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

Schizophrenia Clinical Trial

— METS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00816907
• Other study ID #: N01 MH090001-03
• Secondary ID: N01MH90001 DSIR
• Status: Completed
• Phase: Phase 4
• First received: January 2, 2009
• Last updated: February 13, 2013
• Start date: January 2009
• Est. completion date: March 2010

Study information

• Verified date: November 2010
• Source: National Institute of Mental Health (NIMH)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 146
• Est. completion date: March 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Schizophrenia
• Weight Gain

Intervention

Drug:
• Metformin
500 mg to 1,000 mg taken twice daily for 16 weeks
• Placebo
1 to 2 placebo capsules taken twice daily for 16 weeks

Locations

Country	Name	City	State
United States	New Mexico VA Healthcare System	Albuquerque	New Mexico
United States	Mental Health Advocates	Boca Raton	Florida
United States	Freedom Trail Clinic	Boston	Massachusetts
United States	University of Cincinnati	Cincinnati	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Clinical Insights	Glen Burnie	Maryland
United States	Baylor College of Medicine	Houston	Texas
United States	University of Iowa	Iowa City	Iowa
United States	University of Minnesota School of Medicine	Minneapolis	Minnesota
United States	Vanderbilt University Schizophrenia Research	Nashville	Tennessee
United States	Research Foundation for Mental Hygiene	New York	New York
United States	Stanford University	Palo Alto	California
United States	University of Rochester	Rochester	New York
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Clinical Research Institute	Wichita	Kansas
United States	University of Massachusetts	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Change in Total Cholesterol From Baseline to 16 Weeks	Total cholesterol	16 weeks	No
Secondary	Change in HDL Cholesterol From Baseline to 16 Weeks	high-density lipoprotein	16 weeks	No
Secondary	Change in LDL Cholesterol From Baseline to 16 Weeks	low-density lipoprotein	16 weeks	No
Secondary	Change in Triglycerides From Baseline to 16 Weeks	serum triglycerides	16 weeks	No
Secondary	Change in Fasting Glucose From Baseline to 16 Weeks	fasting blood glucose	16 weeks	No
Secondary	Change in Fasting Insulin From Baseline to 16 Weeks	Fasting insulin	16 weeks	No
Secondary	Change in Hemoglobin A1c From Baseline to 16 Weeks	glycosylated hemoglobin	16 weeks	No