Schizoaffective Disorder, Schizophrenia
Conditions
Keywords
Schizophrenia, Ziprasidone
Brief summary
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
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.
Interventions
DRUGziprasidone
Ziprasidone by mouth 40mg twice a day (bid) for one day, then 80mg bid; may be increased to 120mg bid after three weeks
Sponsors
Pfizer
Buffalo Psychiatric Center
Rochester Psychiatric Center
Bronx Psychiatric Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Positive and Negative Syndrome Scale (PANSS) Measuring Symptoms of Schizophrenia | Baseline to 8 weeks | Minimum score 32 (best) maximum 210 (worst) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Weight | 8 weeks | — |
| Fasting Glucose | 8 weeks | Amount of glucose in the blood in mg/dl |
| Cholesterol | 8 weeks | — |
| Abnormal Involuntary Movement Scale (AIMS) Measures Tardive Dyskinesia | 8 weeks | Scores 0 (none) to 4 (severe) choreo-athetoid and dystonic movements of seven parts of the body with a maximum score 28 |
| Simpson-Angus Scale Measures Drug Induced Parkinsonism | 8 weeks | Measures 10 signs, (not all of which are now considered Parkinsonism), minimum score 0 (no Parkinsonism) maximum 40. |
| Corrected QT Interval (QTc) | 8 weeks | Time interval between Q and T waves on EKG corrected for pulse rate. Over 500 msec may be dangerous |
| Brief Assessment of Cognition in Schizophrenia (BACS) | 8 weeks | 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. |
| Clinical Global Impression (CGI) Scores the Evaluator's Overall Impression of Severity (CGI-S) or Change (CGI-I) in Illness. | 8 weeks | CGI-S scores from 1 = normal to 7 = most extremely ill |
| Personal Evaluation of Transitions in Treatment Scale (PETiTP | 8 weeks | 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. |
| Medical Outcomes Study Cognitive Functioning Scale (MOS-COG) | 8 weeks | 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. |
| Barnes Akathisia Scale | 8 weeks | Barnes Akathisia Scale measures akathisia: a score of zero is none (good) maximum score is 12 |
| HbA1c | 8 weeks | 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. |
| Insulin Level | 8 weeks | 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. |
| Antipsychotic Medication Costs | 8 weeks | No data were collected because it turned out we had no way of measuring the costs. No subjects were analysed by costs |
| Calgary Depression Scale for Schizophrenia | 8 weeks | Score on scale, from 0 to 27, above 6 considered indicative of depression, higher scores mean worse outcome, |
Countries
United States
Participant flow
Recruitment details
40 subjects from three State Hospitals were recruited and participated between 2005 and 2008: four in-patients from Rochester Psychiatric Center, 17 out-patients from Buffalo Psychiatric Center and 19 in-patients from Bronx Psychiatric Center
Participants by arm
| Arm | Count |
|---|---|
| Experimental Open label change to ziprasidone | 40 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lack of Efficacy | 12 |
| Overall Study | Protocol Violation | 2 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Experimental |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 39 Participants |
| Age, Continuous | 42 years STANDARD_DEVIATION 15 |
| Region of Enrollment United States | 40 participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 40 |
| serious Total, serious adverse events | 1 / 40 |
Outcome results
Primary
Positive and Negative Syndrome Scale (PANSS) Measuring Symptoms of Schizophrenia
Minimum score 32 (best) maximum 210 (worst)
Time frame: Baseline to 8 weeks
Population: The four Rochester subjects were dropped as Rochester could not continue the study.19 Bronx and 17 Buffalo subjects were analyzed separately because they were so different(see baseline characteristics)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental | Positive and Negative Syndrome Scale (PANSS) Measuring Symptoms of Schizophrenia | Bronx end | 99 score on scale | Standard Deviation 25 |
| Experimental | Positive and Negative Syndrome Scale (PANSS) Measuring Symptoms of Schizophrenia | Bronx baseline | 95 score on scale | Standard Deviation 16 |
| Experimental | Positive and Negative Syndrome Scale (PANSS) Measuring Symptoms of Schizophrenia | Buffalo baseline | 72 score on scale | Standard Deviation 22 |
| Experimental | Positive and Negative Syndrome Scale (PANSS) Measuring Symptoms of Schizophrenia | Buffalo end | 62 score on scale | Standard Deviation 19 |
Secondary
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
Time frame: 8 weeks
Population: 17 Buffalo subjects and 19 Bronx subjects
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental | Abnormal Involuntary Movement Scale (AIMS) Measures Tardive Dyskinesia | Bronx baseline | 0.3 score on scale | Standard Deviation 0.8 |
| Experimental | Abnormal Involuntary Movement Scale (AIMS) Measures Tardive Dyskinesia | Bronx end | 0.3 score on scale | Standard Deviation 0.7 |
| Experimental | Abnormal Involuntary Movement Scale (AIMS) Measures Tardive Dyskinesia | Buffalo baseline | 2.9 score on scale | Standard Deviation 3.1 |
| Experimental | Abnormal Involuntary Movement Scale (AIMS) Measures Tardive Dyskinesia | Buffalo end | 1.6 score on scale | Standard Deviation 1.4 |
Secondary
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
Time frame: 8 weeks
Population: We had no measure of costs, no data were collected
Secondary
Barnes Akathisia Scale
Barnes Akathisia Scale measures akathisia: a score of zero is none (good) maximum score is 12
Time frame: 8 weeks
Population: All subjects entered, 17 at Buffalo, 19 at Bronx
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental | Barnes Akathisia Scale | Bronx baseline | 0.6 score on a scale | Standard Deviation 1.7 |
| Experimental | Barnes Akathisia Scale | Bronx end | 0.8 score on a scale | Standard Deviation 1.7 |
| Experimental | Barnes Akathisia Scale | Buffalo baseline | 1.4 score on a scale | Standard Deviation 1.5 |
| Experimental | Barnes Akathisia Scale | Buffalo end | 1.1 score on a scale | Standard Deviation 1.7 |
Secondary
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.
