Sex Differences in the Vascular Effects of E-cigarette Use

NCT06159608 | Recruiting Early Phase 1 FDA Drug

• 1 other identifier: 202308025
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

E-cigarette Use

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (4)

Healthy Young Women

OTHER

Young women who do not use e-cigarettes

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

Healthy Young Men

OTHER

Young men who do not use e-cigarettes

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

Young Women using E-cigarettes

OTHER

Young women chronically use e-cigarettes

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

Young Men using E-cigarettes

OTHER

Young men chronically use e-cigarettes

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

Interventions

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

Healthy Young Men; Healthy Young Women; Young Men using E-cigarettes; Young Women using E-cigarettes

Chronic estrogen exposure OTHER

differences in urine estrogen levels across the menstrual cycle between women groups only

Healthy Young Women; Young Women using E-cigarettes

Eligibility Criteria

• Age: 18 Years - 24 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Anna Stanhewicz, PhD: lead

Study Sites (1)

University of Iowa

Iowa City, Iowa, 52242, United States

RECRUITING

MeSH Terms

Conditions

Vaping

Interventions

NG-Nitroarginine Methyl Ester

Condition Hierarchy (Ancestors)

Smoking; Behavior

Intervention Hierarchy (Ancestors)

Arginine; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino

Central Study Contacts

Anna Reid-Stanhewicz, PHD

CONTACT

319-467-1732; anna-stanhewicz@uiowa.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: November 27, 2023
• First Posted: December 7, 2023
• Study Start: December 2, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: December 15, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)