Effect of Varenicline on Cognitive Function in Cigarette Smokers With Schizophrenia
Condition: Schizophrenia; Schizoaffective Disorder
MeSH terms: Schizophrenia; Psychotic Disorders
Study type: Interventional
Phase: Phase 2

Summary: 
      Smokers with schizophrenia have more difficulties quitting smoking than smokers without a
      mental disorder. Varenicline (Champix) is a new stop smoking medication with a unique
      mechanism of action. It is a nicotine-like drug which is not addictive and not associated
      with the health risks of tobacco smoking.

      Varenicline (VAR) binds to sites in the brain called nicotine receptors that play an
      important role in nicotine dependence. People with schizophrenia have difficulties in
      concentrating and remembering. Scientists believe that people with schizophrenia use smoking
      to remedy their cognitive problems. We will test VAR to see if it improves cognitive problems
      in smokers with schizophrenia in comparison to non-mentally ill smokers to determine whether
      people with schizophrenia get direct benefit from this nicotine-like drug. It is hypothesized
      that VAR (in comparison to a placebo) will reduce aspects of cognitive impairment in smokers
      and nonsmokers with schizophrenia.
    

Detailed description: 
      Schizophrenia is characterized by deficits in neurocognitive function, including executive
      function, attention, and spatial and verbal memory. Central nicotinic acetylcholine receptors
      (nAChR) are dysregulated in schizophrenia. It has been shown that neurocognitive deficits in
      schizophrenia improve by administration of nicotine, nicotinic agonists or cigarette smoking.
      Hence, it is believed that cigarette smoking may remedy cognitive deficits in schizophrenia
      and in fact some persons with schizophrenia may be "self-medicating" with tobacco to counter
      such cognitive problems.

      The prevalence rates of cigarette smoking in persons with schizophrenia are higher than in
      the general population (58-88% vs. 25% respectively). This population also has a nicotine
      dependence rate of around 80 % and a high relapse rate after smoking cessation. Additionally
      the leading cause of medical problems and death in people with schizophrenia is tobacco
      addiction. Research that addresses the problem of smoking in schizophrenia is of great
      importance.

      Varenicline (VAR), an α4β2 nAChR partial agonist, approved for smoking cessation, mimics the
      effect of nicotine by stimulating nAChRs, and releasing sufficient dopamine in order to
      reduce craving and withdrawal effects.

      This study will follow four groups of subjects (N=40) that will receive neuropsychological
      and psychiatric testing in three consecutive sessions (smoking satiation, abstinence and
      reinstatement) separated by at least one week over 3 weeks. The groups are:

        1. cigarette smokers with schizophrenia (N=10),

        2. non-smokers with schizophrenia (N=10),

        3. healthy cigarette smoking controls (N=10),

        4. non-smoking controls (N=10).

      All groups will be age- and sex- matched. Pre-treatment with varenicline (VAR) or placebo
      will start on Day 1 of each test session will be as follows: 1) 0.0 mg/day 2) 0.5 mg twice
      daily 3) or 1 mg twice daily for 3 days. Testing days will be separated by at least 1 week
      apart to rule out medication carry-over effects.

      If nicotinic acetylcholine receptors can be stimulated resulting in more dopamine release and
      improved neurocognitive function without inducing deleterious health effects it may be of
      benefit to persons with schizophrenia who smoke tobacco.
    

Intervention name(s): Varenicline
Intervention type(s): Drug
Intervention description(s): 0.0 mg orally twice per day for three days (placebo)
0.5 mg orally twice per day for three days
1.0 mg orally twice per day for three days
Other intervention name(s): Chantix; Champix
Intervention MeSH terms: Varenicline
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Schizophrenia; Schizoaffective Disorder; Varenicline; Champix; Chantix; Nicotine; Nicotinic receptor; Dopamine; Acetylcholine; Cigarette; Smoking; Tobacco; Executive function; Working memory; Verbal memory; Cognitive function; Neuropsychological function