Rosiglitazone for Clozapine Induced Glucose Metabolism Impairment

• Status: Completed
• Trial end date: 2011-01-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Massachusetts General Hospital
• Collaborators: National Alliance for Research on Schizophrenia and Depression; Stanley Medical Research Institute
• Treatments: Clozapine; Rosiglitazone

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)