Glucose and Lipid Metabolism on Antipsychotic Medication

Schizophrenia Clinical Trial

— Glulipid  

Official title:

Glucose and Lipid Metabolism on Antipsychotic Medication

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00515723
• Other study ID #: R01MH063985-04
• Secondary ID: R01MH063985-04
• Status: Completed
• Phase: N/A
• Start date: September 2001
• Est. completion date: December 2008

Study information

• Verified date: October 2019
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 96
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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).

Related Conditions & MeSH terms

• Hyperglycemia
• Psychotic Disorders
• Schizoaffective Disorder
• Schizophrenia
• Type 2 Diabetes Mellitus

Intervention

Drug:
• risperidone
randomized to 12 week trial of risperidone.
• olanzapine
randomized to 12 week trial of olanzapine.
• quetiapine
randomized to 12 week trial of quetiapine.
• ziprasidone
randomized to 12 week trial of ziprasidone.

Locations

Country	Name	City	State
United States	Washington Univeristy School of Medicine	Saint Louis	Missouri
United States	Washington University School of Medicine, Psychiatry Dept.	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Washington University School of Medicine	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	DEXA Total Fat	This study hypothesized that antipsychotic treatment would increase total body fat, as measured by whole body dual energy x-ray absorptiometry (DEXA), with larger adverse effects for olanzapine.	The relevant time points include baseline, week 6 and week 12.
Primary	Clamp Derived Insulin Sensitivity (mg/kg/Min)	This study hypothesized that antipsychotic treatment would decrease insulin sensitivity, with larger adverse effects for olanzapine. Insulin sensitivity describes how sensitive the body is to the effects of insulin.	The relevant time points include baseline and week 12.