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Sponsored by: |
National Heart, Lung, and Blood Institute (NHLBI) |
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Information provided by: | National Heart, Lung, and Blood Institute (NHLBI) |
ClinicalTrials.gov Identifier: | NCT00281255 |
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).
Condition | Intervention | Phase |
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Cardiovascular Diseases Cardiomyopathy, Dilated Heart Diseases Heart Failure, Congestive |
Drug: Allopurinol Drug: Dobutamine |
Phase I |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Placebo Control |
Official Title: | Allopurinol and Cardiac Function Pilot Study in Idiopathic Dilated Cardiomyopathy |
Estimated Enrollment: | 20 |
Study Start Date: | August 2003 |
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) 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 1:1 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.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contraindication to MRI because of one of the following:
United States, Pennsylvania | |
University of Pennsylvania | Recruiting |
Philadelphia, Pennsylvania, United States, 19104 | |
Contact: Kimberly Craig, ESQ, BSN, RN 215-662-6900 craigk@uphs.upenn.edu | |
Study Chair: Thomas P. Cappola |
Study Chair: | Thomas P. Cappola | University of Pennsylvania |
Study ID Numbers: | 353, K23 HL71562 |
Study First Received: | January 20, 2006 |
Last Updated: | June 5, 2006 |
ClinicalTrials.gov Identifier: | NCT00281255 History of Changes |
Health Authority: | United States: Federal Government |
Antimetabolites Neurotransmitter Agents Heart Failure Allopurinol Heart Diseases Antioxidants Adrenergic beta-Agonists Adrenergic Agents Dilated Cardiomyopathy |
Cardiomyopathy, Dilated Cardiovascular Agents Cardiomyopathies Adrenergic Agonists Dobutamine Peripheral Nervous System Agents Antirheumatic Agents Cardiomegaly |
Antimetabolites Neurotransmitter Agents Allopurinol Antioxidants Adrenergic Agents Molecular Mechanisms of Pharmacological Action Cardiotonic Agents Cardiomyopathy, Dilated Physiological Effects of Drugs Gout Suppressants Adrenergic Agonists Therapeutic Uses Free Radical Scavengers Cardiovascular Diseases |
Heart Failure Heart Diseases Adrenergic beta-Agonists Sympathomimetics Enzyme Inhibitors Cardiovascular Agents Cardiomyopathies Protective Agents Pharmacologic Actions Dobutamine Autonomic Agents Peripheral Nervous System Agents Antirheumatic Agents Cardiomegaly |