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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00231894
First Posted: October 4, 2005
Last Update Posted: December 11, 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 (Responsible Party):
Robert C. Smith MD PhD, Nathan Kline Institute for Psychiatric Research
  Purpose
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 first or second-generation antipsychotics, 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 Phase
Diabetes Schizophrenia Insulin Resistance Cognitive Impairment Drug: Pioglitazone Behavioral: Life style diet group Other: Placebo Phase 4

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 Robert C. Smith MD PhD, Nathan Kline Institute for Psychiatric Research:

Primary Outcome Measures:
  • Change From Baseline in Serum Triglycerides at 3 Months ( 3 Months-baseline) US Sample [ Time Frame: pre-treatment and during 3 months of treatment ]
  • Change From Baseline in Serum HDL at 3 Months (3 Months-baseline) US Sample [ Time Frame: pre-treatment and during 3 months of treatment ]
    serum high density lipoprotein (HDL)

  • Change From Baseline in Serum Glucose at 3 Months (3 Months-baseline) US Sample [ Time Frame: pretreatment and during 3 months of drug treatment ]
  • 2 Hour Glucose From Glucose Tolerance Test US Sample [ Time Frame: between baseline and 3 months of study drug treatment ]
    difference between 2 hr glucose for GTT test at baseline vs after 3 months of drug treatment


Secondary Outcome Measures:
  • Change in RBANS List Recognition Scores at 3 Months (3 Months-baseline) US Sample [ Time Frame: pre-treatment and 3 months of treatment ]
    The scale is Repeatable Battery for the Assessment to Neuropsychological Status (RBANS). This scale measure cognitive function in patients with schizophrenia. Range for list learning sub-score is 0 to 20 . Higher values indicate better performance. For change score (3 months -baseline) positive values indicate improved performance for this cognitive function and negative values indicate poorer performance on this cognitive function.

  • Change From Baseline in Serum Glucose at 3 Months ( 3 Months -Baseline) China Sample [ Time Frame: pretreatment and during 3 months of drug treatment ]
  • Change From Baseline in Serum Triglycerides at 3 Months (3 Months-baseline) China Sample [ Time Frame: pretreatment and during 3 months of drug treatment ]
  • 2 Hour Glucose From Glucose Tolerance Test China Sample [ Time Frame: between baseline and 3 months of study drug treatment ]
    difference between 2 hr glucose for GTT test at baseline vs after 3 months of drug treatment

  • Change From Baseline in Serum HDL at 3 Months (3 Months-baseline) China Site [ Time Frame: pretreatment and during 3 months of drug treatment ]

Enrollment: 56
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: Pioglitazone and life-style group
Pioglitazone (30-45 mg/daily) plus life-style diet group
Drug: Pioglitazone
pioglitazone 30-45 mg/day
Other Name: Actos
Behavioral: Life style diet group
life style diet education group 1x/week
Placebo Comparator: Placebo and life style group
Placebo capsules daily plus life-style diet group
Behavioral: Life style diet group
life style diet education group 1x/week
Other: Placebo
placebo comparator capsules

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 first or second-generation antipsychotics.. 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, and some other first or 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.
  Eligibility

Information from the National Library of Medicine

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

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 > 120 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


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

Publications:
Responsible Party: Robert C. Smith MD PhD, Research Psychiatrist, Nathan Kline Institute for Psychiatric Research
ClinicalTrials.gov Identifier: NCT00231894     History of Changes
Other Study ID Numbers: 04T-584 Stanley Foundation
04T-584 ( Other Grant/Funding Number: Stanley Foundation )
First Submitted: October 3, 2005
First Posted: October 4, 2005
Results First Submitted: December 15, 2016
Results First Posted: December 11, 2017
Last Update Posted: December 11, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Robert C. Smith MD PhD, Nathan Kline Institute for Psychiatric Research:
atypical antipsychotics
hyperglycemia
triglycerides
HDL
cholesterol
insulin resistance
schizophrenia
verbal memory

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