Ignite Creation Date:
2024-05-05 @ 4:39 PM
Last Modification Date:
2024-10-26 @ 9:22 AM
Study NCT ID:
NCT00281255
Status:
WITHDRAWN
Last Update Posted:
2013-06-19
First Post:
2006-01-20
Brief Title:
Intravenous Allopurinol to Improve Heart Function in Individuals With Dilated Cardiomyopathy
Sponsor:
University of Pennsylvania
Organization:
University of Pennsylvania
Study Overview
Official Title:
Allopurinol and Cardiac Function Pilot Study in Idiopathic Dilated Cardiomyopathy
Status:
WITHDRAWN
Status Verified Date:
2013-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Infeasible
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will determine whether an acute infusion of intravenous allopurinol improves the inotropic response to dobutamine in patients with idiopathic dilated cardiomyopathy DCM as measured by cardiac magnetic resonance imaging CMR
Detailed Description:
BACKGROUND
DCM is a poorly understood cause of systolic heart failure and is the most common indication for heart transplantation in the United States Despite advances in medical and device therapy the 5-year mortality of patients with DCM remains near 50
Oxidative stress an imbalance between the formation and degradation of free radicals within the myocardium contributes to metabolic derangements in patients with DCM The enzyme xanthine oxidase XO a potent source of oxidative stress is expressed in the failing heart and it uncouples cardiac energy consumption from cardiac contraction in the setting of chronic heart failure These effects can be reversed by inhibiting XO with the XO inhibitor allopurinol resulting in a marked increase in cardiac efficiency These findings provide a rationale for using allopurinol to enhance cardiac function in DCM However there is little data on the effects of allopurinol therapy on cardiac function Therefore the primary aim of this study is to determine whether an acute infusion of intravenous allopurinol improves the inotropic response to beta-adrenergic stimulation in patients with idiopathic DCM
Decreased beta-adrenergic responsiveness is a characteristic feature of DCM that is attributable in part to decreased expression of the beta 1-receptor in chronic heart failure as well as dysregulation of down-stream signaling pathways Improvement in beta-adrenergic responsiveness is a useful surrogate marker for long-term improvement in cardiac structure function and decreased cardiac events Traditionally invasive hemodynamic monitoring using pressure and pressurevolume catheters has been the method of choice to quantify the inotropic response in heart failure However newly developed magnetic resonance imaging MRI techniques now allow precise assessment of the inotropic response non-invasively Studies have shown that tagged CMR is a reproducible noninvasive method to quantify the inotropic response to the beta 1 agonist dobutamine in individuals with structurally normal hearts Specifically radial strain E1 and circumferential strain E2 are measured at increasing doses of dobutamine using tagged CMR Changes in these strain parameters now referred to as delta E1 and delta E2 are precise measurements of the beta-inotropic response
DESIGN NARRATIVE
An estimated 20 patients with DCM will be randomized in a 11 ratio fashion to receive allopurinol or placebo The primary aim of this investigation is to determine whether an acute infusion of intravenous allopurinol improves the inotropic response to dobutamine in patients with idiopathic DCM as measured by CMR Specifically the study will test the hypothesis that a single dose of intravenous allopurinol compared to placebo enhances delta E1 and delta E2 Secondary aims of this study are as follows 1 to determine whether the response to allopurinol is associated with baseline XO activity and levels of natriuretic peptides investigators predict that augmentation in delta E1 and delta E2 will correlate positively with baseline plasma uric acid and plasma B-type natriuretic peptide BNP and 2 to demonstrate that tagged dobutamine CMR is a useful non-invasive technique to assess pharmacologic responses in patients with heart failure
DCM is a poorly understood cause of systolic heart failure and is the most common indication for heart transplantation in the United States Despite advances in medical and device therapy the 5-year mortality of patients with DCM remains near 50
Oxidative stress an imbalance between the formation and degradation of free radicals within the myocardium contributes to metabolic derangements in patients with DCM The enzyme xanthine oxidase XO a potent source of oxidative stress is expressed in the failing heart and it uncouples cardiac energy consumption from cardiac contraction in the setting of chronic heart failure These effects can be reversed by inhibiting XO with the XO inhibitor allopurinol resulting in a marked increase in cardiac efficiency These findings provide a rationale for using allopurinol to enhance cardiac function in DCM However there is little data on the effects of allopurinol therapy on cardiac function Therefore the primary aim of this study is to determine whether an acute infusion of intravenous allopurinol improves the inotropic response to beta-adrenergic stimulation in patients with idiopathic DCM
Decreased beta-adrenergic responsiveness is a characteristic feature of DCM that is attributable in part to decreased expression of the beta 1-receptor in chronic heart failure as well as dysregulation of down-stream signaling pathways Improvement in beta-adrenergic responsiveness is a useful surrogate marker for long-term improvement in cardiac structure function and decreased cardiac events Traditionally invasive hemodynamic monitoring using pressure and pressurevolume catheters has been the method of choice to quantify the inotropic response in heart failure However newly developed magnetic resonance imaging MRI techniques now allow precise assessment of the inotropic response non-invasively Studies have shown that tagged CMR is a reproducible noninvasive method to quantify the inotropic response to the beta 1 agonist dobutamine in individuals with structurally normal hearts Specifically radial strain E1 and circumferential strain E2 are measured at increasing doses of dobutamine using tagged CMR Changes in these strain parameters now referred to as delta E1 and delta E2 are precise measurements of the beta-inotropic response
DESIGN NARRATIVE
An estimated 20 patients with DCM will be randomized in a 11 ratio fashion to receive allopurinol or placebo The primary aim of this investigation is to determine whether an acute infusion of intravenous allopurinol improves the inotropic response to dobutamine in patients with idiopathic DCM as measured by CMR Specifically the study will test the hypothesis that a single dose of intravenous allopurinol compared to placebo enhances delta E1 and delta E2 Secondary aims of this study are as follows 1 to determine whether the response to allopurinol is associated with baseline XO activity and levels of natriuretic peptides investigators predict that augmentation in delta E1 and delta E2 will correlate positively with baseline plasma uric acid and plasma B-type natriuretic peptide BNP and 2 to demonstrate that tagged dobutamine CMR is a useful non-invasive technique to assess pharmacologic responses in patients with heart failure
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| K23HL071562 | NIH | None | httpsreporternihgovquickSearchK23HL071562 |