Sex Differences in the Vascular Effects of E-cigarette Use

NCT06159608 — Early Phase 1, Recruiting, 80 participants, Anna Stanhewicz, PhD

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Registry	NCT06159608
Status	Recruiting
Phase	Early Phase 1
Study type	Interventional; non randomized, parallel, masking: none, basic science
Enrollment	80 (Estimated)
Sponsor	Anna Stanhewicz, PhD (Other)
Conditions	E-cigarette Use
Interventions	Local heating + L-NAME (NG-nitro-L-arginine methyl ester; nitric oxide synthase inhibitor), Chronic estrogen exposure (Drug, other)
Dates	start 2023-12-02, primary completion 2026-12-01 (estimated), completion 2026-12-01 (estimated), first posted 2023-12-07, last updated 2025-12-15
Locations	1 site in United States

-Summary

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.

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+Arms and interventions

Arm	Type	Interventions	Description
Healthy Young Women	Other	Drug: Local heating + L-NAME (NG-nitro-L-arginine methyl ester; nitric oxide synthase inhibitor); Other: Chronic estrogen exposure	Young women who do not use e-cigarettes
Healthy Young Men	Other	Drug: Local heating + L-NAME (NG-nitro-L-arginine methyl ester; nitric oxide synthase inhibitor)	Young men who do not use e-cigarettes
Young Women using E-cigarettes	Other	Drug: Local heating + L-NAME (NG-nitro-L-arginine methyl ester; nitric oxide synthase inhibitor); Other: Chronic estrogen exposure	Young women chronically use e-cigarettes
Young Men using E-cigarettes	Other	Drug: Local heating + L-NAME (NG-nitro-L-arginine methyl ester; nitric oxide synthase inhibitor)	Young men chronically use e-cigarettes

Local heating + L-NAME (NG-nitro-L-arginine methyl ester; nitric oxide synthase inhibitor) (Drug): Differences in endothelium- and nitric oxide (NO)-dependent dilation between groups
Chronic estrogen exposure (Other): differences in urine estrogen levels across the menstrual cycle between women groups only

+Outcome measures

Primary outcomes

Change in microvascular endothelium-dependent dilation response measured by laser-Doppler flowmetry [at the study visit, an average of 4 hours]: 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
monthly estrogen exposure [1 month]: daily estradiol levels will be measured in all women for 1 month/menstrual cycle

+Eligibility

Sex: All, ages: 18 Years to 24 Years, accepts healthy volunteers

Inclusion Criteria:

* 18-24 years old
* one of the following:

  1. have no history of e-cigarette use
  2. 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

+Locations (1)

Facility	City	Country	Status
University of Iowa	Iowa City, Iowa	United States	Recruiting