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

Sponsor:	National Institute of Mental Health (NIMH)
Information provided by:	National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier:	NCT00816907

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 Behavioral: Behavioral therapy Drug: Placebo	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	Metformin in the Treatment of Antipsychotic-Induced Weight Gain in Schizophrenia (METS) - Pilot Study

Resource links provided by NLM:

MedlinePlus related topics: Mental Health Schizophrenia

Drug Information available for: Metformin Metformin hydrochloride

U.S. FDA Resources

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

Primary Outcome Measures:

Identification of appropriate clinical sites to mount the proposed clinical trial [ Time Frame: Measured pre- and post-treatment ] [ Designated as safety issue: No ]
Feasibility of enrolling a cohort of participants meeting the inclusion and exclusion criteria of the study [ Time Frame: Measured pre- and post-treatment ] [ Designated as safety issue: No ]
Feasibility of protocol implementation with a high level of protocol adherence and low participant attrition [ Time Frame: Measured over 16 weeks of study visits ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Mean difference in body weight between participants assigned to metformin and participants assigned to placebo [ Time Frame: Measured at the last study visit ] [ Designated as safety issue: No ]
Effect of metformin on waist-hip ratio, fasting lipid levels (including total cholesterol, high density lipoprotein [HDL], low density lipoprotein [LDL], triglycerides), fasting glucose, fasting insulin, and hemoglobin A1c [ Time Frame: Measured over 16 weeks of study visits ] [ Designated as safety issue: No ]

Estimated Enrollment:	80
Study Start Date:	January 2009
Estimated Study Completion Date:	April 2010
Estimated Primary Completion Date:	February 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Metformin: Experimental	Drug: Metformin 500 mg to 1,000 mg taken twice daily for 16 weeks Behavioral: Behavioral therapy Individualized behavioral treatment aimed at modifying weight and activity level
Placebo: Placebo Comparator	Behavioral: Behavioral therapy Individualized behavioral treatment aimed at modifying weight and activity level Drug: Placebo 1 to 2 placebo tablets taken twice daily for 16 weeks

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

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
Baylor College of Medicine
Houston, Texas, United States, 77030
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78229
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75235

Sponsors and Collaborators

National Institute of Mental Health (NIMH)

Investigators

Principal Investigator:	L. Fredrik Jarskog, MD	Columbia University
Principal Investigator:	Jeffrey A. Lieberman, MD	Columbia University
Principal Investigator:	T. Scott Stroup, MD, MPH	The University of North Carolina, Chapel Hill

More Information

No publications provided

Responsible Party:	University of North Carolina at Chapel Hill ( T. Scott Stroup, MD, MPH )
Study ID Numbers:	N01 MH090001-03, N01MH90001 DSIR AT
Study First Received:	January 2, 2009
Last Updated:	November 13, 2009
ClinicalTrials.gov Identifier:	NCT00816907 History of Changes
Health Authority:	United States: Federal Government

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

Schizoaffective Disorder

Additional relevant MeSH terms:

Tranquilizing Agents
Metformin
Physiological Effects of Drugs
Psychotropic Drugs
Central Nervous System Depressants
Weight Gain
Antipsychotic Agents
Pharmacologic Actions
Schizophrenia

Body Weight
Signs and Symptoms
Hypoglycemic Agents
Mental Disorders
Therapeutic Uses
Body Weight Changes
Central Nervous System Agents
Schizophrenia and Disorders with Psychotic Features

ClinicalTrials.gov processed this record on November 20, 2009