- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00515723
Glucose and Lipid Metabolism on Antipsychotic Medication (Glulipid)
October 1, 2019 updated by: Washington University School of Medicine
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.
Study Overview
Status
Completed
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
96
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Missouri
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Saint Louis, Missouri, United States, 63110
- Washington University School of Medicine, Psychiatry Dept.
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Saint Louis, Missouri, United States, 63110
- Washington Univeristy School of Medicine
-
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 60 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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).
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Olanzapine
Participants in this group were randomized to flexibly-dosed treatment with olanzapine.
|
randomized to 12 week trial of olanzapine.
Other Names:
|
Active Comparator: Risperidone
Participants in this group were randomized to flexibly-dosed treatment with risperidone.
|
randomized to 12 week trial of risperidone.
Other Names:
|
Active Comparator: Quetiapine
Participants in this group were randomized to flexibly-dosed treatment with quetiapine.
|
randomized to 12 week trial of quetiapine.
Other Names:
|
Active Comparator: Ziprasidone
Participants in this group were randomized to flexibly-dosed treatment with ziprasidone.
|
randomized to 12 week trial of ziprasidone.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
DEXA Total Fat
Time Frame: The relevant time points include baseline, week 6 and week 12.
|
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)
Time Frame: The relevant time points include baseline and week 12.
|
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.
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: John W Newcomer, MD, Washington Univerisity School of Medicine and Florida Atlantic University
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
September 1, 2001
Primary Completion (Actual)
December 1, 2008
Study Completion (Actual)
December 1, 2008
Study Registration Dates
First Submitted
August 13, 2007
First Submitted That Met QC Criteria
August 13, 2007
First Posted (Estimate)
August 14, 2007
Study Record Updates
Last Update Posted (Actual)
October 2, 2019
Last Update Submitted That Met QC Criteria
October 1, 2019
Last Verified
October 1, 2019
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Glucose Metabolism Disorders
- Metabolic Diseases
- Endocrine System Diseases
- Diabetes Mellitus
- Schizophrenia Spectrum and Other Psychotic Disorders
- Hyperglycemia
- Diabetes Mellitus, Type 2
- Schizophrenia
- Psychotic Disorders
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Autonomic Agents
- Peripheral Nervous System Agents
- Antiemetics
- Gastrointestinal Agents
- Antipsychotic Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Serotonin Uptake Inhibitors
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Serotonin Agents
- Antidepressive Agents
- Dopamine Agents
- Serotonin Antagonists
- Dopamine Antagonists
- Olanzapine
- Quetiapine Fumarate
- Risperidone
- Ziprasidone
Other Study ID Numbers
- R01MH063985-04 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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