The Use of Metformin in the Treatment of Antipsychotic-Induced Weight Gain in Schizophrenia (The METS Study)
Condition: Schizophrenia
MeSH terms: Weight Gain; Schizophrenia
Intervention: Metformin; Placebo
Intervention description: 500 mg to 1,000 mg taken twice daily for 16 weeks; 1 to 2 placebo capsules taken twice daily for 16 weeks
Intervention MeSH terms: Metformin
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 146.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Schizoaffective Disorder

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.
    

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.