A Randomized Controlled Trial of Progressively Reduced Nicotine Content Cigarettes on Smoking Behaviors, Biomarkers of Exposure, and Subjective Ratings

Abstract

Background: The U.S. FDA has the authority to reduce cigarette nicotine content if found to benefit public health. Reduced nicotine content (RNC) cigarette use does not appear to increase harm exposure, but studies have not rigorously assessed smoking behavior or used a comprehensive panel of biomarkers. This study examined the effects of progressively decreasing RNC cigarettes on smoking behaviors, biomarkers of exposure, and subjective ratings.

Methods: One hundred and fifty-eight daily, non-treatment-seeking smokers participated in a 35-day randomized, unblinded, parallel study. After a 5-day baseline period, participants were randomly assigned to an experimental group (n = 80) that smoked progressively decreasing RNC cigarettes during three 10-day periods, or control group (n = 78) that smoked their own brand throughout the study.

Results: Daily cigarette consumption significantly increased for the intermediate RNCs (P's < 0.001) but approached baseline rate for the lowest RNC (P = 0.686); in contrast, puffing behavior significantly decreased at intermediate levels and increased for the lowest RNC (P's < 0.001). Cotinine and NNAL significantly decreased by RNC period (P's ≤ 0.001-0.02), whereas CO boost initially increased (P's = 0.001-0.005). 1-HOP did not change by period (P = 0.109).

Conclusions: Smoking behaviors changed by RNC period via CPD and puffing behavior. Biomarkers of exposure generally decreased with nicotine content.

Impact: Findings suggest that RNC use does not ubiquitously reduce smoking behaviors or biomarkers, yet the lowest RNC level tested may reduce harm exposure. This emphasizes the importance of using multiple behavioral and biologic measures to address the impact of RNC cigarette smoking. Cancer Epidemiol Biomarkers Prev; 25(7); 1125-33. ©2016 AACR.

Conflict of interest statement

Disclosure of potential conflicts of interest: None.

©2016 American Association for Cancer Research.

Figures

Figure 1

CONSORT flow diagram depicting study recruitment and retention.

Figure 2

Average daily cigarette consumption (A) and total puff volume (B) throughout study in smokers using cigarettes of progressively reduced nicotine content (experimental group) vs. own brand (control group). Product switching days (i.e., Days 5, 15, and 25) are not depicted for 2A. Among the experimental group, daily cigarette consumption was significantly greater during the 0.6 and 0.3 mg nicotine cigarette periods compared to baseline and 0.05 mg nicotine cigarette periods. Total puff volume was significantly lower than baseline during all subsequent periods; total volume during the 0.05 mg nicotine cigarette period was significantly greater than during the 0.6 and 0.3 mg nicotine periods. Among the control group, daily cigarette consumption was significantly greater than baseline during all subsequent periods. There was no change in total puff volume across periods among controls. The experimental group smoked more cigarettes per day than controls during the 0.6 and 0.3 mg nicotine cigarette periods, and had lower total puff volume than controls during all periods following baseline.

Figure 3

Carbon monoxide (CO) boost following each topography session (A), NNAL (B), 1-HOP (C), and cotinine (D) throughout study in smokers using cigarettes of progressively reduced nicotine content (experimental group) vs. own brand (control group). Data for urinary biomarkers are depicted as geometric means and 95% confidence intervals. Among the experimental group, CO boost was significantly greater during the 0.3 mg nicotine cigarette period compared to all other periods and to controls. CO boost was significantly lower during the 0.05 mg nicotine cigarette period relative to all previous periods. Cotinine and nicotine decreased progressively from baseline with each study period, although decreases from baseline were non-significant during the 0.6 mg nicotine period. NNAL levels were significantly lower than baseline during all subsequent periods, and during the 0.05 mg period compared to the 0.6 and 0.3 mg nicotine periods. Compared to controls, cotinine levels in the experimental group were significantly lower at baseline, and cotinine, nicotine, and NNAL levels were significantly lower during the 0.05 mg period. 1-HOP was similar across study periods and groups.