Health Effects of SLT, Cigarette Smoking, and New Tobacco Products

Study Overview
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Brief Summary
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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
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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.

Official Title
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Comparing the Health Effects of Smokeless Tobacco, Cigarette Smoking, and New Tobacco Products Advertised as Safer Alternatives Part of Tobacco Exposure Reduction

Conditions
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Nicotine Dependence

Intervention / Treatment
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* Drug: Nicotine gum and lozenge
* Other: Taboka
* Other: Camel Snus


Participation Criteria
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Eligibility Criteria
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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.

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Nicotine gum or nicotine lozenge; Dosage: 2 or 4 mg; Frequency: Daily; Duration: 5 weeks of use of which 1 week is tapering. | Drug: Nicotine gum and lozenge<br>* Nicotine replacement<br>* Other names: Commit, Nicorette;|
| Experimental: 2<br>Taboka - oral tobacco product Dosage: 0.84 to 1.26 mg free nicotine per g dry weight; Frequency: Daily; Duration: 5 weeks of use of which 1 week is tapering. | Other: Taboka<br>* smokeless tobacco product<br>|
| Experimental: 3<br>Camel Snus - oral tobacco product Dosage: 6.09 to 9.16 mg dry weight; Frequency: Daily; Duration: 5 weeks of use of which 1 week is tapering. | Other: Camel Snus<br>* smokeless tobacco product<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicant Exposure by Products | Levels of carcinogen biomarkers (NNAL) reported as difference between baseline and week 4 scores. | Baseline, 4 weeks | 
| 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. | 4 weeks | 
| 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). | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and 1 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Biomarkers, Smoking, Tobacco, Cessation