Varenicline Treatment in Alcohol and Nicotine Dependent Patients With Schizophrenia
Condition: Schizophrenia; Schizoaffective Disorder; Alcohol Dependence; Nicotine Dependence
MeSH terms: Alcoholism; Tobacco Use Disorder; Schizophrenia; Psychotic Disorders
Study type: Interventional
Phase: Phase 4

Summary: 
      The aim of the proposed pilot study is to find out whether varenicline (ChantixTM) treatment
      decreases alcohol use and smoking in patients with schizophrenia or schizoaffective disorder.
      Varenicline may also improve cognition (memory and concentration) and negative symptoms (e.g.
      poor attention, poverty of speech, apathy, affective flattening, anhedonia) in patients with
      schizophrenia and comorbid nicotine and alcohol dependence.
    

Detailed description: 
      Alcohol use (more than 33%) and smoking (80-90%) commonly occur together in patients with
      schizophrenia. Varenicline (ChantixTM) has been approved by the FDA as a medication for
      smoking cessation. Recent animal studies have shown that chronic varenicline administration
      decreased alcohol consumption. There are no human data available on the effectiveness of
      varenicline in alcohol-use disorders.

      The aim of the proposed pilot study is to find out whether varenicline treatment decreases
      alcohol use and smoking in patients with schizophrenia or schizoaffective disorder.
      Varenicline may also improve cognition (memory and concentration) and negative symptoms (e.g.
      poor attention, poverty of speech, apathy, affective flattening, anhedonia) in patients with
      schizophrenia and comorbid nicotine and alcohol dependence.

      The proposed pilot study will enroll a cohort of up to 30 subjects with schizophrenia or
      schizoaffective disorder and nicotine and alcohol dependence, who are receiving ongoing
      outpatient mental health treatment from community providers. Subjects will be randomly
      assigned to one of the two treatment groups (varenicline vs. placebo). Following a one week
      screening phase, participants will be seen on day 4, day 8, then weekly over an 8-week
      treatment period. One week supply of medication will be dispensed at each study visit, with
      the exception of the first week, when only 4 days supply will be given on 2 days (visit 1 and
      2). One month after discontinuation of medication, a follow-up interview will be conducted.

      Varenicline and placebo will be dispensed in 0.5 mg and 1 mg color coded capsules. During the
      first 3 days of treatment, participants will take one 0.5 mg tablet of varenicline (or
      placebo) by mouth daily. If the medication is well-tolerated, the dose will be increased to
      0.5 mg by mouth twice daily for 4 days. From day 8, the dose will be increased to the
      standard dosing schedule of 1 mg (1 tablet) by mouth twice daily. At the end of the 8th week,
      varenicline will be discontinued.

      A structured clinical psychiatric interview and physical exam will be performed at baseline,
      along with a urine drug screen, which will be repeated on week 8, and at 1 month follow-up.
      Blood tests (complete blood count, basic metabolic panel, liver function tests) will be
      performed at baseline, then monthly.

      During weekly study visits patients will undergo breath carbon-monoxide and breath alcohol
      testing, and they will answer questions about depression, smoking and alcohol use. Detailed
      assessment of psychiatric symptom severity (including neuropsychological testing) will be
      performed at baseline, at the end of the treatment phase (week 8). A functional MRI study
      will be performed at baseline and at the end of study to assess changes in blood flow,
      emotional processing and working memory related to varenicline treatment. In addition,
      genetic polymorphism of the α4β2 nicotinic acetylcholine receptor and gene expression changes
      related to drinking/smoking/psychosis and varenicline treatment will also be assessed.

      The primary objectives of the proposed study are two fold: first to determine the feasibility
      of conducting a similar study on a larger scale, and second to establish pilot data for
      determining the effect size for hypothesized treatment effects on alcohol and nicotine use
      based on objective tests and self report. These estimates will help inform the minimum sample
      size needed for a larger future trial.
    

Intervention name(s): Varenicline; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Varenicline will be dispensed in 0.5 mg and 1 mg tablets taken orally. During the first 3 days of medication, participants will take one 0.5 mg tablet of varenicline daily. If the medication is well-tolerated, the dose will be increased to 0.5 mg po twice daily for 4 days. On day 8, the dose will be increased again to the standard dosing schedule of 1 mg (1 tablet) po twice daily. At the end of the 8th week, varenicline will be discontinued.; Placebo will be dispensed in color-coded capsules. Blue capsules will contain 0.5 mg glucose (placebo), red capsules will contain 1 mg glucose (placebo).
Other intervention name(s): Chantix
Intervention MeSH terms: Varenicline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Varenicline; Smoking cessation; Schizophrenia; Schizoaffective disorder; Alcohol dependence; Nicotine dependence