Electronic Cigarettes for Tobacco Use Disorder

(SHINE Trial)

Overseen By Michael Stein, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Butler Hospital

Must be taking: Methadone

Must not be taking: Bupropion, Varenicline, NRT

Disqualifiers: Unstable psychiatric, Marijuana, Pregnancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 7

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether electronic cigarettes (ECs) or nicotine lozenges more effectively help smokers on methadone transition away from traditional cigarettes. The trial aims to determine how well each method reduces cigarette use and improves health markers. Individuals who smoke at least 10 cigarettes a day, have been on methadone for at least three months, and are interested in trying ECs or lozenges might be suitable candidates. Participants will be randomly assigned to use either ECs or nicotine lozenges for six weeks. As a Phase 4 trial, the treatments are already FDA-approved and proven effective, and this research seeks to understand how they benefit more patients.

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

Yes, you will need to stop taking any medications that may reduce smoking, such as bupropion, varenicline, or nicotine replacement therapy, to participate in this trial.

What is the safety track record for these treatments?

Research has shown that electronic cigarettes (ECs) are generally considered safer than regular cigarettes. They are viewed as at least as safe as other smoking cessation aids, such as nicotine patches or gum. However, it is important to remember that no tobacco products, including ECs, are completely risk-free. E-cigarettes contain nicotine, which is addictive and can harm health.

Some people use ECs to help quit smoking, but the FDA has not yet approved them for this purpose. The long-term safety of ECs is still under investigation, so the full effects of their use over time remain unknown. In the short term, however, users seem to tolerate ECs well. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Electronic cigarettes are unique because they offer a new approach for managing tobacco use disorder by providing nicotine without the harmful byproducts of combustion found in traditional cigarettes. Unlike nicotine patches or gum, which release nicotine slowly, e-cigarettes mimic the hand-to-mouth action of smoking and deliver nicotine more rapidly, which can be more satisfying for users. Researchers are excited about e-cigarettes because they have the potential to reduce harm by eliminating exposure to tar and other toxic substances, offering a potentially safer alternative for smokers looking to quit.

What evidence suggests that this trial's treatments could be effective for tobacco use disorder?

Research has shown that electronic cigarettes (ECs) with nicotine can help people quit smoking more effectively than traditional nicotine replacement therapies (NRTs) like lozenges. In this trial, participants will receive either electronic cigarettes or nicotine lozenges at random. Some studies found that ECs led to higher quit rates compared to NRTs. However, not all research agrees; some studies show ECs do not improve quitting rates. Overall, ECs often prove more effective than NRTs for helping people stop smoking, but results can vary. ^{4 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for moderate to heavy smokers who have been using methadone for at least three months, smoke more than 10 cigarettes a day, and are interested in switching to e-cigarettes or nicotine lozenges. They must attend weekly methadone sessions, speak English, and be reachable by phone. People can't join if they use marijuana often, are pregnant, recently had heart issues, take daily asthma/COPD meds, used e-cigs frequently last month or are on smoking-reduction drugs.

Inclusion Criteria

I can go weekly to get my methadone dose.

Are available over the next 6 weeks

Have a telephone or access to a telephone

Exclusion Criteria

I take daily medication for asthma or COPD.

I had a heart attack or stroke in the last month.

I am currently using medication to help me stop smoking.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Baseline assessments include biomarker measurement, carbon monoxide (CO) readings, smoking history and current cigarette use, spirometry, respiratory symptoms, and tobacco demand

1 day

1 visit (in-person)

Treatment

Participants are randomized to either 6 weeks of EC use (JUUL 5% nicotine pods) or 6 weeks of nicotine replacement therapy (NRT) in the form of nicotine lozenges

6 weeks

5 weekly check-in visits (in-person)

6-week Assessment

Baseline measurements are repeated to determine changes in health effects, biomarkers, and combustible cigarette use

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Electronic Cigarette
• Nicotine Lozenge

Trial Overview The study compares the effectiveness of electronic cigarettes (JUUL with 5% nicotine pods) versus nicotine lozenges in helping methadone-maintained smokers quit traditional cigarettes. Participants will be randomly assigned to one of these two options and followed over six weeks with seven visits involving psychological assessments and biomarker tests.

How Is the Trial Designed?

Group I: Nicotine Lozenges Active Control 1 Intervention

Participants in this arm are randomized to receive nicotine lozenge for the 6-week study period.

Group II: Electronic Cigarettes Active Control 1 Intervention

Participants in this arm are randomized to receive electronic cigarettes for the 6-week study period.

Who Is Running the Clinical Trial?

Butler Hospital

Lead Sponsor

Trials

133

Recruited

16,700+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

A study analyzing calls to U.S. poison centers from September 2010 to February 2014 revealed increasing reports of adverse health effects associated with e-cigarette use, highlighting concerns about acute nicotine toxicity.

