The Use of Metformin in the Treatment of Antipsychotic-Induced Weight Gain in Schizophrenia (The METS Study)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier:
NCT00816907
First received: January 2, 2009
Last updated: February 13, 2013
Last verified: November 2010
  Purpose

This study will test the usefulness of the medication metformin in treating people with schizophrenia or schizoaffective disorder who are overweight and also taking antipsychotic medications.


Condition Intervention Phase
Schizophrenia
Drug: Metformin
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Metformin in the Treatment of Antipsychotic-Induced Weight Gain in Schizophrenia (METS) - Pilot Study

Resource links provided by NLM:


Further study details as provided by National Institute of Mental Health (NIMH):

Primary Outcome Measures:
  • Mean Difference in Body Weight Change Between Participants Assigned to Metformin and Participants Assigned to Placebo [ Time Frame: Measured at the last study visit ] [ Designated as safety issue: No ]
    Mean difference in body weight change between participants assigned to metformin and participants assigned to placebo from baseline to last study visit (up to 16 weeks)


Secondary Outcome Measures:
  • Change in Total Cholesterol From Baseline to 16 Weeks [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Total cholesterol

  • Change in HDL Cholesterol From Baseline to 16 Weeks [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    high-density lipoprotein

  • Change in LDL Cholesterol From Baseline to 16 Weeks [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    low-density lipoprotein

  • Change in Triglycerides From Baseline to 16 Weeks [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    serum triglycerides

  • Change in Fasting Glucose From Baseline to 16 Weeks [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    fasting blood glucose

  • Change in Fasting Insulin From Baseline to 16 Weeks [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Fasting insulin

  • Change in Hemoglobin A1c From Baseline to 16 Weeks [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    glycosylated hemoglobin


Enrollment: 146
Study Start Date: January 2009
Study Completion Date: March 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Metformin
Encapsulated metformin 1000-2000 mg/day
Drug: Metformin
500 mg to 1,000 mg taken twice daily for 16 weeks
Other Name: Glucophage
Placebo Comparator: Placebo
Matching placebo capsules 2-4 daily
Drug: Placebo
1 to 2 placebo capsules taken twice daily for 16 weeks
Other Name: Placebo

Detailed Description:

Schizophrenia is a chronic mental disorder that is characterized, in part, by psychotic symptoms. Psychotic symptoms include hallucinations and delusions, in which a person has abnormal experiences or beliefs, and are commonly treated with antipsychotic medications. Unfortunately, a side effect of many antipsychotics is unwanted weight gain, which can lead to physical illness. Use of the drug metformin has resulted in weight loss among diabetics. Metformin has also been shown to cause weight loss in preliminary studies of people taking atypical antipsychotics—a newer, second generation of antipsychotic medications. Metformin is currently approved by the Food and Drug Administration to treat only people with diabetes. This study will test the usefulness of prescribing metformin as a second medication to treat people with schizophrenia or schizoaffective disorder who are overweight and taking antipsychotics. The study will also provide important feasibility information for future larger studies.

Participation in this study will last 16 weeks. After undergoing baseline assessments, participants will be randomly assigned to receive either metformin or placebo, both of which will be taken twice daily for the duration of the study. All participants will also receive behavioral therapy that will teach them about reducing their weight through diet and exercise. Participants will undergo assessments at 11 study visits: the first 2 will include screening and baseline testing, the next 2 visits will take place after the first and second weeks of receiving treatment, and the last 7 visits will take place every 2 weeks until the end of the study. Assessments will include measurements of body weight, waist-to-hip ratio, and vital signs; clinical interviews about medication adherence, side effects, and alcohol use; and monthly blood tests to assess levels of lipids, glucose, insulin, and hemoglobin A1c.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Outpatients with a diagnosis of schizophrenia or schizoaffective disorder, as defined by DSM-IV-TR criteria and confirmed by the Structured Clinical Interview for DSM-IV (SCID)
  • Duration of illness greater than 1 year, as defined by having initiated antipsychotic treatment at least 1 year prior to study entry
  • Adequate decisional capacity to make a choice about participating in this research study
  • Body mass index (BMI) at or greater than 27
  • Currently being treated with one or a combination of two antipsychotic medications (typical or atypical) and on that drug regimen for at least 2 months prior to study entry, with stable dosages for at least 1 month
  • If taking antidepressants, mood stabilizers, or anxiolytics, the dose must be stable for at least 1 month prior to study entry
  • Willing to use an adequate method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after the study. Acceptable methods include oral, injectable, or implanted contraceptives; intrauterine devices or barrier methods such as condoms; and diaphragms and spermicides.

