Vascular Effects of E-Cigarettes

Overseen By Anna Reid-Stanhewicz, PHD

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Anna Stanhewicz, PhD

Must not be taking: Antihypertensives, Statins, Stimulants, others

Disqualifiers: Cardiovascular, Metabolic, Skin diseases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effects of e-cigarettes on blood vessel health, particularly in young adults who vape regularly. Researchers aim to understand how vaping might impact the small blood vessels in the skin, which can indicate potential heart health issues. The study involves a simple skin test and blood samples to check for inflammation and other health markers. Participants should be healthy young adults aged 18-24, either currently using e-cigarettes for at least six months or never having used them. The trial does not accept individuals with a history of smoking tobacco, high blood pressure, or certain health conditions. As an Early Phase 1 trial, this study focuses on understanding how vaping affects blood vessels, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial requires that you do not currently use antihypertensive or cholesterol-lowering medications, so you would need to stop these if you are taking them. The protocol does not specify about other medications.

What prior data suggests that this technique is safe for examining vascular function?

Research has shown that e-cigarettes might affect heart health. Some studies have found they can cause problems with heart function and blood vessels. For example, the Food and Drug Administration (FDA) reported side effects like seizures and fainting in people using e-cigarettes.

While e-cigarettes are often considered safer than regular cigarettes, growing evidence suggests they might still carry risks. They have been linked to a higher chance of heart problems. Other studies suggest that using e-cigarettes might harm blood vessels, even though they may be less harmful than traditional cigarettes.

This information comes from early research, indicating there is still much to learn about the safety of e-cigarettes for the heart and blood vessels. Anyone considering joining a study on e-cigarettes should be aware of these potential risks. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it aims to uncover how e-cigarettes affect vascular health, especially in young people. Unlike traditional studies that focus on cigarette smoking, this one zeroes in on the impact of e-cigarettes, which are often perceived as a safer alternative. The trial uses unique methods like chronic estrogen exposure and local heating combined with L-NAME to investigate vascular changes. By exploring these specific conditions, researchers hope to better understand the nuances of e-cigarette use and its potential risks, which could lead to more informed public health recommendations.

What evidence suggests that this trial's treatments could be effective for vascular effects of e-cigarettes?

Research shows that e-cigarettes might not be as safe as previously thought, especially for heart health. Studies have found that e-cigarettes can damage blood vessels and increase the risk of heart problems, partly due to nicotine's effect on blood flow. Some reports also link e-cigarettes to serious side effects like seizures and fainting. Overall, growing evidence suggests that e-cigarettes can harm heart health. This trial will compare the vascular effects of e-cigarettes in young men and women who use them with those who do not, to further understand these potential risks. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for healthy young adults aged 18-24 who either have never used e-cigarettes or have been vaping regularly for at least 6 months. Participants should not have any cardiovascular, metabolic, skin diseases, obesity, high blood pressure, a history of smoking tobacco cigarettes or using illegal substances. Pregnant or breastfeeding individuals and those with allergies to latex or study drugs are also excluded.

Inclusion Criteria

I either have never used e-cigarettes or have been using them for over 6 months.

Exclusion Criteria

I have a history of heart, metabolic, or skin conditions.

Currently pregnant or breastfeeding

Body mass index >30 kg/m2

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Study Visit

Participants undergo intradermal microdialysis and local heating to examine microvascular function, with blood and urine samples collected

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in microvascular function and estrogen exposure

1 month

What Are the Treatments Tested in This Trial?

Interventions

• Chronic estrogen exposure
• Local heating + L-NAME

Trial Overview The study investigates how chronic e-cigarette use affects the blood vessels in young adults by comparing non-users to regular users. It involves local heating of the skin and administering L-NAME via microdialysis to test vascular function. Blood and urine samples will be collected from participants to analyze cardiovascular health markers and inflammation.

How Is the Trial Designed?

