Comparative Effects of Chronic Treatment With Olanzapine and Risperidone on Glucose and Lipid Metabolism
Condition: Schizophrenia; Diabetes; Metabolic Syndrome; Hyperglycemia
MeSH terms: Metabolic Syndrome; Hyperglycemia; Schizophrenia
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

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.
    

Intervention name(s): Olanzapine; olanzapine; risperidone
Intervention type(s): Drug; Drug; Drug
Intervention description(s): olanzapine 5-40 mg/day; olanzapine 5-40 ,mg/day; risperidone 1-12 mg/day
Other intervention name(s): ayprexa; zyprexa; riperidal
Intervention MeSH terms: Olanzapine; Risperidone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: schizophrenia; diabetes; metabolic syndrome; hyperglycemia; glucose; insulin; lipids; IL-6; prolactin