Tobacco Use Disorder
Conditions
Keywords
Oral Tobacco Products, Snus, Smoking Substitution, Harm Reduction, Biomarkers of Tobacco Exposure
Brief summary
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
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).
Interventions
OTHEROral tobacco
Snus
DRUGNicotine Gum
4 mg Nicotine gum
Sponsors
National Cancer Institute (NCI)
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
This was an open label trial.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Product Effect on Complete Substitution for Smoking | 6 week post smoking substitution | Number of subjects using only the assigned study product at week 6 |
| Number of Cigarettes Smoked | 6 weeks post cigarette substitution | Cigarettes per day at mid intervention |
| Number of Products Used | 6 weeks post smoking substitution | Pieces of product per week at mid intervention |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Products Effect on Withdrawal Symptoms. | Week 1-12 post switching | 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. |
| Product Effect on Biomarkers of Exposure and Toxicity | Baseline and Week 4 post smoking substitution | 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). |
Countries
United States
Participant flow
Recruitment details
Cigarette smokers interested in completely switching to snus or nicotine gum were recruited from Minneapolis/St Paul, Minnesota, and Eugene, Oregon.
Participants by arm
| Arm | Count |
|---|---|
| Nicotine Gum Nicotine replacement therapy
Nicotine Gum: 4 mg Nicotine gum | 195 |
| Snus Oral tobacco
Oral tobacco: Snus | 196 |
| Total | 391 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Completed 12 Weeks of Treatment | Adverse Event | 0 | 1 |
| Completed 12 Weeks of Treatment | Lack of Efficacy | 0 | 2 |
| Completed 12 Weeks of Treatment | Lost to Follow-up | 5 | 5 |
| Completed 12 Weeks of Treatment | Product Dissatisfaction | 0 | 1 |
| Completed 12 Weeks of Treatment | Withdrawal by Subject | 8 | 2 |
| Completed 6 Weeks of Treatment | Adverse Event | 5 | 12 |
| Completed 6 Weeks of Treatment | Lack of Efficacy | 12 | 8 |
| Completed 6 Weeks of Treatment | Lost to Follow-up | 15 | 17 |
| Completed 6 Weeks of Treatment | Physician Decision | 1 | 0 |
| Completed 6 Weeks of Treatment | Product dissatisfaction | 2 | 6 |
| Completed 6 Weeks of Treatment | Withdrawal by Subject | 6 | 4 |
Baseline characteristics
| Characteristic | Snus | Nicotine Gum | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 196 Participants | 195 Participants | 391 Participants |
| Age, Continuous | 43.2 years STANDARD_DEVIATION 12.5 | 43.9 years STANDARD_DEVIATION 12.5 | 43.9 years STANDARD_DEVIATION 12.5 |
| Region of Enrollment United States | 196 participants | 195 participants | 391 participants |
| Sex: Female, Male Female | 89 Participants | 95 Participants | 184 Participants |
| Sex: Female, Male Male | 107 Participants | 100 Participants | 207 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 195 | 0 / 196 |
| serious Total, serious adverse events | 1 / 195 | 1 / 196 |
Outcome results
Primary
Number of Cigarettes Smoked
Cigarettes per day at mid intervention
Time frame: 6 weeks post cigarette substitution
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine Gum | Number of Cigarettes Smoked | 18.6 cigarettes per day | Standard Deviation 33.8 |
| Snus | Number of Cigarettes Smoked | 18.8 cigarettes per day | Standard Deviation 28.5 |
Primary
Number of Products Used
Pieces of product per week at mid intervention
Time frame: 6 weeks post smoking substitution
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine Gum | Number of Products Used | 37.6 Pieces per week | Standard Deviation 26.3 |
| Snus | Number of Products Used | 39.1 Pieces per week | Standard Deviation 24 |
Primary
Product Effect on Complete Substitution for Smoking
Number of subjects using only the assigned study product at week 6
Time frame: 6 week post smoking substitution
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nicotine Gum | Product Effect on Complete Substitution for Smoking | 56 participants |
| Snus | Product Effect on Complete Substitution for Smoking | 56 participants |
Secondary
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).
Time frame: Baseline and Week 4 post smoking substitution
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nicotine Gum | Product Effect on Biomarkers of Exposure and Toxicity | Baseline | 1.39 pmol//mg creatinine | Standard Deviation 1.04 |
| Nicotine Gum | Product Effect on Biomarkers of Exposure and Toxicity | Week 4 | 0.30 pmol//mg creatinine | Standard Deviation 0.39 |
| Snus | Product Effect on Biomarkers of Exposure and Toxicity | Baseline | 1.28 pmol//mg creatinine | Standard Deviation 0.94 |
| Snus | Product Effect on Biomarkers of Exposure and Toxicity | Week 4 | 1.34 pmol//mg creatinine | Standard Deviation 1.55 |
Secondary
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.
Time frame: Week 1-12 post switching
Population: Using assigned product only. The numbers of subjects that were only using the assigned product were 40 and 37 for nicotine gum and oral tobacco respectively at week 12. Analysis was conducted from weeks 1-12 post-switching.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nicotine Gum | Products Effect on Withdrawal Symptoms. | Baseline Scores | 4.17 units on a scale | Standard Deviation 5.01 |
| Nicotine Gum | Products Effect on Withdrawal Symptoms. | Week 12 Scores | 5.57 units on a scale | Standard Deviation 6.05 |
| Snus | Products Effect on Withdrawal Symptoms. | Baseline Scores | 5.01 units on a scale | Standard Deviation 5.14 |
| Snus | Products Effect on Withdrawal Symptoms. | Week 12 Scores | 5.73 units on a scale | Standard Deviation 6.24 |