UTSW HP [13-C] Pyruvate Injection in HCM

Recruiting

• Conditions: Duchenne Muscular Dystrophy; Becker Muscular Dystrophy; Dilated Cardiomyopathy; Heart Failure With Preserved Ejection Fraction; Heart Failure With Reduced Ejection Fraction; Cardiomyopathy, Hypertrophic; Cardiac Sarcoidosis
• Interventions: Diagnostic Test: Hyperpolarized 13C-Pyruvate

• Registration Number: NCT03057002
• Lead Sponsor: University of Texas Southwestern Medical Center

Brief 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.

Study Timeline

• Study First Submitted: 2017-01-10
• Study First Submitted QC: 2017-02-14
• Study First Posted: 2017-02-17
• Study Start: 2018-05-01
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-11
• Last Update Posted: 2024-12-16
• Primary Completion: 2025-03-08
• Study Completion: 2025-03-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 128

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Cardiomyopathy	Hyperpolarized 13C-Pyruvate	Patients with Cardiomyopathy will be observed for myocardial hyperpolarized 13C-pyruvate flux during magnetic resonance spectroscopic imaging.
Control	Hyperpolarized 13C-Pyruvate	Healthy control subjects will be observed for myocardial hyperpolarized 13C-pyruvate flux during magnetic resonance spectroscopic imaging.

Primary Outcome Measures

Name	Time	Method
Hyperpolarized [1-13C]pyruvate flux	Screening (Baseline) and 1 day of Study Visit	Measurement of change in myocardial hyperpolarized \[1-13C\]pyruvate flux during Magnetic Resonance Spectroscopic Imaging.

Trial Locations

Locations (1)

UT Southwestern Medical Center - Advanced Imaging Research Center; 🇺🇸 Dallas, Texas, United States