Comparisons of Nicotine-free Cigarettes, Extra Low Nicotine Cigarettes vs. Medicinal Nicotine

Study Overview
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Brief Summary
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In this study, smokers will be randomly assigned to one of three conditions for six weeks: 1) nicotine-free cigarettes (0.05mg); 2) extra low nicotine cigarettes (0.3 mg); or 3) medicinal 4 mg nicotine lozenge. The tobacco toxin profiles across these various products will be compared. The effects of these products on biomarkers of exposure and risk factors for disease, compensatory smoking, components of tobacco addiction and short-term smoking cessation will be determined. Predictors of response to these products (e.g., compensatory smoking, compliance with product use, time to lapse) will also be examined. The following primary hypothesis will be tested: 1) Extent of tobacco toxin exposure will be greatest for the extra low nicotine cigarette and least for nicotine lozenge. Other secondary hypotheses include: 2) Compensatory smoking, as calculated by using cotinine, will be greatest for the extra low cigarette compared to the nicotine-free cigarette; 3) Greater positive subjective responses to cigarettes will be observed with extra low nicotine vs. nicotine-free cigarette; 4) Similar withdrawal symptoms and negative affect will be observed with nicotine-free cigarette and nicotine lozenge, and least withdrawal and negative affect with the extra low nicotine cigarette; 6) Least dependence and greatest motivation and self-efficacy to quit will be observed with nicotine lozenge and the greatest dependence and least motivation and self-efficacy to quit with the extra low nicotine cigarette use; 7) Shorter time to lapse will be observed with extra low nicotine vs. nicotine-free cigarettes because of extinction is likely to occur with nicotine-free cigarettes, and the longest time to lapse for nicotine lozenge because the cigarette condition groups will have experienced stronger attentional bias toward cues, and more dependence prior to the quit date and greater withdrawal after the quit date.

Detailed Description
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Smokers (N=150) will be enrolled in the study and will smoke ad libitum for a period of two weeks during which time they will be assessed for baseline measurements. Subjects will then be randomly assigned to one of the three conditions (N=50). Subjects will be blinded as to whether they are assigned to the Quest nicotine-free vs. extra low nicotine condition. There are no distinguishing features between these two cigarettes. Nicotine lozenge assignment is open label. Subjects will be asked to use only their assigned study product (low nicotine, nicotine-free cigarettes or lozenge) for a period of 6 weeks. Study cigarettes will be given to them at each clinic visit and subjects will be told to smoke ad libitum. They will be provided a supply equivalent to 150% of their baseline-smoking rate to allow for compensatory smoking to occur. They will keep record of each cigarette they smoked. If they smoked cigarettes other than those assigned to them, they will be asked to notate on a sheet when that cigarette was smoked. At the end of the 6-week period, they will be asked to quit smoking and NRT. First morning urine and fasting blood samples will be collected at baseline and 2 and 6 weeks on the study products; at 6 weeks of abstinence and the 1 month follow-up. Counseling. In each condition, subjects will be provided brief, structured counseling that is similar in duration. The subjects in the cigarette conditions will discuss any difficulties they experienced with switching cigarettes and problem solving these obstacles. Problem solving each obstacle will be solicited from the subject. However, if no solution or limited solution is provided, the counselor will provide a standardized response for each of the obstacles confronted. Follow-up Phase. Subjects will be followed up 1 month after the end of the 6 week abstinence period.

Official Title
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Study 2: Comparisons of Nicotine-free Cigarettes, Extra Low Nicotine Cigarettes vs. Medicinal Nicotine

Conditions
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Tobacco Dependence

Intervention / Treatment
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* Drug: Nicotine free cigarettes
* Drug: Extra-low nicotine cigarettes
* Drug: Nicotine Lozenge


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: smoking between 10-40 cigarettes daily for the past year; in good physical health (no unstable medical condition; no contraindications for medicinal nicotine; stable, good mental health Exclusion Criteria: unwilling to use study products for 6 weeks; unstable medical or psychiatric condition.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Extra-low nicotine cigarettes<br> | Drug: Extra-low nicotine cigarettes<br>* Quest 2 cigarettes contains 0.3 mg nicotine<br>|
| Experimental: Nicotine-free cigarettes<br> | Drug: Nicotine free cigarettes<br>* Quest Step 2 contains 0.05 mg nicotine<br>|
| Active Comparator: Medicinal Nicotine<br> | Drug: Nicotine Lozenge<br>* 4 mg nicotine lozenge<br>* Other names: Commit;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarkers for tobacco exposure measures: Carbon monoxide, cotinine, NNAL-gluc, NNN, mercapturic acids, 1-hydroxypytrene and biomarkers for cardiovascular risk: WBC, lipid profile, fibrinogen, heart rate, blood pressure. |  | 6 weeks | 
| Tobacco Cessation |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary function |  | 12 weeks | 
| Nicotine withdrawal symptoms |  | 12 weeks | 
| Motivation to quit and self-efficacy |  | 12 weeks | 
| Perceived risk of PREPS and cigarette evaluation |  | 12 weeks | 
| Compensatory smoking |  | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Smoking, PREPS, Harm reduction, Biomarkers of tobacco exposure, Compensatory smoking