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

Trial Summary

What is the purpose of this trial?

To examine vascular reactivity and inflammatory biomarkers via quantitative magnetic resonance imaging (MRI) and blood serum, respectively, in a crossover study where active vapers (electronic cigarette users) and smokers will undergo three separate acute exposure-episodes of electronic cigarette +/- nicotine and tobacco-cig. The MRI exams and blood draws will be performed pre- and post-exposure. The results will be compared against baseline values derived from a group of non-smokers/non-vapers, who will also undergo a blood draw and MRI.

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.

What data supports the effectiveness of the treatment involving Nicotine Research Cigarette, Nicotine Replacement Therapy, NRT, Standardized Electronic Research Cigarette, E-Cigarette, Vaping Device for vascular reactivity?

The research indicates that while e-cigarettes are often marketed as a safer alternative to traditional cigarettes, they can still have negative effects on vascular health, such as increased blood clot formation and reduced blood vessel function. However, in a study where smokers attempted to quit using e-cigarettes or nicotine replacement therapy, all groups showed improved cardiovascular health after three days, suggesting potential benefits in the context of smoking cessation. ^{1 2 3 4 5}

Is using e-cigarettes generally safe for cardiovascular health?

Short-term use of e-cigarettes appears to pose low cardiovascular risk in healthy users, similar to nicotine replacement therapies, but the long-term effects are not well established. Studies show no significant changes in heart rate, blood pressure, or vascular function in the short term, but caution is advised for people with existing cardiovascular disease. ^{4 5 6 7 8}

How does the treatment using Nicotine Research Cigarette and Standardized Electronic Research Cigarette differ from other treatments for vascular reactivity?

This treatment is unique because it involves the use of e-cigarettes, which are often considered a harm reduction tool for smokers, but their impact on vascular health is still not fully understood. Unlike traditional nicotine replacement therapies, e-cigarettes can affect vascular function and inflammation, potentially leading to cardiovascular issues similar to those caused by regular cigarettes. ^{1 2 3 9 10}

Research Team

Felix W Wehrli, PhD

Principal Investigator

University of Pennsylvania

Eligibility Criteria

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 am taking medication that affects blood vessel function.

I have had cancer in the past.

I am HIV positive.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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]

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]

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]

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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Alterations in Vascular Function Associated With the Use of Combustible and Electronic Cigarettes. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Electronic Cigarette Vaping with Nicotine Causes Increased Thrombogenicity and Impaired Microvascular Function in Healthy Volunteers: A Randomised Clinical Trial. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Acute e-cig inhalation impacts vascular health: a study in smoking naïve subjects. [2022]

4. Australia pubmed.ncbi.nlm.nih.gov

Vascular effects of a single bout of electronic cigarette use. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Short-Term Cardiovascular Effects of E-Cigarettes in Adults Making a Stop-Smoking Attempt: A Randomized Controlled Trial. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Nicotine Replacement, Topography, and Smoking Phenotypes of E-cigarettes. [2022]

7. Ireland pubmed.ncbi.nlm.nih.gov

Atherosclerosis inflammation and burden in young adult smokers and vapers measured by PET/MR. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Cardiovascular toxicity of nicotine: Implications for electronic cigarette use. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Long-term electronic cigarette exposure induces cardiovascular dysfunction similar to tobacco cigarettes: role of nicotine and exposure duration. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Acute Impact of Tobacco vs Electronic Cigarette Smoking on Oxidative Stress and Vascular Function. [2017]