Switching to Progressively Reduced Nicotine Content Cigarettes in Smokers with Low Socioeconomic Status

Introduction: The Food and Drug Administration issued an advanced notice of proposed rulemaking for setting a product standard for nicotine levels in cigarettes, with an emphasis on minimally or non-Addicting very low nicotine content (VLNC). Methods: A 33 week, two-Arm, double-blind randomized trial conducted in Hershey, Pennsylvania, USA and Washington, DC, USA included adult daily cigarette smokers (≥5 cigarettes per day) with less than a college degree, and who had no plans to quit within the next six months. Participants were randomized to either reduced nicotine content (RNC) study cigarettes tapered every three weeks to a final VLNC (0.2 mg/cigarette) for six weeks or to usual nicotine content (UNC) study cigarettes (11.6 mg/cigarette). Outcomes included acceptability of study cigarettes measured by attrition (primary outcome), compliance, reduction in cigarette dependence and tobacco biomarkers, and post-intervention cessation. Results: The RNC (n = 122) versus UNC (n = 123) group had higher attrition (adjusted Hazard Ratio 3.4; 95% confidence interval [CI] 1.99 to 5.81). At the end of the intervention, cotinine levels were 50% lower in the RNC group (mean group difference-137 ng/mL; 95% CI-172,-102). The RNC group smoked fewer CPD (-4.1; 95% CI-6.44,-1.75) and had lower carbon monoxide levels (-4.0 ppm; 95% CI-7.7,-0.4). Forty seven percent (29/62) of the RNC group were biochemically-confirmed compliant with smoking VLNC cigarettes (mean cotinine = 8.9 ng/ml). At three month follow-up, only compliant VLNC smokers quit with an assisted quit attempt (N = 6/22, 27%). Conclusions: This study supports a VLNC standard in cigarettes. Implications: Differential dropout and noncompliance indicate some smokers had difficulty transitioning to cigarettes with reduced nicotine. These smokers will benefit from supplemental nicotine in medicinal or noncombustible tobacco products if a nicotine reduction standard is established. Other smokers successfully transitioned to very low nicotine content cigarettes exclusively and substantially reduced their exposure to nicotine.



Work Title Switching to Progressively Reduced Nicotine Content Cigarettes in Smokers with Low Socioeconomic Status
Subtitle A Double-Blind Randomized Clinical Trial
Open Access
  1. Nicolle M. Krebs
  2. Junjia Zhu
  3. Emily Wasserman
  4. Robin Kuprewicz
  5. Diane J. Martinez
  6. Susan Veldheer
  7. Craig Livelsberger
  8. Jennifer Modesto
  9. Lisa Reinhart
  10. Neil Trushin
  11. Samantha M. Reilly
  12. Jason Liao
  13. Alyse Fazzi
  14. Rebecca Bascom
  15. John P. Richie
  16. Jonathan Foulds
  17. Kimberly Horn
  18. Joshua E. Muscat
License In Copyright (Rights Reserved)
Work Type Article
  1. Nicotine and Tobacco Research
Publication Date June 1, 2021
Publisher Identifier (DOI)
  1. https://doi.org/10.1093/ntr/ntaa247
Deposited November 16, 2021




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Work History

Version 1

  • Created
  • Added KrebsetalRNCNTR2021.pdf
  • Added Creator Nicolle M. Krebs
  • Added Creator Junjia Zhu
  • Added Creator Emily Wasserman
  • Added Creator Robin Kuprewicz
  • Added Creator Diane J. Martinez
  • Added Creator Susan Veldheer
  • Added Creator Craig Livelsberger
  • Added Creator Jennifer Modesto
  • Added Creator Lisa Reinhart
  • Added Creator Neil Trushin
  • Added Creator Samantha M. Reilly
  • Added Creator Jason Liao
  • Added Creator Alyse Fazzi
  • Added Creator Rebecca Bascom
  • Added Creator John P. Richie
  • Added Creator Jonathan Foulds
  • Added Creator Kimberly Horn
  • Added Creator Joshua E. Muscat
  • Published
  • Updated
  • Updated
  • Updated