Official Title: “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 Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

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(s) in this Clinical Trial

• Drug: Olanzapine
  • olanzapine 5-40 mg/day
• Drug: olanzapine
  • olanzapine 5-40 ,mg/day
• Drug: risperidone
  • risperidone 1-12 mg/day

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • olanzapine
• Active Comparator: 2
  • risperidone

Primary Measures

• Serum glucose
  • Time Frame: during 5 months of treatment compared to baseline
    Safety Issue?: Yes
• Hb1AC
  • Time Frame: during 5 months of treatment compared to baseline
    Safety Issue?: Yes
• triglycerides
  • Time Frame: during 5 months of treatment compared to baseline
    Safety Issue?: Yes
• cholesterol
  • Time Frame: during 5 months of treatment compared to baseline
    Safety Issue?: Yes
• insulin
  • Time Frame: during 5 months of treatment compared to baseline
    Safety Issue?: Yes
• c-peptide
  • Time Frame: during 5 months of treatment compared to baseline
    Safety Issue?: Yes

Secondary Measures

• ghrelin
  • Time Frame: during 5 months of treatment compared to baseline
    Safety Issue?: No
• CRP
  • Time Frame: during 5 months of treatment compared to baseline
    Safety Issue?: Yes
• Thyroid hormones
  • Time Frame: during 5 months of treatment compared to baseline
    Safety Issue?: No
• prolactin
  • Time Frame: during 5 months of treatment compared to baseline
    
• Il-6
  • Time Frame: during 5 months treatment compared to baseline
    Safety Issue?: No
• PANSS scores
  • Time Frame: during 5 months of treatment compared to baseline
    Safety Issue?: No
• CGI score
  • Time Frame: during 5 months of treatment compared to baseline
    
• EPS scores
  • Time Frame: during 5 months of treatment compared to baseline
    Safety Issue?: Yes
• TD Scores
  • Time Frame: during 5 months of treatment compared to baseline
    Safety Issue?: Yes

Inclusion Criteria:

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

Exclusion Criteria:

• Currently being treated with oral antidiabetics or insulin

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Manhattan Psychiatric Center

Overall Clinical Trial Officials and Contacts

Robert C Smith, MD PhD Principal Investigator NYU Medical School, Dept of Psychiatry and Manhattan Psychiatric Center  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00287820

Study ID Number: FiD-MC-x226(7524)

ClinicalTrials.gov Identifier: NCT00287820

Health Authority: United States: Institutional Review Board