Efficacy and Tolerability of Switching to Ziprasidone From Other Antipsychotics

Study Overview
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Brief Summary
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Because ziprasidone has not been extensively studied and is not widely accepted in the severely mentally ill in State hospitals this study aims to demonstrate its effectiveness and relative lack of side effects. 75 patients with schizophrenia or schizoaffective disorder who need a change of medication because of ineffectiveness or side effects will be changed to ziprasidone and followed with detailed assessments for eight weeks. The hypothesis is that they will improve and have fewer side effects.

Detailed Description
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Ziprasidone has been found in studies and practice to be efficacious and tolerated well but has not been well studied or well accepted in the very severely ill in State Hospitals. This study aims to fill that gap by examining 75 patients with schizophrenia or schizoaffective disorder who require a change of medication because of poor response or unacceptable side effects. After signing consent and having a baseline assessment they will, if necessary, be reduced to one antipsychotic then started on ziprasidone, increasing to 160mg the second day. The one antipsychotic they had been on will be reduced over a week and stopped. The ziprasidone can be increased to 240mg after three weeks if necessary. The study will last eight weeks with efficacy assessed by Clinical Global Impressions (CGI), Positive and Negative Syndrome Scale (PANSS) every two weeks and Brief Assessment of Cognition, Calgary Depression Scale for Schizophrenia, Personal Evaluation of Transitions in Treatment and Medical Outcomes Study Cognitive Questions at the beginning and end. Side effects will be measured by movement disorder scales (Simpson-Angus scale for Parkinsonism (SANRS), Abnormal Involuntary Movement Scale (AIMS) and Barnes Akathisia Scale (BAS)), ECG and weight and blood metabolic measures. The hypothesis is that ziprasidone will be generally effective and that side effects especially metabolic indices will be reduced.

Official Title
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Evaluation of Efficacy and Tolerability of Switching to Ziprasidone From Other Antipsychotic Medications

Conditions
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Schizophrenia, Schizoaffective Disorder

Intervention / Treatment
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* Drug: ziprasidone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Schizophrenia or schizoaffective Capacity to give consent Stable, on the same medication for a month but only partial response or with unacceptable side effects 18-65 years of age Exclusion Criteria: Repeated non-compliance Current depot medication Active medical conditions QTc >500msec Previous non-response Previous treatment with 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>Open label change to ziprasidone | Drug: ziprasidone<br>* Ziprasidone by mouth 40mg twice a day (bid) for one day, then 80mg bid; may be increased to 120mg bid after three weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive and Negative Syndrome Scale (PANSS) Measuring Symptoms of Schizophrenia | Minimum score 32 (best) maximum 210 (worst) | Baseline to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impression (CGI) Scores the Evaluator's Overall Impression of Severity (CGI-S) or Change (CGI-I) in Illness. | CGI-S scores from 1 = normal to 7 = most extremely ill | 8 weeks | 
| Weight |  | 8 weeks | 
| Fasting Glucose | Amount of glucose in the blood in mg/dl | 8 weeks | 
| Cholesterol |  | 8 weeks | 
| Abnormal Involuntary Movement Scale (AIMS) Measures Tardive Dyskinesia | Scores 0 (none) to 4 (severe) choreo-athetoid and dystonic movements of seven parts of the body with a maximum score 28 | 8 weeks | 
| Simpson-Angus Scale Measures Drug Induced Parkinsonism | Measures 10 signs, (not all of which are now considered Parkinsonism), minimum score 0 (no Parkinsonism) maximum 40. | 8 weeks | 
| Corrected QT Interval (QTc) | Time interval between Q and T waves on EKG corrected for pulse rate. Over 500 msec may be dangerous | 8 weeks | 
| Brief Assessment of Cognition in Schizophrenia (BACS) | Scores on the BACS scale, which measures cognition, were changed to Z-scores based on normal controls from Keefe (2008) A Z-score of zero would indicate cognition the same as the normal controls. Negative scores indicate cognition worse than the normal. Theoretically there are no maximum or minimum scores. | 8 weeks | 
| Calgary Depression Scale for Schizophrenia | Score on scale, from 0 to 27, above 6 considered indicative of depression, higher scores mean worse outcome, | 8 weeks | 
| Personal Evaluation of Transitions in Treatment Scale (PETiTP | PETiT is a 30 item self administered scale measuring response to and tolerability and adherence to antipsychotic medication in people with schizophrenia. The range is 30 to 100. Higher scores are better. Although different features are assessed there is a single total score - no subscales. | 8 weeks | 
| Medical Outcomes Study Cognitive Functioning Scale (MOS-COG) | MOS-COG measures day to day problems in six aspects of cognitive functioning. The scores are converted to 0-100 and so can range from 0 to 100 with 100 being the best. Population means are 70 to 80. | 8 weeks | 
| Barnes Akathisia Scale | Barnes Akathisia Scale measures akathisia: a score of zero is none (good) maximum score is 12 | 8 weeks | 
| HbA1c | Lab measure of glycated hemoglobin indicative of blood glucose over the last three months. At that time in the US measured as a percentage (of glucose attached to hemoglobin). No maximum or minimum but over 6.5% is generally considered indicative of diabetes. | 8 weeks | 
| Insulin Level | Measure of the amount of insulin in the blood, in uIU/ml. No minimum or maximum but fasting levels are usually below 25 uIU/ml. After a dose of glucose they may be 30 to 230 uIU/ml. | 8 weeks | 
| Antipsychotic Medication Costs | No data were collected because it turned out we had no way of measuring the costs. No subjects were analysed by costs | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Ziprasidone