Official Title: “Metformin to Prevent the Metabolic Complications of Olanzapine”

We hypothesize that metformin co-administered with olanzapine will be well tolerated and associated with significantly less insulin resistance, weight gain and dyslipidemia as compared to olanzapine plus placebo.

Study Type: Interventional

Study Design: Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Crossover Assignment, Efficacy Study

Study Primary Completion Date: August 2009

Increased risk of metabolic complications with olanzapine therapy, relative to other antipsychotics, may lead clinicians to avoid its use, despite evidence of greater efficacy.

These problems may also pose a therapeutic dilemma for patients who respond well to olanzapine. Metabolic complications negatively impact on morbidity and mortality, impair quality of life and increase illness relapse secondary to medication non-compliance. Thus far, no pharmacologic agent co-administered with olanzapine has proven effective at preventing these untoward effects. The present study proposes to examine the efficacy and safety of metformin to attenuate the metabolic side effects associated with olanzapine.

Intervention(s) in this Clinical Trial

• Drug: Metformin
  • Drug: Metformin 500 mg po daily titrated up to but no greater than 2000 mg based upon fasting blood glucose during study visits over six months. At six months the subject will be on open label metformin with the dosage again based upon fasting blood glucose levels.
• Drug: Placebo
  • Drug: Placebo. Subjects will remain on placebo for 6 months. At 6 months the subject will be crossed over to open label metformin starting with 500 mg and titrated up to but no greater than 2000 mg based upon fasting blood glucose levels over 6 months.

Arms, Groups and Cohorts in this Clinical Trial

• Placebo Comparator: 2
  • Drug: Placebo. Subjects will remain on placebo for 6 months. At 6 months the subject will be crossed over to open label metformin starting with 500 mg and titrated up to but no greater than 2,000 mg based upon fasting blood glucose levels over 6 months.
• Active Comparator: 1
  • Drug: Metformin 500 mg titrated up to but no greater than 2,000 mg based upon fasting blood glucose during study visits over six months. At six months the subject will be on open label metformin with the dosage again based upon fasting blood glucose levels.

Primary Measures

• Phase I and II: Weight Gain and Insulin Resistance
  • Time Frame: I Year
    Safety Issue?: No

Secondary Measures

• Phase I and II: Dislipidemia, OGTT, Hemoglobin A1C
  • Time Frame: 1 Year
    Safety Issue?: No

Inclusion Criteria:

• Diagnosis of: Schizophrenia, Schizoaffective Disorder, Bipolar I or II or major depression with psychotic features who will be started on or who have just started taking Olanzapine (Zyprexa).

Exclusion Criteria:

• Patients with either a history of diabetes mellitus or a baseline FBG>126 or two random blood sugars of > 200 or during a OGTT glucose level of > 200 two hours after a glucose load of 50 grams. (All American Diabetes Association criteria for diabetes mellitus).
• Baseline liver function tests (SGOT, SGPT, AP) greater than 3X normal.
• Chronic alcoholism
• MDRD less than 60 ml/1.73 m2. Modification of Diet in Renal Disease (MDRD) Equation estimates the glomerular filtration rate as a measure of kidney function. This equation takes into account the plasma creatinine, age, race and gender, and is a more accurate estimation of glomerular filtration rate than serum creatinine alone.
• Patients with unstable medical problems, including cardiovascular instability or significant congestive heart failure (as determined by study investigators).
• Prolonged QTc greater than 430 ms on baseline EKG.
• History of lactic acidosis.
• History of hypoglycemia.
• Current treatment with metformin or other antidiabetic agents.
• Treatment with any antihyperlipidemic medication within 3 months of randomization.
• Treatment with olanzapine or clozapine within 3 months of randomization.
• Concurrent treatment with ziprasidone, risperidone, quetiapine or aripiprazole or any other neuroleptic medication.
• Concurrent use of OTC chromium, gymnema or cimetidine will be prohibited. Patient may discontinue these medications up to one day prior to randomization.
• Current treatment with corticosteroids.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Rush University Medical Center

Overall Clinical Trial Officials and Contacts

Jeffrey T Rado, M.D. Principal Investigator Rush University Medical Center  

Overall Contact: Jeffrey Rado, M.D. 312-942-9296 jeffrey_rado@rush.edu

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00682448

Study ID Number: 06122201

ClinicalTrials.gov Identifier: NCT00682448

Health Authority: United States: Institutional Review Board