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

NCT00816907 | Completed Phase 4 Results DMC

• 4 other identifiers: N01 MH090001-03N01MH90001 DSIR ATN01MH90001N01MH090001
• Study Type: interventional
• Target: 146
• Locations: 1 country
• Sites: 16

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.

Conditions

Schizophrenia

Keywords

Schizoaffective Disorder

Outcome Measures

Primary Outcomes (1)

• Mean Difference in Body Weight Change Between Participants Assigned to Metformin and Participants Assigned to Placebo

  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)

  Measured at the last study visit

Secondary Outcomes (7)

• Change in Total Cholesterol From Baseline to 16 Weeks

  16 weeks

• Change in HDL Cholesterol From Baseline to 16 Weeks

  16 weeks

• Change in LDL Cholesterol From Baseline to 16 Weeks

  16 weeks

• Change in Triglycerides From Baseline to 16 Weeks

  16 weeks

• Change in Fasting Glucose From Baseline to 16 Weeks

  16 weeks

Study Arms (2)

Metformin

EXPERIMENTAL

Encapsulated metformin 1000-2000 mg/day

Drug: Metformin

Placebo

PLACEBO COMPARATOR

Matching placebo capsules 2-4 daily

Drug: Placebo

Interventions

Metformin DRUG

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

Also known as: Glucophage

Metformin

Placebo DRUG

1 to 2 placebo capsules taken twice daily for 16 weeks

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (16)

Stanford University

Palo Alto, California, 94305, United States

Location

Mental Health Advocates

Boca Raton, Florida, 33431, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Clinical Research Institute

Wichita, Kansas, 67207, United States

Location

Clinical Insights

Glen Burnie, Maryland, 21061, United States

Location

Freedom Trail Clinic

Boston, Massachusetts, 02114, United States

Location

University of Massachusetts

Worcester, Massachusetts, 01605, United States

Location

University of Minnesota School of Medicine

Minneapolis, Minnesota, 55454, United States

Location

New Mexico VA Healthcare System

Albuquerque, New Mexico, 87108, United States

Location

Research Foundation for Mental Hygiene

New York, New York, 10032, United States

Location

University of Rochester

Rochester, New York, 14623, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Vanderbilt University Schizophrenia Research

Nashville, Tennessee, 37212, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75235, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

Related Publications (3)

• 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.

  PMID: 31009064 DERIVED

• 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.

  PMID: 23846733 DERIVED

• 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.

  PMID: 20859106 DERIVED

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

Metformin

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Limitations and Caveats

Changes over periods of more than 16 weeks are unknown.

Results Point of Contact

• Title: Dr. Scott Stroup
• Organization: Columbia University

stroups@nyspi.columbia.edu

212-543-5676

Study Officials

• L. Fredrik Jarskog, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

• Jeffrey A. Lieberman, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

• T. Scott Stroup, MD, MPH

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2009
• First Posted: January 5, 2009
• Study Start: January 1, 2009
• Primary Completion: February 1, 2010
• Study Completion: March 1, 2010
• Last Updated: March 27, 2013
• Results First Posted: March 27, 2013

Record last verified: 2010-11

Locations

US (16)