Low-Nicotine Cigarettes for Heart Health

(CEV Trial)

Overseen By Maria Anwar, MS

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Wake Forest University Health Sciences

Disqualifiers: Cardiovascular diseases, Hyperthyroidism, 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: 1

Duration: 1 day

49 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how low-nicotine cigarettes affect heart health in people who smoke. Researchers aim to compare the effects of smoking a usual brand of cigarettes versus special SPECTRUM cigarettes, which contain very low nicotine. Individuals who have smoked at least once in the past 30 days and have no recent heart issues might be suitable candidates. Participants will smoke either their usual cigarettes or SPECTRUM cigarettes during the study. As an Early Phase 1 trial, this research focuses on understanding how low-nicotine cigarettes work in people, offering participants a chance to contribute to groundbreaking insights.

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

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that SPECTRUM cigarettes, which have very low nicotine levels, are being tested for their effects on heart health. These cigarettes aim to reduce nicotine addiction in smokers.

Studies indicate that SPECTRUM cigarettes pose similar health risks as regular cigarettes if smoked in the same way. Despite having less nicotine, the dangers of smoking, such as lung damage or cancer, remain.

The research is in the early stages, providing limited information on the safety of these cigarettes. Researchers are currently focused on understanding the body's reaction to them and monitoring for any side effects.

In summary, while SPECTRUM cigarettes contain lower nicotine, they carry similar risks to regular smoking. Safety details are still under study, and more information will emerge as research progresses. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about SPECTRUM cigarettes because they offer a new approach to improving heart health by significantly reducing nicotine content compared to regular cigarettes. Unlike traditional cigarettes, which deliver higher levels of nicotine that contribute to heart disease, SPECTRUM cigarettes aim to minimize nicotine dependence and its associated cardiovascular risks. This unique feature could potentially make it easier for smokers to reduce their nicotine intake, leading to improved heart health outcomes.

What evidence suggests that this trial's treatments could be effective for heart health?

This trial will compare the effects of smoking SPECTRUM cigarettes, which have very low nicotine content (VLNC), with smoking participants' usual brand of cigarettes. Research has shown that VLNC cigarettes like SPECTRUM can help people smoke less and reduce exposure to harmful chemicals. Studies have found that these cigarettes can lower nicotine addiction, making it easier for smokers to cut back or quit. By reducing nicotine levels, these cigarettes might also lower the risk of heart disease over time. Early findings suggest that smokers may feel less controlled by their habit, potentially improving heart health. Overall, these cigarettes carry similar health risks to regular ones if smoked the same way, but their lower nicotine content is important for potential benefits. ^{2 3 6 7 8}

Who Is on the Research Team?

Eric C Donny, PhD

Principal Investigator

Wake Forest University Health Sciences

Are You a Good Fit for This Trial?

This trial is for adults over 21 who smoke cigarettes at least once a month, can understand English well enough for study procedures, and are willing to smoke either very low nicotine content cigarettes or their usual brand during the lab visit. It's not for those trying to quit smoking, with recent cardiovascular diseases, high body temperature, thyroid disorders, pregnant or breastfeeding women, or unstable health conditions affecting ECG readings.

Inclusion Criteria

Willingness to smoke research cigarettes or usual brand cigarettes during lab visit

Ability to speak, comprehend, and read English sufficiently to complete study procedures

Self-reported cigarette smoking at least once in the past 30 days

Exclusion Criteria

Body temperature ≥ 100.4˙F

Unstable health conditions interfering with electrocardiogram (ECG) measurements

Currently pregnant (as indicated by urine pregnancy test at the start of laboratory visit) or breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants smoke two VLNCC and one NNCC while ECG is recorded to measure cardiovascular effects

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• SPECTRUM cigarettes
• usual brand of Cigarettes

Trial Overview The study investigates the cardiovascular effects of 'SPECTRUM' cigarettes which have very low nicotine content compared to smokers' usual brands. Daily and non-daily smokers will participate in lab visits where they'll smoke these research cigarettes to see how they affect heart health.

How Is the Trial Designed?

