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

Overview[ - collapse ][ - ]

Purpose 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.
ConditionMetabolic Complications
InterventionDrug: Metformin
Drug: Placebo
PhasePhase 4
SponsorRush University Medical Center
Responsible PartyRush University Medical Center
ClinicalTrials.gov IdentifierNCT00682448
First ReceivedMay 20, 2008
Last UpdatedDecember 10, 2012
Last verifiedDecember 2012

Tracking Information[ + expand ][ + ]

First Received DateMay 20, 2008
Last Updated DateDecember 10, 2012
Start DateAugust 2007
Estimated Primary Completion DateAugust 2011
Current Primary Outcome MeasuresWeight Gain and Insulin Resistance [Time Frame: 6 months] [Designated as safety issue: No]
Current Secondary Outcome MeasuresDislipidemia, OGTT, Hemoglobin A1C [Time Frame: 6 months] [Designated as safety issue: No]

Descriptive Information[ + expand ][ + ]

Brief TitleMetformin for the Prevention of the Metabolic Side-effects of Zyprexa
Official TitleMetformin to Prevent the Metabolic Complications of Olanzapine
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.
Study TypeInterventional
Study PhasePhase 4
Study DesignAllocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention
ConditionMetabolic Complications
InterventionDrug: 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.
Other Names:
  • Metformin
  • Glucophage
  • Fortamet
  • Riomet
  • Glumetza
  • Diabex
  • Diaformin
Drug: Placebo
Drug: Placebo. Subjects will remain on placebo for 6 months.
Study Arm (s)
  • Active Comparator: 1
    Olanzapine 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.
  • Placebo Comparator: 2
    Olanzapine plus Drug: Placebo. Subjects will remain on olanzapine plus placebo for 6 months.

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment27
Estimated Completion DateAugust 2011
Estimated Primary Completion DateAugust 2011
Eligibility Criteria
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.
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesUnited States

Administrative Information[ + expand ][ + ]

NCT Number NCT00682448
Other Study ID Numbers06122201
Has Data Monitoring CommitteeNo
Information Provided ByRush University Medical Center
Study SponsorRush University Medical Center
CollaboratorsEli Lilly and Company
Investigators Principal Investigator: Jeffrey T Rado, M.D. Rush University Medical Center
Verification DateDecember 2012

Locations[ + expand ][ + ]

Rush University Medical Center
Chicago, Illinois, United States, 60612