Sex Differences in the Vascular Effects of E-cigarette Use

Study Overview
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Brief Summary
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The use of electronic nicotine delivery systems, or e-cigarettes - colloquially referred to as vaping - in the United States has increased exponentially since their introduction to the US market in 2007. Prevalence of ever and current e-cigarette use is highest among teenagers and young adults with 16-28% of this population having reported vaping. While the majority of e-cigarette users are current tobacco smokers, 32.5% of current e-cigarette users are never- or former-smokers, representing a growing population of young adults who exclusively vape. While e-cigarettes have been marketed as a safer alternative to tobacco cigarettes, clinical studies examining these claims are limited. Cardiovascular disease (CVD) is the primary cause of premature death among tobacco cigarette smokers and reductions in vascular endothelial function, a significant predictor of future CVD, are detectible in otherwise healthy young adults who smoke. Despite the explosion in e-cigarette use among young adults, the health effects - especially the effects on mechanisms of vascular function - of these devices remain relatively unexplored. In this study, we use the blood vessels in the skin as a representative vascular bed for examining mechanisms of microvascular dysfunction in humans. Using a minimally invasive technique (intradermal microdialysis for the local delivery of pharmaceutical agents) we examine the blood vessels in a dime-sized area of the skin in otherwise healthy young (18-24yrs) chronic e-cigarette users. Local heating of the skin at the microdialysis sites is used to explore differences in mechanisms governing microvascular control. As a compliment to these measurements, we also draw blood from the subjects to measure circulating factors that may contribute to cardiovascular health and examine markers of inflammatory activation. We will also collect urine from female participants to measure estradiol.

Official Title
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Sex Differences in the Vascular Effects of E-cigarette Use

Conditions
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E-cigarette Use

Intervention / Treatment
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* Drug: Local heating + L-NAME (NG-nitro-L-arginine methyl ester; nitric oxide synthase inhibitor)
* Other: Chronic estrogen exposure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-24 years old one of the following: have no history of e-cigarette use be a current e-cigarette user who has been using e-cigarettes for 6 months or longer Exclusion Criteria: history of cardiovascular, metabolic, and/or skin diseases body mass index >30 kg/m2 blood pressure ≥140 systolic and/or ≥ 90 diastolic current or history of tobacco cigarette use current antihypertensive or cholesterol-lowering medication current use of cannabis, marijuana, and/or other illegal substances current use of stimulant drugs currently pregnant or breastfeeding allergy to materials used during the experiment (e.g. latex), known allergy to study drugs healthy control subjects will also be excluded if they have ever used e-cigarettes in the past

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 24 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Healthy Young Women<br>Young women who do not use e-cigarettes | Drug: Local heating + L-NAME (NG-nitro-L-arginine methyl ester; nitric oxide synthase inhibitor)<br>* Differences in endothelium- and nitric oxide (NO)-dependent dilation between groups<br>Other: Chronic estrogen exposure<br>* differences in urine estrogen levels across the menstrual cycle between women groups only<br>|
| Other: Healthy Young Men<br>Young men who do not use e-cigarettes | Drug: Local heating + L-NAME (NG-nitro-L-arginine methyl ester; nitric oxide synthase inhibitor)<br>* Differences in endothelium- and nitric oxide (NO)-dependent dilation between groups<br>|
| Other: Young Women using E-cigarettes<br>Young women chronically use e-cigarettes | Drug: Local heating + L-NAME (NG-nitro-L-arginine methyl ester; nitric oxide synthase inhibitor)<br>* Differences in endothelium- and nitric oxide (NO)-dependent dilation between groups<br>Other: Chronic estrogen exposure<br>* differences in urine estrogen levels across the menstrual cycle between women groups only<br>|
| Other: Young Men using E-cigarettes<br>Young men chronically use e-cigarettes | Drug: Local heating + L-NAME (NG-nitro-L-arginine methyl ester; nitric oxide synthase inhibitor)<br>* Differences in endothelium- and nitric oxide (NO)-dependent dilation between groups<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in microvascular endothelium-dependent dilation response measured by laser-Doppler flowmetry | cutaneous vascular vasodilator responses to local heating over a microdialysis fiber receiving lactated Ringer's solution, followed by L-NAME infusion to quantify NO-dependent response | at the study visit, an average of 4 hours | 
| monthly estrogen exposure | daily estradiol levels will be measured in all women for 1 month/menstrual cycle | 1 month |