Stress Neuroadaptation in Tobacco Dependence
Condition: Nicotine Dependence
MeSH terms: Tobacco Use Disorder
Intervention: nicotine; placebo
Intervention MeSH terms: Nicotine
Phase: Phase 4
Study type: Interventional
Primary purpose: Health Services Research
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Enrollment: 226.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No

Summary:

      The objective of the current study is to evaluate the validity of the No Shock, Predictable
      Shock, Unpredictable Shock (NPU) stressor task for use as a surrogate endpoint to predict
      short-term clinical outcomes among smokers during a smoking cessation attempt.
    

Eligibility criteria:

        Inclusion Criteria:

          -  cigarette use over 10 cigarettes/day for over two years;

          -  smoking within the first 30 minutes of waking up

          -  expired air carbon monoxide (CO) level >6 ppm

          -  self-reported motivation to quit smoking

          -  and an agreement to respond to ecological momentary assessment prompts (via SMS)
             throughout the day for three weeks.

        Exclusion Criteria:

          -  Health screening are performed by questionnaire and reviewed by study staff (RA or
             Research Specialist) to ensure that smokers can safely use the nicotine patch and
             lozenge. Specifically, smokers will be excluded for FDA contraindications for nicotine
             replacement therapy (i.e., no uncontrolled hypertension, recent myocardial infarction,
             diabetes, heart disease, asthma, stomach ulcers).

          -  All women of child-bearing potential will be required to agree to use an approved
             method of birth control to prevent pregnancy during the course of the study.

          -  All participants will report no medical or psychiatric condition that would
             contraindicate exposure to electric shock.

          -  Participants with uncorrected auditory or visual problems will be excluded.

        Additional Data Exclusions

          1. As part of the NPU stressor task, smokers are asked to indicate if the participant
             "can be shocked in the next 5 seconds" at various points during the task. Responses to
             these questions are used to verify that the participant understands the cue-shock
             contingencies. Smokers who answer < 10 out of 14 questions correctly the NPU stressor
             task during the experimental session will be excluded from all analyses and replaced.

          2. Smokers with 20% of cue trials identified as artifact in the NPU task will be excluded
             from all analyses and replaced.

          3. The analysis will NOT exclude smokers who are startle non-responders given that the
             use of these surrogate endpoints in practice would likely need to include these
             individuals to avoid unnecessary data loss.

          4. Smokers who do not report a complete abstinence between quit date/time and final
             laboratory visit (which occurs 12-36 hours later) will be considered to not have quit
             and will be excluded from all analyses and replaced.

          5. Smokers for whom the investigators cannot definitively quantify an outcome with
             respect to continuous abstinence will be excluded from all analyses and replaced. Any
             report of smoking during the two-week cessation period (reported either during the 4x
             daily web surveys or the laboratory visit at 2 weeks) is sufficient to code the smoker
             to have lapsed (i.e., not continuously abstinent), even if the participants do not
             complete the full two weeks of web surveys and/or the 2-week laboratory visit.
             However, the status of smokers who report no smoking during the cessation attempt but
             have both a high level of missing data from the web surveys (> 25% of reports) and no
             two-week laboratory visit report will be deemed uncertain. These smokers will be
             excluded and replaced.

          6. The investigators will conduct case analyses to identify participants who are model
             outliers with Bonferroni-corrected studentized residuals p < 0.05. These model
             outliers will be excluded but NOT replaced (because the participants are not
             identified until after data collection has been completed).