A Comparative Effectiveness & Long Term Health Study in Wisconsin Smokers
Condition: Smoking Cessation; Smoking; Nicotine Dependence
MeSH terms: Tobacco Use Disorder
Study type: Interventional
Phase: Phase 4

Summary: 
      The overall purpose of this research is two-fold. First, the two smoking cessation medication
      treatments with the strongest evidence of effectiveness have never been directly compared.
      This research will determine how these two treatments compare in effectiveness in a
      head-to-head trial, and which types of smokers benefit most from each. Second, much of the
      data on smoking and health come from studies from many years ago. Today's smokers differ from
      earlier smokers in many ways that could influence the impact of smoking on health (e.g.,
      weight, sex, diet, socio-economic status); the proposed work will determine how smoking
      cessation affects cardiovascular and pulmonary health in today's smokers.
    

Detailed description: 
      The proposed study will recruit and treat a large sample of contemporary smokers and former
      smokers at an age of increasing health risk, to achieve the following over-arching aims that
      are important to the NHLBI mission:

        -  Specific Aim 1: Produce important new data on how to treat smoking optimally by
           conducting an open label comparative effectiveness trial (CET) that for the first time
           directly contrasts the two smoking cessation pharmacotherapies with the strongest extant
           evidence of efficacy: combination NRT and varenicline.

        -  Specific Aim 2: Determine the impact of smoking cessation on biomarkers and health risk
           factors, especially those relevant to CVD, in today's smokers, which will elucidate the
           mechanisms via which cessation benefits health.

        -  Specific Aim 3: Identify which individuals are at greatest risk for exacerbation of
           biomarkers or risk factor status due to continued smoking, and who will benefit most
           from cessation. This will help identify individuals who are most in need of cessation
           intervention. While all smokers need to quit, this evidence could ultimately be used to
           help focus treatment and motivate smokers and clinicians to intervene more intensively
           with patients at greatest risk.

      Two secondary aims are to use the results of Primary Aim 1 to develop a treatment assignment
      algorithm for the optimal treatment of today's smokers and to use the results from Primary
      Aim 2 to determine the relation of health biomarkers to clinically meaningful disease
      outcomes such as CVD events.

      We will re-recruit as many smoking and non smoking participants from our past longitudinal
      cohort study("Wisconsin Smokers' Health study"; NCT01122238) in 2004. We will then recruit
      additional smokers to participate in the comparative effectiveness trial and join the
      longitudinal cohort..

      All participants who enroll will complete questionnaires about their demographics, smoking
      history, withdrawal symptoms, affect, alcohol use, stressors, medication usage and diet. They
      will also complete a structured clinical interview to assess mental health. They will provide
      blood samples for testing of various markers of cardiovascular disease and risk as well as
      for genetics testing. They will all have carotid ultrasounds, pulmonary function tests,
      arterial tonometry assessments, and 12-lead ECGs. Participants in Madison will also have a
      treadmill stress test. Participants will wear a pedometer for 1 week and record the daily
      number of steps. Participants will provide permission for staff to review their medical
      charts to assess smoking-relevant diagnoses and treatment. These assessments will occur at
      baseline and again 3 years later. A smaller subset of these assessments will also be
      conducted 1 year after enrollment. Participants will also complete brief phone assessments at
      6-month intervals up to the 3-year visit.

      Interested and eligible smoking participants from the original cohort study and all newly
      recruited participants will enroll in a new smoking cessation intervention study.
      Participants in the cessation treatment study will be randomly assigned to receive the
      nicotine patch, nicotine patch + nicotine lozenge or varenicline. If the participant from the
      original cohort study is not eligible to use all study medications but is otherwise eligible
      for cessation treatment, s/he will be assigned to a non-randomized treatment arm and will
      receive nicotine patch (if appropriate). All cessation participants will receive 6 individual
      counseling sessions.
    

Intervention name(s): Varenicline; Nicotine lozenge; Nicotine Patch
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Participants will receive 12 weeks of pharmacotherapy during the post-quit period plus an additional 7 day pre-quit run-in. Participants will be asked to take a 0.5 mg pill once a day for the first 3 days and then increase to a 0.5 mg pill twice a day (8 hours apart) for 4 days. On the 8th day, their target quit date, they will increase to their target maintenance dose of a 1 mg pill twice daily. If participants report significant adverse events such as nausea, a dose reduction to two 0.5 mg doses per day will be advised.; Participants will receive 12 weeks NRT. Participants will be given 2 mg or 4 mg lozenges based on morning smoking latency, and will be given package insert use instructions. Medication use will start on the morning of their assigned quit day. They will be urged to use at least 5 pieces/day, unless this amount produces adverse effects.; Participants will receive 12 weeks NRT. Patch dosing will be 8 weeks of 21 mg, then 2 weeks of 14 mg, then 2 weeks of 7 mg (those smoking 5-10 cigs/day will receive reduced patch dosing). Medication use will start on the morning of their assigned quit day. They will be urged to use 1 patch/day, unless it produces adverse effects.
Intervention MeSH terms: Nicotine; Varenicline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Smoking Cessation; Smoking; Nicotine