MRI and Biological Markers of Acute E-Cigarette Exposure in Smokers and Vapers (AeCE)

To examine vascular reactivity and inflammatory biomarkers via quantitative magnetic resonance imaging (MRI) and blood serum, respectively, in a crossover study where active vapers (electronic cigarette users) and smokers will undergo three separate acute exposure-episodes of electronic cigarette +/- nicotine and tobacco-cig. The MRI exams and blood draws will be performed pre- and post-exposure. The results will be compared against baseline values derived from a group of non-smokers/non-vapers, who will also undergo a blood draw and MRI.

Study Overview

• Status: Completed
• Conditions: Serum Biomarkers; Vascular Reactivity
• Intervention / Treatment: Device: Standardized Electronic Research Cigarette; Device: Nicotine Research Cigarette

Detailed Description

This work is an extension of prior funded work on the acute effects of nicotine free electronic cigarette aerosol on vascular function and inflammatory biomarkers in healthy non-smokers. Here, the investigators will examine vascular reactivity and inflammatory biomarkers using quantitative magnetic resonance imagine (MRI) and blood serum in a crossover study, with active vapers (electronic cigarette users) and smokers undergoing three, separate-day, acute exposure-episodes of smoking a tobacco cigarette, an electronic cigarette without nicotine, and an electronic cigarette with nicotine. Participants will undergo an MRI exam and a blood draw pre- and post-exposure-episode.

The investigators hypothesize that all three paradigms will cause a transient response but greatest for tobacco and nicotinized electronic cigarettes. The results will be compared against baseline values derived from a group of non-smokers/non-vapers, who will undergo a blood draw and MRI only. Eligible participants will be healthy, males and females, current, habitual users of electronic or tobacco cigarettes (except for the non-smoking/non-vaping comparison group), 21 to 45 years of age, and without co-morbidities.

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• BMI: 18.5 to 30
• Current users of electronic cigarettes or tobacco cigarettes with a use history of six months or greater.

Exclusion Criteria:

• Cancer
• HIV
• Mental illness in which the participant is not of proper cognizance
• Overt cardio- or neurovascular disease (prior heart attack, stroke, transient ischemic attacks)
• Serious arrhythmias
• Bronchospastic disease
• Upper respiratory tract infection within the past six weeks
• Medication affecting vascular function
• Antibiotics
• Magnetic resonance imaging contraindications (metallic implants/intraocular foreign bodies, claustrophobia, cardiac/cochlear implantable electronic devices, etc.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Smokers; Conventional tobacco cigarette smokers	Device: Standardized Electronic Research Cigarette; Standardized Research Electronic Cigarette Device, Standardized Research Electronic Cigarette Tobacco 5%, Standardized Research Electronic Cigarette Tobacco (placebo) 0% (NJOY, LLC, Tobacco Product Master File #STN MF0000274); Other Names: SREC; Device: Nicotine Research Cigarette; Conventional Nicotine Tobacco Cigarette (National Institute of Drug Abuse, Drug Supply Program, Tobacco Product Master File #NRC600); Other Names: NRC
Experimental: Vapers; Electronic cigarette vapers	Device: Standardized Electronic Research Cigarette; Standardized Research Electronic Cigarette Device, Standardized Research Electronic Cigarette Tobacco 5%, Standardized Research Electronic Cigarette Tobacco (placebo) 0% (NJOY, LLC, Tobacco Product Master File #STN MF0000274); Other Names: SREC; Device: Nicotine Research Cigarette; Conventional Nicotine Tobacco Cigarette (National Institute of Drug Abuse, Drug Supply Program, Tobacco Product Master File #NRC600); Other Names: NRC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in magnetic resonance imaging (MRI) biomarkers of endothelial dysfunction: aortic arch	Changes in stiffness of aortic arch in terms of pulse-wave velocity measured in meters per second.	Pre-Inhalation (baseline) to post-inhalation (60 minutes)
Changes in magnetic resonance imaging (MRI) biomarkers of endothelial dysfunction: cerebral vascular reactivity	Rate of change in the blood flow velocity [centimeters per second (squared)] in a major draining vein in response to volitional apnea.	Pre-Inhalation (baseline) to post-inhalation (60 minutes)
Changes in magnetic resonance imaging (MRI) biomarkers of endothelial dysfunction: femoral artery flow-mediated dilation	Percentage measure of the change of a cross-sectional area of the superficial femoral artery.	Pre-Inhalation (baseline) to post-inhalation (60 minutes)
Changes in magnetic resonance imaging (MRI) biomarkers of endothelial dysfunction: venous oxygen saturation	Assessment of microvascular function by monitoring the changes in tissue blood oxygenation measured in percentage in response to a cuff-induced ischemia.	Pre-Inhalation (baseline) to post-inhalation (60 minutes)
Changes in magnetic resonance imaging (MRI) biomarkers of endothelial dysfunction: blood flow velocity	Macrovascular function is evaluated by monitoring hyperemia in response to a cuff-induced ischemia by measuring femoral artery blood flow velocity in centimeters per second.	Pre-Inhalation (baseline) to post-inhalation (60 minutes)
Changes in blood inflammatory biomarkers	Measured in nanograms/milliliter of plasma, the following biomarkers are collectively associated with damage to blood vessels and recruitment of immune cells into the vascular tissue leading to severe oxidative stress and tissue damage in the vasculature: biomarker of oxidative stress (c-reactive protein) and biomarkers of inflammation (NLR family pyrin domain containing 3, damage-associated molecular pattern protein HMGB1, tumor necrosis factor alpha, interleukin 1β, interleukin 18, interferon gamma, monocyte chemoattractant protein, and macrophage inflammatory protein).	Pre-Inhalation (baseline) to post-inhalation (60 minutes)

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Felix W Wehrli, PhD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): June 7, 2022
• Primary Completion (Actual): June 6, 2025
• Study Completion (Actual): November 28, 2025

Study Registration Dates

• First Submitted: January 20, 2022
• First Submitted That Met QC Criteria: March 8, 2022
• First Posted (Actual): March 9, 2022

Study Record Updates

• Last Update Posted (Estimated): December 16, 2025
• Last Update Submitted That Met QC Criteria: December 15, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Inflammation; Magnetic Resonance Imaging; Nicotine; Endothelial Dysfunction; Electronic Cigarettes
• Additional Relevant MeSH Terms: Pathologic Processes; Pathological Conditions, Signs and Symptoms; Behavior; Smoking; Inflammation; Vaping; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: 850432; R01HL155243 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No