Determining Metabolic Effects of Valproate and Antipsychotic Therapy

Study Overview
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Brief Summary
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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
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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.

Official Title
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Metabolic Effects of Valproate and Antipsychotic Therapy

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Valproate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>50% of participants will receive placebo | Drug: Placebo<br>* Placebo given at same frequency as Valproate<br>|
| Experimental: Experimental<br>50% of participants will receive Depakote ER | Drug: Valproate<br>* Depakote ER 500 mg to 3000 mg taken every night<br>* Other names: Depakote ER;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Measured at baseline and Week 12 | 
| Effects of Medication on Insulin Secretion at Skeletal Muscle (Glucose Disposal) |  | Measured at baseline and Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Metabolic