Efficacy of Oral Tobacco Products Compared to a Medicinal Nicotine

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

Official Title
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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

Conditions
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Tobacco Use Disorder

Intervention / Treatment
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* Other: Oral tobacco
* Drug: Nicotine Gum


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Nicotine Gum<br>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. | Drug: Nicotine Gum<br>* 4 mg Nicotine gum<br>* Other names: Nicorette;|
| Experimental: Snus<br>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. | Other: Oral tobacco<br>* Snus<br>* Other names: Camel Snus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Product Effect on Complete Substitution for Smoking | Number of subjects using only the assigned study product at week 6 | 6 week post smoking substitution | 
| Number of Cigarettes Smoked | Cigarettes per day at mid intervention | 6 weeks post cigarette substitution | 
| Number of Products Used | Pieces of product per week at mid intervention | 6 weeks post smoking substitution | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Products Effect on Withdrawal Symptoms. | 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. | Week 1-12 post switching | 
| Product Effect on Biomarkers of Exposure and Toxicity | 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). | Baseline and Week 4 post smoking substitution | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oral Tobacco Products, Snus, Smoking Substitution, Harm Reduction, Biomarkers of Tobacco Exposure