Official Title: “Metabolic Effects of Valproate and Antipsychotic Therapy”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Single Blind (Subject), Placebo Control, Parallel Assignment, Pharmacodynamics Study

Study Primary Completion Date: December 2008

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.

Intervention(s) in this Clinical Trial

• Drug: Valproate
  • Depakote ER 500 mg to 3000 mg taken every night
• Drug: Placebo
  • Placebo given at same frequency as Valproate

Arms, Groups and Cohorts in this Clinical Trial

• Placebo Comparator: Placebo
  • 50% of participants will receive placebo
• Experimental: Experimental
  • 50% of participants will receive Depakote ER

Primary Measures

• Oral glucose tolerance test (fsOGTT) and hyperinsulinemic pancreatic clamp
  • Time Frame: Measured at baseline and Weeks 6 and 12
    Safety Issue?: No

Secondary Measures

• Body composition using dual energy x-ray absorptiometry, magnetic resonance scans, and anthropomorphic measurements
  • Time Frame: Measured at baseline and Weeks 6 and 12
    Safety Issue?: 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 60 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Institute of Mental Health (NIMH)

Overall Clinical Trial Officials and Contacts

Dan W. Haupt, MD Principal Investigator Washington University School of Medicine  

Overall Contact: Martha J. Hessler, BS 314-362-2423 hesslema@psychiatry.wustl.edu

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00167934

Study ID Number: K23 MH067795

ClinicalTrials.gov Identifier: NCT00167934

Health Authority: United States: Federal Government

Click here for the Washington University Department of Psychiatry