Novel Smoking Cessation Drug for Schizophrenia
Condition: Smoking Cessation
MeSH terms: Schizophrenia
Intervention: Active JNJ Drug; Placebo Pill
Intervention description: 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
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 62.0
Sex: All
Minimum age: 18 Years
Maximum age: 66 Years
Healthy volunteers: No
Keywords: Attempt at Smoking Cessation; Schizophrenia or Schizoaffective disorder; Novel nicotinergic drug

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.
    

Eligibility criteria:

        Inclusion Criteria: List the specific criteria for inclusion of potential subjects.

          -  Men or women of any race, ages 18 to 65 years, (≥18 years, ≤ 66 years)

          -  Willing to provide written informed consent

          -  MINI (Sheehan et al 1998, 2008) chart and/or clinician consensus affirmed DSM IV TR or
             (DSM -V) diagnoses of schizophrenia or schizoaffective disorder.

          -  Patients whose PANSS total scores have been stable for ≥ 4 weeks (clinician and/or
             subject affirmed) and at ≤ 70

          -  No recent ( ≤ 3months) hospitalization, aggression, or suicidal attempts

          -  Stable doses of antipsychotic medication, ≥ 4 weeks

        Smoking Inclusion Criteria:

          -  Smoke ≥ 5 cigarettes/day

          -  Smoking cigarettes ≥ 1 year

        Exclusion Criteria:

        Smoking/Nicotine Exclusions:

          -  Use of smokeless tobacco or snuff or chewing tobacco

          -  Use of e-cigarettes, or any non-tobacco nicotine products (e.g. nicotine gum,
             lozenges, patch, etc.)

          -  Current enrollment or plans to enroll in another smoking cessation program. (Bupropion
             use for depression will be assessed on a case by case basis)

        Alcohol/Illicit Substance Exclusion Criteria:

          -  Recent alcohol or substance dependence (≤ 3 months)

          -  Current alcohol consumption that exceeds 15 standard drinks/week or greater than 2
             standard drinks daily

        Medical Exclusion Criteria:

          -  Women who are pregnant, planning a pregnancy, or lactating; all female participants
             shall undergo a pregnancy test at screening and will be excluded if positive.

          -  Serious or unstable medical disorder within the past 3 months (assessed by the
             investigators)

          -  Epilepsy

          -  Current diagnosis (within last 6-months) of abnormal cardiac rhythms; unstable
             cardiovascular disease e.g. stroke, myocardial infarction in the last 6 months

          -  Evidence impaired liver function test (LFT) defined as serum glutamate oxaloacetate
             transaminase (SGOT) (AST) or serum glutamate pyruvate transaminase (SGPT) (ALT) or
             alkaline phosphatase greater than 1x the upper limit of normal, or bilirubin 1x the
             upper limit of normal

          -  Evidence of kidney failure defined as: Serum creatinine > 1.8 mg/dl for males and 1.6
             mg/dl for females.

          -  Any subject with a history of hematological cancers examples: leukemia, lymphoma etc.
             will be excluded.

          -  Any clinically significant hematological laboratory abnormality (chronic low-grade
             laboratory values just above or below the reference range that are without clinical
             significance will be permitted) will be grounds for exclusion.

        Medication Exclusion Criteria:

          -  Current use or recent discontinuation (within last 14-days) of the following
             medications: any form of smoking cessation medication (Bupropion except when used for
             Depressive Disorders on a case by case basis, Varenicline, NRT); and (b)
             opiate-containing medications for chronic pain. Potent CYP 3A4 inhibitors will be
             reviewed for exclusion, see below.

          -  In view of novel drug being a moderate CYP3A4 inhibitor, any subjects receiving the
             following narrow therapeutic index CYP3A4 substrates will be excluded: Alfentanil,
             astemizole, cisapride, cyclosporine, dihydroergotamine, ergotamine, fentanyl,
             pimozide, quinidine, sirolimus, tacrolimus, terfenadine.

          -  In view of the impact of clozapine on smoking cessation, patients receiving clozapine
             will be excluded.

          -  Stable medical conditions examples: hypertension, diabetes, dyslipidemia etc that are
             treated and ongoing and patients are not receiving the exclusionary drugs noted above
             will be considered for inclusion on a case by case basis.