Group I: Research Cigarettes (SPECTRUM) Experimental Treatment 1 Intervention

Participants will smoke 1-2 SPECTRUM cigarettes

Group II: Usual Brand of Cigarettes Active Control 1 Intervention

Participants will smoke 2-3 cigarettes of their usual brand

SPECTRUM cigarettes is already approved in United States for the following indications:

Approved in United States as SPECTRUM cigarettes for:

• Research use for studying nicotine reduction strategies

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Published Research Related to This Trial

Smokers of long and ultralong cigarettes have significantly higher levels of harmful tobacco biomarkers, such as serum cotinine and urinary NNAL, indicating greater exposure to nicotine and tobacco-related toxins compared to smokers of regular-sized and king-sized cigarettes.

The study analyzed data from 3,699 smokers aged 20 and older, revealing that the perception of reduced harm associated with longer cigarettes is misleading, highlighting the importance of public education on the risks of all tobacco products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cigarette rod length and its impact on serum cotinine and urinary total NNAL levels, NHANES 2007-2010. Agaku, IT., Vardavas, CI., Connolly, GN.[2022]

The study analyzed the smoke emissions from 23 varieties of SPECTRUM variable nicotine research cigarettes, revealing that many emissions were similar to those from the 3R4F research cigarette, indicating comparable safety profiles under standard smoking conditions.

Under intense smoking conditions, the SPECTRUM cigarettes showed varying levels of harmful constituents, with an increase in tobacco-specific nitrosamines (NNN) correlating with higher nicotine levels, highlighting the need for careful monitoring of chemical emissions as nicotine reduction technologies are developed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemical Characterization of Mainstream Smoke from SPECTRUM Variable Nicotine Research Cigarettes. Ding, YS., Richter, P., Hearn, B., et al.[2022]

Both mentholated and regular cigarettes have immediate negative effects on the heart's left and right ventricular functions in chronic smokers, as shown by echocardiographic measurements taken 20-30 minutes after smoking.

Mentholated cigarettes specifically worsen right ventricular function more than regular cigarettes, leading to decreased relaxation and contraction indices, indicating they may pose additional cardiovascular risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mentholated cigarette smoking induced alterations in left and right ventricular functions in chronic smokers. Ciftçi, O., Calişkan, M., Güllü, H., et al.[2023]

Camel Snus and Marlboro Snus have shown significant increases in nicotine levels due to larger pouch sizes, with Camel Snus showing a 1.9-fold increase in total nicotine and a 3.3-fold increase in carcinogenic nitrosamines (NNN and NNK) since 2006.

Marlboro Snus also increased in nicotine content (2.1-fold), but had a lower level of nitrosamines (1.5-fold decrease), highlighting the variability in product formulations and the need for regulatory oversight in tobacco products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased pouch sizes and resulting changes in the amounts of nicotine and tobacco-specific N-nitrosamines in single pouches of Camel Snus and Marlboro Snus. Stepanov, I., Jensen, J., Biener, L., et al.[2021]

In a study of 133 Circle K stores in the Chicago area, 91.1% displayed exterior advertisements for VLN cigarettes, indicating strong marketing presence, while 85.7% of stores offered discounts on these products.

VLN cigarettes were priced similarly to premium brands at an average of $10.90, and some marketing claims were found to be unauthorized by the FDA, suggesting potential compliance issues in their advertising strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid-response surveillance of the first US test market for VLN cigarettes. Henriksen, L., Johnson, TO., Mahoney, M., et al.[2023]

A study involving 341 smokers found that 95% continued using SPECTRUM research cigarettes after an initial 2-week trial, indicating strong acceptance of these reduced nicotine content (RNC) cigarettes.

While satisfaction and craving reduction ratings were slightly lower for SPECTRUMs compared to participants' usual brands, this did not affect their willingness to continue using SPECTRUMs, suggesting that brand loyalty can be overcome in the context of reduced nicotine content smoking alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acceptability of SPECTRUM Research Cigarettes among Participants in Trials of Reduced Nicotine Content Cigarettes. Veldheer, S., Midya, V., Lester, C., et al.[2022]

In a study of 10,289 U.S. adults, menthol cigarette smoking was linked to higher risks of all-cause, cardiovascular, and cancer mortality, similar to nonmenthol cigarette smoking, indicating significant health risks associated with both types of cigarettes.

