Zyprexa and Task Engagement in Schizophrenia

Efficacy of Olanzapine in Improving Task Engagement in Schizophrenia

Individuals with schizophrenia frequently have impairments in attention. These impairments have been shown to be related to overall functioning. Some research suggests that Olanzapine may be associated with improvement in various aspects of attention. The primary purpose of this study is to determine whether switching from a typical antipsychotic to Olanzapine improves task engagement. Individuals who taking typical antipsychotics will be randomly assigned to either 1) remain on their typical antipsychotic medications, or 2) be switched from their typical antipsychotic medications to Olanzapine. All participants will be enrolled in a twice-weekly 20 session cognitive training program that is specifically designed to target attention deficits and promote active engagement. Improvements in attention will be compared between individuals who remained on their typical antipsychotic medications and those that were switched to Olanzapine.

Study Overview

• Status: Withdrawn
• Conditions: Schizophrenia; Schizoaffective Disorder
• Intervention / Treatment: Drug: Olanzapine (Zyprexa); Drug: Typicals

Detailed Description

Objectives: Olanzapine (OLZ) has emerged as one of the promising pharmacologic interventions that not only improves psychotic symptoms but may also target ability to sustain attention on cognitive tests. Pupillary response, as measured by degree of pupil constriction, and visual scanning patterns are unique methods of quantifying attention by gauging the level of psychophysiologic engagement on a visual task. It is reasonable to expect that if a treatment for attention problems is effective, then this will be reflected in more efficient allocation of psychophysiologic attentional resources as measured by pupillometry. Primary purpose of this pilot study is to demonstrate efficacy of switching to OLZ for improving task engagement in schizophrenia. Secondary objectives are to demonstrate improved attention in response to OLZ translates to improved attentional allocation strategies and vocational readiness, and demonstrate efficacy of OLZ as agent that enhances ability to benefit from cognitive training. The proposed study will examine functional implications of improved attention in patients taking OLZ, and it will test the hypothesis that mechanism of this functional improvement is through process of engagement as measured by pupillometry and functional behavioral measures.

Research Design and Methodology: This is an industry-sponsored, investigator initiated trial with 18 patients in an open-label design over 24-month period. Participants will be adult outpatients (ages 18 to 55) with a diagnosis of schizophrenia or schizoaffective disorder who are on any regimen of "typical" antipsychotics. They will be randomly assigned to one of two conditions: 1) Olanzapine Group (OLZ-G). Subjects assigned to the OLZ condition will be switched to OLZ from their previous medication so OLZ is the only antipsychotic medication part of their regimen. Following switch to OLZ, subjects will be enrolled in a twice weekly, 20-session cognitive training program that is specifically designed to target attention deficits and promote active engagement. 2) "Typicals" Group (TYP-G). Subjects assigned to the "typicals" condition will continue with their medication regimen throughout the course of the study as they are enrolled in the same cognitive training program. Research questions are: Compared to participants on any combination of "typical" medications, we hypothesize that persons with schizophrenia on OLZ will (a) show significantly improved performance on psychophysiologic measure of task engagement, (b) show greater engagement in cognitive training, and (c) show greater improvement in attention on vocational task. Primary efficacy measure will be an ASL H6 Series head-mounted optics pupillometer to measure task engagement as function of pupil dilation and visual scanning patterns. Secondary efficacy measures will include computer software specifically developed to assess on-task behavior on computer exercises, brief neuropsychological test battery, global behavior and symptom inventories, and functional assessment of treatment motivation.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of schizophrenia or schizoaffective disorder
• Current medication regimen that includes any combination of first generation neuroleptics, for at least 30 days
• Referring psychiatrist agrees to transfer primary psychiatric care and medication prescription to the study doctor, for the duration of patient's participation in the study

Exclusion Criteria:

• Significant auditory/visual impairment that would interfere with study procedures
• Lack of aptitude in English that may interfere with the administration of the tests
• Current use of psychoactive substances that may affect attention (e.g. Amoxetine, Methylphenidate)
• Deviations from the prescription regimen not approved by study doctor
• Changes in the regimen of antipsychotics not included in the study's protocol
• Chart diagnosis of any other medical or neuropsychiatric illnesses known to impair brain function (e.g. mental retardation, traumatic brain injury, seizure disorder).
• Pregnant or breast-feeding females.
• Use of alcohol or drugs 4 weeks prior to beginning of study.
• For participants with history of substance dependence (excluding nicotine and caffeine) use of illicit substances (e.g. marijuana or crack) during study participation.
• Use of a depot antipsychotic within 4 weeks prior to baseline
• History or evidence of a medical or neurological condition that would expose the subject to an undue risk of a significant adverse event or interfere with study assessments
• Clinically significant abnormal laboratory test results at screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OLZ	Drug: Olanzapine (Zyprexa); OLZ
Active Comparator: Typicals	Drug: Typicals; Stay on typicals regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pupillometry	Baseline, post

Collaborators and Investigators

• Sponsor: VA Connecticut Healthcare System
• Collaborators: Eli Lilly and Company; Clinical Trials Network of Columbia U, Cornell U, and NY Presbyterian Hospital
• Investigators: Principal Investigator: Jimmy Choi, Psy.D., Columbia University

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: February 25, 2007
• First Submitted That Met QC Criteria: February 26, 2007
• First Posted (Estimate): February 27, 2007

Study Record Updates

• Last Update Posted (Estimate): December 23, 2013
• Last Update Submitted That Met QC Criteria: December 19, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: cognition; schizophrenia; antipsychotics; cognitive rehabilitation; attention; task engagement
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Psychotic Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Olanzapine
• Other Study ID Numbers: JC0002; F1D-US-X282