Rosiglitazone for Clozapine Induced Glucose Metabolism Impairment - Full Text View

Sponsor:	Massachusetts General Hospital
Collaborators:	National Alliance for Research on Schizophrenia and Depression Stanley Medical Research Institute
Information provided by:	Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT00337350

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: Drug: Rosiglitazone	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Double-Blind 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:

MedlinePlus related topics: Diabetes Medicines Schizophrenia

Drug Information available for: Dextrose Rosiglitazone Rosiglitazone Maleate Clozapine

U.S. FDA Resources

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:

Compare the effects of treatment with rosiglitazone to placebo in schizophrenia subjects treated with clozapine on insulin SI, SG, and AIRG.
Correlate the findings on SI, SG, and AIRG with change in BMI, body composition, family history, age, sex, race, diet, exercise, weight gain, and lipid abnormalities.
Determine if rosiglitazone, compared to placebo, improves other variables associated with insulin resistance such as cognitive deficits and lipid abnormalities.

Estimated Enrollment:	50
Study Start Date:	September 2003
Estimated Study Completion Date:	January 2011
Estimated Primary Completion Date:	January 2011 (Final data collection date for primary outcome measure)

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

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:

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Hagg S, Joelsson L, Mjorndal T, Spigset O, Oja G, Dahlqvist R. Prevalence of diabetes and impaired glucose tolerance in patients treated with clozapine compared with patients treated with conventional depot neuroleptic medications. J Clin Psychiatry. 1998 Jun;59(6):294-9.

HAMILTON M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960 Feb;23:56-62. No abstract available.

Henderson DC, Cagliero E, Gray C, Nasrallah RA, Hayden DL, Schoenfeld DA, Goff DC. Clozapine, diabetes mellitus, weight gain, and lipid abnormalities: A five-year naturalistic study. Am J Psychiatry. 2000 Jun;157(6):975-81.

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Lamberti JS, Bellnier T, Schwarzkopf SB. Weight gain among schizophrenic patients treated with clozapine. Am J Psychiatry. 1992 May;149(5):689-90.

Nuechterlein KH, Dawson ME, Gitlin M, Ventura J, Goldstein MJ, Snyder KS, Yee CM, Mintz J. Developmental Processes in Schizophrenic Disorders: longitudinal studies of vulnerability and stress. Schizophr Bull. 1992;18(3):387-425.

Newcomer JW, Haupt DW, Fucetola R, Melson AK, Schweiger JA, Cooper BP, Selke G. Abnormalities in glucose regulation during antipsychotic treatment of schizophrenia. Arch Gen Psychiatry. 2002 Apr;59(4):337-45. Review.

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Skre I, Onstad S, Torgersen S, Kringlen E. High interrater reliability for the Structured Clinical Interview for DSM-III-R Axis I (SCID-I). Acta Psychiatr Scand. 1991 Aug;84(2):167-73.

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Valdes CT, Elkind-Hirsch KE. Intravenous glucose tolerance test-derived insulin sensitivity changes during the menstrual cycle. J Clin Endocrinol Metab. 1991 Mar;72(3):642-6.

Ventura J, Liberman RP, Green MF, Shaner A, Mintz J. Training and quality assurance with the Structured Clinical Interview for DSM-IV (SCID-I/P). Psychiatry Res. 1998 Jun 15;79(2):163-73.

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Ware J Jr, Kosinski M, Keller SD. A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. Med Care. 1996 Mar;34(3):220-33.

Wirshing DA, Spellberg BJ, Erhart SM, Marder SR, Wirshing WC. Novel antipsychotics and new onset diabetes. Biol Psychiatry. 1998 Oct 15;44(8):778-83.

Responsible Party:	David C. Henderson, Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT00337350 History of Changes
Other Study ID Numbers:	2003-P-000014
Study First Received:	June 13, 2006
Last Updated:	May 3, 2010
Health Authority:	United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:

Schizophrenia
Glucose Metabolism
Insulin Resistance

Additional relevant MeSH terms:

Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Clozapine
Rosiglitazone
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
GABA Antagonists
GABA Agents
Hypoglycemic Agents

ClinicalTrials.gov processed this record on February 09, 2012