E-Cigarettes for Nicotine Addiction

(SREC22 Trial)

Overseen By Neal Benowitz, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Francisco

Must not be taking: CYP2A6 inducers, Sympatholytics, Nicotine meds, Stimulants

Disqualifiers: Heart disease, Seizures, Cancer, others

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

Compensation: Varies

Number of Visits: 2

Duration: 2 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to compare behaviors, chemical exposures, and effects when using two types of electronic cigarettes (e-cigs): a participant's usual brand and a research-specific one. Participants will try both e-cigs and provide samples for testing. It is ideal for regular e-cig users who have vaped at least half of the past month. This trial excludes individuals with certain health conditions, such as heart disease or asthma requiring an inhaler, or those planning to quit vaping soon. As an unphased trial, it offers participants the opportunity to contribute to important research on e-cigarette use and its effects.

Do I have to stop taking my current medications for the trial?

Yes, you may need to stop certain medications. The trial excludes participants using medications that induce the nicotine metabolizing enzyme CYP2A6, sympatholytic medications for cardiovascular conditions, nicotine-containing medications, and stimulant medications like those for ADHD.

Will I have to stop taking my current medications?

The trial requires you to stop taking certain medications, such as those that affect nicotine metabolism, medications for heart conditions, and any nicotine-containing products. If you're on these medications, you may need to stop them to participate.

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

Research has shown that e-cigarettes, even those available in stores, often contain nicotine. Nicotine can be addictive and may pose health risks. For instance, studies suggest that using e-cigarettes could increase the risk of lung cancer, especially when combined with smoking regular cigarettes. However, compared to traditional cigarettes, e-cigarettes might be somewhat safer because they usually contain fewer harmful chemicals.

Regarding the Standardized Research Electronic Cigarette (SREC), limited safety information is available. Most research focuses on the effects of these e-cigarettes on the heart and lungs, but data collection is ongoing. Currently, these e-cigarettes are primarily used in research and are not widely sold.

In summary, while both types of e-cigarettes are under study, more information is needed to fully understand their safety. Prospective trial participants should consider these factors and ask questions to make an informed decision. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for nicotine addiction because they are exploring e-cigarettes as a potentially less harmful alternative to traditional smoking cessation methods, like nicotine patches and gums. The unique aspect of this trial is the comparison between over-the-counter e-cigarettes, which users typically buy, and a standardized research e-cigarette (SREC). This allows researchers to assess not only how effective e-cigarettes can be in helping individuals quit smoking but also to determine if a standardized version offers any advantages in terms of safety and nicotine delivery. By analyzing both types, the trial aims to provide insights into which e-cigarette might be more beneficial in treating nicotine addiction effectively.

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

Research has shown that over-the-counter e-cigarettes might help people quit smoking more effectively than traditional methods like nicotine patches or gum, potentially reducing nicotine addiction. However, e-cigarettes do carry health risks.

In this trial, participants will use both their usual brand of e-cigarette and the Standardized Research E-Cigarette (SREC) to compare their effectiveness. Studies have not found the SREC to be more effective at easing nicotine withdrawal symptoms than other e-cigarettes. Research continues, with hope that an FDA-approved version could better aid smoking cessation in the future. Both options are being studied in this trial to assess their effectiveness in helping people quit smoking. ^{1 3 6 7 8}

Who Is on the Research Team?

Neal Benowitz, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for adults aged 21-70 who regularly use e-cigarettes, have a heart rate under 105 BPM, BMI <=38.0, and blood pressure within certain limits. They must not be planning to quit smoking soon or have serious health issues like heart disease, seizures, cancer, diabetes, or severe lung conditions.

Inclusion Criteria

Diastolic Blood Pressure < 100 and > 50

Healthy on the basis of medical history and limited physical examination

Heart rate < 105 beats per minute

Exclusion Criteria

I am not taking drugs that affect nicotine breakdown.

I have not had oral thrush, fainting recently, or other severe illnesses as judged by a doctor.

Pregnancy: Pregnancy (self-reported and urine pregnancy test), Breastfeeding (determined by self-report), Women of childbearing potential must be using an acceptable method of contraception, Concurrent participation in another clinical trial, Inability to read and write in English, Planning to quit smoking or vaping within the next 60 days, A known propylene glycol/vegetable glycerin allergy, Uncomfortable with getting blood drawn, Recent onset or change (worsening) in cough, fever and/or abdominal symptoms (vomiting or pain) in the past two weeks

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants undergo two treatment conditions using SREC and usual brand e-cigarettes, with assessments in a hospital setting.

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including cardiovascular and nicotine exposure assessments.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Over the Counter E-Cigarette (EC)
• Standardized Research E-Cigarette (SREC)

Trial Overview The study compares the effects of using a Standardized Research E-Cigarette (SREC) versus regular e-cigarettes on behavior, chemical exposure and biological impact in users of natural or synthetic nicotine through a crossover design.

