Clinical trial NCT00167934: Determining Metabolic Effects of Valproate and Antipsychotic Therapy
Official title: Metabolic Effects of Valproate and Antipsychotic Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Schizophrenia
Keywords: Diabetes
Metabolic
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2005-09-14
Enrollment: 164
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in Total Body Fat Composition Using Dual Energy X-ray Absorptiometry at 12 Weeks
timeFrame: Measured at baseline and Week 12
measure: Effects of Medication on Insulin Secretion at Skeletal Muscle (Glucose Disposal)
timeFrame: Measured at baseline and Week 12
Secondary outcomes:
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Dan W. Haupt, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Haupt DW, Newcomer JW. Hyperglycemia and antipsychotic medications. J Clin Psychiatry. 2001;62 Suppl 27:15-26; discussion 40-1.