Effects of Atypical Antipsychotic and Valproate Combination Therapy on Glucose and Lipid Metabolism in Schizophrenia (DepIVGTT)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2010 by Washington University School of Medicine.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00552500
First received: November 1, 2007
Last updated: March 16, 2010
Last verified: March 2010
  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

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • 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
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00552500

Locations
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
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:
Schizophrenia
Insulin Resistance
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Antipsychotic Agents
Valproic Acid
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Anticonvulsants
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
GABA Agents
Neurotransmitter Agents
Antimanic Agents

ClinicalTrials.gov processed this record on September 18, 2014