Efficacy of Oral Tobacco Products Compared to a Medicinal Nicotine

Oral Tobacco as a Harm Reduction Product: Study 2 - Efficacy of Oral Tobacco Products Compared to Medicinal Nicotine for Complete Cigarette Substitution and Among Non-abstainers, for Reduction in Cigarette Smoking

For the primary goals, we hypothesize that 1) the oral tobacco product will be more efficacious than the medicinal nicotine product in substituting for smoking cigarettes; 2) among non-abstainers, the oral tobacco product will lead to greater reduction in cigarette smoking than medicinal nicotine; and 3) a higher rate of oral tobacco compared to medicinal nicotine use will be observed during and beyond the treatment period. For the secondary goals, we hypothesize that 1) both products will equally reduce withdrawal symptoms from cigarette abstinence; and 2) the toxicant exposure and toxicity will be reduced dramatically when smokers switch from cigarettes to each of these products; however, this reduction will be greater with the use of medicinal nicotine.

This second study under "Oral Tobacco as a Harm Reduction Product" grant is a clinical trial. Subjects will be randomized to the brand of smokeless tobacco that is determined to be most effective in Study 1 or to nicotine gum for 12 weeks to compare complete substitution for smoking. The secondary aims are to determine the effects of the products on biomarkers of exposure and toxicity. Other secondary aim includes examining the effects of the two products on withdrawal symptoms. Two sites will be used for these studies: University of Minnesota and Oregon Research Institute (ORI).

Nicotine replacement therapy (4 mg nicotine gum) was provided to the participants for an 12 weeks. Participants were encouraged to completely substitute nicotine gum for cigarettes and asked to use at least 6-8 pieces a day or optimally every 1-2 h and more if necessary. They were advised to reduce consumption by half during weeks 7-9 and three-quarters during weeks 10-12.

Oral tobacco (Camel Snus) was provided to the participants for an 12 weeks. Participants were encouraged to completely substitute snus for cigarettes and asked to use at least 6-8 pieces a day or optimally every 1-2 h and more if necessary. They were advised to reduce consumption by half during weeks 7-9 and three-quarters during weeks 10-12.

Total withdrawal score on the Minnesota Nicotine Withdrawal Scale for subjects using only their assigned study product. This scale measures withdrawal symptoms from cigarettes. There are 8 items on the scale with scores that range from 0 to 4. Total score is calculated by summing the scores (excluding the craving item). Minimum score is 0 and maximum is 28. The higher the score the more severe the withdrawal.

Total NNAL (e.g., 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides) among those subjects who reported use of assigned product only (baseline and week 4 samples).

Inclusion Criteria: smoking at least 10 cigarettes daily for the past year, in good physical health (no unstable medical condition; no contraindications for medicinal nicotine, as appropriate for the study, stable, good mental health (e.g., no recent unstable or untreated psychiatric diagnosis, including substance abuse, as determined by the DSM-IV criteria). Exclusion Criteria: Subjects must not be currently using other tobacco or nicotine products; Female subjects cannot be pregnant or nursing.

We will share data with both internal and external researchers. Those external researchers interested in accessing the data will be required to submit a data analyses proposal with specific aims, hypotheses, and data analyses plan. These proposals will be reviewed by the investigative team. The requested data will then be provided that includes the variable list, raw data and description of the measures and methods of data collection.

Hatsukami DK, Severson H, Anderson A, Vogel RI, Jensen J, Broadbent B, Murphy SE, Carmella S, Hecht SS. Randomised clinical trial of snus versus medicinal nicotine among smokers interested in product switching. Tob Control. 2016 May;25(3):267-74. doi: 10.1136/tobaccocontrol-2014-052080. Epub 2015 May 19.