Zyprexa and Task Engagement in Schizophrenia

Sponsor

VA Connecticut Healthcare System (U.S. Fed)

Overall Status

Withdrawn

CT.gov ID

NCT00440843

Collaborator

Clinical Trials Network of Columbia U, Cornell U, and NY Presbyterian Hospital (Other), Eli Lilly and Company (Industry)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia Schizoaffective Disorder	Drug: Olanzapine (Zyprexa) Drug: Typicals	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Investigator)

Primary Purpose:

Treatment

Official Title:

Efficacy of Olanzapine in Improving Task Engagement in Schizophrenia

Study Start Date :

Feb 1, 2007

Actual Primary Completion Date :

Jun 1, 2012

Actual Study Completion Date :

Jun 1, 2012

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: OLZ

Drug: Olanzapine (Zyprexa)

OLZ

Active Comparator: Typicals

Drug: Typicals

Stay on typicals regimen

Outcome Measures

Primary Outcome Measures

Pupillometry [Baseline, post]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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