Clinical trial NCT02783768: Ventilation and Pulmonary Endothelium Toxicities of E-cigarettes: A Randomized Crossover Pilot Study
Official title: Ventilation and Pulmonary Endothelium Toxicities (VaPE-Tox) of E-cigarettes: A Randomized Crossover Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Pulmonary Disease, Chronic Obstructive
E-cigarettes
Keywords: E-cigarettes
COPD
Lead sponsor: Columbia University
Sponsor class: OTHER
First posted: 2016-05-26
Enrollment: 12
Sex: ALL
Minimum age (years): 21
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief 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 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.

Eligibility criteria: Inclusion Criteria:

* current use of e-cigarettes (\>1x/month but \<4 days/week)

Exclusion Criteria:

* 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)

Primary outcomes:
measure: Pulmonary Microvascular Blood Flow (PMBF), Measured on Gadolinium-enhanced MRI, Between E-cigarette Exposed and Unexposed Conditions
timeFrame: After exposure (approximately 30 seconds)
measure: Ventilation Defect Percentage (VDP), Measured on Hyperpolarized 3-helium Enhanced MRI
timeFrame: After exposure (approximately 30 seconds)
Secondary outcomes:
measure: Regional PMBF, Measured on Gadolinium-enhanced MRI
timeFrame: After exposure (approximately 30 seconds)
measure: Regional VDP, Measured on Hyperpolarized 3-helium Enhanced MRI
timeFrame: After exposure (approximately 30 seconds)
measure: Lung Function, Measured on Spirometry
timeFrame: After exposure (approximately 30 seconds)
measure: Diffusing Capacity of the Lung for Carbon Monoxide (DLCO)
timeFrame: After exposure (approximately 30 seconds)
measure: Cardiac Output, Measured on Cardiac MRI
timeFrame: After exposure (approximately 30 seconds)
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
Study officials:
affiliation: Columbia University
name: Elizabeth Oelsner, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: