Glucose and Lipid Metabolism on Antipsychotic Medication (Glulipid)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00515723
Recruitment Status : Completed
First Posted : August 14, 2007
Last Update Posted : February 28, 2011
National Institutes of Health (NIH)
Information provided by:
Washington University School of Medicine

Brief Summary:
Hyperglycemia and type 2 diabetes mellitus are more common in schizophrenia than in the general population. Type 2 diabetes mellitus is characterized by disturbances in insulin action on skeletal muscle, liver and adipose tissue. Diabetes causes increased morbidity and mortality due to acute (e.g., diabetic ketoacidosis) and long-term (e.g., cardiovascular disease) complications. The combination of hyperglycemia, dyslipidemia and abdominal adiposity is even more strongly associated with increased cardiovascular morbidity and mortality. The association of type 2 diabetes and hyperglycemia with schizophrenia was first noted prior to the introduction of antipsychotic medications, suggesting that these patients may be at increased risk. Since then, however, additional glucoregulatory abnormalities (e.g., new onset diabetes), dyslipidemia, and increased weight and adiposity have all been associated with antipsychotic medications. Concern about antipsychotic effects on glucose, lipids and adiposity has increased recently, focusing on the widely-used newer medications, clozapine and olanzapine. Increased abdominal adiposity can secondarily decrease insulin sensitivity and antipsychotics can increase adiposity. However, medication effects on glucose control and insulin action may also occur independent of differences in adiposity. This project aims to a) evaluate the effects of selected antipsychotic medications on insulin action in skeletal muscle (glucose disposal), liver (glucose production) and adipose tissue (whole-body lipolysis), b) evaluate the effects of selected antipsychotic medications on abdominal adipose tissue mass, total body fat and total fat-free mass, and c) explore the longitudinal effects of treatment with selected antipsychotics on glucose tolerance, lipid profiles, abdominal adipose tissue mass, total body fat and total fat-free mass. These hypotheses will be evaluated by measuring 1) whole-body glucose and lipid kinetics with the use of "gold-standard" stable isotope tracer methodology, 2) body composition using dual energy x-ray absorptiometry and magnetic resonance imaging, and 3) longitudinal changes in glucose tolerance and lipid profiles. The aims will be addressed in non-diabetic schizophrenia patients chronically treated with risperidone, olanzapine, clozapine, quetiapine, ziprasidone, or haloperidol, and untreated healthy controls. Re-evaluations will also be performed in patients who are randomized to switch from their current antipsychotic (from the above groups) to risperidone, olanzapine, quetiapine, or ziprasidone for 6 months. Relevant data is critically needed to target basic research, identify long-term cardiovascular consequences, and plan therapeutic interventions.

Condition or disease Intervention/treatment Phase
Schizophrenia Schizoaffective Disorder Type 2 Diabetes Mellitus Hyperglycemia Drug: risperidone Drug: olanzapine Drug: quetiapine Drug: ziprasidone Phase 4

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 216 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Glucose and Lipid Metabolism on Antipsychotic Medication
Study Start Date : September 2001
Actual Primary Completion Date : December 2008
Actual Study Completion Date : December 2008

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: 1
Randomized switch from current antipsychotic treatment to either olanzapine, risperidone, ziprasidone, or quetiapine.
Drug: risperidone
randomized switch from current antipsychotic treatment to risperidone
Drug: olanzapine
randomized switch from current antipsychotic treatment to olanzapine
Drug: quetiapine
randomized switch from current antipsychotic treatment to quetiapine
Drug: ziprasidone
randomized switch from current antipsychotic treatment to ziprasidone

Primary Outcome Measures :
  1. measure obesity and risk of heart disease using using euglycemic hyperinsulinemic clamps, DXA and abdominal MRI. [ Time Frame: 12 weeks, 6 months, and 1 year ]

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Aged 18-60 years
  • Patients: otherwise healthy and meets DSM-IV criteria for schizophrenia or schizoaffective disorder, any type, treated with haloperidol, olanzapine, clozapine, quetiapine, ziprasidone, aripiprazole, or risperidone for at least 3 months
  • Controls: healthy
  • 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:

  • Axis I psychiatric disorder criteria met in self except for substance use disorders as below
  • Patients and controls: meets DSM-IV criteria for the diagnoses of substance abuse within the past 3 months
  • Involuntary legal status (as per Missouri law)
  • The presence of any serious medical disorder that may confound the assessment of relevant biologic measures or diagnosis, including: significant organ system dysfunction, metabolic diseases, type 1 diabetes mellitus, symptomatic type 2 diabetes mellitus (see below), pregnancy, endocrine disease, coagulopathy, clinically significant anemia, that would preclude blood sampling (as determined by the PI) or acute infection;
  • Patients taking more than one atypical antipsychotic medication;
  • Subjects taking certain prescription medications (as determined by PI on a case by case basis).

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00515723

United States, Missouri
Washington Univeristy School of Medicine
St. Louis, Missouri, United States, 63110
Washington University School of Medicine, Psychiatry Dept.
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
National Institutes of Health (NIH)
Principal Investigator: John W Newcomer, MD Washington Univerisity Schoole of Medicine

Responsible Party: John Newcomer, MD, Washington University School of Medicine Identifier: NCT00515723     History of Changes
Other Study ID Numbers: R01MH063985-04 ( U.S. NIH Grant/Contract )
First Posted: August 14, 2007    Key Record Dates
Last Update Posted: February 28, 2011
Last Verified: February 2011

Keywords provided by Washington University School of Medicine:

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Psychotic Disorders
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Antipsychotic Agents
Quetiapine Fumarate
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Serotonin Uptake Inhibitors