Clinical Trial: Intravenous Allopurinol to Improve Heart Function in Individuals With Dilated Cardiomyopathy
Study Status: Withdrawn
Recruit Status: Withdrawn
Study Type: Interventional
Official Title: Allopurinol and Cardiac Function Pilot Study in Idiopathic Dilated Cardiomyopathy
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 Summary:
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 pressure/volume catheters has been the method of choice to quantify the inotropic response in heart failure. However, newly developed magnetic resonance imaging (MRI)
Sponsor: University of Pennsylvania
Current Primary Outcome: radial and circumferential strain after infusion of allopurinol as measured by cardiac MRI (measured at Day 1)
Original Primary Outcome:
Current Secondary Outcome:
Original Secondary Outcome:
Information By: University of Pennsylvania
Dates:
Date Received: January 20, 2006
Date Started: June 2003
Date Completion:
Last Updated: June 17, 2013
Last Verified: June 2013
