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| Name | Class |
|---|---|
| Novartis | INDUSTRY |
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Assess if aliskiren is capable of enhancing vascular stiffness and endothelial function and compare theses effects and renin activity and concentration to those obtained with a calcium channel blocker, amlodipine, in patients with diabetes mellitus type 2 and blood pressure not controlled by 100 mg per day of losartan.
Hypertension and diabetes mellitus are important risk factors for cardiovascular morbidity and mortality. Endothelial dysfunction and vascular rigidity are two pathophysiological mechanisms that may explain this relationship. Recent publications showed that both ACEi (angiotensin converting enzyme inhibitor) and ARB (angiotensin receptor blocker) were capable of improving vascular stiffness and endothelial function, and that these effects occurred despite blood pressure reduction. The major debate that persists is which drug to associate with ACEi or ARB to achieve blood pressure control in diabetic patients. Recent studies showed that even in patients under ACEi or ARB therapy there may be residual activity in the renin-angiotensin-aldosterone system (RASS). Direct renin inhibitors (DRI) are a new class of anti-hypertensive drugs that may complement the blockade of the RASS. Aliskiren was the first drug of this class that completed phase 3 studies and marketed in the 21th century. It's main advantage is that DRI may reduce angiotensin II and aldosterone synthesis without increasing renin levels. This study main objective is to assess if aliskiren is capable of enhancing vascular stiffness and endothelial function and compare theses effects to those obtained with a calcium channel blocker, amlodipine, in patients with diabetes mellitus type 2 and blood pressure not controlled by 100 mg per day of losartan. Vascular stiffness and endothelial function will be measured by: pulse wave velocity, augmentation index, brachial artery flow-mediated vasodilation, peripheral arterial tonometry (EndoPat). Another main objective is to compare plasma renin activity and concentration between those groups.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Aliskiren | Active Comparator |
| |
| Amlodipine | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Aliskiren | Drug | 300 mg of aliskiren daily for 8 weeks. |
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| Measure | Description | Time Frame |
|---|---|---|
| Vascular stiffness | Vascular stiffness will be measured by pulse wave velocity and augmentation index and compared between anlodipine and aliskiren. | 8 weeks |
| Endothelial function | Access endothelial function by peripheral arterial tonometry and brachial flow-mediated vasodilation and compare it between anlodipine and aliskiren. | 8 weeks |
| Renin activity and concentration | Access plasma renin activity and concentration and compare it between anlodipine and aliskiren. | 8 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Compare drug effects in office blood pressure measurements to those obtained by home blood pressure monitoring and ambulatory blood pressure monitoring | Compare drug effects in office blood pressure measurements to those obtained by home blood pressure monitoring and ambulatory blood pressure monitoring | 8 weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ronaldo A Gismondi, MD, DsC | HUPedroernesto (UERJ) | Principal Investigator |
| Mario F Neves, MD, PhD | HUPedroernesto (UERJ) | Study Director |
| Wille Oigman, MD, PhD | HUPedroernesto (UERJ) | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Universitario Pedro Ernesto | Rio de Janeiro | Rio de Janeiro | 20551030 | Brazil |
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| ID | Term |
|---|---|
| D006973 | Hypertension |
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
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| ID | Term |
|---|---|
| C446481 | aliskiren |
| D017311 | Amlodipine |
| ID | Term |
|---|---|
| D004095 | Dihydropyridines |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Amlodipine | Drug | Amlodipine 5 mg daily for 8 weeks. |
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| Assess drugs effects in renin-angiotensin-aldosterone system (RAAS) and correlate it to renin concentration/mass and plasmatic renin activity |
Assess drugs effects in RAAS and correlate it to renin concentration/mass and plasmatic renin activity |
| 8 weeks |
| Correlation of drug effects and uric acid plasmatic concentration | Correlation of drug effects and uric acid plasmatic concentration | 8 weeks |
| Correlation of drug effects and glomerular filtration rate | Correlation of drug effects and glomerular filtration rate | 8 weeks |
| Correlation of drug effects and microalbuminuria | Correlation of drug effects and microalbuminuria | 8 weeks |
| Correlation of drug effects and left ventricular mass and function (systolic and diastolic) | Correlation of drug effects and left ventricular mass and function (systolic and diastolic) | 8 weeks |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |