Schizoaffective Disorder, Schizophrenia
Conditions
Brief summary
The study will compare the effectiveness of antipsychotic medications for patients with schizophrenia or schizoaffective disorder for whom a medication change may be indicated because of an increased risk of cardiovascular disease.
Detailed description
Metabolic abnormalities associated with cardiovascular morbidity and premature mortality are more common in patients with schizophrenia than in matched controls. Although there is some evidence that patients with schizophrenia have intrinsic abnormalities in lipid and carbohydrate metabolism, some antipsychotics (i.e., clozapine, olanzapine, quetiapine, and risperidone) are associated with increased rates of metabolic abnormalities that predispose patients to cardiovascular disease. This is an investigator-initiated clinical trial that will be conducted at 30 research sites that are a part of the NIMH Schizophrenia Trials Network. The aims of the study are to (1) determine the relative effects of switching to aripiprazole, versus continued treatment with olanzapine, quetiapine, or risperidone, on metabolic parameters associated with cardiovascular disease, and (2) to determine the effects of switching to aripiprazole versus continued treatment with olanzapine, quetiapine, or risperidone on the clinical stability of schizophrenic illness. This study design is a multi-site, single-blind (rater) randomized controlled trial of 300 patients with schizophrenia or schizoaffective disorder comparing treatment with the following medications: olanzapine, quetiapine, risperidone, and aripiprazole. The study will enroll patients with schizophrenia or schizoaffective disorder for whom a medication change may be indicated because of an increased risk of cardiovascular disease in spite of adequate control of symptoms on their current antipsychotic medication. Patients who are taking olanzapine, quetiapine, or risperidone and who have a body-mass index (BMI) greater than or equal to 27 and non-HDL cholesterol greater than or equal to 130 mg/dl will be eligible (if non-HDL is between 130-139mg/dL, LDL cholesterol must be greater than 100mg/dL). All treatments will be open label. Raters will be blinded to treatment assignment. Patients will be followed for up to 6 months.
Interventions
DRUGRisperidone
Continued treatment with the medication risperidone for schizophrenia for up to 6 months in study
DRUGOlanzapine
Continued treatment with the medication olanzapine for schizophrenia for up to 6 months in study
DRUGQuetiapine
Continued treatment with the medication quetiapine for schizophrenia for up to 6 months in study
DRUGAripiprazole
Switching medication to aripiprazole for schizophrenia for up to 6 months in study
Sponsors
National Institute of Mental Health (NIMH)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosed with schizophrenia or schizoaffective disorder * Currently treated with olanzapine, quetiapine or risperidone * BMI greater than or equal to 27 * Non-HDL cholesterol greater than or equal to 130 mg/dL (if non-HDL cholesterol is between 130 - 139 mg/dL, then LDL cholesterol must be greater than 100 mg/dL).
Exclusion criteria
* Diabetes (FBS greater than or equal to 126) or treatment with oral hypoglycemic drug or insulin * Non-HDL cholesterol greater than 300 mg/dL * Serum triglycerides greater than 500 mg/dL * Patients in the first episode of schizophrenia or schizoaffective disorder * Known hypersensitivity to aripiprazole * On weight loss medications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Non-HDL Cholesterol Level for Patients Assigned to Stay and Patients Assigned to Switch Over 24 Weeks | 24 weeks | Change in non-HDL cholesterol measured at baseline and every 4 weeks for 24 weeks. The efficacy analysis corresponded to a comparison of change in non-HDL cholesterol from baseline to 24 weeks between treatment groups (stay versus switch). Repeated measurements mixed effects linear models were fit for the primary analysis. |
Secondary
| Measure | Time frame |
|---|---|
| Efficacy Failure, Defined as Psychiatric Hospitalization, a 25 Percent Increase From Baseline on the Positive and Negative Syndrome Scale or Substantial Clinical Deterioration on the Clinical Global Impressions-Change (CGI-C) | Measured at Month 6 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Switch Group Participants will switch to aripiprazole. | 109 |
| Stay Group Participants will continue treatment with olanzapine, quetiapine, or risperidone. | 106 |
| Total | 215 |
Baseline characteristics
| Characteristic | Switch Group | Stay Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 109 Participants | 106 Participants | 215 Participants |
| Age, Continuous | 40 years STANDARD_DEVIATION 11.7 | 42 years STANDARD_DEVIATION 10.5 | 41 years STANDARD_DEVIATION 11.1 |
| non-HDL cholesterol | 169 mg/dL STANDARD_DEVIATION 31.9 | 176 mg/dL STANDARD_DEVIATION 33.5 | 173 mg/dL STANDARD_DEVIATION 32.8 |
| Region of Enrollment United States | 109 participants | 106 participants | 215 participants |
| Sex: Female, Male Female | 41 Participants | 37 Participants | 78 Participants |
| Sex: Female, Male Male | 68 Participants | 69 Participants | 137 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 77 / 107 | 77 / 106 |
| serious Total, serious adverse events | 18 / 107 | 9 / 106 |
Outcome results
Primary
Change in Non-HDL Cholesterol Level for Patients Assigned to Stay and Patients Assigned to Switch Over 24 Weeks
Change in non-HDL cholesterol measured at baseline and every 4 weeks for 24 weeks. The efficacy analysis corresponded to a comparison of change in non-HDL cholesterol from baseline to 24 weeks between treatment groups (stay versus switch). Repeated measurements mixed effects linear models were fit for the primary analysis.
Time frame: 24 weeks
Population: The primary efficacy analysis was conducted on the efficacy evaluable population, defined as all patients randomly assigned to a study group who received at least one dose of study medication and completed at least one post-baseline efficacy assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Switch Group | Change in Non-HDL Cholesterol Level for Patients Assigned to Stay and Patients Assigned to Switch Over 24 Weeks | -20.2 mg/dL non-HDL cholesterol | Standard Error 2.87 |
| Stay Group | Change in Non-HDL Cholesterol Level for Patients Assigned to Stay and Patients Assigned to Switch Over 24 Weeks | -10.8 mg/dL non-HDL cholesterol | Standard Error 2.57 |
Secondary
Efficacy Failure, Defined as Psychiatric Hospitalization, a 25 Percent Increase From Baseline on the Positive and Negative Syndrome Scale or Substantial Clinical Deterioration on the Clinical Global Impressions-Change (CGI-C)
Time frame: Measured at Month 6
Population: 2 participants who never took assigned study medication were excluded.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Switch Group | Efficacy Failure, Defined as Psychiatric Hospitalization, a 25 Percent Increase From Baseline on the Positive and Negative Syndrome Scale or Substantial Clinical Deterioration on the Clinical Global Impressions-Change (CGI-C) | 22 participants |
| Stay Group | Efficacy Failure, Defined as Psychiatric Hospitalization, a 25 Percent Increase From Baseline on the Positive and Negative Syndrome Scale or Substantial Clinical Deterioration on the Clinical Global Impressions-Change (CGI-C) | 18 participants |