Safety Study of Olanzapine and a Comparator in Patients With Schizophrenia and Schizoaffective Disorder

Study Overview
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Brief Summary
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This study will assess whether olanzapine and/or risperidone affect the way the human body uses sugar in the blood.

Official Title
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Insulin Sensitivity in Patients With Schizophrenia or Schizoaffective Disorder Treated With Olanzapine and Risperidone

Conditions
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Schizophrenia, Schizoaffective Disorder

Intervention / Treatment
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* Drug: olanzapine
* Drug: risperidone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-65 years old Diagnosed with Schizophrenia or Schizoaffective disorder Ability to visit the doctor's office for scheduled visits Exclusion Criteria: Women who are pregnant or breastfeeding Have a body mass index (BMI) greater than 40 Have diabetes, heart disease or any other unstable illness Have known positive human immunodeficiency virus (HIV) Are currently taking olanzapine, risperidone, clozapine, glucocorticoids, injectable antipsychotics

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Olanzapine<br> | Drug: olanzapine<br>* 5-20 mg, oral, capsules, daily, 12 weeks.<br>* Other names: Zyprexa;|
| Active Comparator: Risperidone<br> | Drug: risperidone<br>* 2-6 mg, oral, capsules, twice daily (BID), 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Baseline to Last Observation In Normalized Insulin Sensitivity Index at Low Insulin Phase Using Change in Weight as a Covariate | Normalized insulin sensitivity index (Mffm/I) was defined as the ratio of whole body glucose disposal rate normalized to fat-free mass (Mffm) divided by the plasma insulin concentration (I) during steady-state conditions of the clamp procedure. Units:[(mg glucose)*min*mL] / [(kg fat free body mass)*(micro IU insulin)] | baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pairwise Correlations Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Weight. | Normalized insulin sensitivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in Mffm/I and changes in weight | 12 weeks | 
| Pairwise Correlations Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Body Mass Index (BMI) | Normalized insulin sensitivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in Mffm/I and changes in BMI | 12 weeks | 
| Pairwise Correlations Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Ratio of Visceral Fat Area to the Subcutaneous Fat Area. | Normalized insulin sensitivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in ratio of visceral far area to subcutaneous fat area | 12 weeks | 
| Pairwise Correlations Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Brief Psychiatric Rating Scale Scores. | Normalized insulin senstivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in Mffm/I and changes in Brief Psychiatric Rating Scale scores | 12 weeks | 
| Pairwise Correlations Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Clinical Global Impression - Severity of Illness Scale Scores. | Normalized insulin sensitivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in Mffm/I and changes in Clinical Global Impression-Severity of Illness scale scores | 12 weeks | 
| Pairwise Correlations Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Abnormal Involuntary Movement Scale Scores. | Normalized insulin sensitivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in Mffm/I and changes in Abnormal Involuntary Movement Scale scores | 12 weeks | 
| Pairwise Correlation Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Barnes Akathisia Scale Scores. | Normalized insulin sensitivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in Mffm/I and changes in Barnes Akathisia scores | 12 weeks | 
| Pairwise Correlations Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in the Simpson Angus Scale Scores. | Normalized insulin sensitivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in the Simpson Angus Scale scores | 12 weeks | 
| Pairwise Correlations Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Waist Circumference. | Normalized insulin sensitivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in Mffm/I and changes in waist circumference | 12 weeks | 
| Pairwise Correlations Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Visceral Fat Area. | Normalized insulin sensitivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in Mffm/I and changes in visceral fat area | 12 weeks | 
| Pairwise Correlations Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Subcutaneous Fat Area. | Normalized insulin sensitivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in Mffm/I and changes in subcutaneous fat area | 12 weeks | 
