Varenicline Treatment in Alcohol and Nicotine Dependent Patients With Schizophrenia
|ClinicalTrials.gov Identifier: NCT00727103|
Recruitment Status : Terminated (Slow recruitment, high drop-out rate in both arms)
First Posted : August 1, 2008
Last Update Posted : June 3, 2011
|Condition or disease||Intervention/treatment||Phase|
|Schizophrenia Schizoaffective Disorder Alcohol Dependence Nicotine Dependence||Drug: Varenicline Drug: Placebo||Phase 4|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||10 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Official Title:||Varenicline Treatment in Alcohol and Nicotine Dependent Patients With Schizophrenia - a Double Blind, Placebo Controlled Trial|
|Study Start Date :||July 2008|
|Actual Primary Completion Date :||May 2011|
|Actual Study Completion Date :||May 2011|
Active Comparator: 1 Varenicline
Varenicline will be dispensed in 0.5 mg (blue capsules containing a 0.5 mg varenicline tablet) and 1 mg (red capsules containing a 1 mg varenicline tablet) capsules taken orally. During the first 3 days of medication, participants will take one blue capsule (0.5 mg tablet) of varenicline daily. If the medication is well-tolerated, the dose will be increased to one blue capsule (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 red capsule (1 mg) po twice daily. At the end of the 8th week, varenicline will be discontinued.
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.
Other Name: Chantix
Placebo Comparator: 2 Placebo
Placebo will be dispensed in blue and red color coded capsules. During the first 3 days, participants will take one blue capsule po daily. If the medication is well-tolerated, the dose will be increased to one blue capsule po twice daily for 4 days. On day 8, the patients will take 1 red capsule po twice daily. At the end of the 8th week, placebo 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).
- The primary outcome measure for alcohol use will be the number of drinks/week at the end of the treatment phase, relative to baseline and during-treatment data. [ Time Frame: 8 weeks ]
- The outcome measure for smoking cessation effectiveness will be the amount of carbon monoxide in expired air at the end of the treatment phase, relative to data collected at baseline and during treatment. [ Time Frame: 8 weeks ]
- The safety of Varenicline use will be determined by examination of adverse events observed during the course of this investigation, with particular emphasis on comparing the frequency of adverse events in Placebo versus Treatment groups. [ Time Frame: 8 weeks ]
- Improvement in cognition will be assessed using the standardized California Verbal Learning Test (CVLT). [ Time Frame: 8 weeks ]
- Improvement in negative symptoms will be assessed using the PANSS negative score. [ Time Frame: 8 weeks ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00727103
|United States, New York|
|SUNY Upstate Medical University|
|Syracuse, New York, United States, 13210|
|Principal Investigator:||Zsuzsa Szombathyne Meszaros, MD, PhD||SUNY Upstate Medical University, Department of Psychiatry|
|Study Director:||Steven L Batki, MD||University of California, San Francisco|