How Is the Trial Designed?

Group I: Usual Brand E-Cigarette (EC) then SREC Experimental Treatment 4 Interventions

Participants will be admitted to hospital research ward within 32 hours of the orientation visit and begin a standardized session of product use using the usual brand of e-cigarette that participants utilize for nicotine use, and will provide expired carbon dioxide samples, pharmacokinetic (PK) blood samples, urine samples, and have cardiovascular and vital signs monitored. Participants will also be asked to complete nicotine-related questionnaires. Participants will then return within 2 weeks to repeat the procedures using the SREC.

Group II: SREC then Usual Brand E-Cigarette (EC) Experimental Treatment 4 Interventions

Participants will be admitted to hospital research ward within 32 hours of the orientation visit and begin a standardized session of product use using the SREC, and will provide expired carbon dioxide samples, pharmacokinetic (PK) blood samples, urine samples, and have cardiovascular and vital signs monitored. Participants will also be asked to complete nicotine-related questionnaires. Participants will then return within 2 weeks to repeat the procedures using the usual brand of e-cigarette that participants utilize for nicotine use.

Over the Counter E-Cigarette (EC) is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Over the Counter E-Cigarette for:

• Nicotine replacement therapy for smoking cessation

Approved in European Union as Over the Counter E-Cigarette for:

• Nicotine replacement therapy for smoking cessation

Approved in Canada as Over the Counter E-Cigarette for:

• Nicotine replacement therapy for smoking cessation

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

The FDA issues boxed warnings for over 400 medications to highlight significant safety risks, which can impact prescribing decisions by healthcare professionals and patient choices.

Despite the potential risks associated with boxed warnings, off-label use of medications is common and legal, emphasizing the importance of informed discussions between prescribers and patients about the benefits and harms of treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Boxed Warnings and Off-Label Use of Allergy Medications: Risks, Benefits, and Shared Decision Making. Greiwe, J., Honsinger, R., Hvisdas, C., et al.[2022]

Electronic nicotine delivery systems (ENDS), like e-cigarettes, may help smokers quit by providing nicotine without the harmful combustion products found in traditional cigarettes, potentially exposing users to lower levels of toxicants.

However, the long-term safety of ENDS is still unknown, and there are concerns about their use among youth, which could limit their effectiveness as smoking cessation aids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Pharmacology of Electronic Nicotine Delivery Systems (ENDS): Implications for Benefits and Risks in the Promotion of the Combusted Tobacco Endgame. Benowitz, NL., St Helen, G., Liakoni, E.[2023]

During a study analyzing dental device adverse events from August 1996 to June 1999, 28,555 reports (10.5% of total) were related to dental devices, with the majority involving injuries (64.4%) and a small number of deaths (0.007%).

Endosseous implants were the most frequently reported dental devices, accounting for over 90% of the reports, highlighting the importance of monitoring these devices for safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dental device-associated problems: an analysis of FDA postmarket surveillance data. Fuller, J., Parmentier, C.[2019]

From 1998 to 2005, serious adverse drug events reported to the FDA increased significantly, with a 2.6-fold rise in total reports and a 2.7-fold increase in fatal events, indicating a growing public health concern.

A small percentage of drugs (20%) were responsible for the majority (87%) of reported adverse events, emphasizing the need for better risk management systems for prescription medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious adverse drug events reported to the Food and Drug Administration, 1998-2005. Moore, TJ., Cohen, MR., Furberg, CD.[2022]

In a study involving 40 adult smokers, the JUUL2 prototype with 18 mg/mL nicotine delivered more nicotine than the JUUL 59 mg/mL, suggesting it could be more effective in helping smokers switch from combustible cigarettes.

The JUUL2 prototype 40 mg/mL was found to be more aversive than other products, indicating it may need adjustments to be appealing for adult smokers, while the JUUL products generally provided greater satisfaction and craving reduction compared to the IQOS heated tobacco product.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and subjective assessment of prototype JUUL2 electronic nicotine delivery system in two nicotine concentrations, JUUL system, IQOS, and combustible cigarette. Goldenson, NI., Augustson, EM., Chen, J., et al.[2022]

In a randomized trial involving 68 adult smokers, those using electronic nicotine delivery systems (ENDS) showed a significant reduction in cigarette smoking compared to a control group, indicating potential efficacy in smoking cessation.

Participants using the higher nicotine (24 mg) ENDS were more likely to continue using the product and make independent purchases, suggesting that higher nicotine delivery may enhance user engagement and support smoking reduction efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Naturalistic, Randomized Pilot Trial of E-Cigarettes: Uptake, Exposure, and Behavioral Effects. Carpenter, MJ., Heckman, BW., Wahlquist, AE., et al.[2018]

There is a significant lack of scientific research on the safety and efficacy of electronic nicotine delivery systems (ENDS), which are often used as smoking cessation aids, highlighting the need for comprehensive studies to inform regulatory decisions.

