Comparative Effects of Chronic Treatment With Olanzapine and Risperidone on Glucose and Lipid Metabolism

Study Overview
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Brief Summary
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The primary objective of the study is to assess whether chronic treatment with olanzapine over a five-month period produces a significant increase in abnormalities in glucose levels. The main secondary objective is to evaluate whether the increase in glucose levels and rate of glucose abnormalities differs between Olanzapine and Risperidone during this treatment period. Additional secondary objectives of the study are to investigate similar questions with respect to glycohemoglobin, triglycerides and other measures of glucose and lipid metabolism. We hypothesize that Olanzapine will not be inferior to Risperidone in extent of increase in the primary outcome measure of serum glucose, and secondary measures of glycohemoglobin, insulin and lipids.

Detailed Description
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In the on-going study in progress we use an extensive battery of assessments to investigate a)fasting levels of glucose and lipids at baseline and monthly during 5 months of treatment, b) glucose tolerance tests to investigate glucose and insulin abnormalities after a glucose load at baseline and during study treatment, and c)the effects of treatment with olanzapine and risperidone of post prandial glucose metabolism after a fatty meal (as detailed in the body of the proposal). Recent studies have shown that increased postprandial lipidemia is an important feature of many patients with type 2 diabetes and atherosclerosis. In addition to the biochemical measures, we will also assess clinical effects (PANSS and CGI ratings) and other side-effects (weight gain, appetite, somnolence, and EPS and TD). The specific plan calls for inpatients in a tertiary care hospital to be randomly assigned to olanzapine or risperidone, using a stratified random assignment procedure, and treated for five months with either olanzapine or risperidone. We estimate that we will have to enroll a sample of approximately 50-55 patients to obtain 46 acceptable complete cases(as specified in proposal below). On the basis of preliminary results from our prior and ongoing studies we predict no significant increase in glucose abnormalities from baseline during chronic treatment with olanzapine and no significant differences in development of glucose abnormalities in patients in patient treated with olanzapine and risperidone. Additional measures being investigated include: comparison of olanzapine and risperidone in glucose and lipid responses to a fatty meal, ghrelin changes in response to a fatty mean, and CRP and IL-6, and thyroid and prolactin response to five months of treatment with the two drugs.

Official Title
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Independent Investigator Grant Study-Comparative Effects of Chronic Treatment With Olanzapine and Risperidone on Glucose and Lipid Metabolism

Conditions
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Schizophrenia, Diabetes, Metabolic Syndrome, Hyperglycemia

Intervention / Treatment
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* Drug: Olanzapine
* Drug: olanzapine
* Drug: risperidone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis Schizophrenia or schizoaffective psychosis 18-65 years of age Exclusion Criteria: Currently being treated with oral antidiabetics or insulin

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>olanzapine | Drug: Olanzapine<br>* olanzapine 5-40 mg/day<br>* Other names: ayprexa;Drug: olanzapine<br>* olanzapine 5-40 ,mg/day<br>* Other names: zyprexa;|
| Active Comparator: 2<br>risperidone | Drug: risperidone<br>* risperidone 1-12 mg/day<br>* Other names: riperidal;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum glucose |  | during 5 months of treatment compared to baseline | 
| Hb1AC |  | during 5 months of treatment compared to baseline | 
| triglycerides |  | during 5 months of treatment compared to baseline | 
| cholesterol |  | during 5 months of treatment compared to baseline | 
| insulin |  | during 5 months of treatment compared to baseline | 
| c-peptide |  | during 5 months of treatment compared to baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ghrelin |  | during 5 months of treatment compared to baseline | 
| CRP |  | during 5 months of treatment compared to baseline | 
| Thyroid hormones |  | during 5 months of treatment compared to baseline | 
| prolactin |  | during 5 months of treatment compared to baseline | 
| Il-6 |  | during 5 months treatment compared to baseline | 
| PANSS scores |  | during 5 months of treatment compared to baseline | 
| CGI score |  | during 5 months of treatment compared to baseline | 
| EPS scores |  | during 5 months of treatment compared to baseline | 
| TD Scores |  | during 5 months of treatment compared to baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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schizophrenia, diabetes, metabolic syndrome, hyperglycemia, glucose, insulin, lipids, IL-6, prolactin