Nicotine Dependence
Conditions
Keywords
Biomarkers, Smoking, Tobacco, Cessation
Brief summary
The use of smokeless tobacco (ST) as a substitute for cigarette smoking has been suggested since it is considered by some to be a less harmful tobacco product (Russell, Jarvis and Feyerabend, 1980; Russell et al, 1981; Rodu, 1994). ST does not have the volatile constituents and carbon monoxide (CO) that are found in cigarette smoke. Since ST is not smoked there would be less risk of cardiovascular and lung disease. In addition the harm associated with second hand smoke would be eliminated. Although the health risks are reduced in ST users, they still exist due to the presence of nitrosamines found in ST. A better approach would be to use nicotine replacement that did not contain carcinogens, however the cost of such NRT could be prohibitive especially in third world countries where the rate of smoking is continuing to rise and the per capita income is much lower than in the United States. Purpose: The goal of this study is to evaluate the health effects of Camel Snus, the new oral tobacco product produced by RJ Reynolds and Taboka, produced by Phillip Morris. These products are pasteurized rather than fermented and contain less moisture to eliminate spitting. They are marketed as an alternative to cigarette smoking.
Detailed description
Cigarette smokers (n=125) will be recruited from the local metropolitan area using multiple media outlets. Subjects who are medically and psychologically healthy will be recruited for the study. Cigarette smokers will be informed of the study over the telephone and asked to answer a brief tobacco use history and medical screening questionnaire. If subjects pass the initial screening for the study, they will be asked to attend an orientation meeting at the Tobacco Use Research Center where the study will be explained in more detail, informed consent will be obtained and a full screening evaluation will occur. This evaluation includes the completion of several comprehensive tobacco use and social history forms and a complete physical and psychological screening. Subjects will be required to attend the clinic once during Week 1 and once during Week 2 of the study in order to obtain baseline data. At the end of Week 2, cigarette smokers will be randomly assigned to either: 1) quit tobacco use and will be offered the choice of using nicotine gum or lozenge, depending on personal preference (n= 25) or they will be assigned to switch to: 2) Taboka (n=50) or 3) Camel Snus (n=50). Subjects sampled different flavors of the products for 1 week and then used the product for the next 4 weeks. During the four weeks, subjects will be asked to attend weekly clinic visits during which time study data will be collected. After the 4 weeks of study product use, subjects will be required to taper off of the tobacco or nicotine product over the next one week and then cease all tobacco use. Follow-up visits will be conducted 1 week and 11 weeks after completion of the study and outcome measures will be taken at that time. Blood and urine samples will be collected and analyzed for tobacco related toxicants during the treatment period.
Interventions
DRUGNicotine gum and lozenge
Nicotine replacement
OTHERTaboka
smokeless tobacco product
OTHERCamel Snus
smokeless tobacco product
Sponsors
National Cancer Institute (NCI)
National Institute on Drug Abuse (NIDA)
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects between 18-70 years of age * Smoking at least 10 cigarettes/day for at least one year * Good physical and mental health as evidenced by a medical history with no unstable medical conditions.
Exclusion criteria
* Uncontrolled chronic disease or condition that requires medical attention during the course of the study * Contraindications for nicotine replacement products: active ulcers, recent heart attack, heart disease or irregular heart beat, uncontrolled high blood pressure, or medication use that might affect tobacco use * Current unstable psychiatric diagnoses or persons who currently are adjusting medication dose. (within the last 3 months) * Subjects with current or recent (within 6 months) alcohol or drug abuse problem * Other regular tobacco use such as regular cigar or pipe smoking * Currently using other nicotine replacement products * Chronic use of any drug that could interact with the study drugs.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Toxicant Exposure by Products | Baseline, 4 weeks | Levels of carcinogen biomarkers (NNAL) reported as difference between baseline and week 4 scores. |
| Product Use at Week 4 of Intervention | 4 weeks | Self-reported daily use of the assigned study product. Range of scores is from 0 to about 20. Higher scores do not represent either a better or a worse outcome. Higher number of product used per day may indicate higher abuse liability of the product but may lead to a greater suppression in usual brand cigarette smoking. Lower number of product use per day may indicate lower abuse liability but may lead to lower suppression of usual brand smoking. |
| Abstinence From Tobacco at End of Treatment, 1 Week and 11 Weeks Post-intervention. | 12 weeks | This study was not powered to detect differences in smoking cessation rates between groups; however, smoking status was collected at each visit to obtain preliminary data. Point prevalence (no smoking during the previous 7 days) cigarette abstinence rates were calculated at the end of treatment and at each of the 2 follow-up visits (week 1 and 11 post-intervention). Continuous abstinence rates were calculated for the 4 week period between the week 1 and week 4 visits. Abstinence at all visits was assessed by self-report (i.e., no cigarettes smoked) and confirmed by an exhaled CO of less than 8 ppm. At the follow-up visits, abstinence was also confirmed by both exhaled CO concentrations and urinary cotinine concentration (\<35 ng/mL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Product Effect on Craving and Nicotine Withdrawal Symptoms at 1 Week. | Baseline and 1 week | Changes in craving and withdrawal symptoms were assessed at the time of discontinuation of usual brand cigarettes (i.e., baseline compared to week 1). Assessments were made using the Minnesota Nicotine Withdrawal Scale, which measures abstinence effects from usual brand cigarettes. Total Score: Range of scores is from 0 to 28. All items with the exclusion of craving are summed. Craving Score: Range of score is from 0 to 4. A higher score would indicate more severe withdrawal. |
Countries
United States
Participant flow
Recruitment details
Healthy smokers were recruited from the Twin Cities, MN metro area from November of 2006 through October of 2008.
