Schizophrenia
Conditions
Keywords
Diabetes, Metabolic
Brief summary
This study will determine the metabolic processes responsible for high levels of blood glucose, metabolism disorders, and weight gain in people with schizophrenia who have been treated with antipsychotic medications in combination with valproate.
Detailed description
This project aims to study the whole-body metabolic processes responsible for hyperglycemia, dyslipidemia and increased adiposity in schizophrenia patients treated with antipsychotic medications in combination with valproate. The project hypothesizes that combined treatment with valproate and antipsychotic medications will decrease insulin sensitivity at the level of skeletal muscle, liver and adipose tissue, in comparison to antipsychotic monotherapy. The decrease in insulin sensitivity is hypothesized to be associated with defects in glucose and lipid metabolism and increased adiposity Treatment effects of antipsychotic/valproate combination therapy on different components of insulin secretion and action, and treatment effects on abdominal versus peripheral adiposity, are unknown despite the availability of gold-standard methods and the prognostic significance of these issues. Relevant data are needed to target basic research, to identify the potential for acute and long-term complications, and to plan therapeutic interventions. The following specific aims will be addressed in non-diabetic schizophrenia patients treated with atypical antipsychotics who will be randomized to open label treatment with either valproate or no adjuvant. Evaluations are performed at baseline and 3 months of treatment.
Interventions
DRUGValproate
Depakote ER 500 mg to 3000 mg taken every night
DRUGPlacebo
Placebo given at same frequency as Valproate
Sponsors
National Institute of Mental Health (NIMH)
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Meets DSM-IV criteria for schizophrenia, any type, treated with the same antipsychotic for at least 6 months * No antipsychotic medication dose changes for 1 month, and no other medication changes for 1 month prior to study entry
Exclusion criteria
* Meets DSM-IV criteria for substance abuse within 3 months of study entry * Involuntary legal status (as per Missouri law) * Any serious medical disorder that may confound the assessment of relevant biologic measures or diagnosis, including: significant organ system dysfunction, metabolic diseases, type 1 or 2 diabetes mellitus, pregnancy, endocrine disease, coagulopathy, anemia, or acute infection * Currently taking more than one antipsychotic medication * Currently taking prescription medications (except certain psychotropic medications as discussed below), including oral contraceptive pills, any glucose lowering agent, lipid lowering agent, exogenous testosterone, recombinant human growth hormone, or any other endocrine agent that might confound substrate metabolism
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Total Body Fat Composition Using Dual Energy X-ray Absorptiometry at 12 Weeks | Measured at baseline and Week 12 | Change in body composition (total body fat) was assessed using dual energy x-ray absorptiometry |
| Effects of Medication on Insulin Secretion at Skeletal Muscle (Glucose Disposal) | Measured at baseline and Week 12 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo 50% of participants will receive placebo | 25 |
| Experimental 50% of participants will receive Depakote ER | 25 |
| Total | 50 |
Baseline characteristics
| Characteristic | Placebo | Experimental | Total |
|---|---|---|---|
| Age, Continuous | 40.6 years STANDARD_DEVIATION 10.1 | 41.3 years STANDARD_DEVIATION 8.4 | 40.9 years STANDARD_DEVIATION 9.2 |
| Race/Ethnicity, Customized African American | 19 participants | 18 participants | 37 participants |
| Race/Ethnicity, Customized Caucasian | 6 participants | 7 participants | 13 participants |
| Sex: Female, Male Female | 7 Participants | 6 Participants | 13 Participants |
| Sex: Female, Male Male | 18 Participants | 19 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 23 | 12 / 24 |
| serious Total, serious adverse events | 0 / 23 | 0 / 24 |
Outcome results
Primary
Change From Baseline in Total Body Fat Composition Using Dual Energy X-ray Absorptiometry at 12 Weeks
Change in body composition (total body fat) was assessed using dual energy x-ray absorptiometry
Time frame: Measured at baseline and Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Total Body Fat Composition Using Dual Energy X-ray Absorptiometry at 12 Weeks | -0.51 percent change | Standard Deviation 2.13 |
| Experimental | Change From Baseline in Total Body Fat Composition Using Dual Energy X-ray Absorptiometry at 12 Weeks | 2.03 percent change | Standard Deviation 2.17 |
p-value: <0.0001ANCOVA
Primary
Effects of Medication on Insulin Secretion at Skeletal Muscle (Glucose Disposal)
Time frame: Measured at baseline and Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Effects of Medication on Insulin Secretion at Skeletal Muscle (Glucose Disposal) | 0.27 percent change | Standard Deviation 1.23 |
| Experimental | Effects of Medication on Insulin Secretion at Skeletal Muscle (Glucose Disposal) | -0.35 percent change | Standard Deviation 1.13 |
p-value: 0.04ANCOVA