Rosiglitazone for Clozapine Induced Glucose Metabolism Impairment
Condition: Schizophrenia
MeSH terms: Schizophrenia
Intervention: rosiglitazone; placebo
Intervention description: Rosiglitazone 4mg, one capsule per day for eight weeks; matched placebo for rosiglitazone 4mg/day
Intervention MeSH terms: Rosiglitazone
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Schizophrenia; Glucose Metabolism; Insulin Resistance

Summary:

      We propose an eight-week, double-blind, placebo-controlled trial of rosiglitazone in
      schizophrenia subjects treated with clozapine using Bergman's Minimal Model (MINMOD)
      intravenous glucose tolerance test. Bergman's Minimal Model analysis with frequent sampled
      intravenous glucose tolerance test (FSIVGTT) provides a sensitive and reliable method to
      measure glucose effectiveness, insulin secretion and insulin sensitivity. The MINMOD
      determines the relationship between insulin sensitivity, insulin secretion and the degree of
      obesity and can be used to study drug effects upon these variables.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female

          -  Age 18-65 years

          -  Diagnosis of schizophrenia, any subtype, schizoaffective disorder, any subtype or
             schizophreniform disorder

          -  Well established compliance with out-patient medications

          -  Current treatment with clozapine for a minimum of one year

          -  Evidence of insulin resistance: impaired fasting glucose (glucose ≥100 mg/dl) or
             hyperinsulinemia (fasting insulin ≥ 15 ng/dl) or a HOMA-IR (homeostasis model
             assessment for insulin resistance) (fasting glucose X fasting insulin/22.5) ≥2 or a SI
             (insulin sensitivity index)

        Exclusion Criteria:

          -  Inability to provide informed consent

          -  Current substance abuse

          -  Significant medical illness, including congestive heart failure, severe cardiovascular
             disease, renal disease (serum creatinine > 1.5), anemia (Hemoglobin < 11.0 gm/dL) or
             psychiatrically unstable

          -  Severe hepatic impairment, active liver disease or increased serum transaminase levels
             (ALT>2.0X upper limit of normal) If at any time, ALT increases to 2X ULN, the
             subject's participation in the study will be terminated.

          -  Women of child bearing potential who are pregnant, breastfeeding, or who are unwilling
             or unable to use an effective form of birth control during the entire study

          -  Treatment with agents that induce weight loss

          -  History of diabetes mellitus or thyroid disease

          -  Current treatment with an oral hypoglycemic agent or insulin

          -  Known hypersensitivity to rosiglitazone or any of its components

          -  Fasting Glucose >126 mg/dL11. Treatment with other atypical antipsychotic agents
             thought to impair glucose metabolism (olanzapine) or low potency conventional agents
             (thioridazine, chlorpromazine)