Side Effects of Antipsychotic Medications

Insulin Resistance Clinical Trial

Official title:

Does Olanzapine Inhibit the Secretory Response to Insulin Resistance?

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00363181
• Other study ID #: F1DMC-X280
• Status: Completed
• Start date: April 2006
• Est. completion date: December 2011

Study information

• Verified date: March 2021
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Medications like olanzapine have been associated with the development of weight gain and diabetes in some patients. It is not known if the increased risk of developing diabetes is a direct effect on insulin or simply related to weight gain.

We hope to learn in this study whether or not olanzapine directly slows down insulin secretion from the pancreas, thereby increasing the risk of developing diabetes.

Description:

Objectives: The use of atypical antipsychotics has been associated with increased weight gain, the development of type-2 diabetes, and, in rare cases, diabetic ketoacidosis. It is not clear if these changes are a direct function of antipsychotics on either insulin action or insulin secretion, or simply related to their ability to induce weight gain in a population at increased risk to develop hyperglycemia. The objective of this investigation is to determine if treatment with the atypical antipsychotics olanzapine impairs the ability of the pancreatic beta cell to increase its insulin secretory response to graded increases in plasma glucose concentration in non-diabetic, insulin resistant individuals. In addition, we will compare the range of insulin-mediated glucose uptake (IMGU) in olanzapine-treated versus non-antipsychotic treated patients.

Research Plan and Methods: 120 subjects with psychiatric disorders will be enrolled; 60 patients on olanzapine and 60 patients with similar psychiatric diagnoses on a different antipsychotic medication (ziprasidone, risperidone or aripiprazole). All subjects will have a fasting plasma glucose concentration <126 mg/dL, and on no medication with a direct effect on IMGU. Subjects will be admitted to the General Clinical Research Center (GCRC) at Stanford Medical Center and evaluated by an insulin suppression test (IST) to determine their IMGU. Subjects with a steady state plasma glucose (SSPG) concentration during the IST that is >180 mg/dL will be defined as being insulin resistant. From this population of subjects, 15 patients on olanzapine and 15 patients not on any antipsychotic, will return to the GCRC to determine their glucose-stimulated insulin secretory dose-response curves (GS-ISR). The GS-ISR at the same glucose concentration will be compared between the subjects on olanzapine (n=15) and the not on an antipsychotic (n=15) by analysis of variance. Analyses of the 120 subjects screened for insulin resistance will compare 1) the means and distribution of the SSPG concentrations in olanzapine and non-olanzapine treated patients with psychiatric diagnoses; and 2) the means of the two experimental groups with psychiatric diagnoses to Dr. Reaven's data base of volunteers without psychiatric disorders.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 76
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 66 Years

Eligibility

Inclusion Criteria:

• Participants 30-66 years of age

• Body mass index (BMI) >25 < 35 kg/m2.

• Fasting plasma glucose concentration < 126 mg/dL

• Stable on one of the following psychiatric medication: Olanzapine (Zyprexa®), Ziprasidone (Geodon®), Aripiprazole (Abilify®), or Risperidone (Risperdal®)

• Stable on psychiatric medication for at least 3 months

Exclusion Criteria:

• Medications that directly affect insulin-mediated glucose disposal

• Intense suicidal impulses/intent

• Alcohol or substance abuse for 3 months.

• Major medical problems, i.e., clinically unstable medical disorder or condition; cardiovascular, hepatic, renal, gastrointestinal, pulmonary, endocrine or other systemic disease that would, in the investigator's clinical judgment interfere with the endocrine measures obtained in this study.

Related Conditions & MeSH terms

• Disease
• Insulin Resistance
• Mental Disorders
• Metabolic Syndrome
• Metabolic Syndrome X
• Mood Disorders
• Psychotic Disorders
• Schizophrenia
• Schizophrenia and Disorders With Psychotic Features
• Schizophrenia Spectrum and Other Psychotic Disorders

Locations

Country	Name	City	State
United States	VA Palo Alto Health Care System	Palo Alto	California

Sponsors (1)

Lead Sponsor	Collaborator
Stanford University

Country where clinical trial is conducted

United States,