Time frame: 8 weeks
Population: The overall number of participants is made up of 17 at Buffalo and 19 in the Bronx
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental | Brief Assessment of Cognition in Schizophrenia (BACS) | Bronx baseline | -14 Z-score from score on scale | Standard Deviation 6 |
| Experimental | Brief Assessment of Cognition in Schizophrenia (BACS) | Bronx end | -13 Z-score from score on scale | Standard Deviation 5.3 |
| Experimental | Brief Assessment of Cognition in Schizophrenia (BACS) | Buffalo baseline | -12 Z-score from score on scale | Standard Deviation 5.9 |
| Experimental | Brief Assessment of Cognition in Schizophrenia (BACS) | Buffalo end | -11 Z-score from score on scale | Standard Deviation 6.5 |
Secondary
Calgary Depression Scale for Schizophrenia
Score on scale, from 0 to 27, above 6 considered indicative of depression, higher scores mean worse outcome,
Time frame: 8 weeks
Population: 19 at Bronx, 17 at Buffalo
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental | Calgary Depression Scale for Schizophrenia | Bronx baseline | 5.4 score on a scale | Standard Deviation 4.4 |
| Experimental | Calgary Depression Scale for Schizophrenia | Bronx end | 5.3 score on a scale | Standard Deviation 3.8 |
| Experimental | Calgary Depression Scale for Schizophrenia | Buffalo baseline | 3.4 score on a scale | Standard Deviation 3.7 |
| Experimental | Calgary Depression Scale for Schizophrenia | Buffalo end | 1.3 score on a scale | Standard Deviation 2 |
Secondary
Cholesterol
Time frame: 8 weeks
Population: See PANSS above
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental | Cholesterol | Bronx baseline | 185 mg/dL | Standard Deviation 44 |
| Experimental | Cholesterol | Bronx end | 160 mg/dL | Standard Deviation 28 |
| Experimental | Cholesterol | Buffalo baseline | 186 mg/dL | Standard Deviation 42 |
| Experimental | Cholesterol | Buffalo end | 179 mg/dL | Standard Deviation 36 |
Secondary
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
Time frame: 8 weeks
Population: 17 Buffalo subjects and 19 Bronx subjects
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental | Clinical Global Impression (CGI) Scores the Evaluator's Overall Impression of Severity (CGI-S) or Change (CGI-I) in Illness. | Bronx baseline | 4.6 score on scale | Standard Deviation 0.6 |
| Experimental | Clinical Global Impression (CGI) Scores the Evaluator's Overall Impression of Severity (CGI-S) or Change (CGI-I) in Illness. | Bronx end | 4.9 score on scale | Standard Deviation 0.8 |
| Experimental | Clinical Global Impression (CGI) Scores the Evaluator's Overall Impression of Severity (CGI-S) or Change (CGI-I) in Illness. | Buffalo baseline | 3.5 score on scale | Standard Deviation 0.9 |
| Experimental | Clinical Global Impression (CGI) Scores the Evaluator's Overall Impression of Severity (CGI-S) or Change (CGI-I) in Illness. | Buffalo end | 2.8 score on scale | Standard Deviation 0.8 |
Secondary
Corrected QT Interval (QTc)
Time interval between Q and T waves on EKG corrected for pulse rate. Over 500 msec may be dangerous
Time frame: 8 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental | Corrected QT Interval (QTc) | Bronx baseline | 396 msec | Standard Deviation 18 |
| Experimental | Corrected QT Interval (QTc) | Bronx end | 411 msec | Standard Deviation 15 |
| Experimental | Corrected QT Interval (QTc) | Buffalo baeline | 412 msec | Standard Deviation 21 |
| Experimental | Corrected QT Interval (QTc) | Buffalo end | 427 msec | Standard Deviation 17 |
Secondary
Fasting Glucose
Amount of glucose in the blood in mg/dl
Time frame: 8 weeks
Population: See PANSS above
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental | Fasting Glucose | Bronx baseline | 91 mg/dl | Standard Deviation 28 |
| Experimental | Fasting Glucose | Bronx end | 82 mg/dl | Standard Deviation 24 |
| Experimental | Fasting Glucose | Buffalo baseline | 94 mg/dl | Standard Deviation 18 |
| Experimental | Fasting Glucose | Buffalo end | 93 mg/dl | Standard Deviation 19 |
Secondary
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.
