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

NCT02783768 | Completed Early Phase 1 Results DMC FDA Drug FDA Device

• 1 other identifier: AAAQ8089
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Pulmonary Disease, Chronic Obstructive; E-cigarettes

Keywords

E-cigarettes; COPD

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  After exposure (approximately 30 seconds)

Secondary Outcomes (5)

• Regional PMBF, Measured on Gadolinium-enhanced MRI

  After exposure (approximately 30 seconds)

• Regional VDP, Measured on Hyperpolarized 3-helium Enhanced MRI

  After exposure (approximately 30 seconds)

• Lung Function, Measured on Spirometry

  After exposure (approximately 30 seconds)

• Diffusing Capacity of the Lung for Carbon Monoxide (DLCO)

  After exposure (approximately 30 seconds)

• Cardiac Output, Measured on Cardiac MRI

  After exposure (approximately 30 seconds)

Study Arms (2)

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.

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.

Device: E-cigarette; Other: Sham; Drug: Hyperpolarized 3-Helium; Drug: Gadolinium

Interventions

E-cigarette 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.

E-cigarette first; Sham first

Sham OTHER

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

E-cigarette first; Sham first

Hyperpolarized 3-Helium 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.

Also known as: 3-He

E-cigarette first; Sham first

Gadolinium 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).

Also known as: Gd

E-cigarette first; Sham first

Eligibility Criteria

• Age: 21 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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 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)

Sponsors & Collaborators

• Columbia University: lead

Study Sites (1)

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Vaping

Interventions

salicylhydroxamic acid; Gadolinium

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Smoking; Behavior

Intervention Hierarchy (Ancestors)

Lanthanoid Series Elements; Metals, Rare Earth; Elements; Inorganic Chemicals; Metals

Results Point of Contact

• Title: Elizabeth C. Oelsner, MD, MPH
• Organization: CUIMC

eco7@cumc.columbia.edu

212-305-9056

Study Officials

• Elizabeth Oelsner, MD, MPH

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: May 24, 2016
• First Posted: May 26, 2016
• Study Start: March 1, 2017
• Primary Completion: July 24, 2018
• Study Completion: July 24, 2018
• Last Updated: October 22, 2020
• Results First Posted: October 22, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)