E-cigarette exposure calls were compared to conventional tobacco cigarette exposure calls to assess their relative safety, but the overall impact of e-cigarettes on public health remains uncertain, especially given the lack of regulation and potential access for minors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Notes from the field: calls to poison centers for exposures to electronic cigarettes--United States, September 2010-February 2014. Chatham-Stephens, K., Law, R., Taylor, E., et al.[2022]

Electronic cigarettes are marketed as safe alternatives to traditional tobacco products, but there are growing concerns about their potential negative health impacts.

There is a call for regulatory measures on the manufacturing and marketing of e-cigarettes, as well as further research to better understand their health effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electronic cigarettes: health risks and workplace policy. Phillips, JA.[2017]

This study outlines a randomized controlled trial involving 657 participants in Auckland, New Zealand, to evaluate the efficacy and safety of nicotine e-cigarettes compared to nicotine patches and placebo e-cigarettes for smoking cessation.

The primary outcome will be the rate of biochemically verified continuous abstinence from smoking at six months, which will provide crucial data on whether e-cigarettes can serve as effective smoking cessation aids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study protocol for a randomised controlled trial of electronic cigarettes versus nicotine patch for smoking cessation. Bullen, C., Williman, J., Howe, C., et al.[2022]

In a study using two validated in vitro models, e-cigarette vapor extracts from three popular brands did not show significant increases in mutations in either mouse or human cells, suggesting limited mutagenic effects.

The research indicates that, at the concentrations tested, e-cig vapor may not pose a significant risk of inducing genetic mutations, which is important for understanding the potential carcinogenic effects of e-cigarette use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Limited mutagenicity of electronic cigarettes in mouse or human cells in vitro. Tommasi, S., Bates, SE., Behar, RZ., et al.[2018]

E-cigarettes have been shown to significantly reduce the desire to smoke and the number of cigarettes smoked per day in small clinical studies, suggesting they may help modify smoking habits.

While e-cigarettes may have fewer adverse effects compared to nicotine patches and can aid in short-term smoking reduction, there is limited evidence for their long-term effectiveness in achieving sustained smoking cessation beyond 6 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of electronic cigarettes for smoking cessation. Orr, KK., Asal, NJ.[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]

The E3 trial is a comprehensive study involving 376 participants over 12 weeks, aimed at evaluating the effectiveness of nicotine e-cigarettes compared to non-nicotine e-cigarettes and no e-cigarettes for smoking cessation, with follow-ups extending to 52 weeks.

This trial will provide crucial data on the efficacy and safety of e-cigarettes as a smoking cessation tool, helping inform healthcare professionals and regulators about their potential role in helping smokers quit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Controlled Trial Evaluating the Efficacy of E-Cigarette Use for Smoking Cessation in the General Population: E3 Trial Design. Hébert-Losier, A., Filion, KB., Windle, SB., et al.[2022]

Electronic cigarettes (ECIGs) can vary widely in their nicotine delivery, with some delivering very little and others exceeding the nicotine levels of traditional cigarettes, which complicates their use as a smoking cessation tool.

The variability in nicotine content poses risks for both smokers trying to switch to ECIGs and non-smokers who may start using them, potentially leading to nicotine dependence and increased public health concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electronic cigarettes and nicotine dependence: evolving products, evolving problems. Cobb, CO., Hendricks, PS., Eissenberg, T.[2018]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38189560/

Electronic cigarettes for smoking cessation Authors' conclusions: There is high-certainty evidence that ECs with nicotine increase quit rates compared to NRT and moderate-certainty ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4752870/

E-cigarettes and smoking cessation in real-world ... As currently being used, e-cigarettes are associated with significantly less quitting among smokers. According to the results of our systematic review and meta- ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2308815

Electronic Nicotine-Delivery Systems for Smoking Cessation The addition of e-cigarettes to standard smoking-cessation counseling resulted in greater abstinence from tobacco use among smokers than smoking ...

4. tobaccocontrol.bmj.com tobaccocontrol.bmj.com/content/32/e2/e145

Effectiveness of e-cigarettes as aids for smoking cessation On average, using e-cigarettes for cessation in 2017 did not improve successful quitting or prevent relapse.

5. sciencedirect.com sciencedirect.com/science/article/pii/S0376871624014455

Examining e-cigarettes as a smoking cessation treatment The analysis found that in 8 of 11 comparisons, e-cigarettes were more effective, and 3 of 11 comparisons reported no statistically significant ...

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6179561/

Safety and Efficacy of Electronic Cigarettes: A Review - PMC Electronic cigarettes are safer than conventional cigarettes and at least as safe as other approved nicotine replacement therapies.

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

Tobacco: E-cigarettes Evidence reveals that these products are harmful to health and are not safe. However, it is too early to provide a clear answer on the long-term impact of using ...

9. truthinitiative.org truthinitiative.org/research-resources/emerging-tobacco-products/e-cigarettes-facts-stats-and-regulations

E-cigarettes: Facts, stats and regulations To date, no e-cigarette product has been approved by the FDA for smoking cessation. In contrast, nicotine replacement therapies (e.g., patch, gum, lozenge) and ...