Low-Nicotine Cigarettes for Tobacco Use

Overseen By Dorothy Hatsukami, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Masonic Cancer Center, University of Minnesota

Must not be taking: Exclusionary medications

Disqualifiers: Unstable health, mental health, pregnancy, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

11 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this pilot project is to explore the feasibility of a real-world marketplace study design examining the effects of a reduced nicotine product standard for cigarettes on smoking in the context of a flavor restriction vs. no restriction on e-cigarettes in smokers switched to very low nicotine content cigarettes.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that taking certain medications or having unstable dosing could exclude you from participating. It's best to discuss your specific medications with the trial's medical professional.

What data supports the effectiveness of the treatment Tobacco Product Standard (VLNC) for tobacco use?

Research shows that using very low nicotine content (VLNC) cigarettes can lead to more quit attempts, reduced smoking, and lower exposure to harmful substances. Additionally, combining VLNC cigarettes with other support like nicotine replacement therapy and behavioral support can help people quit smoking. ^{1 2 3 4 5}

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

Studies show that switching to very low nicotine content (VLNC) cigarettes can decrease smoking with minimal or no negative side effects, even in vulnerable groups like those with mental health conditions or low socioeconomic status. ^{1 5 6 7 8}

How is the treatment with VLNC cigarettes different from other smoking cessation treatments?

VLNC cigarettes are unique because they contain very low levels of nicotine, which makes them less addictive compared to regular cigarettes. This approach aims to help smokers reduce their nicotine intake gradually, potentially leading to smoking cessation without the need for nicotine replacement therapies like patches or gum. ^{1 2 5 8 9}

Eligibility Criteria

This trial is for daily smokers of 5 to 25 cigarettes for over three months, who have regular access to a device with a camera and internet for virtual visits. Participants must live where very low nicotine content (VLNC) cigarettes are sold and show carbon monoxide levels indicating regular smoking.

Inclusion Criteria

Carbon monoxide indicative of regular smoking (CO > 6ppm) prior to randomization

I have been smoking 5 to 25 cigarettes daily for more than 3 months.

Has regular access to a smartphone, tablet or computer with functioning camera and internet access for telehealth visits and surveys and to take photos of receipts

Exclusion Criteria

Household member enrolled in the study concurrently

Participated in prior research study during the past three months that would impact baseline smoking or response to study products

Inability to independently read and comprehend the consent form and follow other written study instructions, materials or measures or behavior indicating inability to fully participate in study procedures. Participants are required to complete the protocol at home independently and must show ability to comply with directions

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Remote monitoring

Monitoring

Participants undergo 2 weeks of monitoring of usual brand smoking

2 weeks

Remote monitoring

Intervention

Participants are randomly assigned to a 4-week intervention with VLNC cigarettes and e-cigarettes

4 weeks

Remote monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Remote monitoring

Treatment Details

Interventions

• Tobacco Product Standard (VLNC)

Trial Overview The study examines the impact of reduced nicotine in cigarettes on smoker behavior when e-cigarettes are either flavor-restricted or not. It involves switching smokers to VLNC cigarettes and monitoring their usage through telehealth technologies.

Participant Groups

Group I: VLNC cigarettes plus access to tobacco and non-tobacco flavored e-cigarettes Experimental Treatment 1 Intervention

Smokers who meet eligibility criteria will enter 2 weeks of monitoring of usual brand smoking. Participants will then be randomly assigned to a 4-week intervention

Group II: VLNC cigarettes plus access to only tobacco flavored e-cigarettes Experimental Treatment 1 Intervention

Smokers who meet eligibility criteria will enter 2 weeks of monitoring of usual brand smoking. Participants will then be randomly assigned to a 4-week intervention

Tobacco Product Standard (VLNC) is already approved in United States for the following indications:

Approved in United States as VLNC cigarettes for:

• Smoking cessation aid
• Nicotine reduction

Who Is Running the Clinical Trial?

Masonic Cancer Center, University of Minnesota

Lead Sponsor

Trials

285

Recruited

15,700+

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 729 participants, switching to very low nicotine content cigarettes (VLNCs) led to significant reductions in certain toxicant exposures, particularly in those who only smoked cigarettes, while co-users of cannabis and cigarettes showed less reduction in non-tobacco-specific toxicants.

