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

Trial Summary

What is the purpose of this trial?

This is a crossover study that will examine use behaviors, chemical exposures, and biological effects of Standardized Research Electronic Cigarette (SREC) compared to usual brand e-cigarette use in natural or synthetic nicotine users.

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.

What data supports the idea that E-Cigarettes for Nicotine Addiction is an effective treatment?

The available research shows that e-cigarettes can help people reduce their smoking habits. In a study where smokers were given e-cigarettes, those who used them reduced their smoking more than those who didn't use e-cigarettes. About 57% of people using a higher nicotine e-cigarette even bought their own after the study, suggesting they found it helpful. However, while e-cigarettes show promise in helping people quit smoking, the long-term safety and effectiveness are still being studied. Compared to other treatments, e-cigarettes might expose users to fewer harmful chemicals than regular cigarettes, but more research is needed to fully understand their benefits and risks. ^{1 2 3 4 5}

What data supports the effectiveness of e-cigarettes as a treatment for nicotine addiction?

Research suggests that e-cigarettes, also known as electronic nicotine delivery systems (ENDS), may help reduce smoking behavior and promote smoking cessation. Studies indicate that smokers using e-cigarettes tend to smoke less and show positive changes in quitting-related behaviors compared to those who do not use them. ^{1 2 3 4 5}

What safety data exists for e-cigarettes used in nicotine addiction treatment?

The provided research does not contain specific safety data on e-cigarettes or related devices for nicotine addiction treatment. It focuses on dental devices, allergy medications, gadolinium-based contrast agents, adverse drug events, and medical devices in general. For safety data on e-cigarettes, one would need to consult studies or reports specifically addressing electronic nicotine delivery systems (ENDS) or similar devices. ^{6 7 8 9 10}

Is using e-cigarettes a promising treatment for nicotine addiction?

E-cigarettes, also known as vapes or electronic nicotine delivery systems, are being studied as a way to help people stop smoking traditional cigarettes. They deliver nicotine without burning tobacco, which might make it easier for smokers to switch and eventually quit smoking altogether. Some studies suggest that e-cigarettes can provide enough nicotine to satisfy cravings, which could help people move away from smoking regular cigarettes. ^{1 5 11 12 13}

How is the treatment using e-cigarettes for nicotine addiction different from other treatments?

E-cigarettes (also known as vapes or electronic nicotine delivery systems) are unique because they provide a noncombustible alternative to traditional smoking, delivering nicotine without burning tobacco. This method may help people switch from smoking by offering a similar experience to smoking but with potentially reduced harm. ^{1 5 11 12 13}

Research Team

Neal Benowitz, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

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

Body Mass Index <= 38.0

Exclusion Criteria

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

I am not taking drugs that affect nicotine breakdown.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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 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]

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]

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]

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]

References

1. Canada pubmed.ncbi.nlm.nih.gov

e-Cigarette Use and the Cessation of Tobacco Cigarette Smoking: Protocol for an Umbrella Review. [2023]

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

A Naturalistic, Randomized Pilot Trial of E-Cigarettes: Uptake, Exposure, and Behavioral Effects. [2018]

3. England 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. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Electronic nicotine delivery systems: a research agenda. [2022]

5. England 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. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Dental device-associated problems: an analysis of FDA postmarket surveillance data. [2019]

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

Boxed Warnings and Off-Label Use of Allergy Medications: Risks, Benefits, and Shared Decision Making. [2022]

8. England 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. [2022]

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

Serious adverse drug events reported to the Food and Drug Administration, 1998-2005. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Safety cases for medical devices and health information technology: involving health-care organisations in the assurance of safety. [2013]

11. Germany 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. [2022]

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

College students' perceptions of risk and addictiveness of e-cigarettes and cigarettes. [2018]

13. England 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. [2023]