Comparisons of Nicotine-free Cigarettes, Extra Low Nicotine Cigarettes vs. Medicinal Nicotine
Condition: Tobacco Dependence
MeSH terms: Tobacco Use Disorder
Study type: Interventional
Phase: Phase 2

Summary: 
      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: 
      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.
    

Intervention name(s): Nicotine free cigarettes; Extra-low nicotine cigarettes; Nicotine Lozenge
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Quest Step 2 contains 0.05 mg nicotine; Quest 2 cigarettes contains 0.3 mg nicotine; 4 mg nicotine lozenge
Other intervention name(s): Commit
Intervention MeSH terms: Nicotine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Treatment
Keywords: Smoking; PREPS; Harm reduction; Biomarkers of tobacco exposure; Compensatory smoking