Comparative Effects of Chronic Treatment With Olanzapine and Risperidone on Glucose and Lipid Metabolism

Independent Investigator Grant Study-Comparative Effects of Chronic Treatment With Olanzapine and Risperidone on Glucose and Lipid Metabolism

The primary objective of the study is to assess whether chronic treatment with olanzapine over a five-month period produces a significant increase in abnormalities in glucose levels. The main secondary objective is to evaluate whether the increase in glucose levels and rate of glucose abnormalities differs between Olanzapine and Risperidone during this treatment period. Additional secondary objectives of the study are to investigate similar questions with respect to glycohemoglobin, triglycerides and other measures of glucose and lipid metabolism.

We hypothesize that Olanzapine will not be inferior to Risperidone in extent of increase in the primary outcome measure of serum glucose, and secondary measures of glycohemoglobin, insulin and lipids.

Study Overview

• Status: Completed
• Conditions: Hyperglycemia; Diabetes; Schizophrenia; Metabolic Syndrome
• Intervention / Treatment: Drug: Olanzapine; Drug: risperidone; Drug: olanzapine

Detailed Description

In the on-going study in progress we use an extensive battery of assessments to investigate a)fasting levels of glucose and lipids at baseline and monthly during 5 months of treatment, b) glucose tolerance tests to investigate glucose and insulin abnormalities after a glucose load at baseline and during study treatment, and c)the effects of treatment with olanzapine and risperidone of post prandial glucose metabolism after a fatty meal (as detailed in the body of the proposal). Recent studies have shown that increased postprandial lipidemia is an important feature of many patients with type 2 diabetes and atherosclerosis. In addition to the biochemical measures, we will also assess clinical effects (PANSS and CGI ratings) and other side-effects (weight gain, appetite, somnolence, and EPS and TD). The specific plan calls for inpatients in a tertiary care hospital to be randomly assigned to olanzapine or risperidone, using a stratified random assignment procedure, and treated for five months with either olanzapine or risperidone. We estimate that we will have to enroll a sample of approximately 50-55 patients to obtain 46 acceptable complete cases(as specified in proposal below). On the basis of preliminary results from our prior and ongoing studies we predict no significant increase in glucose abnormalities from baseline during chronic treatment with olanzapine and no significant differences in development of glucose abnormalities in patients in patient treated with olanzapine and risperidone.

Additional measures being investigated include: comparison of olanzapine and risperidone in glucose and lipid responses to a fatty meal, ghrelin changes in response to a fatty mean, and CRP and IL-6, and thyroid and prolactin response to five months of treatment with the two drugs.

• Study Type: Interventional
• Enrollment (Anticipated): 46
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10035
      • Manhattan Psychaitric Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis
• Schizophrenia or schizoaffective psychosis
• 18-65 years of age

Exclusion Criteria:

• Currently being treated with oral antidiabetics or insulin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; olanzapine	Drug: Olanzapine; olanzapine 5-40 mg/day; Other Names: ayprexa
Active Comparator: 2; risperidone	Drug: risperidone; risperidone 1-12 mg/day; Other Names: riperidal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Serum glucose	during 5 months of treatment compared to baseline
Hb1AC	during 5 months of treatment compared to baseline
triglycerides	during 5 months of treatment compared to baseline
cholesterol	during 5 months of treatment compared to baseline
insulin	during 5 months of treatment compared to baseline
c-peptide	during 5 months of treatment compared to baseline

Secondary Outcome Measures

Outcome Measure	Time Frame
ghrelin	during 5 months of treatment compared to baseline
CRP	during 5 months of treatment compared to baseline
Thyroid hormones	during 5 months of treatment compared to baseline
prolactin	during 5 months of treatment compared to baseline
Il-6	during 5 months treatment compared to baseline
PANSS scores	during 5 months of treatment compared to baseline
CGI score	during 5 months of treatment compared to baseline
EPS scores	during 5 months of treatment compared to baseline
TD Scores	during 5 months of treatment compared to baseline

Collaborators and Investigators

• Sponsor: Nathan Kline Institute for Psychiatric Research
• Collaborators: Eli Lilly and Company
• Investigators: Principal Investigator: Robert C Smith, MD PhD, NYU Medical School, Dept of Psychiatry and Manhattan Psychiatric Center

Publications and helpful links

General Publications

• Smith RC, Rachakonda S, Dwivedi S, Davis JM. Olanzapine and risperidone effects on appetite and ghrelin in chronic schizophrenic patients. Psychiatry Res. 2012 Oct 30;199(3):159-63. doi: 10.1016/j.psychres.2012.03.011. Epub 2012 Apr 3.
• Smith RC, Lindenmayer JP, Hu Q, Kelly E, Viviano TF, Cornwell J, Vaidhyanathaswamy S, Marcovina S, Davis JM. Effects of olanzapine and risperidone on lipid metabolism in chronic schizophrenic patients with long-term antipsychotic treatment: a randomized five month study. Schizophr Res. 2010 Jul;120(1-3):204-9. doi: 10.1016/j.schres.2010.04.001. Epub 2010 May 10.
• Smith RC, Lindenmayer JP, Davis JM, Kelly E, Viviano TF, Cornwell J, Hu Q, Khan A, Vaidhyanathaswamy S. Effects of olanzapine and risperidone on glucose metabolism and insulin sensitivity in chronic schizophrenic patients with long-term antipsychotic treatment: a randomized 5-month study. J Clin Psychiatry. 2009 Nov;70(11):1501-13. doi: 10.4088/JCP.08m04446yel. Epub 2009 Oct 6.

Study record dates

Study Major Dates

• Study Start: February 1, 2004
• Study Completion (Actual): September 1, 2007

Study Registration Dates

• First Submitted: February 6, 2006
• First Submitted That Met QC Criteria: February 6, 2006
• First Posted (Estimate): February 7, 2006

Study Record Updates

• Last Update Posted (Estimate): July 25, 2011
• Last Update Submitted That Met QC Criteria: July 22, 2011
• Last Verified: December 1, 2007

More Information

Terms related to this study

• Keywords: diabetes; schizophrenia; insulin; metabolic syndrome; lipids; hyperglycemia; IL-6; glucose; prolactin
• Additional Relevant MeSH Terms: Mental Disorders; Glucose Metabolism Disorders; Metabolic Diseases; Schizophrenia Spectrum and Other Psychotic Disorders; Insulin Resistance; Hyperinsulinism; Hyperglycemia; Schizophrenia; Metabolic Syndrome; 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; Dopamine Agents; Serotonin Antagonists; Dopamine Antagonists; Olanzapine; Risperidone
• Other Study ID Numbers: FiD-MC-x226(7524)