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| ID | Type | Description | Link |
|---|---|---|---|
| 5R01HL061912-14 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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This study tests the hypothesis that allopurinol, a xanthine oxidase inhibitor, improves heart metabolism in patients with heart failure.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Allopurinol | Experimental | One time intravenous administration of Allopurinol 300 mg infused over approximately 20 minutes. |
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| Placebo | Placebo Comparator | One time intravenous administration of 50 ml dose of 5% dextrose infused over approximately 20 minutes. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Allopurinol | Drug | intravenous infusion of allopurinol (300mg) |
|
| 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) |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Robert G Weiss, MD | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins Hospital | Baltimore | Maryland | 21287 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22361399 | Derived | Hirsch GA, Bottomley PA, Gerstenblith G, Weiss RG. Allopurinol acutely increases adenosine triphospate energy delivery in failing human hearts. J Am Coll Cardiol. 2012 Feb 28;59(9):802-8. doi: 10.1016/j.jacc.2011.10.895. |
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The study drug allocation was randomized in a 4:1 fashion by the research pharmacy. Participants were randomized to Placebo only for the purposes of blinding; Adverse Events were collected for the Placebo arm.
Participants with Non-Ischemic Cardiomyopathy were recruited as approved by the Johns Hopkins Institutional Review Board for Human Investigation.
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| ID | Title | Description |
|---|---|---|
| FG000 | Allopurinol | Each participant underwent magnetic resonance spectroscopy before and following infusion of either allopurinol 300mg or placebo. |
| FG001 | Placebo | Each participant underwent magnetic resonance spectroscopy before and following infusion of either allopurinol 300mg or placebo. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Intravenous Allopurinol | We randomized patients with nonischemic cardiomyopathy in a double-blind fashion to allopurinol (300 mg intravenously) or placebo infusion, 4-to-1, the latter for purposes of blinding only. The myocardial concentrations of ATP and creatine phosphate (PCr) and the rate of adenosine triphosphate (ATP) synthesis through CK (CK flux) were determined by 31-Phosphorus (31P) magnetic resonance spectroscopy. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Myocardial Creatine Kinase (CK) Flux Pre Intravenous Allopurinol Infusion | Magnetic resonance spectroscopy (MRS) Measurement of Myocardial CK Flux Pre Intravenous Allopurinol Infusion | Data were analyzed for all participants who completed the MRS per protocol. | Posted | Mean | Standard Deviation | umol/g/sec | Onset of imaging acquisition. |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm 1 - Intravenous Allopurinol | Each participant received pre and post MRS images following infusion of 50 cc of Aloprim 300mg in 5% Dextrose. |
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The limitations of the current study include the small placebo group sample size and the etiologic heterogeneity of the nonischemic cardiomyopathy group.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Robert G. Weiss, MD | Johns Hopkins University | 410-955-1703 | rweiss@jhmi.edu |
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| ID | Term |
|---|---|
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D000493 | Allopurinol |
| D005947 | Glucose |
| ID | Term |
|---|---|
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| Placebo | Drug | intravenous infusion of 50 ml dose of 5% dextrose |
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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) |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Secondary | 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. | Data were analyzed for all participants who completed the MRS per protocol. | Posted | Mean | Standard Deviation | ratio | Onset of image acquisition. |
|
|
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| Primary | Myocardial CK Flux Post Intravenous Allopurinol Infusion. | The mean rate of adenosine triphosphate (ATP) flux through the creatine kinase reaction in the heart. | Data were analyzed for all participants who completed the MRS per protocol. | Posted | Mean | Standard Deviation | umol/g/sec | acute (within 15 minutes of single infusion) |
|
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|
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| Secondary | 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. | Data were analyzed for all participants who completed the MRS per protocol. | Posted | Mean | Standard Deviation | ratio | acute (within 15 minutes of single infusion) |
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| 0 |
| 13 |
| 0 |
| 13 |
| EG001 | Arm 2 - Placebo | Each participant received pre and post MRS images following infusion of 50 cc of 5% Dextrose (equivalent volume to active treatment arm). | 0 | 3 | 0 | 3 |
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| D006601 | Hexoses |
| D009005 | Monosaccharides |
| D000073893 | Sugars |
| D002241 | Carbohydrates |