COPD (Chronic Obstructive Pulmonary Disease), Sarcopenia in Elderly
Not yet recruitingPhase 2
Study of Treprostinil Administered Via Soft Mist Inhaler (SMI) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
RecruitingPhase 3
A Study to Investigate the Efficacy and Safety of Belumosudil Compared With Best Available Therapy in Participants Aged 12 Years or Older With Chronic Graft-versus-host Disease
Chronic Graft Versus Host Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elizabeth Oelsner, MD, MPH principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing E-cigarette, Hyperpolarized 3-Helium and Gadolinium in people with Pulmonary Disease, Chronic Obstructive and E-cigarettes, run by Columbia University 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 1 inclusion and 8 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: finished, as of the sponsor's last update on 22 Oct 2020. 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.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Oct 2020). 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?
Pulmonary Microvascular Blood Flow (PMBF), Measured on Gadolinium-enhanced MRI, Between E-cigarette Exposed and Unexposed Conditions (time frame: After exposure (approximately 30 seconds)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Oct 2020.