Sex Differences in the Vascular Effects of E-cigarette Use

Anna Stanhewicz, PhD

Status and phase: Enrolling; Early Phase 1

Conditions: E-cigarette Use

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

Study type: Interventional

Funder types: Other

Identifiers

NCT06159608

202308025

Details and patient eligibility

About

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.

Enrollment: 80 estimated patients

Sex: All

Ages: 18 to 24 years old

Volunteers: 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

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

80 participants in 4 patient groups

Healthy Young Women

Other group

Description:

Young women who do not use e-cigarettes

Treatment:

Other: Chronic estrogen exposure

Drug: Local heating + L-NAME (NG-nitro-L-arginine methyl ester; nitric oxide synthase inhibitor)

Healthy Young Men

Other group

Description:

Young men who do not use e-cigarettes

Treatment:

Drug: Local heating + L-NAME (NG-nitro-L-arginine methyl ester; nitric oxide synthase inhibitor)

Young Women using E-cigarettes

Other group

Description:

Young women chronically use e-cigarettes

Treatment:

Other: Chronic estrogen exposure

Drug: Local heating + L-NAME (NG-nitro-L-arginine methyl ester; nitric oxide synthase inhibitor)

Young Men using E-cigarettes

Other group

Description:

Young men chronically use e-cigarettes

Treatment:

Drug: Local heating + L-NAME (NG-nitro-L-arginine methyl ester; nitric oxide synthase inhibitor)