Varenicline and Smoking Cessation in Schizophrenia (VSCS)

This study has been completed.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier:
NCT01111149
First received: April 23, 2010
Last updated: February 5, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Schizophrenia
Smoking Cessation
Other: Sugar Pill
Drug: Varenicline
Drug: Bupropion HCl
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Varenicline and Smoking Cessation in Schizophrenia

Resource links provided by NLM:


Further study details as provided by University of Minnesota - Clinical and Translational Science Institute:

Primary Outcome Measures:
  • Smoking abstinence [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Measured by self-report of the subject and verified by exhaled carbon monoxide and blood/urine tests for nicotine and its break-down product cotinine.


Secondary Outcome Measures:
  • Reduction in smoking [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Successful outcome will be defined as a 50% or greater reduction in self-reported cigarettes per day and a 30% greater reduction in carbon monoxide and cotinine levels.

  • Positive and Negative Symptoms of Schizophrenia [ Time Frame: Each week for the 12 weeks of the study ] [ Designated as safety issue: Yes ]
    These will be measured with the Positive and Negative Syndrome Scale, a clinical evaluation of the presence/absence and severity of principal positive and negative symptoms of schizophrenia

  • Impulsivity and Inattention [ Time Frame: At the beginning of the study and at weeks 4, 8, and 12 ] [ Designated as safety issue: No ]
    Impulsivity and inattention will be measured using the continuous performance test.

  • Side effects [ Time Frame: Each week for the 12 weeks of the study ] [ Designated as safety issue: Yes ]
    Side effects will be monitored by a physician and/or assistant and recorded (SEP). All patients withdrawn from the study because of emerging side effects will be followed until the side effects are resolved

  • Abstinence-related symptoms [ Time Frame: Recorded at weeks 0, 4, 8, and 12 of the study ] [ Designated as safety issue: No ]
    These symptoms will be assessed using the Minnesota Nicotine Withdrawl Scale, evaluating symptoms such as irritability, tension/anxiety, craving for cigarettes, etc

  • Suicidality [ Time Frame: Measured each week of the 12 week study ] [ Designated as safety issue: Yes ]
    Patients are assessed at each visit with regards to depression and suicidiality using two other psychometric tests: the Brief Psychiatric Rating Scale (BPRS) and the Beck Depression Inventory (BDI). Specifically, item 4 of the BPRS and item 9 of the BDI ask about suicidal ideation. Additionally on weeks 0, 4, 8, and 12 the Columbia Suicide Severity Rating Scale (C-SSRS) will be employed.

  • Abnormal movements [ Time Frame: Each week of the 12 week study ] [ Designated as safety issue: Yes ]
    The Simpson-Angus Scale, will be used to evaluate patients experiencing neuroleptic-induced parkinsonism and other extrapyramidal side effects. Additionally, the Abnormal Involuntary Movement Scale will be used to assess abnormal involuntary movements associated with antipsychotic drugs, such as tardive dystonia and dyskinesia and akathisia, as well as 'spontaneous' motor disturbance related to the illness itself

  • Vital Signs [ Time Frame: Each week of the 12 week study ] [ Designated as safety issue: Yes ]
    blood pressure, pulse, and weight will be measured.


Enrollment: 60
Study Start Date: December 2009
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Sugar Pill
Sugar pill will be given to patients as a comparison group to the active varenicline group. In the fist week, one placebo pill will be given per patient, followed by 2 pills per day for the remaining 12 weeks of the study.
Other: Sugar Pill
Sugar pill created and masked by the pharmacy to be used as a control.
Experimental: Varenicline
Varenicline has not previously been examined for its efficacy and safety in subjects with schizophrenia. Subjects in the varenicline group will receive one 1mg pill/day for week 0, followed by two 1mg pills/day for the rest of the study. This is an experimental group to be compared against both placebo and bupropion HCl.
Drug: Varenicline
Subjects in the varenicline group will receive one 1mg pill/day for week 0, followed by two 1mg pills/day for the rest of the study.
Other Name: Chantix
Active Comparator: Bupropion HCl
Bupropion HCl is an established smoking cessation agent and will be used to compare its efficacy and safety against varenicline. Subjects in the Bupropion HCl group will receive one 150mg pill/day for week 0, followed by two 150mg pills/day for the rest of the study.
Drug: Bupropion HCl
in the Bupropion HCl group will receive one 150mg pill/day for week 0, followed by two 150mg pills/day for the rest of the study
Other Names:
  • Wellbutrin
  • Zyban

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

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female subjects, 18-75 years old
  • Diagnosis of schizophrenia or schizoaffective disorder based on 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 noncigarette 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 MAOI inhibitors
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01111149

Locations
United States, Minnesota
University of Minnesota, University of Minnesota Medical Center
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
University of Minnesota - Clinical and Translational Science Institute
Investigators
Principal Investigator: S. Hossein Fatemi, M.D., Ph.D. University of Minnesota - Clinical and Translational Science Institute
  More Information

Publications:
Responsible Party: University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier: NCT01111149     History of Changes
Other Study ID Numbers: 0904M64601, R01DA024674
Study First Received: April 23, 2010
Last Updated: February 5, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Minnesota - Clinical and Translational Science Institute:
Schizophrenia
Smoking cessation
Varenicline
Bupropion

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Smoking
Mental Disorders
Habits
Contraceptives, Oral
Bupropion
Varenicline
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Dopamine Uptake Inhibitors
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Uptake Inhibitors
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents

ClinicalTrials.gov processed this record on April 22, 2014