Participants by arm
| Arm | Count |
|---|---|
| Assigned to NRT Nicotine gum or nicotine lozenge | 27 |
| Assigned to Taboka Taboka - oral tobacco product | 52 |
| Assigned to Camel Snus Camel Snus - oral tobacco product | 51 |
| Total | 130 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 3 | 2 |
| Overall Study | Ineligible | 0 | 1 | 0 |
| Overall Study | Lack of Efficacy | 3 | 8 | 5 |
| Overall Study | Lost to Follow-up | 4 | 8 | 10 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 2 |
Baseline characteristics
| Characteristic | Assigned to Camel Snus | Total | Assigned to NRT | Assigned to Taboka |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 51 Participants | 130 Participants | 27 Participants | 52 Participants |
| Age, Continuous | 43.6 years STANDARD_DEVIATION 11.5 | 42.8 years STANDARD_DEVIATION 11.8 | 42.4 years STANDARD_DEVIATION 12.8 | 42.4 years STANDARD_DEVIATION 11.2 |
| Fagerstrom Test for Nicotine Dependence Score | 4.4 Scores on a scale STANDARD_DEVIATION 1.6 | 4.5 Scores on a scale STANDARD_DEVIATION 1.3 | 5.2 Scores on a scale STANDARD_DEVIATION 1.2 | 3.8 Scores on a scale STANDARD_DEVIATION 1.1 |
| Region of Enrollment United States | 51 participants | 130 participants | 27 participants | 52 participants |
| Sex: Female, Male Female | 20 Participants | 53 Participants | 12 Participants | 21 Participants |
| Sex: Female, Male Male | 31 Participants | 77 Participants | 15 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 18 / 27 | 28 / 52 | 39 / 51 |
| serious Total, serious adverse events | 0 / 27 | 0 / 52 | 0 / 51 |
Outcome results
Primary
Abstinence From Tobacco at End of Treatment, 1 Week and 11 Weeks Post-intervention.
This study was not powered to detect differences in smoking cessation rates between groups; however, smoking status was collected at each visit to obtain preliminary data. Point prevalence (no smoking during the previous 7 days) cigarette abstinence rates were calculated at the end of treatment and at each of the 2 follow-up visits (week 1 and 11 post-intervention). Continuous abstinence rates were calculated for the 4 week period between the week 1 and week 4 visits. Abstinence at all visits was assessed by self-report (i.e., no cigarettes smoked) and confirmed by an exhaled CO of less than 8 ppm. At the follow-up visits, abstinence was also confirmed by both exhaled CO concentrations and urinary cotinine concentration (\<35 ng/mL).
Time frame: 12 weeks
Population: Intent to treat model.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Medicinal Nicotine | Abstinence From Tobacco at End of Treatment, 1 Week and 11 Weeks Post-intervention. | 1 week post-intervention point prevalence | 15 participants |
| Medicinal Nicotine | Abstinence From Tobacco at End of Treatment, 1 Week and 11 Weeks Post-intervention. | End of intervention continuous abstinence | 11 participants |
| Medicinal Nicotine | Abstinence From Tobacco at End of Treatment, 1 Week and 11 Weeks Post-intervention. | 11 weeks post intervention point prevalence | 9 participants |
| Taboka | Abstinence From Tobacco at End of Treatment, 1 Week and 11 Weeks Post-intervention. | 1 week post-intervention point prevalence | 22 participants |
| Taboka | Abstinence From Tobacco at End of Treatment, 1 Week and 11 Weeks Post-intervention. | End of intervention continuous abstinence | 17 participants |
| Taboka | Abstinence From Tobacco at End of Treatment, 1 Week and 11 Weeks Post-intervention. | 11 weeks post intervention point prevalence | 12 participants |
| Snus | Abstinence From Tobacco at End of Treatment, 1 Week and 11 Weeks Post-intervention. | End of intervention continuous abstinence | 22 participants |
| Snus | Abstinence From Tobacco at End of Treatment, 1 Week and 11 Weeks Post-intervention. | 11 weeks post intervention point prevalence | 16 participants |
| Snus | Abstinence From Tobacco at End of Treatment, 1 Week and 11 Weeks Post-intervention. | 1 week post-intervention point prevalence | 24 participants |
Comparison: This study was not powered to detect differences in smoking cessation rates between groups; however, smoking status was collected to obtain preliminary data. Point prevalence (no smoking during the previous 7 days) cigarette abstinence rates were calculated at the week-4 visit and at each of the 2 follow-up visits. Continuous abstinence rates were calculated for the 4 week period between the week 1 and week 4 visits. Abstinence at all visits was assessed by self-report and confirmed by CO.p-value: <0.05Mixed Models Analysis
Primary
Product Use at Week 4 of Intervention
Self-reported daily use of the assigned study product. Range of scores is from 0 to about 20. Higher scores do not represent either a better or a worse outcome. Higher number of product used per day may indicate higher abuse liability of the product but may lead to a greater suppression in usual brand cigarette smoking. Lower number of product use per day may indicate lower abuse liability but may lead to lower suppression of usual brand smoking.