Co-users of cannabis and cigarettes who switched to VLNCs experienced similar reductions in cigarette consumption and tobacco-specific exposure as cigarette-only users, but they were at a higher risk for increased exposure to harmful substances and a slight increase in cannabis use over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immediate Switching to Reduced Nicotine Cigarettes in a U.S.-Based Sample: The Impact on Cannabis Use and Related Variables at 20 Weeks. Meier, E., Rubin, N., Dermody, SS., et al.[2023]

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]

Smokers with serious mental illness (SMI) who used very low nicotine content (VLNC) cigarettes smoked fewer cigarettes per day and reported lower cravings and carbon monoxide levels compared to those using normal nicotine content cigarettes, suggesting that a reduced-nicotine standard could help decrease smoking rates in this population.

Despite the benefits of reduced smoking and lower craving scores, participants did not show a decrease in total nicotine exposure, indicating that they may seek alternative nicotine sources, which raises concerns about compliance with VLNC cigarettes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of 6-Week Use of Very Low Nicotine Content Cigarettes in Smokers With Serious Mental Illness. Tidey, JW., Colby, SM., Denlinger-Apte, RL., et al.[2023]

Smoking very low nicotine content (VLNC) cigarettes for 6 weeks led to greater reductions in nicotine exposure, which was associated with higher rates of smoking abstinence one month later among 112 adult daily smokers.

The study found that lower nicotine yield in VLNC cigarettes and reduced use of normal nicotine content cigarettes enhanced the effectiveness of nicotine reduction strategies, suggesting that maximizing nicotine reduction could support smoking cessation efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Greater reductions in nicotine exposure while smoking very low nicotine content cigarettes predict smoking cessation. Dermody, SS., Donny, EC., Hertsgaard, LA., et al.[2022]

Participants in a study of 20 individuals with depression and anxiety found that using e-cigarettes alongside very low nicotine content (VLNC) cigarettes helped them transition away from their usual brand, suggesting that e-cigarettes may support smoking reduction efforts.

Some participants had misconceptions about the safety and cancer risk of VLNC cigarettes, highlighting the need for targeted education on the risks and benefits of both VLNC and e-cigarettes, especially for those with mental health conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subjective experiences, contexts, and risk perceptions of very low nicotine content cigarettes and electronic cigarettes among people with depression and anxiety disorders who smoke. DeAtley, T., Harrison, A., Cassidy, R., et al.[2023]

Switching to very low nicotine content (VLNC) cigarettes has been shown to decrease smoking rates among vulnerable populations, such as those with mental health conditions and opioid use disorder, with minimal negative consequences.

Current evidence suggests that implementing a reduced-nicotine standard could have beneficial effects on smoking reduction across various groups, including socioeconomically disadvantaged adults and youth, indicating a promising regulatory approach for the FDA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of very low nicotine content cigarettes on smoking across vulnerable populations. Tidey, JW., Snell, LM., Colby, SM., et al.[2023]

In a 33-week study involving 245 adult daily smokers, those who switched to very low nicotine content (VLNC) cigarettes showed a 50% reduction in nicotine levels and smoked fewer cigarettes per day compared to those who continued with usual nicotine content (UNC) cigarettes.

However, the VLNC group experienced higher attrition rates, indicating that some smokers struggled to adapt to the lower nicotine levels, suggesting that additional support or nicotine alternatives may be necessary for successful transition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Switching to Progressively Reduced Nicotine Content Cigarettes in Smokers With Low Socioeconomic Status: A Double-Blind Randomized Clinical Trial. Krebs, NM., Zhu, J., Wasserman, E., et al.[2023]

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]

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

Immediate Switching to Reduced Nicotine Cigarettes in a U.S.-Based Sample: The Impact on Cannabis Use and Related Variables at 20 Weeks. [2023]

3. 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]

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

Effects of 6-Week Use of Very Low Nicotine Content Cigarettes in Smokers With Serious Mental Illness. [2023]

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

Greater reductions in nicotine exposure while smoking very low nicotine content cigarettes predict smoking cessation. [2022]

6. Ireland pubmed.ncbi.nlm.nih.gov

Subjective experiences, contexts, and risk perceptions of very low nicotine content cigarettes and electronic cigarettes among people with depression and anxiety disorders who smoke. [2023]

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

Effects of very low nicotine content cigarettes on smoking across vulnerable populations. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Switching to Progressively Reduced Nicotine Content Cigarettes in Smokers With Low Socioeconomic Status: A Double-Blind Randomized Clinical Trial. [2023]

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

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