NCT00770445已完成4 期
Impact of Pioglitazone, Metformin and the Combination of Both on Cardiovascular Risk in Insulin-treated Patients With Type 2 Diabetes - The PIOcomb Study
Takeda0 个研究点目标入组 121 人开始时间: 2008年5月最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 121
- 主要终点
- Change from Baseline in Matrix Metallo Proteinase 9.
研究概览
简要总结
The purpose of this study is to determine the Anti-Inflammation Effects of Pioglitazone, twice daily (BID), and Pioglitazone/Metformin Combination Therapy BID in Type 2 Diabetes Subjects Treated with Insulin.
详细描述
It is established that matrix metalloproteinases play an essential role in the degradation of collagen and other extra cellular matrix macromolecules. In addition, matrix metalloproteinases are implicated in plaque rupture through their capacity to thin the protective cap of the plaque, thus rendering it more vulnerable. In fact, matrix metalloproteinase-9 levels are elevated in patients with unstable plaques and in patients with acute coronary syndrome. In patients with type 2 diabetes mellitus, matrix metalloproteinase-1 and matrix metalloproteinase-9 levels are usually elevated and the atherosclerotic plaques are more vulnerable compared to non-diabetic patients, confirming the role of this proteinase in the development of acute coronary syndrome. Therefore, therapeutic strategies that reduce blood glucose levels and attenuate inflammation and matrix metalloproteinases activity may be a tool for reducing cardiovascular risk in patients with diabetes.
The purpose of this trial is to investigate whether the anti-inflammatory effects of pioglitazone are maintained and sustained over a longer observation period when given in combination with insulin in comparison to the metformin plus insulin combination. The duration of treatment for patients completing the study is approximately 6 months.
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
- 30 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has Diabetes Mellitus type
- •A glycosylated hemoglobin level greater than or equal to 6.5% and less than 8.5%.
- •Treatment with the following insulins with or without Oral Antidiabetic Therapy since 3 months:
- •Long acting basal insulin analogs
- •NPH insulin
- •Combination insulin with 1-2 daily doses except intensified insulin therapies.
- •A body mass index greater than or equal to
- •Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.
排除标准
- •Has a history of type 1 diabetes mellitus.
- •Has uncontrolled hypertension (systolic blood pressure greater than 160mmHg and/or diastolic blood pressure greater than 95mmHg) or change of antihypertensive treatment within the last 2 weeks.
- •Has acute infections.
- •Has anamnestic history of hypersensitivity to the study drugs or to drugs with similar chemical structure.
- •Has a history of severe or multiple allergies.
- •History of drug or alcohol abuse in the past 5 years
- •A history of significant cardiovascular (New York Heart Association stage I - IV), respiratory, gastrointestinal, hepatic (Alanine Aminotransferase and/or Aspartate Aminotransferase greater than 2.5 times the upper limit of the normal reference range), renal (serum creatinine greater than 1.2 mg/dL in women and greater than 1.5 mg/dL in men, Glomerular Filtration Rate less than 60 ml/min as estimated by the Cockroft-Gault formula), neurological, psychiatric and/or hematological disease as judged by the investigator
- •History of macular edema.
- •State after kidney transplantation.
- •Serum potassium greater than 5.5 mmol/L.
- •History of primary hyperaldosteronism.
- •Acute myocardial infarction, open heart surgery or cerebral event (stroke/ Transitory Ischemic Attack) within the previous 12 months.
- •Is required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:
- •Pre-treatment with gemfibrozil within the last 12 weeks.
- •Pre-treatment with rifampicin within the last 12 weeks.
- •Treatment with thiazolidinediones within the past 3 months.
- •If statin therapy applicable: Change of medication within the last 4 weeks.
- •Has used non-steroidal anti-inflammatory agents including low dose ASA or Cox-2-inhibitors if therapy has been initiated within the last 4 weeks.
- •Treatment with any other investigational drug within 4 weeks before trial entry.
- •Any elective surgery during study participation.
- •Have had more than one unexplained episode of severe hypoglycemia (defined as requiring assistance of another person due to disabling hypoglycemia) within 6 months prior to screening visit.
- •History of dehydration, precoma diabeticorum or shock or diabetic ketoacidosis within the past year prior to screening visit.
- •Acute or scheduled investigation with iodine containing radiopaque material.
- •Uncontrolled unstable angina pectoris.
- •Medical history of acute and clinically relevant pericarditis, myocarditis, endocarditis, recent pulmonary embolism, hemodynamic relevant aortic stenosis, aortic aneurysm.
