Novel Smoking Cessation Drug for Schizophrenia
Condition: Smoking Cessation
MeSH terms: Schizophrenia
Study type: Interventional
Phase: Phase 2

Summary: 
      The investigators will evaluate effects of a novel drug that improves nicotinergic receptor
      function vs. placebo on short-term smoking abstinence in smokers with schizophrenia who have
      a high interest in quitting. The investigators predict that the novel drug will increase days
      of abstinence, compared with placebo, identifying potential evidence of efficacy for smoking
      cessation in smokers with schizophrenia.

      The investigators will also assess if this new drug decreases nicotine withdrawal, craving,
      and cognitive impairment during early abstinence, as well as evaluate adverse effects.
    

Detailed description: 
      Objective:

      This is a Proof of Concept study planned over nearly 2 years to determine the potential
      efficacy of a novel drug for smokers with schizophrenia.

      This study will assess 60 smokers with a diagnosis of either schizophrenia or schizoaffective
      disorder with high quit interest on their ability to quit during a week-long attempt to
      abstain while receiving a novel drug vs. placebo, using a within-subjects cross-over design.

      Research Plan:

      Active drug or placebo will be provided to participants in double-blind fashion.

      Study participation will last 6 weeks after subjects enter the study following the screening
      and physical exam sessions (about 8 weeks total). Participants will engage in two identical
      study phases, each involving visits over 3 weeks and varying only in whether active drug or
      placebo is administered. The 3 weeks will involve: baseline visits, dose run-up (week 2), and
      week 3 (for abstinence assessments). The first week of each period will be a baseline week in
      which they smoke normally without any medication. During week 2, subjects will begin the dose
      run-up of active drug or placebo, increasing over 4 days from 1 tablet of 50 mg once daily to
      100 mg b.i.d. (two 50 mg tablets twice/day), which will continue through the second and third
      weeks. Active drug or placebo will be administered in counter-balanced order in a cross-over
      design. During week 3, subjects will be instructed to try to abstain on each day, i.e.
      Mon-Friday. Most visits will last 60 mins and involve psychiatric assessments (including
      psychopathology and neurological and other side effects) ratings, providing an expired breath
      carbon monoxide (CO) measure that assesses smoking exposure in the past 24 hrs, as well as
      completing brief self-report measures of craving, withdrawal, and mood. On week 3 of each
      phase, one visit will involve cognitive testing. On Fri of week 3, subjects will discontinue
      all medication and resume ad lib smoking prior to the next study period, involving the same
      3-week procedure (but with the other medication condition): baseline, dose run-up, full dose
      administration plus abstinence assessment. Note that active medication will be taken during
      only one period, with placebo taken during the other period. Pill counts will be used to
      measure adherence.

      Primary and secondary dependent measures are described separately in this report.

      Psychopathology will be assessed using standard rating scales to evaluate psychoses and
      general psychopathology and severity of illness ratings, and suicide rating scales. These and
      clinical impressions of patients in the study will assist in monitoring for stability or
      worsening of psychoses or suicidal behavior and/or the need to exit patients from the study.

      Laboratory and EKG monitoring at the beginning and end of the study will also be part of the
      subject safety procedures.

      Patients will be offered their choice of one of the FDA approved smoking cessation agents,
      i.e. nicotine replacement therapy, bupropion or varenicline for a 3-month period upon
      completion of the study. If patients decline open-label smoking cessation participation, they
      will be requested to come in for one post-study visit, 14 ± 4 days later. At the first
      post-study visit, if there are no adverse events, their participation will end.

      Methods:

      The novel drug or placebo will be administered double-blind in counter-balanced order in a
      cross-over design. This is not a clinical trial that assesses long term smoking cessation but
      a within-subjects comparison of the short-term effects of this drug on abstinence and
      abstinence symptoms over a week-long period, relative to placebo.

      Significance:

      This study addresses an important question of whether the novel drug shows potential efficacy
      for smoking cessation, relative to placebo, in smokers with schizophrenia. This procedure
      could have enormous implications for accelerating the development of this medication and
      similar compounds to help people quit smoking by increasing the efficiency of early
      medication evaluation.
    

Intervention name(s): Active JNJ Drug; Placebo Pill
Intervention type(s): Drug; Drug
Intervention description(s): 200 mg/day (100 mg b.i.d.) of Active JNJ Drug will be used for one week while attempting to briefly quit smoking on Mon-Fri of that week; Placebo pill will be taken daily to assess ability to briefly quit smoking on Mon-Fri for one week
Other intervention name(s): JNJ-39393406
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Attempt at Smoking Cessation; Schizophrenia or Schizoaffective disorder; Novel nicotinergic drug