Low-Nicotine Cigarettes for Heart Health

(CEV Trial)

Overseen By Maria Anwar, MS

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: Wake Forest University Health Sciences

Disqualifiers: Cardiovascular diseases, Hyperthyroidism, Pregnancy, others

No Placebo Group

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial is studying the effects of cigarettes with very low nicotine on smokers' hearts. It includes both daily and occasional smokers. Researchers will compare heart rate and other heart functions when participants smoke low-nicotine and regular cigarettes to see how reducing nicotine impacts heart health.

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.

What data supports the effectiveness of the treatment SPECTRUM and VLN cigarettes for heart health?

Research shows that SPECTRUM and VLN cigarettes have reduced nicotine content, which may help smokers feel less controlled by their smoking habit. This could potentially lead to reduced smoking and improved heart health, as smoking less is generally better for the heart. ^{1 2 3 4 5}

Is it safe to use low-nicotine cigarettes like VLN for heart health?

The available research does not provide specific safety data for low-nicotine cigarettes like VLN in terms of heart health, but studies on menthol cigarettes, which are similar, show no increased risk of heart disease or death compared to regular cigarettes. ^{4 5 6 7 8}

How is the treatment with SPECTRUM cigarettes different from other treatments for heart health?

SPECTRUM cigarettes are unique because they are designed with reduced nicotine content, which may help in reducing nicotine dependence and potentially improve heart health by lowering the harmful effects associated with regular nicotine intake. Unlike traditional cigarettes, they offer varying levels of nicotine, allowing for a gradual reduction in nicotine exposure. ^{1 2 3 9 10}

Research Team

Eric C Donny, PhD

Principal Investigator

Wake Forest University Health Sciences

Eligibility Criteria

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

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

I am 21 years old or older.

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

Exclusion Criteria

I have had heart or blood vessel problems like heart attack, stroke, or clots in the last 3 months.

Body temperature ≥ 100.4˙F

Unstable health conditions interfering with electrocardiogram (ECG) measurements

Trial Timeline

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

Treatment Details

Interventions

• SPECTRUM cigarettes (Nicotine Replacement Therapy)
• usual brand of Cigarettes (Behavioural Intervention)

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.

Participant Groups

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

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Findings from Research

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]

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]

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 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]

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 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]

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]

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]

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]

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]

References

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

Acceptability of SPECTRUM Research Cigarettes among Participants in Trials of Reduced Nicotine Content Cigarettes. [2022]

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

Chemical Characterization of Mainstream Smoke from SPECTRUM Variable Nicotine Research Cigarettes. [2022]

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

Pharmacokinetic Profile of Spectrum Reduced Nicotine Cigarettes. [2022]

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

Rapid-response surveillance of the first US test market for VLN cigarettes. [2023]

5. 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]

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

Menthol cigarettes and health risks in Lung Health Study data. [2023]

7. United States 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. [2021]

8. England 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. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Cigarette rod length and its impact on serum cotinine and urinary total NNAL levels, NHANES 2007-2010. [2022]

10. Turkey pubmed.ncbi.nlm.nih.gov

Mentholated cigarette smoking induced alterations in left and right ventricular functions in chronic smokers. [2023]