E-Cigarette Exposure for Vascular Reactivity

(AeCE Trial)

Overseen By Sri Kumar

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Pennsylvania

Must not be taking: Antibiotics, Vascular medications

Disqualifiers: Cancer, HIV, Mental illness, others

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

Compensation: Varies

Number of Visits: 3

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how vaping and smoking affect blood vessels and inflammation in the body. Participants will use either electronic cigarettes (also known as Standardized Electronic Research Cigarettes), with or without nicotine, or tobacco cigarettes, and undergo MRI scans and blood tests before and after exposure. The trial compares these results with those from non-smokers to determine how smoking habits impact health. It seeks individuals who have been vaping or smoking for at least six months and have a BMI between 18.5 and 30.

As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research on the health impacts of vaping and smoking.

Do I need to stop my current medications for the trial?

Yes, you will need to stop taking any medications that affect vascular function and antibiotics, as these are part of the exclusion criteria for the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that nicotine, whether from smoking or vaping, affects the heart and blood vessels. Some studies suggest nicotine replacement therapies might increase the risk of heart disease, but they don't worsen conditions in people with stable heart issues.

For e-cigarettes, some studies have found they can raise blood pressure and heart rate, stressing the heart. However, clear long-term information on vaping's overall health effects is lacking.

This trial studies both traditional cigarettes and e-cigarettes with nicotine. Both have links to heart and blood vessel problems, but the effects can differ. While nicotine affects the heart and blood vessels, people with stable heart conditions did not show increased risk when using nicotine replacements.

Before joining any trial, consider these findings and consult a healthcare provider about 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 different forms of smoking, like traditional tobacco cigarettes and electronic cigarettes, affect blood vessel function. Unlike existing research focused solely on the health impacts of smoking or vaping, this study specifically looks at vascular reactivity, which is how well blood vessels respond to stimuli. This could offer new insights into the cardiovascular risks associated with nicotine and vaping, potentially leading to better guidelines for smokers and vapers. By comparing conventional smoking with vaping, scientists hope to understand if one method is less harmful to the heart and blood vessels, which could significantly impact public health recommendations.

What evidence suggests that this trial's treatments could be effective for vascular reactivity?

This trial will compare the effects of conventional tobacco cigarette smoking with electronic cigarette use on vascular reactivity. Studies have shown that electronic cigarettes can affect blood vessels. Research indicates that e-cigarette use can increase stress on the body and cause issues with the inner lining of blood vessels, potentially leading to damage. Some studies suggest that e-cigarettes might stiffen arteries, making it harder for blood to flow smoothly. Overall, e-cigarettes are considered a risk factor for heart and blood vessel problems. ^{6 7 8 9 10}

Who Is on the Research Team?

Felix W Wehrli, PhD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for adults with a BMI of 18.5 to 30 who have been using electronic or tobacco cigarettes for at least six months. It's not suitable for individuals with mental illness impairing judgment, cancer, HIV, significant heart or brain vascular disease, serious arrhythmias, severe lung conditions like asthma, recent respiratory infections, those on medication affecting blood vessels or anyone unable to undergo MRI scans due to metal implants or claustrophobia.

Inclusion Criteria

Current users of electronic cigarettes or tobacco cigarettes with a use history of six months or greater.

BMI: 18.5 to 30

Exclusion Criteria

I have had cancer in the past.

I am taking medication that affects blood vessel function.

I am HIV positive.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Acute Exposure Episodes

Participants undergo three separate-day, acute exposure-episodes of smoking a tobacco cigarette, an electronic cigarette without nicotine, and an electronic cigarette with nicotine. MRI exams and blood draws are performed pre- and post-exposure.

3 days

3 visits (in-person)

Follow-up

Participants are monitored for changes in MRI and blood inflammatory biomarkers after exposure episodes.

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nicotine Research Cigarette
• Standardized Electronic Research Cigarette

Trial Overview The study investigates how different smoking methods (electronic and nicotine cigarettes) affect blood vessel function and inflammation markers in the body. Participants will experience three exposure sessions followed by MRI scans and blood tests before and after each session. Results from smokers/vapers will be compared with non-smokers/non-vapers.

How Is the Trial Designed?

Group I: Vapers Experimental Treatment 2 Interventions

Electronic cigarette vapers

Group II: Smokers Experimental Treatment 2 Interventions

Conventional tobacco cigarette smokers

Nicotine Research Cigarette is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Nicotine Research Cigarette for:

• Smoking cessation

Approved in European Union as Nicotine Replacement Therapy for:

• Smoking cessation
• Nicotine dependence

Approved in Canada as NRT for:

• Smoking cessation
• Nicotine withdrawal

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

Long-term exposure to e-cigarette vaping (ECV) in a mouse model showed that it can lead to cardiovascular disease similar to that caused by tobacco cigarette smoking (TCS), with significant impairments in blood vessel function and increased blood pressure observed after 16 weeks.

The severity of cardiovascular damage from ECV increased with both the duration of exposure and the nicotine content in the e-cigarette liquid, indicating that even without nicotine, vaping can still cause harm, but higher nicotine levels exacerbate the effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term electronic cigarette exposure induces cardiovascular dysfunction similar to tobacco cigarettes: role of nicotine and exposure duration. El-Mahdy, MA., Mahgoup, EM., Ewees, MG., 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]

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]

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]

E-cigarettes provide significantly lower nicotine levels (25%-50%) compared to traditional cigarettes, which may affect their efficacy as a smoking cessation tool.

