Colored Packaging for Cigarette Smoking

Overseen By Valentina Souprountchouk

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Abramson Cancer Center at Penn Medicine

Disqualifiers: Substance abuse, Alcohol overuse, Pregnancy, Schizophrenia, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 30 days

575 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to examine the effect of changes in cigarette package color on smoking behaviors, harm exposure, and risk perceptions when using low nicotine content (LNC) cigarettes.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you have a serious or unstable medical condition or are taking medications that could affect your safety or the study, you may be excluded. It's best to discuss your specific situation with the study team.

What data supports the effectiveness of the treatment Colored Packaging, Branded Packaging, Plain Packaging, LNC Cigarettes, Very Low Nicotine Content (VLNC) cigarettes, Low Nicotine Cigarettes for cigarette smoking?

Research shows that using very low nicotine content (VLNC) cigarettes can help reduce the number of cigarettes smoked, lower exposure to harmful substances, and decrease dependence on nicotine. Additionally, VLNC cigarettes have been found to increase quit attempts and are more acceptable to smokers compared to simply reducing the number of cigarettes smoked per day. ^{1 2 3 4 5}

Is it safe to use very low nicotine content (VLNC) cigarettes?

Research indicates that using very low nicotine content (VLNC) cigarettes can lead to a reduction in the number of cigarettes smoked and exposure to harmful substances, suggesting they are generally safe for human use. ^{1 3 6 7 8}

How do Very Low Nicotine Content (VLNC) cigarettes differ from other smoking cessation treatments?

VLNC cigarettes are unique because they contain significantly less nicotine than regular cigarettes, which may help reduce smoking by decreasing nicotine dependence. Unlike other smoking cessation treatments like nicotine replacement therapies (e.g., patches, gums) or e-cigarettes, VLNC cigarettes aim to lower nicotine intake directly through the cigarette itself, potentially altering smoking behavior without introducing alternative nicotine sources. ^{1 6 7 8 9}

Research Team

Andrew Strasser, Ph.D.

Principal Investigator

University of Pennsylvania

Eligibility Criteria

This trial is for individuals who smoke at least 5 non-menthol, filtered cigarettes daily for the past year and plan to stay in the study area for about 5 weeks. They must not be trying to quit smoking or participating in cessation treatment during the study, speak English fluently, and give informed consent. Pregnant women, those planning pregnancy, heavy drinkers, people with certain mental health conditions or serious medical issues are excluded.

Inclusion Criteria

Able to communicate fluently in English (i.e., speaking, writing, and reading)

I am not trying to quit smoking nor plan to during the study.

You must be willing to stay in the study area for the duration of the study.

Exclusion Criteria

You smoke menthol cigarettes more than 20% of the time.

You smoke cigarettes that are not the regular size.

Significant non-compliance with protocol and/or study design as determined by the Principal Investigator and/or Study Physician. Participants may be withdrawn at any point throughout the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline

Participants smoke their own brand of cigarettes for a 5-day baseline period

5 days

1 visit (in-person)

Treatment

Participants are randomized to a 30-day experimental period with low nicotine content cigarettes in different packaging or their own brand

30 days

5 visits (in-person), 4 visits (virtual)

Follow-up

Participants are monitored for smoking behavior, exposure, and risk perception after the treatment period

4 weeks

Treatment Details

Interventions

• Colored Packaging
• LNC Cigarettes

Trial Overview The study investigates how changing cigarette package color affects smokers' behaviors and perceptions when using low nicotine content (LNC) cigarettes compared to their own brand of regular cigarettes.

Participant Groups

Group I: Own Brand Experimental Treatment 1 Intervention

After completing a 5-day baseline period of smoking their own brand, participants will complete a 30-day experimental period when they will continue to receive their own preferred brand of cigarettes (i.e., control group).

Group II: LNC Cigarettes + Red Packaging Experimental Treatment 1 Intervention

After completing a 5-day baseline period of smoking their own brand, participants will be randomized to a 30-day experimental period when they will receive low nicotine content cigarettes in red packaging.

Group III: LNC Cigarettes + Plain Packaging Experimental Treatment 1 Intervention

After completing a 5-day baseline period of smoking their own brand, participants will be randomized to a 30-day experimental period when they will receive low nicotine content cigarettes in plain packaging.