Time frame: 8 weeks
Population: All subjects entered, 19 in the Bronx, 17 at Buffalo
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental | HbA1c | Bronx baseline | 5.3 HbA1c | Standard Deviation 0.6 |
| Experimental | HbA1c | Bronx end | 5.4 HbA1c | Standard Deviation 0.7 |
| Experimental | HbA1c | Buffalo baseline | 6.0 HbA1c | Standard Deviation 0.9 |
| Experimental | HbA1c | Buffalo end | 5.7 HbA1c | Standard Deviation 0.8 |
Secondary
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.
Time frame: 8 weeks
Population: All subjects entered, 17 at Buffalo, 19 at Bronx
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental | Insulin Level | Bronx baseline | 10 uIU/ml | Standard Deviation 7.2 |
| Experimental | Insulin Level | Bronx end | 13 uIU/ml | Standard Deviation 14 |
| Experimental | Insulin Level | Buffalo baseline | 12 uIU/ml | Standard Deviation 9.2 |
| Experimental | Insulin Level | Buffalo end | 17 uIU/ml | Standard Deviation 14 |
Secondary
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.
Time frame: 8 weeks
Population: All subjects, 17 at Buffalo, 19 in the Bronx
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental | Medical Outcomes Study Cognitive Functioning Scale (MOS-COG) | Bronx baseline | 17 score on a scale | Standard Deviation 5.8 |
| Experimental | Medical Outcomes Study Cognitive Functioning Scale (MOS-COG) | Bronx end | 16 score on a scale | Standard Deviation 6.3 |
| Experimental | Medical Outcomes Study Cognitive Functioning Scale (MOS-COG) | Buffalo baseline | 18 score on a scale | Standard Deviation 5.4 |
| Experimental | Medical Outcomes Study Cognitive Functioning Scale (MOS-COG) | Buffalo end | 19 score on a scale | Standard Deviation 3.9 |
Secondary
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.
Time frame: 8 weeks
Population: 36 subjects entered, 17 at Buffalo and 19 in the Bronx
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental | Personal Evaluation of Transitions in Treatment Scale (PETiTP | Bronx baseline | 43 score on a scale | Standard Deviation 9.7 |
| Experimental | Personal Evaluation of Transitions in Treatment Scale (PETiTP | Bronx end | 45 score on a scale | Standard Deviation 11 |
| Experimental | Personal Evaluation of Transitions in Treatment Scale (PETiTP | Buffalo baseline | 46 score on a scale | Standard Deviation 11 |
| Experimental | Personal Evaluation of Transitions in Treatment Scale (PETiTP | Buffalo end | 48 score on a scale | Standard Deviation 13 |
Secondary
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.
Time frame: 8 weeks
Population: see PANNS above
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental | Simpson-Angus Scale Measures Drug Induced Parkinsonism | Bronx baseline | 0.2 score on scale | Standard Deviation 0.5 |
| Experimental | Simpson-Angus Scale Measures Drug Induced Parkinsonism | Bronx end | 0.1 score on scale | Standard Deviation 0.2 |
| Experimental | Simpson-Angus Scale Measures Drug Induced Parkinsonism | Buffalo baseline | 3.6 score on scale | Standard Deviation 3.6 |
| Experimental | Simpson-Angus Scale Measures Drug Induced Parkinsonism | Buffalo end | 2.5 score on scale | Standard Deviation 2.6 |
Secondary
Weight
Time frame: 8 weeks
Population: Same as PANNS above
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental | Weight | Bronx baseline | 195 pounds | Standard Deviation 43 |
| Experimental | Weight | Bronx end | 193 pounds | Standard Deviation 41 |
| Experimental | Weight | Buffalo baseline | 213 pounds | Standard Deviation 57 |
| Experimental | Weight | Buffalo end | 204 pounds | Standard Deviation 52 |