Rosiglitazone for Clozapine Induced Glucose Metabolism Impairment

NCT00337350 | Completed Phase 4 Results

• 1 other identifier: 2003-P-000014
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Schizophrenia

Keywords

Schizophrenia; Glucose Metabolism; Insulin Resistance

Outcome Measures

Primary Outcomes (3)

• Change From Baseline in Insulin Sensitivity

  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).

  baseline, week 8

• Change From Baseline on Glucose Utilization (SG)

  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.

  baseline, week 8

• Change From Baseline in Acute Insulin Response to Glucose (AIRG)

  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.

  baseline, week 8

Study Arms (2)

rosiglitazone

ACTIVE COMPARATOR

rosiglitazone 4mg/day

Drug: rosiglitazone

placebo

PLACEBO COMPARATOR

matched placebo for 4mg rosiglitazone

Drug: placebo

Interventions

rosiglitazone DRUG

Rosiglitazone 4mg, one capsule per day for eight weeks

rosiglitazone

placebo DRUG

matched placebo for rosiglitazone 4mg/day

placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Alliance for Research on Schizophrenia and Depression: collaborator
• Stanley Medical Research Institute: collaborator

Study Sites (1)

Massachusetts General Hospital Schizophrenia Program

Boston, Massachusetts, 02114, United States

Location

Related Publications (24)

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MeSH Terms

Conditions

Schizophrenia; Insulin Resistance

Interventions

Rosiglitazone

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Our findings in this study were limited by the small sample size. It is possible that with a larger sample, significant improvements might be observed not only in glucose metabolism but also in lipid metabolism.

Results Point of Contact

• Title: Dr. David Henderson
• Organization: Massachusetts General Hospital Schizophrenia Research Program

dchenderson@partners.org

(617) 912-7800

Study Officials

• David C Henderson, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Psychiatry

Study Record Dates

• First Submitted: June 13, 2006
• First Posted: June 15, 2006
• Study Start: September 1, 2003
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: May 8, 2015
• Results First Posted: March 6, 2013

Record last verified: 2015-04

Locations

US (1)