Ignite Creation Date:
2024-05-05 @ 10:12 PM
Last Modification Date:
2024-10-26 @ 10:15 AM
Study NCT ID:
NCT01052272
Status:
COMPLETED
Last Update Posted:
2012-12-17
First Post:
2010-01-15
Brief Title:
Impact of Diabetes on Left Ventricular Remodeling
Sponsor:
University of Alabama at Birmingham
Organization:
University of Alabama at Birmingham
Study Overview
Official Title:
Phase 23 Study of Effect of AT1RB Versus ACE Inhibitor in Addition to XO Inhibitor on Progression of LV Remodeling and Dysfunction in Diabetic Patients With Acute MI
Status:
COMPLETED
Status Verified Date:
2012-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
P3
Brief Summary:
The investigators hypothesize that in patients with diabetes and acute myocardial infarction MI Ang II type-1 receptor blockade AT1RB attenuates left ventricle LV remodeling to a greater extent than angiotensin converting enzyme ACE inhibitor therapy and that the addition of xanthine oxidase XO inhibitor Allopurinol results in further improvement in LV remodeling and function in the follow-up phase after MI
Detailed Description:
Following myocardial infarction MI the incidence of heart failure and mortality rates are approximately two-fold higher in patients with diabetes compared to those without diabetes This increased risk for heart failure and mortality appears to be refractory to currently available treatments such as angiotensin converting enzyme ACE inhibitors despite the effectiveness of such treatments in reducing overall morbidity and mortality following MI Hyperglycemia stimulates cardiomyocyte angiotensin II Ang II formation which has been implicated in increased myocyte cell death in diabetes Furthermore in humans chymase is the predominant pathway of Ang II formation and this pathway of Ang II production is not blocked by ACE inhibition Therefore in diabetes where Ang II levels may already be elevated due to hyperglycemia the increase in Ang II formation associated with left ventricular LV remodeling continued Ang II formation from chymase could be particularly detrimental
In addition to enhanced Ang II production hyperglycemia and diabetes also amplify the production of reactive oxygen species ROS ROS are associated with increased in LV remodeling and myocyte apoptosis Furthermore xanthine oxidase XO an important source of ROS in myocytes is increased in a rat model of myocardial infarction and in diabetes Thus increased XO-mediated ROS production following MI may be especially damaging in diabetic patients where ROS production is already elevated Interestingly acute treatment with Allopurinol an inhibitor of XO improves cardiac function in heart failure and improves endothelial dysfunction in patients with type-2 diabetes
To test our hypothesis the investigators will investigate the following aims in diabetic patients after acute MI
Aim 1 Show that the progression of LV remodeling and dysfunction in diabetic patients will be attenuated to greater extent by AT1RB than by ACE inhibitor
Aim 2 Show that the addition of XO inhibition results in further attenuation of LV remodeling than with AT1RB or ACE inhibitor alone
Aim 3 Show that baseline and follow-up LV remodeling and dysfunction and inflammatory markers differ in diabetic and non-diabetic patients post-MI
In addition to enhanced Ang II production hyperglycemia and diabetes also amplify the production of reactive oxygen species ROS ROS are associated with increased in LV remodeling and myocyte apoptosis Furthermore xanthine oxidase XO an important source of ROS in myocytes is increased in a rat model of myocardial infarction and in diabetes Thus increased XO-mediated ROS production following MI may be especially damaging in diabetic patients where ROS production is already elevated Interestingly acute treatment with Allopurinol an inhibitor of XO improves cardiac function in heart failure and improves endothelial dysfunction in patients with type-2 diabetes
To test our hypothesis the investigators will investigate the following aims in diabetic patients after acute MI
Aim 1 Show that the progression of LV remodeling and dysfunction in diabetic patients will be attenuated to greater extent by AT1RB than by ACE inhibitor
Aim 2 Show that the addition of XO inhibition results in further attenuation of LV remodeling than with AT1RB or ACE inhibitor alone
Aim 3 Show that baseline and follow-up LV remodeling and dysfunction and inflammatory markers differ in diabetic and non-diabetic patients post-MI
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None