Exclusion Criteria:

  • Inpatient status
  • Clinical Global Impression Severity (CGI-S) score greater than 6
  • Currently being treated with more than two antipsychotic medications
  • Fasting glucose greater than 125
  • Diagnosis of diabetes mellitus or treatment with insulin or oral hypoglycemics
  • Previous or current treatment with metformin
  • Diagnosis of congestive heart failure
  • Renal impairment, as defined by a serum creatinine level greater than 1.5 in males or greater than 1.4 in females, or creatinine estimated glomerular filtration rate (GFR) outside of normal limits
  • Hepatic disease, as defined by aspartate transaminase (AST), alanine transaminase (ALT), or c-glutamyl transferase (CGT) greater than 1.5 times upper limit of normal (ULN), or total bilirubin greater than 1.2 times ULN
  • Metabolic acidosis, as defined by serum carbon dioxide less than the lower limit of normal
  • Known hypersensitivity to metformin
  • Pregnant or breastfeeding
  • Recent (in the past 30 days) or scheduled radiological studies involving iodinated contrast material
  • Alcohol abuse or dependence within the past month, as determined by the SCID
  • Other serious and unstable medical condition in the judgment of the investigator
  • Diagnosis of mental retardation, delirium, or dementia, as defined by DSM-IV-TR
  • Failed to discontinue 4 weeks prior to study entry any medication used for weight loss
  • Concurrent treatment with certain drugs that are known to increase metformin blood levels should be discussed with the Project Medical Officer.
  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: NCT00816907

Locations
United States, California
Stanford University
Palo Alto, California, United States, 94305
United States, Florida
Mental Health Advocates
Boca Raton, Florida, United States, 33431
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, Kansas
Clinical Research Institute
Wichita, Kansas, United States, 67207
United States, Maryland
Clinical Insights
Glen Burnie, Maryland, United States, 21061
United States, Massachusetts
Freedom Trail Clinic
Boston, Massachusetts, United States, 02114
University of Massachusetts
Worcester, Massachusetts, United States, 01605
United States, Minnesota
University of Minnesota School of Medicine
Minneapolis, Minnesota, United States, 55454
United States, New Mexico
New Mexico VA Healthcare System
Albuquerque, New Mexico, United States, 87108
United States, New York
Research Foundation for Mental Hygiene
New York, New York, United States, 10032
University of Rochester
Rochester, New York, United States, 14623
United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45267
United States, Tennessee
Vanderbilt University Schizophrenia Research
Nashville, Tennessee, United States, 37212
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75235
Baylor College of Medicine
Houston, Texas, United States, 77030
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Investigators
Principal Investigator: L. Fredrik Jarskog, MD Columbia University
Principal Investigator: Jeffrey A. Lieberman, MD Columbia University
Principal Investigator: T. Scott Stroup, MD, MPH Columbia University
  More Information

No publications provided by National Institute of Mental Health (NIMH)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier: NCT00816907     History of Changes
Other Study ID Numbers: N01 MH090001-03, N01MH90001 DSIR AT
Study First Received: January 2, 2009
Results First Received: January 3, 2013
Last Updated: February 13, 2013
Health Authority: United States: Federal Government

Keywords provided by National Institute of Mental Health (NIMH):
Schizoaffective Disorder

Additional relevant MeSH terms:
Schizophrenia
Weight Gain
Body Weight
Body Weight Changes
Mental Disorders
Schizophrenia and Disorders with Psychotic Features
Signs and Symptoms
Antipsychotic Agents
Metformin
Central Nervous System Agents
Central Nervous System Depressants
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on October 30, 2014