All e-cigarette brands tested reduced withdrawal symptoms and cravings in smokers, but participants reported lower satisfaction and liking for e-cigarettes compared to cigarettes, indicating a difference in user experience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotine Replacement, Topography, and Smoking Phenotypes of E-cigarettes. Strasser, AA., Souprountchouk, V., Kaufmann, A., et al.[2022]

In a study of 60 young adults (ages 18-30), electronic cigarette (EC) users showed no significant increase in vascular inflammation compared to nonsmokers, suggesting that vaping may not exacerbate this aspect of cardiovascular health.

However, both EC users and traditional smokers exhibited significantly higher carotid plaque burden compared to nonsmokers, indicating potential long-term cardiovascular risks associated with both forms of smoking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atherosclerosis inflammation and burden in young adult smokers and vapers measured by PET/MR. Sahota, A., Naidu, S., Jacobi, A., et al.[2021]

A study involving 248 adult smokers showed that quitting smoking for just three days led to significant improvements in cardiovascular health markers, regardless of whether they used nicotine e-cigarettes, nicotine-free e-cigarettes, or nicotine replacement therapy (NRT).

The positive cardiovascular effects were consistent across all groups, indicating that the method of cessation (e-cigarettes with or without nicotine or NRT) did not significantly impact the short-term benefits of smoking cessation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-Term Cardiovascular Effects of E-Cigarettes in Adults Making a Stop-Smoking Attempt: A Randomized Controlled Trial. Klonizakis, M., Gumber, A., McIntosh, E., et al.[2021]

In a study of 31 healthy nonsmokers, acute inhalation of nonnicotinized e-cigarette aerosol led to significant increases in blood markers of inflammation and oxidative stress, indicating potential harm to vascular health.

The vaping session resulted in impaired vascular function, as shown by reduced peripheral vascular reactivity and altered metabolic parameters, suggesting that even short-term e-cigarette use can negatively affect blood vessel function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute e-cig inhalation impacts vascular health: a study in smoking naïve subjects. Chatterjee, S., Caporale, A., Tao, JQ., et al.[2022]

In a study involving 467 participants, including nonsmokers, combustible cigarette smokers, e-cigarette users, and dual users, e-cigarette use did not show a better vascular profile compared to combustible cigarette smoking, indicating potential cardiovascular risks associated with e-cigarettes.

Both e-cigarette users and combustible cigarette smokers exhibited impaired endothelial function, as evidenced by lower nitric oxide production, suggesting that e-cigarettes may not be a safer alternative for vascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alterations in Vascular Function Associated With the Use of Combustible and Electronic Cigarettes. Fetterman, JL., Keith, RJ., Palmisano, JN., et al.[2021]

Nicotine, while having potential cardiovascular effects, poses lower risks when delivered through electronic cigarettes compared to traditional cigarette smoking, especially in healthy users.

Short-term use of electronic cigarettes appears to have a low cardiovascular risk, but caution is advised for individuals with pre-existing cardiovascular conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular toxicity of nicotine: Implications for electronic cigarette use. Benowitz, NL., Burbank, AD.[2022]

Citations

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How Electronic Cigarette Affects the Vascular System - PMC Electronic cigarette use is associated with adverse events in the vascular, including the incident of elevated oxidative stress, endothelial dysfunction, ...

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Impact of Electronic Cigarettes on the Cardiovascular System In this review, we will discuss the current state of literature regarding the potential negative cardiovascular effects of direct/active and passive e‐ ...

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Evidence of Vaping's Harmful Effects on Blood Vessels and ... The researchers found that electronic cigarettes harm blood vessels while standard cigarettes impair the heart.

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Electronic cigarettes and cardiovascular disease A large body of epidemiological evidence has indicated that e-cigarettes are considered an independent risk factor for increased rates of cardiovascular ...

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The impact of e-cigarettes versus traditional ... (8) demonstrated that e-cigarette exposure resulted in arterial stiffness and impaired cardiovascular function in mice, whereas Xu et al. (14) ...

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Cardiovascular risks in smokers treated with nicotine ... Previous research suggests exposure to nicotine replacement therapy (NRT) may be associated with an increased risk of cardiovascular disease (CVD).

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Nicotine Replacement Therapy and Cardiovascular Disease People with cardiovascular disease who continue to smoke have an increased risk of myocardial infarction, cerebrovascular accident, and other serious vascular ...

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Impact of Smokeless Oral Nicotine Products on ... Smokeless oral nicotine products are addictive, and their use has potential adverse effects on some but not all biomarkers of cardiovascular risk.

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Cardiovascular Toxicity of Nicotine: Implications for ... Clinical trials of NRT in patients with underlying, stable coronary disease suggest that nicotine does not increase cardiovascular risk.

10. globalheartjournal.com globalheartjournal.com/articles/10.5334/gh.1292

When Poison is Addictive – a WHF Policy Brief Numerous studies have demonstrated that nicotine can harm multiple organs, including the respiratory and cardiovascular systems.