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

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Jeffrey Rado, MD, Rush University Medical Center
ClinicalTrials.gov Identifier:
NCT00682448
First received: May 20, 2008
Last updated: December 10, 2012
Last verified: December 2012
  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 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Metformin to Prevent the Metabolic Complications of Olanzapine

Resource links provided by NLM:


Further study details as provided by Rush University Medical Center:

Primary Outcome Measures:
  • Weight Gain and Insulin Resistance [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Dislipidemia, OGTT, Hemoglobin A1C [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment: 27
Study Start Date: August 2007
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.
Other Names:
  • Metformin
  • Glucophage
  • Fortamet
  • Riomet
  • Glumetza
  • Diabex
  • Diaformin
Placebo Comparator: 2
Olanzapine plus Drug: Placebo. Subjects will remain on olanzapine plus placebo for 6 months.
Drug: Placebo
Drug: Placebo. Subjects will remain on placebo for 6 months.

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

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

No publications provided

Responsible Party: Jeffrey Rado, MD, MD, Rush University Medical Center
ClinicalTrials.gov Identifier: NCT00682448     History of Changes
Other Study ID Numbers: 06122201
Study First Received: May 20, 2008
Last Updated: December 10, 2012
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

Additional relevant MeSH terms:
Metformin
Olanzapine
Antiemetics
Antipsychotic Agents
Autonomic Agents
Central Nervous System Agents
Central Nervous System Depressants
Gastrointestinal Agents
Hypoglycemic Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Uptake Inhibitors
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on October 21, 2014