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Metformin for the Prevention of the Metabolic Side-effects of Zyprexa

Phase 4
Completed
Conditions
Metabolic Complications
Interventions
Drug: Placebo
Registration Number
NCT00682448
Lead Sponsor
Rush University Medical Center
Brief Summary

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.

Detailed Description

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
25
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
1MetforminOlanzapine plus metformin: olanzapine plus metformin 500 mg titrated up to but no greater than 2,000 mg based upon fasting blood glucose during study visits over six months.
2PlaceboOlanzapine plus Drug: Placebo. Subjects will remain on olanzapine plus placebo for 6 months.
Primary Outcome Measures
NameTimeMethod
Weight GainBaseline and 6 months

Change from Baseline in weight

Secondary Outcome Measures
NameTimeMethod
Hemoglobin A1CBaseline and 6 months

change from baseline in hemoglobin AIC

Trial Locations

Locations (1)

Rush University Medical Center

🇺🇸

Chicago, Illinois, United States

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