Glucose and Lipid Metabolism on Antipsychotic Medication

NCT ID: NCT00515723

Last Updated: 2019-10-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 96 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-09-30
• Study Completion Date: 2008-12-31

Brief Summary

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.

Detailed Description

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.

Conditions

Schizophrenia; Schizoaffective Disorder; Type 2 Diabetes Mellitus; Hyperglycemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Olanzapine

Participants in this group were randomized to flexibly-dosed treatment with olanzapine.

Group Type: ACTIVE_COMPARATOR

olanzapine

Intervention Type: DRUG

randomized to 12 week trial of olanzapine.

Risperidone

Participants in this group were randomized to flexibly-dosed treatment with risperidone.

Group Type: ACTIVE_COMPARATOR

risperidone

Intervention Type: DRUG

randomized to 12 week trial of risperidone.

Quetiapine

Participants in this group were randomized to flexibly-dosed treatment with quetiapine.

Group Type: ACTIVE_COMPARATOR

quetiapine

Intervention Type: DRUG

randomized to 12 week trial of quetiapine.

Ziprasidone

Participants in this group were randomized to flexibly-dosed treatment with ziprasidone.

Group Type: ACTIVE_COMPARATOR

ziprasidone

Intervention Type: DRUG

randomized to 12 week trial of ziprasidone.

Interventions

risperidone

randomized to 12 week trial of risperidone.

Intervention Type: DRUG

olanzapine

randomized to 12 week trial of olanzapine.

Intervention Type: DRUG

quetiapine

randomized to 12 week trial of quetiapine.

Intervention Type: DRUG

ziprasidone

randomized to 12 week trial of ziprasidone.

Intervention Type: DRUG

Other Intervention Names

Risperdal; Zyprexa; Seroquel; Geodon

Eligibility 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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John W Newcomer, MD

Role: PRINCIPAL_INVESTIGATOR

Washington Univerisity School of Medicine and Florida Atlantic University

Locations

Washington Univeristy School of Medicine

St Louis, Missouri, United States

Washington University School of Medicine, Psychiatry Dept.

St Louis, Missouri, United States

Countries

United States

Other Identifiers

R01MH063985-04

Identifier Type: NIH

Identifier Source: secondary_id

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R01MH063985-04

Identifier Type: NIH

Identifier Source: org_study_id

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