Efficacy and Safety of Pioglitazone in Treating Subjects With Vascular Complications Associated With Type 2 Diabetes Mellitus. (SPLENDOR)
|Diabetes Mellitus||Drug: Pioglitazone and Metformin Drug: Glibenclamide and Metformin||Phase 4|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Effects of Pioglitazone on Endothelial Progenitor Cells in Type 2 Diabetic Patients With Vascular Complications - The SPLENDOR Study.|
- Increase from Baseline in the number of Endothelial Progenitor Cells (CD34+KDR+). [ Time Frame: Baseline and Final Visit. ]
- Change from Baseline in Circulating Progenitor Cells Integrated Markers of cardiovascular risk (CD34+). [ Time Frame: Baseline and Weeks 12 and 24. ]
- Change from Baseline in Flow Mediated Dilation Integrated Markers of cardiovascular risk. [ Time Frame: Baseline and Final Visit. ]
- Modulation of Endothelial Progenitor Cell recruitment (vascular endothelial growth factor, erythropoietin and stromal cell-derived factor-1). [ Time Frame: Weeks: 4, 12 and 24. ]
- Measure of Glucose Control (glycosylated hemoglobin and fasting plasma glucose). [ Time Frame: Weeks: 4, 12 and 24. ]
- Measure of Lipid Parameters (total lipids, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein B and apolipoprotein A1). [ Time Frame: Weeks: 4, 12 and 24. ]
- Change from Baseline in lipid parameters (free fatty acids and oxidized low-density lipoprotein). [ Time Frame: Baseline and Weeks 12 and 24. ]
- Change from Baseline in insulin sensitivity (insulin indexes by 2 hour oral glucose tolerance test with glucose, insulin and C-peptide estimation). [ Time Frame: Baseline and Final Visit. ]
- Change from Baseline in Inflammation Markers (high-sensitivity C-reactive protein, IL-6, vascular adhesion molecules (E-selectin, vascular cell adhesion molecule-1), monocyte chemotactic protein-1 and tumor necrosis factor-alpha). [ Time Frame: Baseline and Weeks 12 and 24. ]
- Change from Baseline in Adipokines (adiponectin). [ Time Frame: Baseline and Weeks 12 and 24. ]
- Change from Baseline in Oxidative Stress (maleic dialdehyde, ferric reducing antioxidant power and lipid hydroperoxide. [ Time Frame: Baseline and Weeks 12 and 24. ]
- Urinary albumin excretion. [ Time Frame: Weeks: 12 and 24. ]
|Study Start Date:||March 2009|
|Study Completion Date:||May 2011|
|Primary Completion Date:||May 2011 (Final data collection date for primary outcome measure)|
Experimental: Pioglitazone and Metformin QD
(along with lifestyle modification)
Drug: Pioglitazone and Metformin
Pioglitazone 30 mg, tablets, orally, once daily, metformin stable dose and lifestyle modification for up to 24 weeks.
Active Comparator: Glibenclamide and Metformin QD
(along with lifestyle modification)
Drug: Glibenclamide and Metformin
Glibenclamide 10 mg, tablets, orally, once daily and metformin stable dose and lifestyle modification for up to 24 weeks.
Diabetes is one of the most common chronic diseases worldwide, affecting nearly 200 million people, almost all suffering from Type 2 Diabetes. It is the fourth leading cause of death in developed countries due to the negative impact of the disease on the cardiovascular system. Treatment, aimed to the reduction of this intrinsic cardiovascular risk, is based on tight control of glucose and all coexisting metabolic abnormalities as well as of biomarkers of inflammation and atherogenesis.
Macrovascular complications account for the vast majority of morbidity and mortality in diabetic patients, and there is growing evidence that pathophysiologic mechanisms other than hyperglycemia are responsible. The condition of the vascular endothelium in particular has been shown to effect the health and disease of the cardiovascular system.
The number and function of endothelial progenitor cells correlate inversely with cardiovascular risk factors and may be a surrogate biologic marker for vascular function and cumulative cardiovascular risk.
Pioglitazone is an orally active thiazolidinedione derivative. It is a ligand for peroxisome proliferator-activated receptor-gamma activation that alters transcription of various genes regulating carbohydrate and lipid metabolism.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00770835
|Study Director:||Medical Director||Takeda|