The systematic review suggested that while menthol smokers had a lower risk of cancer compared to nonmenthol smokers, they showed an increased risk for cardiovascular disease, highlighting the complex health implications of menthol cigarette use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Smoking, menthol cigarettes and all-cause, cancer and cardiovascular mortality: evidence from the National Health and Nutrition Examination Survey (NHANES) and a meta-analysis. Jones, MR., Tellez-Plaza, M., Navas-Acien, A.[2021]

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]

The study involving 12 daily smokers demonstrated that Spectrum research cigarettes produce a dose-dependent increase in blood nicotine levels, with high nicotine content cigarettes providing a similar boost to preferred brand cigarettes.

High nicotine Spectrum cigarettes were found to effectively reduce the urge to smoke compared to lower nicotine options, suggesting their potential utility in studies evaluating nicotine reduction policies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic Profile of Spectrum Reduced Nicotine Cigarettes. Kamens, HM., Silva, CP., Nye, RT., et al.[2022]

In a study involving 5,887 adult smokers monitored for 14 years, there were no significant differences in mortality risk between menthol and plain cigarette smokers for conditions like coronary heart disease, lung cancer, or overall death.

Menthol cigarette users smoked fewer pack-years on average and showed no difference in smoking cessation success compared to non-menthol smokers, suggesting that mentholation does not increase the hazards associated with smoking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Menthol cigarettes and health risks in Lung Health Study data. Murray, RP., Connett, JE., Skeans, MA., et al.[2023]

Citations

1. withpower.com withpower.com/trial/early-phase-1-tobacco-use-3-2023-ffd47

Low-Nicotine Cigarettes for Heart Health (CEV Trial) Research shows that SPECTRUM and VLN cigarettes have reduced nicotine content, which may help smokers feel less controlled by their smoking habit. This could ...

2. fda.gov fda.gov/media/133633/download

PMTA Scientific Review: Technical Project Lead (TPL) The VLN™ King and VLN™ Menthol King cigarettes have similar adverse health risks as. NNC cigarettes if used in a similar manner given that the ...

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

Effects of Very Low Nicotine Content Cigarettes on ... Across menthol status, VLNC cigarette use led to reductions in smoking and toxicant exposure, and increases in abstinence. However, effects tended to be smaller ...

4. federalregister.gov federalregister.gov/documents/2025/01/16/2025-00397/tobacco-product-standard-for-nicotine-yield-of-cigarettes-and-certain-other-combusted-tobacco

Tobacco Product Standard for Nicotine Yield of Cigarettes ... A tobacco product standard that would regulate nicotine yield by establishing a maximum nicotine level in cigarettes and certain other combusted tobacco ...

5. lung.org lung.org/getmedia/26a825f0-7dac-4933-94b8-bb5afa75f4e9/Coalition-Comments-on-Nicotine-Standard-Proposed-Rule-8-25-25.pdf

Tobacco Partner Comments re FDA Nicotine Reduction ... For instance, within just the first year or two of quitting smoking, the risk of coronary heart disease, including having a heart attack, ...

6. fda.gov fda.gov/media/155090/download

Technical Project Lead (TPL) Review of Modified Risk ... Much of the evidence reviewed in these MRTPAs is based on studies of SPECTRUM NRC102 (non- menthol) and NRC103 (menthol) very low nicotine ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9680144/

Impact of a reduced nicotine standard on young adult ... Experimentation with menthol cigarettes is linked to smoking progression, as well as greater nicotine dependence relative to non-menthol cigarette use.

8. clivebates.com clivebates.com/fda-spreads-confusion-about-nicotine-and-smoking/

FDA spreads confusion about nicotine and smoking FDA has authorised 22nd Century to claim a reduced nicotine cigarette is a reduced risk product. This will spread confusion and divert smokers from better ...