Clinical trial NCT03057002: UTSW HP [13-C] Pyruvate Injection in HCM
Official title: Detection of Myocardial Metabolic Changes in Patients With Cardiomyopathy Using Hyperpolarized Carbon 13 Magnetic Resonance Spectroscopic Imaging
Study type: OBSERVATIONAL
Overall status: COMPLETED
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
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2017-02-17
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 5 Cardiomyopathy (CMP) Patients and 5 Healthy Controls

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.

Eligibility criteria: 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

Primary outcomes:
measure: Hyperpolarized [1-13C]pyruvate flux
timeFrame: Screening (Baseline) and 1 day of Study Visit
Secondary outcomes:
Other outcomes:
Locations:
city: Dallas
country: United States
facility: UT Southwestern Medical Center - Advanced Imaging Research Center
state: Texas
Study officials:
affiliation: Advanced Imaging Research Center
name: Vlad G Zaha, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: