Pioglitazone as a Treatment for Lipid and Glucose Abnormalities In Patients With Schizophrenia Treated With Antipsychotic Medication And Potential Effects on Cognitive Function
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- Change From Baseline in Serum Triglycerides at 3 Months ( 3 Months-baseline) US Sample
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Pioglitazone and life-style group
Pioglitazone (30-45 mg/daily) plus life-style diet group
干预措施: Pioglitazone (Drug)
Pioglitazone and life-style group
Pioglitazone (30-45 mg/daily) plus life-style diet group
干预措施: Life style diet group (Behavioral)
Placebo and life style group
Placebo capsules daily plus life-style diet group
干预措施: Life style diet group (Behavioral)
Placebo and life style group
Placebo capsules daily plus life-style diet group
干预措施: Placebo (Other)
结局指标
主要结局
Change From Baseline in Serum Triglycerides at 3 Months ( 3 Months-baseline) US Sample
时间窗: pre-treatment and during 3 months of treatment
Change From Baseline in Serum HDL at 3 Months (3 Months-baseline) US Sample
时间窗: pre-treatment and during 3 months of treatment
serum high density lipoprotein (HDL)
2 Hour Glucose From Glucose Tolerance Test US Sample
时间窗: 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 Glucose at 3 Months (3 Months-baseline) US Sample
时间窗: pretreatment and during 3 months of drug treatment
次要结局
- Change in RBANS List Recognition Scores at 3 Months (3 Months-baseline) US Sample(pre-treatment and 3 months of treatment)
- Change From Baseline in Serum Glucose at 3 Months ( 3 Months -Baseline) China Sample(pretreatment and during 3 months of drug treatment)
- Change From Baseline in Serum Triglycerides at 3 Months (3 Months-baseline) China Sample(pretreatment and during 3 months of drug treatment)
- 2 Hour Glucose From Glucose Tolerance Test China Sample(between baseline and 3 months of study drug treatment)
- Change From Baseline in Serum HDL at 3 Months (3 Months-baseline) China Site(pretreatment and during 3 months of drug treatment)
研究者
Robert C. Smith MD PhD
Research Psychiatrist
Nathan Kline Institute for Psychiatric Research