Glucose and Lipid Metabolism on Antipsychotic Medication

NCT00515723 | Completed Results DMC

• 1 other identifier: R01MH063985-04
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 2

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.

Conditions

Schizophrenia; Schizoaffective Disorder; Type 2 Diabetes Mellitus; Hyperglycemia

Keywords

control; risperidone; olanzapine; quetiapine; ziprasidone

Outcome Measures

Primary Outcomes (2)

• 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.

• 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.

Study Arms (4)

Olanzapine

ACTIVE COMPARATOR

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

Drug: olanzapine

Risperidone

ACTIVE COMPARATOR

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

Drug: risperidone

Quetiapine

ACTIVE COMPARATOR

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

Drug: quetiapine

Ziprasidone

ACTIVE COMPARATOR

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

Drug: ziprasidone

Interventions

risperidone DRUG

randomized to 12 week trial of risperidone.

Also known as: Risperdal

Risperidone

olanzapine DRUG

randomized to 12 week trial of olanzapine.

Also known as: Zyprexa

Olanzapine

quetiapine DRUG

randomized to 12 week trial of quetiapine.

Also known as: Seroquel

Quetiapine

ziprasidone DRUG

randomized to 12 week trial of ziprasidone.

Also known as: Geodon

Ziprasidone

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Washington University School of Medicine: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (2)

Washington Univeristy School of Medicine

St Louis, Missouri, 63110, United States

Location

Washington University School of Medicine, Psychiatry Dept.

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders; Diabetes Mellitus, Type 2; Hyperglycemia

Interventions

Risperidone; Olanzapine; Quetiapine Fumarate; ziprasidone

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Dibenzothiazepines; Thiazepines; Thiepins; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring

Results Point of Contact

• Title: John Newcomer, M.D.
• Organization: Washington University School of Medicine and Florida Atlantic University

jnewcomer@fau.edu

561-297-0252

Study Officials

• John W Newcomer, MD

  Washington Univerisity School of Medicine and Florida Atlantic University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2007
• First Posted: August 14, 2007
• Study Start: September 1, 2001
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: October 2, 2019
• Results First Posted: October 2, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)