Time frame: 4 weeks
Population: All subjects who completed intervention.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Medicinal Nicotine | Product Use at Week 4 of Intervention | 7.27 uses per day | Standard Error 0.55 |
| Taboka | Product Use at Week 4 of Intervention | 5.27 uses per day | Standard Error 0.42 |
| Snus | Product Use at Week 4 of Intervention | 6.76 uses per day | Standard Error 0.4 |
Comparison: Product use is by self-report and daily diaries.p-value: 0.05Mixed Models Analysis
Primary
Toxicant Exposure by Products
Levels of carcinogen biomarkers (NNAL) reported as difference between baseline and week 4 scores.
Time frame: Baseline, 4 weeks
Population: All subjects who continued in the protocol were analyzed. Non-parametric Kruskal-Wallis method of analysis was used.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Medicinal Nicotine | Toxicant Exposure by Products | Total NNAL | 0.157 ng/ml |
| Medicinal Nicotine | Toxicant Exposure by Products | Cotinine | 835.3 ng/ml |
| Medicinal Nicotine | Toxicant Exposure by Products | Total NNN | 0.010 ng/ml |
| Taboka | Toxicant Exposure by Products | Total NNAL | 0.281 ng/ml |
| Taboka | Toxicant Exposure by Products | Cotinine | 782.1 ng/ml |
| Taboka | Toxicant Exposure by Products | Total NNN | 0.011 ng/ml |
| Snus | Toxicant Exposure by Products | Cotinine | 726.8 ng/ml |
| Snus | Toxicant Exposure by Products | Total NNN | 0.026 ng/ml |
| Snus | Toxicant Exposure by Products | Total NNAL | 0.296 ng/ml |
p-value: 0.002Mixed Models Analysis
Secondary
Product Effect on Craving and Nicotine Withdrawal Symptoms at 1 Week.
Changes in craving and withdrawal symptoms were assessed at the time of discontinuation of usual brand cigarettes (i.e., baseline compared to week 1). Assessments were made using the Minnesota Nicotine Withdrawal Scale, which measures abstinence effects from usual brand cigarettes. Total Score: Range of scores is from 0 to 28. All items with the exclusion of craving are summed. Craving Score: Range of score is from 0 to 4. A higher score would indicate more severe withdrawal.
Time frame: Baseline and 1 week
Population: All subjects completing the intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Medicinal Nicotine | Product Effect on Craving and Nicotine Withdrawal Symptoms at 1 Week. | Craving Scores | 2.55 units on a scale | Standard Error 0.18 |
| Medicinal Nicotine | Product Effect on Craving and Nicotine Withdrawal Symptoms at 1 Week. | Nicotine Withdrawal Scores | 8.15 units on a scale | Standard Error 1.17 |
| Taboka | Product Effect on Craving and Nicotine Withdrawal Symptoms at 1 Week. | Craving Scores | 2.76 units on a scale | Standard Error 0.14 |
| Taboka | Product Effect on Craving and Nicotine Withdrawal Symptoms at 1 Week. | Nicotine Withdrawal Scores | 8.89 units on a scale | Standard Error 0.86 |
| Snus | Product Effect on Craving and Nicotine Withdrawal Symptoms at 1 Week. | Craving Scores | 2.62 units on a scale | Standard Error 0.13 |
| Snus | Product Effect on Craving and Nicotine Withdrawal Symptoms at 1 Week. | Nicotine Withdrawal Scores | 8.61 units on a scale | Standard Error 0.83 |
Comparison: A generalized linear mixed model was used for outcomes that had been repeatedly measured from baseline through the end of the treatment period. Each repeated-measures model included the treatment effect, a visit effect, the interaction between treatment and visit, the interaction between subject error and within-subject error terms.p-value: >0.1Mixed Models Analysis