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Pioglitazone as a Treatment for Lipid and Glucose Abnormalities In Patients With Schizophrenia

This study has been completed.
ClinicalTrials.gov Identifier:
First Posted: October 4, 2005
Last Update Posted: October 12, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by:
Nathan Kline Institute for Psychiatric Research
This is a study with an approved drug for treating type 2 diabetes, for its effects on treating glucose and lipid abnormalities in patients being treated with olanzapine and clozapine, and comparison of effects of this drug with another treatment lifestyle modification. Patients who meet inclusion criteria will be treated with pioglitazone for 12 weeks. They will be evaluated for fasting glucose and lipids, glucose-tolerance tests, and neurocognitive battery and tests of verbal memory at baseline and during treatment with pioglitazone.

Condition Intervention
Diabetes Schizophrenia Insulin Resistance Cognitive Impairment Drug: Pioglitazone Behavioral: Life style diet group Other: placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pioglitazone as a Treatment for Lipid and Glucose Abnormalities In Patients With Schizophrenia Treated With Antipsychotic Medication And Potential Effects on Cognitive Function

Resource links provided by NLM:

Further study details as provided by Nathan Kline Institute for Psychiatric Research:

Primary Outcome Measures:
  • serum triglycerides [ Time Frame: pre tereatment and during 3 months of treatment ]
  • HDL [ Time Frame: pretreatment and during 3 months of treatment ]
  • atherosclerotic risk ratios (total cholesterol/HDL and triglycerides/HDL) [ Time Frame: pretreatment and during 3 months of treatment ]
  • serum glucose [ Time Frame: pretreatment and during 3 months of drug treatment ]

Secondary Outcome Measures:
  • immediate and delayed verbal memory performance [ Time Frame: preteatment and during 3 months of treatment ]
  • memory improvement during GTT glucose test, on paired words and short story of the RANDT Memory Scale [ Time Frame: pre-treatment and during 3 months of treatment ]

Estimated Enrollment: 40
Study Start Date: May 2005
Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Drug: Pioglitazone
pioglitazone 15-45 mg/day
Other Name: Actos
Behavioral: Life style diet group
life style diet education group 1x/week
Placebo Comparator: 2
Behavioral: Life style diet group
life style diet education group 1x/week
Other: placebo
placebo comparator

Detailed Description:
The aim of this study is to investigate the effects of pioglitazone added to weight-lifestyle intervention vs. placebo plus lifestyle intervention on reversing or reducing impaired or abnormal triglycerides, HDL and glucose metabolism in schizophrenics treated with clozapine or olanzapine. Another aim is to examine the effects of impaired glucose metabolism on verbal memory and other cognitive function in schizophrenic patients treated with these medications and the relationship to improvements in impaired glucose metabolism to impairments in cognitive function. Clozapine and olanzapine, two second generation antipsychotics effective for treating schizophrenia and bipolar disorders, have been reported to be associated with increased incidence of diabetic type metabolic abnormalities, decreases in insulin sensitivity, and abnormal glucose tolerance tests. This can lead to the development of type 2 diabetes and also abnormal lipid metabolic levels which can lead to atherosclerotic changes and increased risk of cardiovascular disease and other diabetes related complications. Drug treatments which could reduce or correct these diabetic metabolic changes would permit many patients to continue to receive the benefits of these antipsychotic medications with reduced drug-induced comorbidity. Previous research using non-psychotic subjects has shown that diabetes and impaired glucose tolerance are associated with cognitive impairments, especially in verbal memory, and provides a rationale for testing whether corrections of impaired glucose metabolism are associated with cognitive improvements in schizophrenic patients.

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients will be males or females, 18-70 yrs of age, with a diagnosis of schizophrenia or schizoaffective disorder, and currently being treated with olanzapine or clozapine.
  2. Patients will have evidence of:

    1. glucose levels indicating at least impaired fasting glucose: fasting glucose 100 mg/dL or 2 hr glucose tolerance test 140 mg/dL, or current treatment with oral antidiabetic drugs with history of hyperglycemia;
    2. Triglyceride levels > 150 mg/dL and/or HDL levels < 40 mg/dL

Exclusion Criteria:

  1. Diabetes mellitus, type 1
  2. Recent diabetic ketoacidosis;
  3. Patients not currently treated with oral antidiabetic drugs but fasting is glucose 140 mg/dL [WHO criteria] on repeat testing in last three months, or random blood glucose >200 mg/dL plus 2 hr glucose on GTT >200 mg/dL; (these patients may need more immediate treatment with antidiabetic drugs and it is less certain if weight-lifestyle treatment would be effective in treating such high glucose levels);
  4. Patients with active liver disease with clinical abnormalities which need current treatment, or liver enzymes (Alt) 3 times upper limit for normal values in chart records in last year, or patients who are recorded as positive for hepatitis C;
  5. Congestive heart failure (Class III or IV cardiac status) or history of MI in medical record (because pioglitazone can increase blood volume slightly);
  6. Hematocrit greater than 10% below normal (hematocrit may be decreased 2 to 4% due to increased plasma volume);
  7. Female patients on current oral contraceptives (because pioglitazone may interfere with effects of some oral contraceptives);
  8. Patients taking ketoconazole,
  9. Patients who have started on atorvastatin or gemfibrozil in the past 2 months or have had a dose increase in atorvastatin in the last month (since these drugs can also lower triglycerides and raise HDL, recent start of therapy with these drugs could be a confound).
  10. Patients are not concomitantly treated with aripiprazole or ziprasidone.
  Contacts and Locations
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): NCT00231894

United States, New York
Manhattan Psychiatric Center
New York, New York, United States, 10035
Sponsors and Collaborators
Nathan Kline Institute for Psychiatric Research
Principal Investigator: Robert C Smith, MD PhD NYU School of Medicine & Manhattan Psychiatric Center
  More Information

Responsible Party: Robert C. Smith MD, PhD, Manattan Psychiatric Center, NYU Medical School
ClinicalTrials.gov Identifier: NCT00231894     History of Changes
Other Study ID Numbers: 04T-584 Stanley Foundation
First Submitted: October 3, 2005
First Posted: October 4, 2005
Last Update Posted: October 12, 2017
Last Verified: April 2010

Keywords provided by Nathan Kline Institute for Psychiatric Research:
atypical antipsychotics
insulin resistance
verbal memory

Additional relevant MeSH terms:
Insulin Resistance
Cognitive Dysfunction
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Glucose Metabolism Disorders
Metabolic Diseases
Cognition Disorders
Neurocognitive Disorders
Antipsychotic Agents
Hypoglycemic Agents
Physiological Effects of Drugs
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs