Pioglitazone as a Treatment for Lipid and Glucose Abnormalities In Patients With Schizophrenia
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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 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 Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, 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 |
- serum triglycerides [ Time Frame: pre tereatment and during 3 months of treatment ] [ Designated as safety issue: No ]
- HDL [ Time Frame: pretreatment and during 3 months of treatment ] [ Designated as safety issue: No ]
- atherosclerotic risk ratios (total cholesterol/HDL and triglycerides/HDL) [ Time Frame: pretreatment and during 3 months of treatment ] [ Designated as safety issue: No ]
- serum glucose [ Time Frame: pretreatment and during 3 months of drug treatment ] [ Designated as safety issue: No ]
- immediate and delayed verbal memory performance [ Time Frame: preteatment and during 3 months of treatment ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
| 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
pioglitazone
|
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
placebo
|
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.
Eligibility| Ages Eligible for Study: | 18 Years to 70 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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.
Patients will have evidence of:
- 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;
- Triglyceride levels > 150 mg/dL and/or HDL levels < 40 mg/dL
Exclusion Criteria:
- Diabetes mellitus, type 1
- Recent diabetic ketoacidosis;
- 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);
- 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;
- Congestive heart failure (Class III or IV cardiac status) or history of MI in medical record (because pioglitazone can increase blood volume slightly);
- Hematocrit greater than 10% below normal (hematocrit may be decreased 2 to 4% due to increased plasma volume);
- Female patients on current oral contraceptives (because pioglitazone may interfere with effects of some oral contraceptives);
- Patients taking ketoconazole,
- 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).
- Patients are not concomitantly treated with aripiprazole or ziprasidone.
Contacts and Locations| United States, New York | |
| Manhattan Psychiatric Center | |
| New York, New York, United States, 10035 | |
| Principal Investigator: | Robert C Smith, MD PhD | NYU School of Medicine & Manhattan Psychiatric Center |
More Information
No publications provided
| 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, 04T-584 |
| Study First Received: | October 3, 2005 |
| Last Updated: | July 22, 2011 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by Nathan Kline Institute for Psychiatric Research:
|
atypical antipsychotics hyperglycemia triglycerides HDL |
cholesterol insulin resistance schizophrenia verbal memory |
Additional relevant MeSH terms:
|
Congenital Abnormalities Insulin Resistance Schizophrenia Cognition Disorders Hyperinsulinism Glucose Metabolism Disorders Metabolic Diseases Schizophrenia and Disorders with Psychotic Features Mental Disorders Delirium, Dementia, Amnestic, Cognitive Disorders |
Antipsychotic Agents Pioglitazone Tranquilizing Agents Central Nervous System Depressants Physiological Effects of Drugs Pharmacologic Actions Central Nervous System Agents Therapeutic Uses Psychotropic Drugs Hypoglycemic Agents |
ClinicalTrials.gov processed this record on May 23, 2013