Group IV: LNC Cigarettes + Gray Packaging Experimental Treatment 1 Intervention

After completing a 5-day baseline period of smoking their own brand, participants will be randomized to a 30-day experimental period when they will receive low nicotine content cigarettes in standard investigational packaging (gray).

Group V: LNC Cigarettes + Blue Packaging Experimental Treatment 1 Intervention

After completing a 5-day baseline period of smoking their own brand, participants will be randomized to a 30-day experimental period when they will receive low nicotine content cigarettes in blue packaging.

LNC Cigarettes is already approved in United States, European Union for the following indications:

Approved in United States as VLNC cigarettes for:

• Smoking cessation aid
• Reduced nicotine exposure

Approved in European Union as VLNC cigarettes for:

• Tobacco harm reduction
• Smoking cessation aid

Who Is Running the Clinical Trial?

Abramson Cancer Center at Penn Medicine

Lead Sponsor

Trials

425

Recruited

464,000+

Andrew Strasser

Lead Sponsor

Trials

3

Recruited

700+

Food and Drug Administration (FDA)

Collaborator

Trials

184

Recruited

1,553,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

University of Pennsylvania

Collaborator

Trials

2,118

Recruited

45,270,000+

Findings from Research

Participants in a study of very low nicotine content (VLNC) cigarettes (N = 16) reported that they did not increase their smoking frequency despite expectations to compensate for lower nicotine levels, suggesting potential for reduced dependence.

Many participants felt less dependent on nicotine after smoking VLNC cigarettes and indicated they would continue to use them if they were the only option available, highlighting VLNC cigarettes as a possible tool for smoking reduction or cessation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

"I actually finally feel like the cigarettes aren't controlling me." - Interviews with participants smoking very low nicotine content cigarettes during a residential study. Denlinger-Apte, RL., White, CM., Donny, EC., et al.[2022]

In a study involving 1410 smokers, those using very low nicotine content (VLNC) cigarettes alongside standard Quitline support had a higher smoking abstinence rate at 6 months (33%) compared to those receiving usual care alone (28%).

The addition of VLNC cigarettes also significantly extended the median time to relapse, with participants in the intervention group relapsing after 2 months, while those in the usual care group relapsed after just 2 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The combined effect of very low nicotine content cigarettes, used as an adjunct to usual Quitline care (nicotine replacement therapy and behavioural support), on smoking cessation: a randomized controlled trial. Walker, N., Howe, C., Bullen, C., et al.[2018]

In a study of 235 participants, very low nicotine content (VLNC) cigarettes combined with a nicotine patch were more effective in reducing cigarette use and withdrawal symptoms in males compared to females.

Females showed a higher likelihood of quitting smoking when using VLNC cigarettes, while males had better success quitting with the nicotine patch alone, suggesting that sex differences play a significant role in the effectiveness of smoking cessation strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sex differences in response to reduced nicotine content cigarettes. Vogel, RI., Hertsgaard, LA., Dermody, SS., et al.[2022]

In a study of 68 adult daily smokers, reducing the number of cigarettes smoked per day (CPD) led to a higher rate of quit attempts (41%) compared to switching to very low nicotine content (VLNC) cigarettes (17%), suggesting that reducing smoking frequency may be more effective for encouraging quit attempts.

Participants using VLNC cigarettes showed an increase in self-efficacy to quit smoking, indicating that while VLNC may help with confidence in quitting, it did not lead to more quit attempts compared to simply smoking fewer cigarettes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increasing Quit Attempts by Transitioning to Very Low Nicotine Content Cigarettes Versus Reducing Number of Cigarettes Per Day: A Secondary Analysis of an Exploratory Randomized Trial. Klemperer, EM., Hughes, JR., Callas, PW.[2020]

In a trial with 68 adult smokers, transitioning to very low nicotine content (VLNC) cigarettes combined with nicotine patches led to a greater reduction in nicotine dependence compared to simply reducing the number of cigarettes smoked per day.

