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

NCT ID: NCT00816907

Last Updated: 2013-03-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 146 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-31
• Study Completion Date: 2010-03-31

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.

Conditions

Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Metformin

Encapsulated metformin 1000-2000 mg/day

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

500 mg to 1,000 mg taken twice daily for 16 weeks

Placebo

Matching placebo capsules 2-4 daily

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

1 to 2 placebo capsules taken twice daily for 16 weeks

Interventions

Metformin

500 mg to 1,000 mg taken twice daily for 16 weeks

Intervention Type: DRUG

Placebo

1 to 2 placebo capsules taken twice daily for 16 weeks

Intervention Type: DRUG

Other Intervention Names

Glucophage

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

L. Fredrik Jarskog, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Jeffrey A. Lieberman, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

T. Scott Stroup, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Stanford University

Palo Alto, California, United States

Mental Health Advocates

Boca Raton, Florida, United States

University of Iowa

Iowa City, Iowa, United States

Clinical Research Institute

Wichita, Kansas, United States

Clinical Insights

Glen Burnie, Maryland, United States

Freedom Trail Clinic

Boston, Massachusetts, United States

University of Massachusetts

Worcester, Massachusetts, United States

University of Minnesota School of Medicine

Minneapolis, Minnesota, United States

New Mexico VA Healthcare System

Albuquerque, New Mexico, United States

Research Foundation for Mental Hygiene

New York, New York, United States

University of Rochester

Rochester, New York, United States

University of Cincinnati

Cincinnati, Ohio, United States

Vanderbilt University Schizophrenia Research

Nashville, Tennessee, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Baylor College of Medicine

Houston, Texas, United States

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Countries

United States

References

Wang B, Ogburn EL, Rosenblum M. Analysis of covariance in randomized trials: More precision and valid confidence intervals, without model assumptions. Biometrics. 2019 Dec;75(4):1391-1400. doi: 10.1111/biom.13062. Epub 2019 Jun 3.

Reference Type: DERIVED

PMID: 31009064 (View on PubMed)

Jarskog LF, Hamer RM, Catellier DJ, Stewart DD, Lavange L, Ray N, Golden LH, Lieberman JA, Stroup TS; METS Investigators. Metformin for weight loss and metabolic control in overweight outpatients with schizophrenia and schizoaffective disorder. Am J Psychiatry. 2013 Sep;170(9):1032-40. doi: 10.1176/appi.ajp.2013.12010127.

Reference Type: DERIVED

PMID: 23846733 (View on PubMed)

Khan AY, Macaluso M, McHale RJ, Dahmen MM, Girrens K, Ali F. The adjunctive use of metformin to treat or prevent atypical antipsychotic-induced weight gain: a review. J Psychiatr Pract. 2010 Sep;16(5):289-96. doi: 10.1097/01.pra.0000388624.91039.a3.

Reference Type: DERIVED

PMID: 20859106 (View on PubMed)

Other Identifiers

N01MH90001 DSIR AT

Identifier Type: OTHER

Identifier Source: secondary_id

N01MH90001

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01MH090001

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01 MH090001-03

Identifier Type: -

Identifier Source: org_study_id