Schizophrenia, Metabolic Syndrome X, Insulin Resistance
Conditions
Keywords
Ziprasidone, Olanzapine, Risperidone, Schizoaffective Disorder, Insulin Sensitivity, Visceral Adiposity, Metabolic Syndrome
Brief summary
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
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.
Interventions
DRUGSwitch
Participants who are switched to ziprasidone will take a max daily dose of 200 mg, flexibly dosed based on symptoms and adverse effects.
DRUGControl
Participants will remain taking the same medications of risperidone or olanzapine as they were before study entry.
Sponsors
National Institute of Mental Health (NIMH)
Pfizer
Veterans Medical Research Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Insulin Sensitivity Index From Baseline to Week 26 ((1/mU/L) x 1/Min) | Measured at Baseline and Week 26 | As measured by frequently sampled intravenous glucose tolerance testing (units: 1/mU/L) x 1/Min) |
| Change in Visceral Fat Mass From Baseline to Week 26 | Baseline and Week 26 | CT measured change in visceral fat mass from baseline to week 26 (mm\^3) |
Countries
United States
Participant flow
Recruitment details
Recruitment started 06/01/2006. Eligibility: nondiabetic, overweight/obese psychiatrically stable adult outpatients in San Diego with schizophrenia/schizoaffective disorder, on risperidone or olanzapine. Recruitment ended: 12/31/2009
Pre-assignment details
Exclusions: unstable housing, psychiatric hospitalization in the past 90 days, ongoing substance abuse (except nicotine), history of diabetes mellitus, pregnancy, refractory schizophrenia, prior failure of or intolerance to ziprasidone, oral glucose tolerance test indicative of diabetes mellitus, or corrected QT interval ≥ 500 msec on EKG.
Participants by arm
| Arm | Count |
|---|---|
| Control Remain on risperidone or olanzapine. | 25 |
| Switch Switch from risperidone or olanzapine to ziprasidone. Ziprasidone will be flexibly dosed based on tolerability and psychiatric response (max dose 200 PO mg/d with food). | 30 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Randomization | Adverse Event | 0 | 5 |
| Randomization | Withdrawal by Subject | 1 | 0 |
| Subject Screening | Screen failures | 11 | 11 |
Baseline characteristics
| Characteristic | Control | Switch | Total |
|---|---|---|---|
| Age, Continuous | 47.15 Years STANDARD_DEVIATION 8.15 | 48.73 Years STANDARD_DEVIATION 8.42 | 48.00 Years STANDARD_DEVIATION 8.3 |
| Baseline Antipsychotic Olanzapine | 8 participants | 9 participants | 17 participants |
| Baseline Antipsychotic Risperidone | 17 participants | 21 participants | 38 participants |
| BMI | 32.52 kg/m^2 STANDARD_DEVIATION 4.49 | 34.64 kg/m^2 STANDARD_DEVIATION 7.6 | 33.68 kg/m^2 STANDARD_DEVIATION 6.19 |
| Central visceral fat volume by CT | 28442 mm^3 STANDARD_DEVIATION 10634 | 26939 mm^3 STANDARD_DEVIATION 12060 | 27622 mm^3 STANDARD_DEVIATION 11412 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 4 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants | 26 Participants | 49 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Family Diabetes Mellitus History Family Hx | 4 participants | 5 participants | 9 participants |
| Family Diabetes Mellitus History No Family Hx | 21 participants | 25 participants | 46 participants |
| Insulin sensitivity index | 1.596 (1/mU/L) x 1/Min STANDARD_DEVIATION 1 | 1.504 (1/mU/L) x 1/Min STANDARD_DEVIATION 0.902 | 1.55 (1/mU/L) x 1/Min STANDARD_DEVIATION 0.95 |
| PANSS Total Score | 62.72 units on a scale STANDARD_DEVIATION 11.7 | 65.20 units on a scale STANDARD_DEVIATION 10.66 | 64.07 units on a scale STANDARD_DEVIATION 11.13 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 10 Participants | 17 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 18 Participants | 20 Participants | 38 Participants |
| Region of Enrollment United States | 25 participants | 30 participants | 55 participants |
| Sex: Female, Male Female | 6 Participants | 7 Participants | 13 Participants |
| Sex: Female, Male Male | 19 Participants | 23 Participants | 42 Participants |
| Smoking Status Nonsmoker | 9 participants | 12 participants | 21 participants |
| Smoking Status Smoker | 16 participants | 18 participants | 34 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 25 | 3 / 30 |
| serious Total, serious adverse events | 1 / 25 | 2 / 30 |
Outcome results
Primary
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)
Time frame: Measured at Baseline and Week 26
Population: Completers
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Change in Insulin Sensitivity Index From Baseline to Week 26 ((1/mU/L) x 1/Min) | 0.072 (1/mU/L) x 1/Min | Standard Deviation 0.955 |
| Switch | Change in Insulin Sensitivity Index From Baseline to Week 26 ((1/mU/L) x 1/Min) | 0.407 (1/mU/L) x 1/Min | Standard Deviation 0.822 |
p-value: 0.228t-test, 2 sided
Primary
Change in Visceral Fat Mass From Baseline to Week 26
CT measured change in visceral fat mass from baseline to week 26 (mm\^3)
Time frame: Baseline and Week 26
Population: Completers
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Change in Visceral Fat Mass From Baseline to Week 26 | 315 mm^3 | Standard Deviation 5693 |
| Switch | Change in Visceral Fat Mass From Baseline to Week 26 | 392 mm^3 | Standard Deviation 4340 |
p-value: 0.958t-test, 2 sided