NCT03057002

UTSW HP [13-C] Pyruvate Injection in HCM

Detection of Myocardial Metabolic Changes in Patients With Cardiomyopathy Using Hyperpolarized Carbon 13 Magnetic Resonance Spectroscopic Imaging

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 7 (actual)
• Sponsor: University of Texas Southwestern Medical Center · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Accepted

Summary

The study objective is to identify the earliest changes in energy substrate metabolism in patients with cardiomyopathies (CMP). To achieve this objective, we plan first to test the hypothesis that patients with CMP present focal alterations in myocardial hyperpolarized \[1-13C\]pyruvate flux.

Detailed description

To measure the regional myocardial \[1-13C\]lactate to \[13C\]bicarbonate ratio as an index of mitochondrial oxidation and glycolysis coupling in the heart. Advanced cardiac MRI will be used to characterize cardiac morphology, function, myocardial blood flow and fibrosis. Heart failure is a major source of morbidity and mortality in the United States. Multiple studies have demonstrated that development of heart failure is related to alteration in cardiac metabolism. Specifically, such changes include a shift from fatty acid oxidation to increased glucose utilization as energy source, with uncoupling of glycolysis and mitochondrial oxidation at the level of the pyruvate dehydrogenase complex. In human subject who were referred for LVAD placement, excised heart muscle samples exhibited significant increase in expression of pyruvate kinase M2 (PKM2) compared to subjects with normal LV function. Additionally, mechanical unloading decreased PKM2 expression suggesting a correlation between pyruvate utilization and severity of heart failure. Such changes metabolic alterations appear to precede the actual structural changes and might be a possible target for future therapies, although the timeline of such changes remains to be elucidated. Currently, it is unknown whether different types of CMP have different metabolic signatures.

Conditions

• Cardiomyopathy, Hypertrophic
• Dilated Cardiomyopathy
• Duchenne Muscular Dystrophy
• Cardiac Sarcoidosis
• Becker Muscular Dystrophy
• Heart Failure With Preserved Ejection Fraction
• Heart Failure With Reduced Ejection Fraction

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	Hyperpolarized 13C-Pyruvate	All subjects will be observed for myocardial hyperpolarized \[1-13C\]pyruvate flux during magnetic resonance spectroscopic imaging.

Timeline

• Start date: 2018-05-01
• Primary completion: 2023-05-17
• Completion: 2023-05-17
• First posted: 2017-02-17
• Last updated: 2025-03-26

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study