Back to resultsPioglitazone as a Treatment for Lipid and Glucose Abnormalities In Patients With Schizophrenia
Primary Purpose
Diabetes, Schizophrenia, Insulin Resistance
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Pioglitazone
Life style diet group
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Diabetes focused on measuring atypical antipsychotics, hyperglycemia, triglycerides, HDL, cholesterol, insulin resistance, schizophrenia, verbal memory
Eligibility Criteria
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 > 120 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.
Sites / Locations
- Nathan Kline Institute for Psychiatric Research
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Pioglitazone and life-style group
Placebo and life style group
Arm Description
Pioglitazone (30-45 mg/daily) plus life-style diet group
Placebo capsules daily plus life-style diet group
Outcomes
Primary Outcome Measures
Change From Baseline in Serum Triglycerides at 3 Months ( 3 Months-baseline) US Sample
Change From Baseline in Serum HDL at 3 Months (3 Months-baseline) US Sample
serum high density lipoprotein (HDL)
Change From Baseline in Serum Glucose at 3 Months (3 Months-baseline) US Sample
2 Hour Glucose From Glucose Tolerance Test US Sample
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
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
Change From Baseline in Serum Triglycerides at 3 Months (3 Months-baseline) China Sample
2 Hour Glucose From Glucose Tolerance Test China Sample
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
Full Information
NCT ID
NCT00231894
First Posted
October 3, 2005
Last Updated
November 9, 2017
Sponsor
Nathan Kline Institute for Psychiatric Research
1. Study Identification
Unique Protocol Identification Number
NCT00231894
Brief Title
Pioglitazone as a Treatment for Lipid and Glucose Abnormalities In Patients With Schizophrenia
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2017
Overall Recruitment Status
Completed
Study Start Date
May 2005 (undefined)
Primary Completion Date
January 2010 (Actual)
Study Completion Date
January 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Nathan Kline Institute for Psychiatric Research
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes, Schizophrenia, Insulin Resistance, Cognitive Impairment
Keywords
atypical antipsychotics, hyperglycemia, triglycerides, HDL, cholesterol, insulin resistance, schizophrenia, verbal memory
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
56 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pioglitazone and life-style group
Arm Type
Active Comparator
Arm Description
Pioglitazone (30-45 mg/daily) plus life-style diet group
Arm Title
Placebo and life style group
Arm Type
Placebo Comparator
Arm Description
Placebo capsules daily plus life-style diet group
Intervention Type
Drug
Intervention Name(s)
Pioglitazone
Other Intervention Name(s)
Actos
Intervention Description
pioglitazone 30-45 mg/day
Intervention Type
Behavioral
Intervention Name(s)
Life style diet group
Intervention Description
life style diet education group 1x/week
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
placebo comparator capsules
Primary Outcome Measure Information:
Title
Change From Baseline in Serum Triglycerides at 3 Months ( 3 Months-baseline) US Sample
Time Frame
pre-treatment and during 3 months of treatment
Title
Change From Baseline in Serum HDL at 3 Months (3 Months-baseline) US Sample
Description
serum high density lipoprotein (HDL)
Time Frame
pre-treatment and during 3 months of treatment
Title
Change From Baseline in Serum Glucose at 3 Months (3 Months-baseline) US Sample
Time Frame
pretreatment and during 3 months of drug treatment
Title
2 Hour Glucose From Glucose Tolerance Test US Sample
Description
difference between 2 hr glucose for GTT test at baseline vs after 3 months of drug treatment
Time Frame
between baseline and 3 months of study drug treatment
Secondary Outcome Measure Information:
Title
Change in RBANS List Recognition Scores at 3 Months (3 Months-baseline) US Sample
Description
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.
Time Frame
pre-treatment and 3 months of treatment
Title
Change From Baseline in Serum Glucose at 3 Months ( 3 Months -Baseline) China Sample
Time Frame
pretreatment and during 3 months of drug treatment
Title
Change From Baseline in Serum Triglycerides at 3 Months (3 Months-baseline) China Sample
Time Frame
pretreatment and during 3 months of drug treatment
Title
2 Hour Glucose From Glucose Tolerance Test China Sample
Description
difference between 2 hr glucose for GTT test at baseline vs after 3 months of drug treatment
Time Frame
between baseline and 3 months of study drug treatment
Title
Change From Baseline in Serum HDL at 3 Months (3 Months-baseline) China Site
Time Frame
pretreatment and during 3 months of drug treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 > 120 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert C Smith, MD PhD
Organizational Affiliation
NYU School of Medicine & Nathan Kline Institute for Psychiatric Research
Official's Role
Principal Investigator
Facility Information:
Facility Name
Nathan Kline Institute for Psychiatric Research
City
New York
State/Province
New York
ZIP/Postal Code
10035
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
Citation
Smith RC et al Pioglitazone as a treatment for glucose and lipid abnormalities in schizophrenic patents: A double-blind placebo controlled trial. NCDEU 51lst Annual Meeting Oral Presentation Abstract Book, 2011, p.13.
Results Reference
result
PubMed Identifier
23200554
Citation
Smith RC, Jin H, Li C, Bark N, Shekhar A, Dwivedi S, Mortiere C, Lohr J, Hu Q, Davis JM. Effects of pioglitazone on metabolic abnormalities, psychopathology, and cognitive function in schizophrenic patients treated with antipsychotic medication: a randomized double-blind study. Schizophr Res. 2013 Jan;143(1):18-24. doi: 10.1016/j.schres.2012.10.023. Epub 2012 Nov 29.
Results Reference
result
Learn more about this trial
Pioglitazone as a Treatment for Lipid and Glucose Abnormalities In Patients With Schizophrenia
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