Ziprasidone for Improving Insulin Sensitivity in People With Schizophrenia Who Are at Risk for Diabetes

Study Overview
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Brief Summary
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This study will evaluate the effectiveness of ziprasidone treatment versus treatment with a standard atypical antipsychotic drug in improving insulin sensitivity and reducing excess abdominal fat storage in people with schizophrenia who are at risk for diabetes.

Detailed Description
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People with schizophrenia often lead more sedentary lifestyles than people without the disease, and they are frequently treated with antipsychotic medications that cause weight gain. Combined, these factors produce an increased risk for metabolic syndrome, which can lead to heart disease and type 2 diabetes. Characteristics of metabolic syndrome include carrying excess weight around the abdominal region; high blood pressure; high blood sugar levels; high levels of fat in the blood; and low levels of HDL cholesterol. Recent studies have shown that certain atypical antipsychotic drugs are relatively weight-neutral. Switching from a drug that promotes weight gain to a weight-neutral medication, such as ziprasidone, may result in significant weight loss. There is insufficient evidence, however, demonstrating the extent of improvement in insulin sensitivity after switching medications. This study will evaluate the effectiveness of ziprasidone treatment versus treatment with a standard atypical antipsychotic drug in improving insulin sensitivity and reducing excess abdominal fat storage in people with schizophrenia who are at risk for diabetes. Participants in this open label study will currently be undergoing treatment with risperidone or olanzapine at the time of study entry. Upon study entry, they will be randomly assigned to either switch to ziprasidone treatment or remain on their current medications. Both groups will be treated for 26 weeks. Participants will report to the study site for evaluations biweekly until week 10 and then monthly for the duration of the study. The primary outcomes at Week 26 will be: change from baseline in insulin sensitivity, using an intravenous glucose tolerance test; change from baseline in ivisceral fat mass, using a CT scan.

Official Title
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The Metabolic Syndrome in Patients With Schizophrenia

Conditions
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Schizophrenia, Metabolic Syndrome X, Insulin Resistance

Intervention / Treatment
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* Drug: Switch
* Drug: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of schizophrenia or schizoaffective disorder Currently receiving antipsychotic therapy with risperidone or olanzapine Overweight Exclusion Criteria: Diagnosis of diabetes Hospitalization for schizophrenia or schizoaffective disorder within 90 days prior to study entry Refractory schizophrenia or schizoaffective disorder Currently receiving therapy with clozapine No stable residence and phone number for 90 days prior to study entry Prior unsuccessful treatment with ziprasidone Intolerance to ziprasidone

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: Control<br>Participants on risperidone or olanzapine who will remain on risperidone or olanzapine and do not switch to ziprasidone | Drug: Control<br>* Participants will remain taking the same medications of risperidone or olanzapine as they were before study entry.<br>* Other names: olanzapine;|
| Experimental: Switch<br>Participants who enter on risperidone or olanzapine and switch to ziprasidone | Drug: Switch<br>* Participants who are switched to ziprasidone will take a max daily dose of 200 mg, flexibly dosed based on symptoms and adverse effects.<br>* Other names: ziprasidone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Insulin Sensitivity Index From Baseline to Week 26 ((1/mU/L) x 1/Min) | As measured by frequently sampled intravenous glucose tolerance testing (units: 1/mU/L) x 1/Min) | Measured at Baseline and Week 26 | 
| Change in Visceral Fat Mass From Baseline to Week 26 | CT measured change in visceral fat mass from baseline to week 26 (mm^3) | Baseline and Week 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ziprasidone, Olanzapine, Risperidone, Schizoaffective Disorder, Insulin Sensitivity, Visceral Adiposity, Metabolic Syndrome