| Pairwise Correlations Between Between Changes in Normalized Insulin Sensitivity Index at Low Insulin Phase and Changes in Eating Behavior Assessment Scale Scores. | Normalized insulin sensitivity index (Mffm/I) at low insulin phase-pairwise correlations between changes in Mffm/I and changes in Eating Behavior Assessment Scale scores | 12 weeks | 
| Change From Baseline to 12 Week Endpoint in Body Mass Index | Within-and Between-Treatment Group changes in Body Mass Index from baseline to last observation carried forward. | baseline and 12 weeks | 
| Change From Baseline to 12 Week Endpoint in Weight | Weight change from baseline to last visit (last observation carried forward) | baseline and 12 weeks | 
| Change From Baseline to 12 Week Endpoint in Waist Circumference | Waist circumference change from baseline to last observation carried forward. | baseline and 12 weeks | 
| Change From Baseline to 12 Week Endpoint in Visceral Fat Area | Visceral fat area change from baseline to last observation carried forward, all randomized patients, double-blind treatment period | baseline and 12 weeks | 
| Change From Baseline to 12 Week Endpoint in Subcutaneous Fat Area | Subcutaneous fat area change from baseline to last observation carried forward, all randomized patients, double-blind treatment period | baseline and 12 weeks | 
| Change From Baseline to 12 Week Endpoint in the Ratio of the Visceral Fat Area to the Subcutaneous Fat Area | Ratio of the visceral fat area to the subcutaneous fat area change from baseline to last observation carried forward, all randomized patients, double-blind treatment period | baseline and 12 weeks | 
| Change From Baseline to 12 Week Endpoint in Brief Psychiatric Rating Scale (BPRS) Scores | Brief Psychiatric Rating Scale (BPRS) is an 18-item clinician-administered scale used to assess the degree of severity of a subject's general psychopathological symptoms. Item scores range from 0 (not present) to 6 (extremely severe). Total Scores range from 0 to 108; Positive Subscale Scores range from 0 to 24. Negative Subscale Scores range from 0 to 18. Anxiety-Depression Subscale Scores range from 0 to 24. | baseline and 12 weeks | 
| Change From Baseline to 12 Week Endpoint in Clinical Global Impression - Severity of Illness Scores | Measures severity of illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients. | baseline and 12 weeks | 
| Change From Baseline to 12 Week Endpoint in Abnormal Involuntary Movement Scale Scores | A 12-item instrument assesses observed abnormal movements in different parts of body. Seven items are scored in a 5-point scale (0 = none/normal, 4 = severe) which evaluates abnormal movements in 3 main anatomic areas (orofacial area, extremities, and trunk). Total scores range from 0 to 28. Five collected elements are not used in this total. | baseline and 12 weeks | 
| Change From Baseline to 12 Week Endpoint in Barnes Akathisia Rating Scale (BARS) Scores | The BARS is a 4-item instrument that evaluates akathisia associated with use of antipsychotic medications. Item 4 is the Global clinical assessment and is rated 0 to 5 (0 = absent, 5 = severe). The other 3 items (related to objective and subjective assessments) are not used for these analyses. | baseline and 12 weeks | 
| Change From Baseline to 12 Week Endpoint in Simpson Angus Scale Scores | Measures neuroleptic-induced parkinsonism. Total score of Simpson Angus Scale consists of the sum of 10 items rated on a 5-point severity scale where 0=normal and 4=extreme. The total score ranges from 0 to 40. | baseline and 12 weeks | 
| Change From Baseline to 12 Week Endpoint in Eating Behavior Assessment Scale Scores | Eating Behavior Assessment Scale is a 9-item self-rated tool used to evaluate appetite and eating behaviors. Item scores range from 0 (never) to 4 (always). | baseline and 12 weeks | 
| Change From Baseline to 12 Week Endpoint in Fasting Lipid Parameters Including Total Cholesterol | Fasting lipid parameters including total cholesterol, change from baseline to last observation carried forward. | baseline and 12 weeks | 
| Change From Baseline to 12 Week Endpoint in Fasting Lipid Parameters Including Direct Low Density Lipoprotein (LDL) | Fasting lipid parameters including Direct LDL, change from baseline to last observation carried forward. | baseline and 12 weeks | 
| Change From Baseline to 12 Week Endpoint in Fasting Lipid Parameters Including High Density Lipoprotein (HDL) | Fasting lipid parameters including HDL change from baseline to last observation carried forward. | baseline and 12 weeks | 
| Change From Baseline to 12 Week Endpoint in Fasting Lipid Parameters Including Triglycerides | Changes in fasting lipid parameters including triglycerides last observation carried forward (LOCF) mean change from baseline | baseline and 12 weeks | 
| Change From Baseline to 12 Week Endpoint in Fasting Lipid Parameters Including Lipoprotein Subclasses | Changes in lipid parameters and subclass lipoproteins last observation carried forward (LOCF) mean change from baseline. HDL=High Density Lipoprotein, IDL=Intermdiate Density Lipoprotein, LDL=Low Density Lipoprotein, VLDL=Very Low Density Lipoprotein. | baseline and 12 weeks. |