The authors emphasize that the first research priority should be to assess the long-term safety of ENDS, and only after establishing safety should their effectiveness in helping people quit smoking be evaluated in well-designed trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electronic nicotine delivery systems: a research agenda. Etter, JF., Bullen, C., Flouris, AD., et al.[2022]

17% of e-cigarette users reported feeling very addicted, and 40% viewed e-cigarettes as equally or more addictive than traditional tobacco cigarettes, indicating a notable perception of addiction among users.

The study suggests that self-reported perceived addiction could be a useful indicator of actual addiction, with factors like daily use and enjoyment influencing these perceptions, although overall addiction levels appear to be relatively low.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Understanding perceived addiction to and addictiveness of electronic cigarettes among electronic cigarette users: a cross-sectional analysis of the International Tobacco Control Smoking and Vaping (ITC 4CV) England Survey. Lohner, V., McNeill, A., Schneider, S., et al.[2023]

The FDA Adverse Event Reporting System (FAERS) reported the highest number of nephrogenic systemic fibrosis (NSF) cases (1395), while the International Centre for Nephrogenic Systemic Fibrosis Registry (ICNSFR) provided the most complete histopathological data (335 cases).

The legal data set revealed that gadodiamide was the most commonly implicated gadolinium-based contrast agent (GBCA) in NSF cases, with 76.2% of cases linked to it, highlighting the importance of using diverse data sources for comprehensive safety evaluations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advancing pharmacovigilance through academic-legal collaboration: the case of gadolinium-based contrast agents and nephrogenic systemic fibrosis-a Research on Adverse Drug Events and Reports (RADAR) report. Edwards, BJ., Laumann, AE., Nardone, B., et al.[2022]

In the UK, over 9000 adverse event reports related to medical devices highlight significant concerns about the effectiveness of current regulatory processes in ensuring patient safety.

Implementing 'safety cases'—a practice used in other safety-critical industries—could enhance transparency in the safety certification of medical devices and improve communication among manufacturers, service providers, regulators, and patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety cases for medical devices and health information technology: involving health-care organisations in the assurance of safety. Sujan, MA., Koornneef, F., Chozos, N., et al.[2013]

A study analyzing posts from 1023 unique US users on a smoking cessation website found that 92% referred to Electronic Nicotine Delivery Systems (ENDS) as 'e-cigarettes' or related terms, indicating these are widely recognized among smokers.

The term 'vape' gained popularity starting in 2013, while less common brand names like 'NJoy' and 'blu' were used by fewer than 2% of users, suggesting that researchers should focus on familiar terminology to improve communication and research in tobacco control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How US Smokers Refer to E-cigarettes: An Examination of User-Generated Posts From a Web-Based Smoking Cessation Intervention, 2008-2015. Pearson, JL., Amato, MS., Wang, X., et al.[2020]

This umbrella review aims to synthesize findings from various systematic reviews on the effectiveness of electronic nicotine delivery systems (ENDS) for smoking cessation, comparing quit rates with other established treatments.

The review will assess the quality and bias of existing studies, providing a comprehensive analysis of ENDS' effectiveness and informing future treatment guidelines and policies for smoking cessation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

e-Cigarette Use and the Cessation of Tobacco Cigarette Smoking: Protocol for an Umbrella Review. O'Leary, R., Polosa, R.[2023]

Among college students, dual users of e-cigarettes and cigarettes perceive e-cigarettes as significantly less harmful compared to exclusive cigarette users and non-users, indicating a potential underestimation of risks associated with e-cigarette use.

All user groups, including dual and exclusive users, reported lower perceptions of addictiveness for both e-cigarettes and conventional cigarettes compared to non-users, suggesting a concerning trend in how these products are viewed in terms of addiction risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

College students' perceptions of risk and addictiveness of e-cigarettes and cigarettes. Cooper, M., Loukas, A., Harrell, MB., et al.[2018]

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Electronic nicotine delivery systems (ENDS) This review begins by describing how cigarette smoking led to the development of ENDS as a means of combatting nicotine addiction.

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E-Cigarettes, Vapes, and other Electronic Nicotine Delivery ... Get an overview of FDA regulation of e-cigarettes, vapes, and other electronic nicotine delivery systems. You can also find statistics about ...

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Vaping Devices (Electronic Cigarettes) DrugFacts A plain-language research summary that describes how e-cigarettes work, how safe they are compared to traditional cigarettes, ...

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E-Cigarettes, “Vapes” and Other Electronic Nicotine ... E-Cigarettes, “Vapes” and Other Electronic Nicotine Delivery Systems (ENDS) Authorized by the FDA ; JUULpods (Virginia Tobacco 3.0%), JUULpods ( ...