UTSW HP [13-C] Pyruvate Injection in HCM (HPHCM)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Duchenne Muscular Dystrophy; Becker Muscular Dystrophy; Dilated Cardiomyopathy; Cardiomyopathy, Hypertrophic; Heart Failure With Reduced Ejection Fraction; Cardiac Sarcoidosis; Heart Failure With Preserved Ejection Fraction
• Intervention / Treatment: Diagnostic test: Hyperpolarized 13C-Pyruvate

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 Type: Observational
• Enrollment (Estimated): 128

Contacts and Locations

• Study Contact: Name: Syed Ahsan; Phone Number: 214-645-9269; Email: Syed.Ahsan@utsouthwestern.edu
• Study Contact Backup: Name: Egzona Tan, RN; Phone Number: 2146452726; Email: Egzona.Tan@UTSouthwestern.edu

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • UT Southwestern Medical Center - Advanced Imaging Research Center
      • Principal Investigator: Craig R Malloy, MD
      • Principal Investigator: Vlad Zaha, MD, PhD
      • Contact: Syed Ahsan, MPH; Phone Number: 214-645-2726; Email: Syed.Ahsan@utsouthwestern.edu
      • Contact: Egzona Tan, RN; Phone Number: 214-645-2726; Email: Egzona.Tan@UTSouthwestern.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

5 Cardiomyopathy (CMP) Patients and 5 Healthy Controls

Description

Inclusion Criteria for Control Subjects:

• Subjects who are 18.
• Subjects who have the ability to understand and the willingness to sign a written informed consent.
• While all races and ethnicities will be included, subjects must be able to read and speak the English language. Once the protocol is established, Spanish-speaking participants will be included.
• Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

Inclusion Criteria for participants with Cardiomyopathy:

• Subjects who are 18.
• Subjects who have the ability to understand and the willingness to sign a written informed consent.
• While all races and ethnicities will be included, subjects must be able to read and speak the English language. Once the protocol is established, Spanish-speaking participants will be included.
• Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

Exclusion criteria:

• Subjects who are receiving any other investigational agents.
• Intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled chronic diseases such as hypertension, lung disease, liver disease, kidney disease, diabetes, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Subjects who are taking thyroid hormone replacements, have a history of alcohol abuse or illicit drug use.
• Subjects who have contraindication to contrast enhanced MRI examination.

Contraindications to MRI examinations include:

• Medically unstable
• Acute Heart failure
• Severe LVOT obstruction
• Unstable angina
• Child bearing
• Lactating
• Any contraindication per MRI Screening Form including
• Implants contraindicated at 3Tesla, pacemakers
• Implantable Cardioverter Defibrillator (ICD)
• Claustrophobia
• Since each subject is receiving a gadolinium based contrast agent intravenously:
• eGFR ≤ 30 mL/min/1.73m2
• Sickle cell disease
• Hemolytic anemia

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cardiomyopathy; Patients with Cardiomyopathy will be observed for myocardial hyperpolarized 13C-pyruvate flux during magnetic resonance spectroscopic imaging.	Diagnostic test: Hyperpolarized 13C-Pyruvate; All subjects will be observed for myocardial hyperpolarized [1-13C]pyruvate flux during magnetic resonance spectroscopic imaging.; Other Names: HP [1-13C]pyruvate
Control; Healthy control subjects will be observed for myocardial hyperpolarized 13C-pyruvate flux during magnetic resonance spectroscopic imaging.	Diagnostic test: Hyperpolarized 13C-Pyruvate; All subjects will be observed for myocardial hyperpolarized [1-13C]pyruvate flux during magnetic resonance spectroscopic imaging.; Other Names: HP [1-13C]pyruvate

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Investigators: Principal Investigator: Vlad G Zaha, MD, PhD, Advanced Imaging Research Center

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2018
• Primary Completion (Estimated): November 8, 2024
• Study Completion (Estimated): November 8, 2024

Study Registration Dates

• First Submitted: January 10, 2017
• First Submitted That Met QC Criteria: February 14, 2017
• First Posted (Actual): February 17, 2017

Study Record Updates

• Last Update Posted (Estimated): February 5, 2024
• Last Update Submitted That Met QC Criteria: February 1, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Nervous System Diseases; Immune System Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Aortic Valve Disease; Heart Valve Diseases; Hypersensitivity; Muscular Disorders, Atrophic; Cardiomegaly; Laminopathies; Hypersensitivity, Delayed; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Heart Failure; Muscular Dystrophies; Cardiomyopathies; Cardiomyopathy, Dilated; Muscular Dystrophy, Duchenne; Cardiomyopathy, Hypertrophic; Sarcoidosis
• Other Study ID Numbers: STU 102016-046

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No