Glucose and Lipid Metabolism on Antipsychotic Medication (Glulipid)

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00515723
First received: August 13, 2007
Last updated: February 25, 2011
Last verified: February 2011
  Purpose

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 Intervention Phase
Schizophrenia
Schizoaffective Disorder
Type 2 Diabetes Mellitus
Hyperglycemia
Drug: risperidone
Drug: olanzapine
Drug: quetiapine
Drug: ziprasidone
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Glucose and Lipid Metabolism on Antipsychotic Medication

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 216
Study Start Date: September 2001
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).
  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: NCT00515723

Locations
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
Investigators
Principal Investigator: John W Newcomer, MD Washington Univerisity Schoole of Medicine
  More Information

No publications provided

Responsible Party: John Newcomer, MD, Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00515723     History of Changes
Other Study ID Numbers: R01 MH063985-04
Study First Received: August 13, 2007
Last Updated: February 25, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Washington University School of Medicine:
control
risperidone
olanzapine
quetiapine
ziprasidone

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Hyperglycemia
Psychotic Disorders
Schizophrenia
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Antipsychotic Agents
Risperidone
Quetiapine
Olanzapine
Ziprasidone
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Dopamine Antagonists
Dopamine Agents
Antiemetics
Autonomic Agents

ClinicalTrials.gov processed this record on August 19, 2014