Nicotine Vaping Variability for Vaping Study

Overseen By Stylianos C Mysirlidis, B.S.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Yale University

Must not be taking: Anticoagulants, Blood thinners

Disqualifiers: Cardiovascular, Pulmonary, Pregnancy, Allergies, others

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

Compensation: Varies

Number of Visits: 2

Duration: 3 weeks

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different forms and rates of nicotine delivery from vaping devices affect the speed and intensity of nicotine absorption in the body, which is crucial for understanding addiction risk. Participants will use e-cigarettes with varying nicotine levels to assess how these differences impact nicotine intake. The study seeks individuals who have vaped regularly (at least three times a week) for at least three months, do not have major health issues, and are not planning to quit nicotine soon. As an unphased study, this trial allows participants to contribute to important research on vaping and nicotine addiction.

What prior data suggests that these ENDS devices are safe for human use?

Research shows that vaping devices, like electronic nicotine delivery systems (ENDS), expose users to nicotine, which is highly addictive. Studies have found that vaping can cause side effects such as coughing, throat irritation, nausea, and changes in heart rate and blood pressure. However, experts generally consider vaping less risky than traditional smoking.

ENDS devices release harmful substances, increasing the risk of breathing problems and nicotine addiction. While these risks exist, vaping might still be safer than smoking regular cigarettes. Prospective study participants should consider these factors and consult healthcare professionals to understand any personal health risks. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Nicotine Flux treatment because it examines how different forms of nicotine and their delivery rates might influence vaping behavior. Unlike traditional nicotine replacement therapies, which often deliver nicotine in a consistent, controlled manner, this approach explores variability in nicotine flux to better understand user preferences and potential impacts on vaping habits. By studying both free-base and protonated forms of nicotine at varying fluxes, the trial could lead to insights that help fine-tune vaping devices for harm reduction or cessation efforts, offering a tailored approach to meet individual needs.

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

This trial will examine how different forms of nicotine—either salt-based or freebase—affect nicotine absorption. Participants will receive either the free-base or protonated form of nicotine at varying fluxes during two separate visits. Research has shown that salt-based nicotine leads to higher nicotine intake than freebase nicotine. Additionally, studies have found that disposable e-cigarettes deliver nicotine as effectively as regular cigarettes and more effectively than pod e-cigarettes. Increasing the speed of nicotine delivery can change puffing behavior and liquid consumption. These findings suggest that both the type and delivery speed of nicotine are important in determining how quickly and how much nicotine is absorbed, which could impact its potential for addiction. ^{6 7 8 9 10}

Who Is on the Research Team?

Stephen R Baldassarri, M.D.

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for adults over 21 who regularly use electronic nicotine delivery systems (ENDS) at least three times a week for the past three months. They must be willing to consent and attend lab sessions, abstain from tobacco/nicotine when required, and have normal blood flow in their hands as shown by an Allen test.

Inclusion Criteria

Be willing to provide informed consent, attend the lab, and abstain from tobacco/nicotine as required

Have a normal Allen test

I am over 21 years old.

Exclusion Criteria

I have a condition affecting the blood vessels outside my heart and brain.

History of environmental - bronchospastic allergies, multiple chemical sensitivities, or other airway sensitivities that require the use of an epi pen or that in the investigator's view would make it risky for participation

I do not have ongoing lung or heart issues like chest pain or severe infections.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants will attend two lab visits to test different nicotine fluxes and forms using ENDS devices, with arterial blood sampling to measure nicotine delivery.

3 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nicotine Flux

Trial Overview The study investigates how different forms of nicotine in vaping devices affect the speed and amount of nicotine entering the bloodstream. Participants will try vaping devices with varying levels of nicotine flux and form while having their arterial blood sampled frequently to measure these effects.

How Is the Trial Designed?

Group I: Nicotine vaping group visit 2 Experimental Treatment 2 Interventions

The same subjects from visit 1 will receive the either free-base or protonated form of four nicotine fluxes: 9, 18, 27, 35 μg/sec at their second study visit, using the opposite nicotine form that was used during the first visit.

Group II: Nicotine vaping group visit 1 Experimental Treatment 2 Interventions

Subjects will receive the either free-base or protonated form of four nicotine fluxes: 9, 18, 27, 35 μg/sec at their first of two visits. In the first visit, participants will use the ENDS device with one nicotine form and four fluxes in random order. Participants will be instructed to attend the lab for a second visit, to test the four fluxes but with the other nicotine form.

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

American University of Beirut Medical Center

Collaborator

Trials

153

Recruited

113,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9361466/

Nicotine forms: why and how do they matter ... - PubMed Central The research on nicotine forms is limited and studies have reported contradictory results about absorption profiles of nicotine forms.

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2822152

E-Cigarette Nicotine Delivery Among Young Adults by ... Salt-based (vs freebase) nicotine resulted in higher nicotine intake after both 5-minute standardized and 30-minute ad libitum vaping, particularly at 5% (vs 1 ...

3. nature.com nature.com/articles/s41598-025-97491-5

Disposable e-cigarettes and their nicotine delivery, usage ... The results showed that the disposable e-cigarette was as effective in nicotine delivery as the cigarette and more effective than the pod e ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10513228/

Nicotine flux as a powerful tool for regulating nicotine delivery ... The outcome will indicate the degree to which nicotine flux and form determine the speed and dose of EC nicotine delivery, and thus, contribute ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0376871623012905

Influence of nicotine form and nicotine flux on puffing ... Increasing nicotine flux from 14 to 35 µg/sec was associated with lower total puff duration in both bouts, as well as lower liquid consumption.

6. cdc.gov cdc.gov/tobacco/e-cigarettes/health-effects.html

Health Effects of Vaping | Smoking and Tobacco Use No tobacco products, including e-cigarettes, are safe. Most e-cigarettes contain nicotine, which is highly addictive and is a health danger for ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39398779/

A Systematic Review of Toxicity Mechanisms and Adverse ... Reported adverse effects include cough, throat irritation, nausea, and hemodynamic changes. However, ENDS are associated with fewer risks ...

8. who.int who.int/news-room/questions-and-answers/item/tobacco-e-cigarettes

Tobacco: E-cigarettes The aerosols generated by ENDS typically raise the concentration of particulate matter in indoor environments and contain nicotine and other potentially toxic ...

9. tobaccocontrol.bmj.com tobaccocontrol.bmj.com/content/33/3/373

Risk and safety profile of electronic nicotine delivery systems ... We found high-level evidence that ENDS exposes users to toxic substances; increases the risk of respiratory disease; leads to nicotine dependence; causes ...

10. my.clevelandclinic.org my.clevelandclinic.org/health/treatments/21162-vaping

Vaping (E-Cigarettes): What It Is, Side Effects & Dangers Vaping is when you use a handheld device to breathe in a mist (“vapor”). Vaping can cause breathing problems, organ damage, addiction and other conditions.