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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how switching to cigarettes with very low nicotine affects smoking habits. Researchers aim to determine if allowing different e-cigarette flavors makes a difference. Participants will use these low-nicotine cigarettes (Tobacco Product Standard, VLNC) and have access to either all e-cigarette flavors or only tobacco-flavored ones. Those who smoke at least 5 cigarettes a day and have done so for over 3 months might be a good fit. As an unphased trial, this study offers a unique opportunity to contribute to research that could influence future smoking cessation strategies.

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 prior data suggests that this tobacco product standard is safe?

Research has shown that cigarettes with very low nicotine content (VLNC) are generally safe to use. Studies have found that people who smoke VLNC cigarettes experience fewer cravings and less satisfaction compared to regular cigarettes. Importantly, little evidence suggests that people smoke more to compensate for the lower nicotine. This indicates that VLNC cigarettes are well-tolerated and may help reduce smoking without introducing new health risks. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the use of low-nicotine cigarettes (VLNC) in tobacco use treatment because they offer a unique approach to reducing nicotine dependence. Unlike traditional cessation methods such as nicotine replacement therapy or medications like varenicline, VLNC cigarettes aim to lower nicotine intake by using cigarettes with drastically reduced nicotine content. This approach allows smokers to maintain their smoking habits while gradually decreasing their addiction to nicotine. Additionally, the trial explores the impact of combining VLNC cigarettes with e-cigarettes, both flavored and tobacco-only, to enhance the quitting process, potentially offering a more customizable and less abrupt transition away from traditional smoking.

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

Studies have shown that switching to Very Low Nicotine Content (VLNC) cigarettes can help people smoke fewer cigarettes each day. In this trial, participants will join one of two groups: one group will receive VLNC cigarettes plus access to tobacco and non-tobacco flavored e-cigarettes, while the other group will receive VLNC cigarettes plus access to only tobacco flavored e-cigarettes. Research indicates that those who use VLNC cigarettes have lower levels of carbon monoxide in their bodies and experience less craving for regular cigarettes. They also find these cigarettes less satisfying, which might help them smoke less overall. Additionally, using VLNC cigarettes can reduce exposure to harmful chemicals and decrease nicotine dependence, potentially supporting smoking cessation. These findings suggest that VLNC cigarettes may effectively help people cut down on their smoking habit. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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 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 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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9699899/

Effects of Very Low Nicotine Content Cigarettes on ... Those assigned to VLNC cigarettes had lower CPD, CO levels and craving, and reported lower cigarette satisfaction and reward than those assigned to NNC ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0376871624003168?dgcid=rss_sd_all

Associations between compliance with very low nicotine ... Switching to Very Low Nicotine Content (VLNC) cigarettes reduces toxicant exposure and nicotine dependence, and may improve smoking cessation.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9328411/

Effects of Very Low Nicotine Content Cigarette use on ... Specifically, VLNC use led to significantly lower demand intensity for both study and UB cigarettes, and sensitivity to price for study cigarettes was higher ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03060083

Switching to Very Low Nicotine Content Cigarettes vs ... A review of clinical trials suggest that switching to VLNC cigarettes with and without nicotine replacement therapy (NRT) reduces dependence, carcinogens, and ...

5. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2823300

Reduced Nicotine Cigarettes and E-Cigarettes in High ... This report of 3 randomized clinical trials investigates smoking reduction in adults with psychiatric conditions or lower educational level ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0091743522001475

Effects of very low nicotine content cigarettes on smoking ... Low nicotine content descriptors reduce perceived health risks and positive cigarette ratings in participants using very low nicotine content cigarettes ...

7. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/87/NCT05320887/Prot_SAP_001.pdf

Effects of Very Low Nicotine Content Cigarettes There is very little evidence of adverse outcomes associated with VLNC use, including compensatory smoking. As noted above, data available to date indicate ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5831363/

A review of the effects of very low nicotine content ... The results from this review suggest that smoking VLNC cigarettes may fail to reverse withdrawal-induced disruptions in performance following complete smoking ...

9. fda.gov fda.gov/media/133633/download

PMTA Scientific Review: Technical Project Lead (TPL) Existing data in adolescent and young adult smokers suggest VLNC cigarettes are associated with lower positive subjective effects ratings (e.g., ...