Clinical trial NCT01111149: Varenicline and Smoking Cessation in Schizophrenia
Official title: Varenicline and Smoking Cessation in Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Schizophrenia
Smoking Cessation
Keywords: Schizophrenia
Smoking cessation
Varenicline
Bupropion
Lead sponsor: University of Minnesota
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute on Drug Abuse (NIDA)
First posted: 2010-04-27
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: There is a strong association between smoking and schizophrenia with prevalence rates ranging from 74% to 90%, versus a national average of 30% in nonschizophrenic individuals. A number of hypotheses have been proposed to explain the relationship between high smoking rates and schizophrenia, mostly relating to self-medication primarily for the negative symptoms of schizophrenia. Smoking cessation rates among schizophrenic patients are considerably lower than for other psychiatric disorders. The negative health effects of smoking increase the morbidity and mortality in schizophrenic patients. Currently, the efficacy of bupropion HCl in the treatment of smoking by schizophrenic subjects is inconclusive, and there have not been any published studies of the efficacy of varenicline in schizophrenic subjects. As varenicline appears to be a promising treatment in non-psychiatric patients, it would be useful to expand these studies to examine its effects in schizophrenic patients. Identifying effective and safe means of smoking cessation for this vulnerable population has the potential to reduce morbidity and mortality among individuals with schizophrenia.

Detailed description: There is a strong association between smoking and schizophrenia with prevalence rates ranging from 74% to 90%, versus a national average of 30% in nonschizophrenic individuals. A number of hypotheses have been proposed to explain the relationship between high smoking rates and schizophrenia, mostly relating to self-medication primarily for the negative symptoms of schizophrenia. Smoking cessation rates among schizophrenic patients are considerably lower than for other psychiatric disorders. The negative health effects of smoking increase the morbidity and mortality in schizophrenic patients. The smoking cessation agent bupropion HCl has been tested in schizophrenics, but the results on its efficacy are inconclusive. Recent works by different laboratories have shown the safety and efficacy of varenicline, a partial alpha4beta2 and full alpha7 nicotinic acetylcholine receptor agonist, as a smoking cessation agent. However, to date, no published studies have tested the safety and efficacy of varenicline in treatment of nicotine dependence in schizophrenic patients. As varenicline appears to be a promising treatment in non-psychiatric patients, it would be beneficial to examine its effects in schizophrenic patients. The central hypothesis of this application is that treatment with varenicline will safely increase smoking abstinence rates in schizophrenic patients when compared to those receiving placebo. This central hypothesis will be tested and the objectives of this application accomplished by pursuing two Specific Aims: 1) Treatment with varenicline or bupropion HCl for a period of three months will increase smoking abstinence rates in schizophrenic patents when compared to placebo; and 2) Treatment with varenicline or bupropion HCl for a period of three months will not increase psychosis in schizophrenic patients when compared to placebo. For our General Investigational Plan, we will employ a double-blind randomized placebo controlled study to assess varenicline's safety and efficacy. It is our expectation that we will demonstrate that varenicline is safe and effective in decreasing smoking rates in schizophrenic patients without exacerbating psychotic symptoms. Such outcomes will be significant, because they will offer a new treatment for smoking cessation in this vulnerable population.

Eligibility criteria: Inclusion Criteria:

* Male or female subjects, 18-75 years old
* Diagnosis of schizophrenia or schizoaffective disorder based on Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria
* Smoking at least 10 cigarettes per day
* Weight of at least 100 lbs (45.4 kg)
* Motivation to quit smoking
* Stabilized psychotic symptoms
* Provision of informed consent for testing and treatment

Exclusion Criteria:

* Serious cardiac, renal, hypertensive, pulmonary, endocrine, or neurologic disorder
* Seizure disorder, recent withdrawal from alcohol or anxiolytics
* History of bulimia nervosa, anorexia nervosa, or dementia
* History of depression, panic, or bipolar disorders
* Pregnancy or lactation
* Prior use of varenicline or bupropion HCl within three months prior to initiation of the study
* Current use of other smoking cessation treatments
* Regular use of non-cigarette tobacco products (\> than once/week)
* Past substance abuse (alcohol or non-nicotine containing drugs) in the preceding 6 months
* Patients with suicidal ideations or plans
* Florid psychosis or increasing psychosis following varenicline or bupropion HCl treatment
* History of, or current, alcohol dependence/abuse
* Current use of monoamine oxidase inhibitors (MAOI)

Primary outcomes:
measure: Smoking Abstinence - Serum/Urine Measurements
timeFrame: Week 12
measure: Smoking Abstinence - Number of Cigarettes Smoked
timeFrame: Week 12
measure: Smoking Abstinence - Exhaled Carbon Monoxide
timeFrame: Week 12
Secondary outcomes:
measure: Reduction in Smoking
timeFrame: Week 12
measure: Negative Symptoms of Schizophrenia - SANS
timeFrame: Week 12
measure: Impulsivity and Inattention
timeFrame: Week 12
measure: Side Effects
timeFrame: Week 12
measure: Abstinence-related Symptoms - MNWS and FTND
timeFrame: Week 12
measure: Depression
timeFrame: Week 12
measure: Abnormal Movements - BAS and SAS
timeFrame: Week 12
measure: Vital Signs
timeFrame: Week 12
measure: Vital Signs - Weight
timeFrame: Week 12
measure: Vital Signs - Pulse
timeFrame: Week 12
measure: Suicidality
timeFrame: Week 12
measure: Positive Symptoms of Schizophrenia (SAPS)
timeFrame: Week 12
measure: General Psychopathology
timeFrame: Week 12
measure: Hit Reaction Time - CPT
timeFrame: Week 12
measure: Variability of Standard Error - CPT
timeFrame: Week 12
measure: Detectibility (d') of Continuous Performance Test
timeFrame: Week 12
measure: Response Style Indicator (Beta) for CPT
timeFrame: Week 12
measure: Abstinence Related Symptoms - WISDM
timeFrame: Week 12
measure: Urge to Smoke - MNWS
timeFrame: Week 12
measure: Abnormal Movements - AIMS
timeFrame: Week 12
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota, University of Minnesota Medical Center
state: Minnesota
Study officials:
affiliation: University of Minnesota
name: S. Hossein Fatemi, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yousefi MK, Folsom TD, Fatemi SH. A Review of Varenicline's Efficacy and Tolerability in Smoking Cessation Studies in Subjects with Schizophrenia. J Addict Res Ther. 2011 Dec 20;S4(1):3045. doi: 10.4172/2155-6105.S4-001.
citation: Fatemi SH. Varenicline efficacy and tolerability in a subject with schizophrenia. Schizophr Res. 2008 Aug;103(1-3):328-9. doi: 10.1016/j.schres.2008.05.002. Epub 2008 Jun 24. No abstract available.
citation: Fatemi SH, Yousefi MK, Kneeland RE, Liesch SB, Folsom TD, Thuras PD. Antismoking and potential antipsychotic effects of varenicline in subjects with schizophrenia or schizoaffective disorder: a double-blind placebo and bupropion-controlled study. Schizophr Res. 2013 May;146(1-3):376-8. doi: 10.1016/j.schres.2013.02.015. Epub 2013 Mar 16. No abstract available.