Participants using VLNC cigarettes experienced a mean decrease in nicotine dependence of 1.0 Z-score, while those reducing their cigarette count had a decrease of only 0.5 Z-score, indicating that VLNC may be a more effective strategy for reducing dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of switching to very low nicotine content cigarettes plus nicotine patch versus reducing daily cigarette consumption plus nicotine patch to decrease dependence: an exploratory randomized trial. Klemperer, EM., Hughes, JR., Callas, PW., et al.[2020]

Messaging that highlights the mortality effects of very low nicotine content (VLNC) cigarettes led to higher perceived lung cancer risks among both smokers and non-smokers, indicating that such communication can improve understanding of the health risks associated with VLNC cigarettes.

Despite improved perceptions, about one-third of participants still believed that VLNC cigarettes were safer than regular cigarettes, suggesting that further refinement of messaging is needed to fully convey the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Educating the Public on the Health Risks of Very Low Nicotine Content Cigarettes: Results From a US-Based Convenience Sample. Differding, M., Katz, SJ., Strayer, LG., et al.[2023]

A significant number of adult smokers perceive low nicotine content (LNC) cigarettes, e-cigarettes, and snus as having similar harmfulness and addictiveness to conventional cigarettes, indicating a misunderstanding of their relative risks.

The study highlights that these misperceptions about nicotine harms and alternative nicotine delivery systems are prevalent across various demographic groups, including different racial/ethnic identities, sexual orientations, and gender identities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk Perceptions of Low Nicotine Cigarettes and Alternative Nicotine Products across Priority Smoking Populations. Denlinger-Apte, RL., Pacek, LR., Ross, JC., et al.[2022]

In a study with 23 participants who exclusively smoked very low nicotine content (VLNC) cigarettes for 4 days, significant reductions in nicotine exposure biomarkers were observed, with total cotinine levels dropping by 92%.

The findings suggest that participants using VLNC cigarettes are unlikely to exceed specific biomarker thresholds, providing a useful reference for future research on VLNC cigarette use and compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotine and Anatabine Exposure from Very Low Nicotine Content Cigarettes. Denlinger, RL., Smith, TT., Murphy, SE., et al.[2022]

Reducing the nicotine content in cigarettes (from normal to very low) significantly decreased the number of cigarettes smoked per day by participants, indicating that lower nicotine levels can help reduce smoking behavior.

The characteristics of e-cigarettes, such as nicotine content and flavor options, did not significantly influence smoking reduction, suggesting that the effectiveness of nicotine reduction in cigarettes may depend more on the cigarettes themselves rather than the e-cigarette alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary evidence on cigarette nicotine reduction with concurrent access to an e-cigarette: Manipulating cigarette nicotine content, e-liquid nicotine content, and e-liquid flavor availability. White, CM., Tessier, KM., Koopmeiners, JS., et al.[2023]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

"I actually finally feel like the cigarettes aren't controlling me." - Interviews with participants smoking very low nicotine content cigarettes during a residential study. [2022]

2. England pubmed.ncbi.nlm.nih.gov

The combined effect of very low nicotine content cigarettes, used as an adjunct to usual Quitline care (nicotine replacement therapy and behavioural support), on smoking cessation: a randomized controlled trial. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Sex differences in response to reduced nicotine content cigarettes. [2022]

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

Increasing Quit Attempts by Transitioning to Very Low Nicotine Content Cigarettes Versus Reducing Number of Cigarettes Per Day: A Secondary Analysis of an Exploratory Randomized Trial. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Effectiveness of switching to very low nicotine content cigarettes plus nicotine patch versus reducing daily cigarette consumption plus nicotine patch to decrease dependence: an exploratory randomized trial. [2020]

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

Educating the Public on the Health Risks of Very Low Nicotine Content Cigarettes: Results From a US-Based Convenience Sample. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Risk Perceptions of Low Nicotine Cigarettes and Alternative Nicotine Products across Priority Smoking Populations. [2022]

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

Nicotine and Anatabine Exposure from Very Low Nicotine Content Cigarettes. [2022]

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

Preliminary evidence on cigarette nicotine reduction with concurrent access to an e-cigarette: Manipulating cigarette nicotine content, e-liquid nicotine content, and e-liquid flavor availability. [2023]