Intravenous Allopurinol in Heart Failure

Study Overview
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Brief Summary
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This study tests the hypothesis that allopurinol, a xanthine oxidase inhibitor, improves heart metabolism in patients with heart failure.

Detailed Description
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Xanthine oxidase have been reported to improve mechano-energetic coupling in failing hearts. The investigators developed a means to directly measure creatine kinase flux, the major energy reserve of the heart, in the human heart exploiting new magnetic resonance technologies. The investigators propose to study 10 healthy subjects and up to 25 with heart failure (dilated cardiomyopathy) before and after a single 300mg IV infusion of allopurinol.

Official Title
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Effects of Xanthine Oxidase Inhibition on Mechano-Energetic Coupling in Heart Failure

Conditions
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Congestive Heart Failure

Intervention / Treatment
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* Drug: Allopurinol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years The patient is willing and able to provide informed consent Clinical diagnosis of chronic heart failure Ejection fraction (EF) < 40% by echocardiography, nuclear multigated acquisition (MUGA) or cath ventriculography No significant coronary disease at cardiac catheterization New York Heart Association (NYHA) Class I-IV symptoms Clinical stabilization for two weeks if following recent congestive heart failure (CHF) decompensation. Exclusion Criteria: Metallic implant prohibiting magnetic resonance (MR) evaluation Inability to lie flat for MR study Administration of additional investigational drugs Calculated creatinine clearance < 50 mL/min Allergy to allopurinol Current gout flare Currently taking oral allopurinol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Allopurinol<br>One time intravenous administration of Allopurinol 300 mg infused over approximately 20 minutes. | Drug: Allopurinol<br>* intravenous infusion of allopurinol (300mg)<br>* Other names: Aloprim;|
| Placebo Comparator: Placebo<br>One time intravenous administration of 50 ml dose of 5% dextrose infused over approximately 20 minutes. | Drug: Placebo<br>* intravenous infusion of 50 ml dose of 5% dextrose<br>* Other names: 5% Dextrose;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial Creatine Kinase (CK) Flux Pre Intravenous Allopurinol Infusion | Magnetic resonance spectroscopy (MRS) Measurement of Myocardial CK Flux Pre Intravenous Allopurinol Infusion | Onset of imaging acquisition. | 
| Myocardial CK Flux Post Intravenous Allopurinol Infusion. | The mean rate of adenosine triphosphate (ATP) flux through the creatine kinase reaction in the heart. | acute (within 15 minutes of single infusion) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac PCr/ATP Pre Intravenous Infusion | The mean ratio of creatine phosphate (PCr) to ATP in the heart. This measure, as a ratio, is unitless. | Onset of image acquisition. | 
| Cardiac PCr/ATP Post Intravenous Infusion | The mean ratio of creatine phosphate (PCr) to ATP in the heart. This measure, as a ratio, is unitless. | acute (within 15 minutes of single infusion) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metabolism, congestive heart failure, allopurinol, Adenosine triphosphate (ATP)