Effects of Atypical Antipsychotic and Valproate Combination Therapy on Glucose and Lipid Metabolism in Schizophrenia (DepIVGTT)
Recruitment status was Active, not recruiting
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Purpose
This project aims to a) evaluate the effects of haloperidol, olanzapine, and risperidone in combination with valproate on insulin secretion and insulin actions, b) evaluate medication effects on abdominal fat, total body fat and total fat-free mass, and c) evaluate treatment effects on glucose tolerance, lipid profiles, and plasma levels of leptin, adiponectin, ghrelin and C-reactive protein. Hypotheses will be evaluated by measuring 1) insulin action and secretion using frequently sampled intravenous glucose tolerance tests, 2) body composition using dual energy x-ray absorptiometry, magnetic resonance scans, and anthropomorphic measurements, and 3) changes in hormone levels and lipid profiles. The aims will be addressed in non-diabetic schizophrenia patients chronically treated with haloperidol, olanzapine or risperidone who will have valproate added to their treatment. Relevant data is critically needed to target basic research, identify long-term cardiovascular risks, and plan therapeutic interventions.
| Condition | Intervention |
|---|---|
|
Insulin Resistance Body Composition |
Drug: Depakote (valproate) |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Effects of Atypical Antipsychotic and Valproate Combination Therapy on Glucose and Lipid Metabolism in Schizophrenia |
- Hypotheses will be evaluated by measuring insulin action and secretion using frequently sampled intravenous glucose tolerance tests [ Time Frame: 2 years ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 120 |
| Study Start Date: | February 2003 |
| Estimated Study Completion Date: | December 2010 |
| Primary Completion Date: | December 2004 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Schizophrenics
i) meets DSM-IV criteria for schizophrenia, any type, treated with atypical or high potency typical neuroleptics for at least 3 months; ii) aged 18 to 60 years; iii) able to give informed consent; iv) no antipsychotic medication changes for 3 months, and no other medication changes for 2 weeks prior to Baseline Evaluations.
|
Drug: Depakote (valproate)
500 mg -2000 mg QD based on individual tolerance and VPA levels
|
Detailed Description:
Schizophrenia is associated with increased rates of obesity, hyperglycemia, dyslipidemia and type 2 diabetes mellitus, causing increased morbidity and mortality due to acute (e.g., diabetic ketoacidosis) and long-term (e.g., vascular disease) complications. The association of type 2 diabetes and hyperglycemia with schizophrenia was first noted prior to the introduction of antipsychotic medications. However, additional glucoregulatory abnormalities, dyslipidemia, and increased adiposity have all been associated with antipsychotics. Risperidone and olanzapine are the most prescribed antipsychotics for schizophrenia in the U.S. In addition, schizophrenia patients in clinical practice are commonly treated with multi-class polypharmacy, with 35% of atypical antipsychotic prescriptions accompanied by co-prescription of valproate. This combination continues to increase in popularity, despite reports that the addition of valproate may further disturb glucose and lipid metabolism and weight regulation. While sensitive and validated measures of glucose and lipid metabolism and weight regulation are available, very few studies have addressed the metabolic consequences of this common type of polypharmacy.
This project aims to a) evaluate the effects of haloperidol, olanzapine, and risperidone in combination with valproate on insulin secretion and insulin actions, b) evaluate medication effects on abdominal fat, total body fat and total fat-free mass, and c) evaluate treatment effects on glucose tolerance, lipid profiles, and plasma levels of leptin, adiponectin, ghrelin and C-reactive protein. Hypotheses will be evaluated by measuring 1) insulin action and secretion using frequently sampled intravenous glucose tolerance tests, 2) body composition using dual energy x-ray absorptiometry, magnetic resonance scans, and anthropomorphic measurements, and 3) changes in hormone levels and lipid profiles. The aims will be addressed in non-diabetic schizophrenia patients chronically treated with haloperidol, olanzapine or risperidone who will have valproate added to their treatment. Relevant data is critically needed to target basic research, identify long-term cardiovascular risks, and plan therapeutic interventions.
Eligibility| Ages Eligible for Study: | 18 Years to 60 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Meets DSM-IV criteria for schizophrenia, any type, treated with atypical or high potency typical neuroleptics for at least 3 months
- Aged 18 to 60 years
- Able to give informed consent
- No antipsychotic medication changes for 3 months, and no other medication changes for 2 weeks prior to Baseline Evaluations.
Exclusion Criteria:
- Meets DSM-IV criteria for the diagnoses of substance abuse or dependence within the past 6 months
- Involuntary legal status (as per Missouri law)
The presence of any serious medical disorder that may (as confirmed by peer-reviewed literature) confound the assessment of symptoms, relevant biologic measures or diagnosis. The following conditions are currently identified:
- Type 1 diabetes mellitus or symptomatic type 2 diabetes mellitus
- Any intra-abdominal or intrathoracic surgery or limb amputation within the prior 6 months
- Any diagnosed cardiac condition causing documented hemodynamic compromise
- Any diagnosed respiratory condition causing documented or clinically recognized hypoxia
- Pregnancy or high dose estrogens, fever, narcotic therapy, acute sedative hypnotic withdrawal, corticosteroid or spironolactone therapy, dehydration, epilepsy, endocrine disease, high-dose benzodiazepine therapy (> 25 mg/day of diazepam), or any medical condition known to interfere with glucose utilization
- Meets DSM-IV criteria for Mental Retardation (mild or worse).
Contacts and Locations| United States, Missouri | |
| Washington University School of Medicine | |
| St. Louis, Missouri, United States, 63110 | |
| Principal Investigator: | Daniel W Haupt, MD | Washington University School of Medicine |
More Information
No publications provided
| Responsible Party: | Dan Haupt MD, Washington University |
| ClinicalTrials.gov Identifier: | NCT00552500 History of Changes |
| Obsolete Identifiers: | NCT00161512 |
| Other Study ID Numbers: | NARSAD 43625, NARSAD |
| Study First Received: | November 1, 2007 |
| Last Updated: | March 16, 2010 |
| Health Authority: | United States: Institutional Review Board |
Additional relevant MeSH terms:
|
Insulin Resistance Schizophrenia Hyperinsulinism Glucose Metabolism Disorders Metabolic Diseases Schizophrenia and Disorders with Psychotic Features Mental Disorders Valproic Acid Antipsychotic Agents Anticonvulsants Central Nervous System Agents |
Therapeutic Uses Pharmacologic Actions Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action GABA Agents Neurotransmitter Agents Physiological Effects of Drugs Antimanic Agents Tranquilizing Agents Central Nervous System Depressants Psychotropic Drugs |
ClinicalTrials.gov processed this record on May 23, 2013