Metformin for the Prevention of the Metabolic Side-Effects of Zyprexa - Full Text View

Sponsors and Collaborators:	Rush University Medical Center Eli Lilly and Company
Information provided by:	Rush University Medical Center
ClinicalTrials.gov Identifier:	NCT00682448

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.

Condition	Intervention	Phase
Metabolic Complications	Drug: Metformin Drug: Placebo	Phase IV

Drug Information available for: Metformin Metformin hydrochloride Olanzapine Dextrose

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Crossover Assignment, Efficacy Study
Official Title:	Metformin to Prevent the Metabolic Complications of Olanzapine

Further study details as provided by Rush University Medical Center:

Primary Outcome Measures:

Phase I and II: Weight Gain and Insulin Resistance [ Time Frame: I Year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Phase I and II: Dislipidemia, OGTT, Hemoglobin A1C [ Time Frame: 1 Year ] [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	August 2007
Estimated Study Completion Date:	August 2009
Estimated Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
2: Placebo Comparator 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.	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.
1: Active Comparator 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.	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.

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00682448

Contacts

Contact: Jeffrey Rado, M.D.	312-942-9296	jeffrey_rado@rush.edu
Contact: Stephanie Cavanaugh, M.D.	312-942-7023	stephanie_cavanaugh@rush.edu

Locations

United States, Illinois
Rush University Medical Center	Recruiting
Chicago, Illinois, United States, 60612
Contact: Jeffrey Rado, M.D. 312-942-9296 jeffrey_rado@rush.edu
Contact: Ferren Farah, B.S. 312-563-3157 ferren_farah@rush.edu
Principal Investigator: Jeffrey Rado, M.D.
Sub-Investigator: Stephanie Cavanaugh, M.D.

Sponsors and Collaborators

Rush University Medical Center

Eli Lilly and Company

Investigators

Principal Investigator:

Jeffrey T Rado, M.D.

Rush University Medical Center

More Information

Responsible Party:	Rush University Medical Center ( Jeffrey Rado, M.D. / Assistant Professor )
Study ID Numbers:	06122201
Study First Received:	May 20, 2008
Last Updated:	November 20, 2008
ClinicalTrials.gov Identifier:	NCT00682448
Health Authority:	United States: Institutional Review Board

Keywords provided by Rush University Medical Center:

Olanzapine
Zyprexa
Weight Gain
Antipsychotics
Metformin
Glucophage
Bipolar Disorder
Schizophrenia

Depression
Diabetes
Side effects
Metabolic complications
Prevention
Treatment
Metabolic side effects of olanzapine

Study placed in the following topic categories:

Schizophrenia
Body Weight
Depression
Bipolar Disorder
Metformin

Olanzapine
Diabetes Mellitus
Depressive Disorder
Weight Gain
Serotonin

Additional relevant MeSH terms:

Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Tranquilizing Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Gastrointestinal Agents
Psychotropic Drugs
Antiemetics
Central Nervous System Depressants

Antipsychotic Agents
Serotonin Uptake Inhibitors
Pharmacologic Actions
Serotonin Agents
Hypoglycemic Agents
Autonomic Agents
Therapeutic Uses
Peripheral Nervous System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 16, 2009