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

Primary Purpose

Schizophrenia

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Metformin
Placebo
Sponsored by
National Institute of Mental Health (NIMH)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Schizophrenia focused on measuring Schizoaffective Disorder

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Stanford University
  • Mental Health Advocates
  • University of Iowa
  • Clinical Research Institute
  • Clinical Insights
  • Freedom Trail Clinic
  • University of Massachusetts
  • University of Minnesota School of Medicine
  • New Mexico VA Healthcare System
  • Research Foundation for Mental Hygiene
  • University of Rochester
  • University of Cincinnati
  • Vanderbilt University Schizophrenia Research
  • University of Texas Southwestern Medical Center
  • Baylor College of Medicine
  • University of Texas Health Science Center at San Antonio

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Metformin

Placebo

Arm Description

Encapsulated metformin 1000-2000 mg/day

Matching placebo capsules 2-4 daily

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

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

Full Information

First Posted
January 2, 2009
Last Updated
February 13, 2013
Sponsor
National Institute of Mental Health (NIMH)
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1. Study Identification

Unique Protocol Identification Number
NCT00816907
Brief Title
The Use of Metformin in the Treatment of Antipsychotic-Induced Weight Gain in Schizophrenia (The METS Study)
Acronym
METS
Official Title
Metformin in the Treatment of Antipsychotic-Induced Weight Gain in Schizophrenia (METS) - Pilot Study
Study Type
Interventional

2. Study Status

Record Verification Date
November 2010
Overall Recruitment Status
Completed
Study Start Date
January 2009 (undefined)
Primary Completion Date
February 2010 (Actual)
Study Completion Date
March 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Mental Health (NIMH)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia
Keywords
Schizoaffective Disorder

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
146 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Metformin
Arm Type
Experimental
Arm Description
Encapsulated metformin 1000-2000 mg/day
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebo capsules 2-4 daily
Intervention Type
Drug
Intervention Name(s)
Metformin
Other Intervention Name(s)
Glucophage
Intervention Description
500 mg to 1,000 mg taken twice daily for 16 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
1 to 2 placebo capsules taken twice daily for 16 weeks
Primary Outcome Measure Information:
Title
Mean Difference in Body Weight Change Between Participants Assigned to Metformin and Participants Assigned to Placebo
Description
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)
Time Frame
Measured at the last study visit
Secondary Outcome Measure Information:
Title
Change in Total Cholesterol From Baseline to 16 Weeks
Description
Total cholesterol
Time Frame
16 weeks
Title
Change in HDL Cholesterol From Baseline to 16 Weeks
Description
high-density lipoprotein
Time Frame
16 weeks
Title
Change in LDL Cholesterol From Baseline to 16 Weeks
Description
low-density lipoprotein
Time Frame
16 weeks
Title
Change in Triglycerides From Baseline to 16 Weeks
Description
serum triglycerides
Time Frame
16 weeks
Title
Change in Fasting Glucose From Baseline to 16 Weeks
Description
fasting blood glucose
Time Frame
16 weeks
Title
Change in Fasting Insulin From Baseline to 16 Weeks
Description
Fasting insulin
Time Frame
16 weeks
Title
Change in Hemoglobin A1c From Baseline to 16 Weeks
Description
glycosylated hemoglobin
Time Frame
16 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
L. Fredrik Jarskog, MD
Organizational Affiliation
Columbia University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jeffrey A. Lieberman, MD
Organizational Affiliation
Columbia University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
T. Scott Stroup, MD, MPH
Organizational Affiliation
Columbia University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Mental Health Advocates
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33431
Country
United States
Facility Name
University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Clinical Research Institute
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67207
Country
United States
Facility Name
Clinical Insights
City
Glen Burnie
State/Province
Maryland
ZIP/Postal Code
21061
Country
United States
Facility Name
Freedom Trail Clinic
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
University of Massachusetts
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01605
Country
United States
Facility Name
University of Minnesota School of Medicine
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55454
Country
United States
Facility Name
New Mexico VA Healthcare System
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87108
Country
United States
Facility Name
Research Foundation for Mental Hygiene
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
University of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14623
Country
United States
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Vanderbilt University Schizophrenia Research
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37212
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Texas Health Science Center at San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
31009064
Citation
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.
Results Reference
derived
PubMed Identifier
23846733
Citation
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.
Results Reference
derived
PubMed Identifier
20859106
Citation
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.
Results Reference
derived

Learn more about this trial

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

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