研究组 & 干预措施
Pioglitazone 15mg BID
Experimental
Insulin therapy added
干预措施: Pioglitazone and insulin (Drug)
Pioglitazone 15mg + Metformin 850mg BID
Experimental
Insulin Therapy Added
干预措施: Pioglitazone and metformin and insulin (Drug)
Metformin 850mg BID
Active Comparator
Insulin therapy added
干预措施: Metformin and insulin (Drug)
结局指标
主要结局
Change from Baseline in Matrix Metallo Proteinase 9.
时间窗: Baseline and Week 24.
The change between Matrix Metallo Proteinase 9 collected at final visit or week 24 and Matrix Metallo Proteinase 9 collected at baseline.
次要结局
- Change from Baseline in 24-hour Blood Pressure Profile.(Baseline and Week 24.)
- Change from Baseline in Intima Media Thickness.(Baseline and Week 24.)
- Change from Baseline in 24-hour Urinary Sample.(Baseline and Week 24.)
- Change from Baseline in N-terminal Pro-hormone Brain Natriuretic Peptide.(Baseline and Week 24.)
- Change from Baseline in 8-iso Prostaglandin F2 alpha.(Baseline and Week 24.)
- Change from Baseline in Albumin.(Baseline and Week 24.)
- Change from Baseline in Creatinine.(Baseline and Week 24.)
- Change from Baseline in C/A-quotient.(Baseline and Week 24.)
- Change from Baseline in Homeostasis Model Assessment - Insulin Sensitivity.(Baseline and Week 24.)
- Change from Baseline in Total Cholesterol.(Baseline and Week 24.)
- Change from Baseline in Low-Density Lipoprotein.(Baseline and Week 24.)
- Change from Baseline in High-Density Lipoprotein.(Baseline and Week 24.)
- Change from Baseline in Triglycerides.(Baseline and Week 24.)
- Change from Baseline in Glycosylated Hemoglobin.(Baseline and Week 24.)
- Change from Baseline in Glucose.(Baseline and Week 24.)
- Change from Baseline in Insulin.(Baseline and Week 24.)
- Change from Baseline in Intact Proinsulin.(Baseline and Week 24.)
- Change from Baseline in C-peptide.(Baseline and Week 24.)
- Change from Baseline in Adiponectin.(Baseline and Week 24.)
- Change from Baseline in High Molecular Weight Adiponectin.(Baseline and Week 24.)
- Change from Baseline in High-Sensitivity C-Reactive Protein.(Baseline and Week 24.)
- Change from Baseline in Fibrinogen.(Baseline and Week 24.)
- Change from Baseline in E-selectin(Baseline and Week 24.)
- Change from Baseline in Nuclear Factor-kappa B.(Baseline and Week 24.)
- Change from Baseline in Plasminogen Activator Inhibitor-1.(Baseline and Week 24.)
- Change from Baseline in Nitrotyrosine.(Baseline and Week 24.)
- Change from baseline in Insulin Consumption.(Baseline and Week 24.)
- Change from Baseline in Endothelial Function measured by Laser-Doppler-flowmetry.(Baseline and Week 24.)
- Change from Baseline in Body Weight.(Baseline and Week 24.)
- Change from Baseline in Electrocardiograms(Baseline and Week 24.)
- Change from Baseline in Alanine Aminotransferase Laboratory Safety Variable.(Baseline and Week 24.)
- Change from Baseline in Aspartate Aminotransferase Laboratory Safety Variable.(Baseline and Week 24.)
- Change from Baseline in Gamma-glutamyl transferase Laboratory Safety Variable.(Baseline and Week 24.)
- Change from Baseline in Glomerular Filtration Rate Laboratory Safety Variable.(Baseline and Week 24.)
- Change from Baseline in Alkaline Phosphatase Laboratory Safety Variable.(Baseline and Week 24.)
- Change from Baseline in Leucocytes Laboratory Safety Variable.(Baseline and Week 24.)
- Change from Baseline in Hemoglobin Laboratory Safety Variable.(Baseline and Week 24.)
- Change from Baseline in Thrombocytes Laboratory Safety Variable.(Baseline and Week 24.)
- Change from Baseline in Creatinine Kinase Laboratory Safety Variable.(Baseline and Week 24.)
- Change from Baseline in Creatinine Laboratory Safety Variable.(Baseline and Week 24.)
- Change from Baseline in Capillary Blood Glucose Laboratory Safety Variable.(Baseline and Week 24.)
- Change from Baseline in Potassium Laboratory Safety Variable.(Baseline and Week 24.)
- Change from Baseline in Circadian (7 point) Blood Glucose Profile (Week 24).(Baseline and Week 24.)
- Change from Baseline in Circadian (7 point) Blood Glucose Profile (Week 12).(Baseline and Week 12.)
研究者
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