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| ID | Type | Description | Link |
|---|---|---|---|
| R01HL155243 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Smokers | Experimental | Conventional tobacco cigarette smokers |
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| Vapers | Experimental | Electronic cigarette vapers |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Standardized Electronic Research Cigarette | Device | 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) |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Felix W Wehrli, PhD | University of Pennsylvania | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
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| ID | Term |
|---|---|
| D000072137 | Vaping |
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D012907 | Smoking |
| D001519 | Behavior |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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The study will be conducted in a three-period crossover design and will involve active e-cig (electronic cigarette) and tobacco cigarette users undergoing three different interventions (blinded to the investigators).
The three periods will consist of (1) electronic cigarette vaping without nicotine, (2) electronic cigarette vaping with nicotine, (3) tobacco cigarette smoking. Sequence order will be established by means of a computer-generated randomization scheme.
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Blinding to nicotine and placebo containing standardized electronic research cigarettes and standardized tobacco research cigarettes.
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| Nicotine Research Cigarette | Device | Conventional Nicotine Tobacco Cigarette (National Institute of Drug Abuse, Drug Supply Program, Tobacco Product Master File #NRC600) |
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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) |