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Rosiglitazone for Clozapine Induced Glucose Metabolism Impairment

This study has been completed.
Sponsor:
Collaborators:
National Alliance for Research on Schizophrenia and Depression
Stanley Medical Research Institute
Information provided by (Responsible Party):
David C. Henderson, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00337350
First received: June 13, 2006
Last updated: January 30, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Schizophrenia
Drug: rosiglitazone
Drug: placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Double-Blind, Placebo-Controlled Trial of Rosiglitazone for Clozapine Induced Glucose Metabolism Impairment: Bergman's Minimal Model Analysis

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Change From Baseline in Insulin Sensitivity [ Time Frame: baseline, week 8 ] [ Designated as safety issue: No ]
    Insulin Sensitivity (IS) was assessed using a Frequently Sampled Intravenous Glucose Tolerance Test (FSIVGTT), performed at Baseline and at week 8 (study endpoint). Subjects in the Rosiglitazone treatment arm were compared to subjects in the placebo treatment arm on their change in IS between Baseline and week 8. SI was calculated from plasma glucose and serum insulin values using the MINMOD Millennium computer program. SI represents the increase in net fractional glucose clearance rate per unit change in serum insulin concentration after the intravenous glucose load (microUnits/mL).

  • Change From Baseline on Glucose Utilization (SG) [ Time Frame: baseline, week 8 ] [ Designated as safety issue: No ]
    Glucose utilization (SG) was assessed using a Frequently Sampled Intravenous Glucose Tolerance Test (FSIVGTT), performed at Baseline and at week 8 (study endpoint). Subjects in the Rosiglitazone treatment arm were compared to subjects in the placebo treatment arm on their change in SG between Baseline and week 8. SG was calculated from plasma glucose and serum insulin values using the MINMOD Millennium computer program. SG represents the net fractional glucose clearance rate because of the increase in glucose independent of any increase in circulating insulin concentrations above baseline.

  • Change From Baseline in Acute Insulin Response to Glucose (AIRG) [ Time Frame: baseline, week 8 ] [ Designated as safety issue: No ]
    Acute insulin response to glucose (AIRG) was assessed using a Frequently Sampled Intravenous Glucose Tolerance Test (FSIVGTT), performed at Baseline and at week 8 (study endpoint). Subjects in the Rosiglitazone treatment arm were compared to subjects in the placebo treatment arm on their change in SG between Baseline and week 8. AIRG was calculated from plasma glucose and serum insulin values using the MINMOD Millennium computer program. AIRG measures the acute(0-10 min) beta\ cell response to a glucose load calculated by the areas under the curve higher than basal insulin values. The AIRG was assessed as the incremental area under the curve (calculated by the trapezoid rule) from 0 to 10 min of the FSIVGTT.


Enrollment: 20
Study Start Date: September 2003
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: rosiglitazone
rosiglitazone 4mg/day
Drug: rosiglitazone
Rosiglitazone 4mg, one capsule per day for eight weeks
Placebo Comparator: placebo
matched placebo for 4mg rosiglitazone
Drug: placebo
matched placebo for rosiglitazone 4mg/day

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00337350

Locations
United States, Massachusetts
Massachusetts General Hospital Schizophrenia Program
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
National Alliance for Research on Schizophrenia and Depression
Stanley Medical Research Institute
Investigators
Principal Investigator: David C Henderson, MD Massachusetts General Hospital
  More Information

Publications:

Responsible Party: David C. Henderson, Associate Professor of Psychiatry, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00337350     History of Changes
Other Study ID Numbers: 2003-P-000014
Study First Received: June 13, 2006
Results First Received: December 19, 2012
Last Updated: January 30, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
Schizophrenia
Glucose Metabolism
Insulin Resistance

Additional relevant MeSH terms:
Schizophrenia
Mental Disorders
Schizophrenia and Disorders with Psychotic Features
Rosiglitazone
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 25, 2014