Sex Differences in the Vascular Effects of E-cigarette Use

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.

Study Overview

• Status: Recruiting
• Conditions: E-cigarette Use
• Intervention / Treatment: Drug: Local heating + L-NAME (NG-nitro-L-arginine methyl ester; nitric oxide synthase inhibitor); Other: Chronic estrogen exposure

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Anna Reid-Stanhewicz, PHD; Phone Number: 319-467-1732; Email: anna-stanhewicz@uiowa.edu

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa
      • Contact: Anna Stanhewicz; Phone Number: 319-467-1732; Email: anna-stanhewicz@uiowa.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Anna Stanhewicz, PhD

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: November 27, 2023
• First Submitted That Met QC Criteria: December 4, 2023
• First Posted (Actual): December 7, 2023

Study Record Updates

• Last Update Posted (Estimated): December 15, 2025
• Last Update Submitted That Met QC Criteria: December 8, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavior; Smoking; Vaping; Amino Acids, Peptides, and Proteins; Amino Acids; Amino Acids, Basic; Amino Acids, Diamino; Arginine; NG-Nitroarginine Methyl Ester
• Other Study ID Numbers: 202308025

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No