Ventilation and Pulmonary Endothelium Toxicities of E-cigarettes: A Randomized Crossover Pilot Study

NCT ID: NCT02783768

Last Updated: 2020-10-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-01
• Study Completion Date: 2018-07-24

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.

Conditions

Pulmonary Disease, Chronic Obstructive; E-cigarettes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: DOUBLE

Study Groups

E-cigarette first

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.

Group Type: EXPERIMENTAL

E-cigarette

Intervention Type: DEVICE

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.

Sham

Intervention Type: OTHER

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-Helium

Intervention Type: DRUG

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.

Gadolinium

Intervention Type: DRUG

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).

Sham first

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.

Group Type: EXPERIMENTAL

E-cigarette

Intervention Type: DEVICE

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.

Sham

Intervention Type: OTHER

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-Helium

Intervention Type: DRUG

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.

Gadolinium

Intervention Type: DRUG

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).

Interventions

E-cigarette

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.

Intervention Type: DEVICE

Sham

The "unexposed" condition will be breathing from the study e-cigarette (10 puffs with 30-second inter-puff intervals) with the battery off.

Intervention Type: OTHER

Hyperpolarized 3-Helium

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.

Intervention Type: DRUG

Gadolinium

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).

Intervention Type: DRUG

Other Intervention Names

3-He; Gd

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)

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Columbia University

OTHER

Sponsor Role: lead

Responsible Party

Elizabeth Oelsner

Assistant Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Elizabeth Oelsner, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Columbia University Irving Medical Center

New York, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

AAAQ8089

Identifier Type: -

Identifier Source: org_study_id