Effects of Varenicline on Smoking Lapse in Smokers With and Without Schizophrenia
Condition: Craving; Smoking; Schizophrenia
MeSH terms: Schizophrenia
Study type: Interventional
Phase: Phase 4

Summary: 
      The objective of this study is to determine the mechanisms by which varenicline, an effective
      smoking cessation treatment, protects against relapse. Varenicline will be administered in
      smokers with schizophrenia and control smokers using a randomized, double-blind, cross-over
      design. Smokers will be asked to stop smoking overnight; the next day the ability to resist
      smoking will be assessed in a laboratory smoking lapse paradigm. Measures of tobacco craving,
      reinforcement and withdrawal-related cognitive dysfunction will be correlated with time to
      lapse. The results could have significant clinical implications by identifying mechanisms by
      which smokers with schizophrenia are at more risk for relapse than the general population,
      leading to the development of more effective smoking cessation therapies.
    

Detailed description: 
      One way to facilitate medication development for smoking cessation is through the use of
      human laboratory paradigms that can provide an efficient, cost-effective and mechanistic
      evaluation of a medication signal on smoking behavior and bridge pre-clinical studies and
      costly clinical trials. This study will take advantage of the recent development and
      validation of a smoking lapse procedure to evaluate the effects of varenicline in smokers
      with and without schizophrenia. We will extend our recent work with varenicline by relating
      its effects on reinforcement, craving and cognition to clinical outcome (i.e., lapse - a
      strong predictor of relapse). It is pertinent to study smokers with schizophrenia because as
      smoking rates decline in the general population we will be left with a group of'hardcore'
      smokers for whom current smoking cessation strategies have limited efficacy.

      The objective of this study is to determine the effect of varenicline versus placebo, on time
      to lapse, as a function of craving, reinforcement and cognitive dysfunction, in smokers with
      and without schizophrenia. We hypothesize that:

        1. Smokers with schizophrenia will have reduced ability to resist smoking during the
           placebo condition compared to controls; and secondarily, this will be related to the
           higher levels of cognitive dysfunction during abstinence.

        2. Varenicline will increase the ability to resist smoking in both control and
           schizophrenia smokers; and secondarily, this will be mediated via its effects on
           cognition in smokers with schizophrenia, and its effects on craving in control smokers.

      The exploratory aims are to determine:

        1. Varenicline's effect on cue-reactivity in smokers with and without schizophrenia and its
           relationship to time to lapse.

        2. Varenicline's effects on tobacco reinforcement and its relationship to ad lib smoking in
           the lapse period

      The current study will advance the development of tobacco addiction treatments in the
      following ways: 1) Identification of mechanisms by which varenicline facilitates abstinence
      in different subtypes of smokers (schizophrenia vs. controls) is critical to improve
      treatment response. 2) Identification of predictors of relapse in different subtypes of
      smokers (schizophrenia vs. controls) could guide future medication development efforts. 3)
      Relating measures of tobacco abstinence and addiction collected in the laboratory to proxy
      measures of treatment outcome (i.e., smoking lapse) will provide further validation that
      evaluation of medications in such paradigms is a useful and cost-effective screening
      strategy. 4) Our approach could also be used to identify smokers most at risk for tobacco
      abstinence symptoms who would benefit from treatments targeting the most prominent aspects of
      withdrawal. This could lead to improved health outcomes in smokers.
    

Intervention name(s): Varenicline; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): This is an approved smoking cessation medication.
Other intervention name(s): Champix, Chantix
Intervention MeSH terms: Varenicline
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: Varenicline; Schizophrenia; smoking; Lapse