Group I: Young Women using E-cigarettes Experimental Treatment 2 Interventions

Young women chronically use e-cigarettes

Group II: Young Men using E-cigarettes Experimental Treatment 1 Intervention

Young men chronically use e-cigarettes

Group III: Healthy Young Women Experimental Treatment 2 Interventions

Young women who do not use e-cigarettes

Group IV: Healthy Young Men Experimental Treatment 1 Intervention

Young men who do not use e-cigarettes

Who Is Running the Clinical Trial?

Anna Stanhewicz, PhD

Lead Sponsor

Trials

12

Recruited

460+

Published Research Related to This Trial

In a study involving 40 healthy adults (20 smokers and 20 nonsmokers), both e-cigarettes and traditional cigarettes significantly increased oxidative stress and decreased endothelial function, as measured by flow-mediated dilation (FMD).

However, e-cigarettes appeared to have a lesser impact on certain oxidative stress markers compared to traditional cigarettes, suggesting they may be somewhat less harmful in the short term, although both still have negative vascular effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute Impact of Tobacco vs Electronic Cigarette Smoking on Oxidative Stress and Vascular Function. Carnevale, R., Sciarretta, S., Violi, F., et al.[2017]

A study using intravital microscopy on anesthetized mice showed that both electronic cigarette (E-cig) aerosol and traditional cigarette smoke caused similar vasoconstriction responses in skeletal muscle, indicating that E-cigs may not be safer for vascular health than regular cigarettes.

The research found that the vasoconstriction effect was not dependent on nicotine and was consistent regardless of the e-liquid's base solution composition, suggesting that harmful components other than nicotine in both E-cigs and cigarettes contribute to adverse vascular effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotine and Microvascular Responses in Skeletal Muscle from Acute Exposure to Cigarettes and Vaping. Pitzer, CR., Aboaziza, EA., O'Reilly, JM., et al.[2023]

A new method for self-administering vaporized nicotine in rats shows that both male and female rats can consistently engage in nicotine vapor self-administration, indicating its potential for studying nicotine's effects.

The study found that while male rats achieved similar blood levels of nicotine's metabolite, cotinine, from vapor as from intravenous administration, female rats had lower cotinine levels with vapor, highlighting significant sex differences in nicotine intake and response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotine e-cigarette vapor inhalation and self-administration in a rodent model: Sex- and nicotine delivery-specific effects on metabolism and behavior. Lallai, V., Chen, YC., Roybal, MM., et al.[2022]

In a study involving 22 healthy volunteers, inhaling electronic cigarette aerosol with nicotine significantly increased both platelet and fibrin-rich thrombus formation shortly after exposure, indicating a potential risk for vascular health.

The same exposure also reduced the capacity for microvascular dilation, suggesting that nicotine in e-cigarettes can negatively impact blood vessel function, while no significant effects were observed with nicotine-free aerosol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electronic Cigarette Vaping with Nicotine Causes Increased Thrombogenicity and Impaired Microvascular Function in Healthy Volunteers: A Randomised Clinical Trial. Lyytinen, G., Brynedal, A., Anesäter, E., et al.[2023]

Inhaling aerosol from nicotine-free e-cigarettes significantly impaired endothelial function in healthy nonsmokers, as evidenced by reduced luminal flow-mediated dilation and other markers of vascular reactivity, based on a study of 31 participants.

The study found that even without nicotine, e-cigarette aerosol can lead to transient changes in vascular health, suggesting potential long-term risks that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute Effects of Electronic Cigarette Aerosol Inhalation on Vascular Function Detected at Quantitative MRI. Caporale, A., Langham, MC., Guo, W., et al.[2020]

In a study involving 32 participants (19 exclusive ENDS users and 13 dual users), it was found that lower nicotine concentrations combined with higher device power settings led to increased abuse liability, as users worked harder for puffs in the low nicotine/high watt condition.

