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

Phase 4

Completed

• Conditions: Schizophrenia
• Interventions: Drug: Metformin; Drug: Placebo

• Registration Number: NCT00816907
• Lead Sponsor: National Institute of Mental Health (NIMH)

Brief Summary

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.

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.

Study Timeline

• Study Start: 2009-01
• Study First Submitted: 2009-01-02
• Study First Submitted QC: 2009-01-02
• Study First Posted: 2009-01-05
• Primary Completion: 2010-02
• Study Completion: 2010-03
• Status Verified: 2010-11
• Results First Submitted: 2013-01-03
• Results First Submitted QC: 2013-02-13
• Last Update Submitted: 2013-02-13
• Results First Posted: 2013-03-27
• Last Update Posted: 2013-03-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 146

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Metformin	Metformin	Encapsulated metformin 1000-2000 mg/day
Placebo	Placebo	Matching placebo capsules 2-4 daily

Primary Outcome Measures

Name	Time	Method
Mean Difference in Body Weight Change Between Participants Assigned to Metformin and Participants Assigned to Placebo	Measured at the last study visit	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

Name	Time	Method
Change in Total Cholesterol From Baseline to 16 Weeks	16 weeks	Total cholesterol
Change in HDL Cholesterol From Baseline to 16 Weeks	16 weeks	high-density lipoprotein
Change in LDL Cholesterol From Baseline to 16 Weeks	16 weeks	low-density lipoprotein
Change in Triglycerides From Baseline to 16 Weeks	16 weeks	serum triglycerides
Change in Fasting Glucose From Baseline to 16 Weeks	16 weeks	fasting blood glucose
Change in Fasting Insulin From Baseline to 16 Weeks	16 weeks	Fasting insulin
Change in Hemoglobin A1c From Baseline to 16 Weeks	16 weeks	glycosylated hemoglobin

Trial Locations

Locations (16)

Baylor College of Medicine; 🇺🇸 Houston, Texas, United States

Mental Health Advocates; 🇺🇸 Boca Raton, Florida, United States

University of Texas Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

Clinical Research Institute; 🇺🇸 Wichita, Kansas, United States

University of Rochester; 🇺🇸 Rochester, New York, United States

University of Iowa; 🇺🇸 Iowa City, Iowa, United States

Clinical Insights; 🇺🇸 Glen Burnie, Maryland, United States

University of Massachusetts; 🇺🇸 Worcester, Massachusetts, United States

University of Minnesota School of Medicine; 🇺🇸 Minneapolis, Minnesota, United States

Research Foundation for Mental Hygiene; 🇺🇸 New York, New York, United States

Vanderbilt University Schizophrenia Research; 🇺🇸 Nashville, Tennessee, United States

University of Cincinnati; 🇺🇸 Cincinnati, Ohio, United States

University of Texas Health Science Center at San Antonio; 🇺🇸 San Antonio, Texas, United States

Stanford University; 🇺🇸 Palo Alto, California, United States

Freedom Trail Clinic; 🇺🇸 Boston, Massachusetts, United States

New Mexico VA Healthcare System; 🇺🇸 Albuquerque, New Mexico, United States