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Rosiglitazone for Clozapine Induced Glucose Metabolism Impairment

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ClinicalTrials.gov Identifier: NCT00337350
Recruitment Status : Completed
First Posted : June 15, 2006
Results First Posted : March 6, 2013
Last Update Posted : May 8, 2015
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

Brief 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.

Condition or disease Intervention/treatment Phase
Schizophrenia Drug: rosiglitazone Drug: placebo Phase 4

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple (Participant, 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
Study Start Date : September 2003
Actual Primary Completion Date : January 2011
Actual Study Completion Date : January 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia

Arm Intervention/treatment
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




Primary Outcome Measures :
  1. Change From Baseline in Insulin Sensitivity [ Time Frame: baseline, week 8 ]
    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).

  2. Change From Baseline on Glucose Utilization (SG) [ Time Frame: baseline, week 8 ]
    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.

  3. Change From Baseline in Acute Insulin Response to Glucose (AIRG) [ Time Frame: baseline, week 8 ]
    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.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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

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
First Posted: June 15, 2006    Key Record Dates
Results First Posted: March 6, 2013
Last Update Posted: May 8, 2015
Last Verified: April 2015

Keywords provided by David C. Henderson, Massachusetts General Hospital:
Schizophrenia
Glucose Metabolism
Insulin Resistance

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Rosiglitazone
Clozapine
Hypoglycemic Agents
Physiological Effects of Drugs
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
GABA Antagonists
GABA Agents