Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03057002
Recruitment Status : Suspended (Study temporarily on hold due to COVID19)
First Posted : February 17, 2017
Last Update Posted : March 5, 2021
Sponsor:
Information provided by (Responsible Party):
Vlad Zaha, University of Texas Southwestern Medical Center

Tracking Information
First Submitted Date January 10, 2017
First Posted Date February 17, 2017
Last Update Posted Date March 5, 2021
Actual Study Start Date May 1, 2018
Estimated Primary Completion Date December 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: February 14, 2017)
Hyperpolarized [1-13C]pyruvate flux [ Time Frame: Screening (Baseline) and 1 day of Study Visit ]
Measurement of change in myocardial hyperpolarized [1-13C]pyruvate flux during Magnetic Resonance Spectroscopic Imaging.
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title UTSW HP [13-C] Pyruvate Injection in HCM
Official Title Detection of Regional Myocardial Metabolic Changes in Patients With Hypertrophic Cardiomyopathy Using Hyperpolarized Carbon 13 Magnetic Resonance Spectroscopic Imaging (MRSI)
Brief Summary In this study the investigators propose to detect early mitochondrial metabolic changes in the heart in patients with a positive genotype and phenotype for Hypertrophic Cardiomyopathy (HCM) using a novel hyperpolarized [1-13C]pyruvate Magnetic Resonance Imaging (MRI) methodology.
Detailed Description

In this study the investigators propose to detect early mitochondrial metabolic changes in the heart in patients with a positive genotype and phenotype for HCM using a novel hyperpolarized [1-13C]pyruvate MRI methodology. Carbon-13 is a stable isotope (not radioactive) that makes up approximately 1.1% of all natural carbon. Carbon-13 has a non-zero spin quantum number that allows the investigation of carbon containing substances using magnetic resonance. However, compared with other analytical methods, carbon-13 magnetic resonance has been limited by an intrinsically low sensitivity [2}.

Recent experimental studies suggest that altered energy substrate metabolism may precede structural changes in myocardial hypertrophy. A better understanding of the myocardial metabolic changes in HCM is important, as the elucidation of such changes may precede the clinical development of myocardial fibrosis and malignant arrhythmias. Hyperpolarized [1-13C]pyruvate and its cellular metabolic flux can be assessed with a more than 10,000-fold higher sensitivity compared to traditional methods. The aim of this pilot study is to test the hypothesis that patients with HCM present focal alterations in myocardial hyperpolarized [1-13C]pyruvate flux.

To achieve this aim the investigators will assess myocardial metabolic changes in HCM subjects with a positive HCM genotype and phenotype (n=5) and in healthy control subjects (n=5) who are matched for age, sex, and Body Mass Index (BMI). Total target enrollment will be set at 15 subjects to allow for attrition and screen failures.

Cardiac function and structure will be evaluated with MRI (proton imaging) before and after contrast administration. Then myocardial metabolism will be assessed utilizing MRS (carbon spectroscopy) before and after intravenous injection with hyperpolarized [1-13C]pyruvate. The study agent, hyperpolarized [1-13C]pyruvate, will be administered under a Food and Drug Administration (FDA) Investigational New Drug (IND), currently in review process, PI Dr. Craig Malloy.

Human preliminary data are essential to secure larger scale funding required for clinical studies. The identification of mitochondrial metabolic changes preceding replacement fibrosis and malignant arrhythmias may generate a paradigm shift to early detection and more targeted treatment of HCM with potentially improved clinical outcomes. Cardiac focused applications at the Advanced Imaging Research Center, genetic disease diagnosis at the Eugene McDermott Center for Human Genetics and the development of a dedicated HCM Clinic at the UT Southwestern Medical Center offer today a unique opportunity to lead globally the translational scientific efforts in this field.

Study Type Observational
Study Design Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population 5 Hypertrophic cardiomyopathy (HCM) Patients and 5 Healthy Controls
Condition Cardiomyopathy, Hypertrophic
Intervention Drug: Hyperpolarized 13C-Pyruvate
All subjects will be observed for myocardial hyperpolarized [1-13C]pyruvate flux during magnetic resonance spectroscopic imaging.
Other Name: HP [1-13C]pyruvate
Study Groups/Cohorts
  • HCM Group
    HCM patients will be observed for myocardial hyperpolarized 13C-pyruvate flux during magnetic resonance spectroscopic imaging.
    Intervention: Drug: Hyperpolarized 13C-Pyruvate
  • Control Group
    Healthy control subjects will be observed for myocardial hyperpolarized 13C-pyruvate flux during magnetic resonance spectroscopic imaging.
    Intervention: Drug: Hyperpolarized 13C-Pyruvate
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Suspended
Estimated Enrollment
 (submitted: February 14, 2017)
10
Original Estimated Enrollment Same as current
Estimated Study Completion Date December 30, 2022
Estimated Primary Completion Date December 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria for Control Subjects:

  • Subjects who are 18 through 60 years of age.
  • 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 HCM subjects:

  • Definitive diagnosis of HCM by genotype and imaging which demonstrates abnormal Left Ventricular (LV) wall thickness in the absence of other cause (Unexplained maximal wall thickness >15 mm in any myocardial segment [6-8]).
  • Subjects who are 18 through 60 years of age.
  • 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 for Controls and HCM Subjects:

  • 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
  • Heart failure
  • Severe Left Ventricular Outflow Tract (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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers Yes
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT03057002
Other Study ID Numbers STU 102016-046
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Vlad Zaha, University of Texas Southwestern Medical Center
Study Sponsor University of Texas Southwestern Medical Center
Collaborators Not Provided
Investigators
Principal Investigator: Vlad G Zaha, MD, PhD Advanced Imaging Research Center
PRS Account University of Texas Southwestern Medical Center
Verification Date March 2021