Limiting nicotine concentration alone may not effectively reduce the risk of abuse associated with electronic nicotine delivery systems, as users may compensate by increasing device power to achieve desired nicotine delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The interaction of nicotine concentration and device power on electronic nicotine delivery system (ENDS) abuse liability among exclusive ENDS users and dual users of ENDS and combustible cigarettes. Hoetger, C., Bono, RS., White, AM., et al.[2022]

Identifying selective biomarkers for electronic nicotine delivery systems (ENDS) is challenging because their aerosols do not contain unique substances, making it hard to distinguish ENDS use from other tobacco or environmental sources.

The study introduces two new LC-MS/MS methods to measure specific tobacco alkaloids and metabolites that can help confirm the use of conventional tobacco products, which can improve the accuracy of assessing ENDS exposure and dual use with traditional cigarettes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minor Tobacco Alkaloids as Biomarkers to Distinguish Combusted Tobacco Use From Electronic Nicotine Delivery Systems Use. Two New Analytical Methods. Jacob, P., Chan, L., Cheung, P., et al.[2022]

In a study involving 45 participants (22 cigarette smokers and 23 ENDS users), higher concentrations of protonated nicotine and increased device power led to greater plasma nicotine delivery, indicating that both factors significantly affect nicotine absorption.

ENDS users experienced higher nicotine delivery compared to cigarette smokers, and they also took longer and larger puffs, suggesting that device design and liquid formulation play crucial roles in user experience and nicotine intake.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interactive effects of protonated nicotine concentration and device power on ENDS nicotine delivery, puff topography, and subjective effects. Eversole, A., Budd, S., Karaoghlanian, N., et al.[2023]

The study successfully developed an e-cigarette nicotine delivery system that produced effects similar to subcutaneous nicotine injection in both female and male mice, demonstrating its efficacy in delivering pharmacologically active doses of nicotine.

Sex differences were observed in the effects of nicotine, with females experiencing greater hypothermia from aerosol exposure and males from injection, while females consistently had higher nicotine and cotinine levels in plasma and brain, regardless of the administration route.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delivery of nicotine aerosol to mice via a modified electronic cigarette device. Lefever, TW., Lee, YO., Kovach, AL., et al.[2019]

In a study involving 16 young, healthy participants, vaping electronic cigarettes with either 0% or 5.4% nicotine did not result in significant changes to heart rate, blood pressure, or vascular functions over a 2-hour period.

The findings suggest that, at least in the short term, vaping does not have acute adverse effects on vascular health in tobacco product naïve individuals, challenging the perception that e-cigarettes are inherently harmful compared to traditional tobacco cigarettes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vascular effects of a single bout of electronic cigarette use. Cossio, R., Cerra, ZA., Tanaka, H.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9021536/

Electronic Cigarette Use and the Risk of Cardiovascular ... This review outlines the contribution of e-cigarettes in the development of cardiovascular diseases and their molecular underpinnings.

2. ahajournals.org ahajournals.org/doi/10.1161/CIRCRESAHA.123.321565

Electronic Nicotine Delivery Systems and Cardiovascular/ ... Data is beginning to show that e-cigs can cause both short- and long-term issues on cardiac function, vascular integrity and cardiometabolic issues.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12516984/

Health impacts of electronic nicotine delivery systems The Food and Drug Administration has reported the side effects of ENDS, such as seizures, tremors, fainting and severe neurological symptoms.

4. globalheartjournal.com globalheartjournal.com/articles/10.5334/gh.1076

E-Cigarettes: A New Threat to Cardiovascular Health A growing body of literature suggests that e-cigarettes are associated with an increased risk of cardiovascular morbidity and mortality.

5. ahajournals.org ahajournals.org/doi/10.1161/CIR.0000000000001160

Cardiopulmonary Impact of Electronic Cigarettes and ... Studies comparing ENDS products that contain nicotine with nicotine-free products suggest that many of the acute vascular effects relate to nicotine exposure.

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0167527325008320

Exposure to electronic cigarettes impairs vascular and ... While several studies suggest that e-cigarettes are less likely to be associated with cardiovascular disease, others have found evidence for vascular injury in ...