Efficacy of Pioglitazone and Metformin on Cardiovascular Risk in Subjects With Insulin-Treated Type 2 Diabetes Mellitus.
Overview[ - collapse ][ - ]
Purpose | 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. |
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Condition | Diabetes Mellitus |
Intervention | Drug: Pioglitazone and insulin Drug: Pioglitazone and metformin and insulin Drug: Metformin and insulin |
Phase | Phase 4 |
Sponsor | Takeda |
Responsible Party | Takeda |
ClinicalTrials.gov Identifier | NCT00770445 |
First Received | October 9, 2008 |
Last Updated | August 17, 2010 |
Last verified | August 2010 |
Tracking Information[ + expand ][ + ]
First Received Date | October 9, 2008 |
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Last Updated Date | August 17, 2010 |
Start Date | May 2008 |
Estimated Primary Completion Date | July 2010 |
Current Primary Outcome Measures | Change from Baseline in Matrix Metallo Proteinase 9. [Time Frame: Baseline and Week 24.] [Designated as safety issue: No]The change between Matrix Metallo Proteinase 9 collected at final visit or week 24 and Matrix Metallo Proteinase 9 collected at baseline. |
Current Secondary Outcome Measures |
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Descriptive Information[ + expand ][ + ]
Brief Title | Efficacy of Pioglitazone and Metformin on Cardiovascular Risk in Subjects With Insulin-Treated Type 2 Diabetes Mellitus. |
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Official Title | Impact of Pioglitazone, Metformin and the Combination of Both on Cardiovascular Risk in Insulin-treated Patients With Type 2 Diabetes - The PIOcomb Study |
Brief Summary | 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. |
Detailed Description | 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. |
Study Type | Interventional |
Study Phase | Phase 4 |
Study Design | Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment |
Condition | Diabetes Mellitus |
Intervention | Drug: Pioglitazone and insulin Pioglitazone 15 mg, tablets, orally, twice daily and metformin placebo-matching tablets, orally, twice daily and insulin glargine stable dose for up to 24 weeks. Other Names: ACTOS®Drug: Pioglitazone and metformin and insulin Pioglitazone 15 mg, tablets, orally, twice daily and metformin 850 mg, tablets, orally, twice daily and insulin glargine stable dose for up to 24 weeks. Other Names: ACTOS®Drug: Metformin and insulin Pioglitazone placebo-matching tablets, orally, twice daily and metformin 850 mg, tablets, orally, twice daily and insulin glargine stable dose for up to 24 weeks. |
Study Arm (s) |
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Recruitment Information[ + expand ][ + ]
Recruitment Status | Completed |
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Estimated Enrollment | 121 |
Estimated Completion Date | July 2010 |
Estimated Primary Completion Date | July 2010 |
Eligibility Criteria | Inclusion Criteria: - Has Diabetes Mellitus type 2. - 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 25. - 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. Exclusion Criteria: - 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. |
Gender | Both |
Ages | 30 Years |
Accepts Healthy Volunteers | No |
Contacts | Not Provided |
Location Countries | Germany |
Administrative Information[ + expand ][ + ]
NCT Number | NCT00770445 |
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Other Study ID Numbers | ATS K028 |
Has Data Monitoring Committee | No |
Information Provided By | Takeda |
Study Sponsor | Takeda |
Collaborators | Not Provided |
Investigators | Study Director: Medical Director Takeda Pharma GmbH, Aachen (Germany) |
Verification Date | August 2010 |
Locations[ + expand ][ + ]
Germany, Bavaria | Lichtenfels, Bavaria, Germany |
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Germany, Hessen | Frankfurt, Hessen, Germany |
Germany, Hessen | Kassel, Hessen, Germany |
Germany, Hessen | Wiesbaden, Hessen, Germany |
Germany, North Rhine-Westphalia | Bad Oeynhausen, North Rhine-Westphalia, Germany |
Germany, North Rhine-Westphalia | Dinslaken, North Rhine-Westphalia, Germany |
Germany, North Rhine-Westphalia | Duisburg, North Rhine-Westphalia, Germany |
Germany, North Rhine-Westphalia | Essen, North Rhine-Westphalia, Germany |
Germany, North Rhine-Westphalia | Münster, North Rhine-Westphalia, Germany |
Germany, North Rhine-Westphalia | Wuppertal, North Rhine-Westphalia, Germany |
Germany, Rheinland-Pfalz | Mainz, Rheinland-Pfalz, Germany |
Germany, Rhineland-Palatinate | Diez, Rhineland-Palatinate, Germany |
Germany, Rhineland-Palatinate | Landau, Rhineland-Palatinate, Germany |
Germany, Saxony | Dresden, Saxony, Germany |
Germany, Saxony | Leipzig, Saxony, Germany |
Germany, Thüringen | Jena, Thüringen, Germany |
Germany | Berlin, Germany |
Germany | Hamburg, Germany |