UTSW HP [13-C] Pyruvate Injection in HCM

Duchenne Muscular Dystrophy Clinical Trial

— HPHCM  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03057002
• Other study ID #: STU 102016-046
• Status: Recruiting
• Start date: May 1, 2018
• Est. completion date: November 8, 2024

Study information

• Verified date: February 2024
• Source: University of Texas Southwestern Medical Center
• Contact: Syed Ahsan
• Phone: 214-645-9269
• Email: Syed.Ahsan[@]utsouthwestern.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 128
• Est. completion date: November 8, 2024
• Est. primary completion date: November 8, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Diagnostic Test:
• Hyperpolarized 13C-Pyruvate
All subjects will be observed for myocardial hyperpolarized [1-13C]pyruvate flux during magnetic resonance spectroscopic imaging.

Locations

Country	Name	City	State
United States	UT Southwestern Medical Center - Advanced Imaging Research Center	Dallas	Texas

Sponsors (1)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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