Clinical Trial: Heart and Muscle Metabolism in Barth Syndrome

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Heart and Skeletal Muscle Metabolism, Energetics and Function in Barth Syndrome

Brief Summary: Barth syndrome (BTHS) is an X-linked disorder caused by abnormal cardiolipin metabolism and is characterized by skeletal and cardiomyopathy and high mortality rates. Through clinical metabolism and imaging studies and pluripotent stem cell induction and molecular techniques on skin biopsy samples, this project will produce novel translational information regarding the pathogenesis of BTHS, reveal potential targets for interventions and provide unique data regarding nutrient metabolism and abnormal cardiolipin and mitochondrial function. This project has the potential to provide information that could significantly improve morbidity and mortality in children and young adults with BTHS and may have relevance to other non-BTHS related conditions such as aging and adult heart failure.

Detailed Summary:

Barth syndrome (BTHS) is an X-linked disorder characterized by abnormal cardiolipin metabolism, mitochondrial dysfunction, muscle wasting and heart failure. BTHS is a particularly significant disease as it is often fatal in childhood and there are no approved therapies for BTHS other than the standard treatment of heart failure. Therefore novel areas of research and platforms in which to test new therapies are highly needed. Through state-of-the-art and innovative methodologies, this project will focus on the novel role of skeletal muscle and heart nutrient (glucose, fatty acid, and amino acid) metabolism in the pathogenesis of BTHS. Phenotypic information regarding skeletal muscle and heart nutrient metabolism in BTHS and how it may relate to energy production and function of these organs is lacking and is significant as this may advance our understanding of the underlying pathogenesis of BTHS. With this understanding, safe and efficacious therapies can be targeted for BTHS. The investigators' overall hypothesis is that impaired fatty acid metabolism in skeletal muscle and the heart produces a fuel deficit in these organs leading to impaired energy production, exercise intolerance and heart failure. Further, as a consequence of impaired fatty acid metabolism in skeletal muscle and the heart, protein breakdown (wasting) in skeletal muscle and the heart occurs to provide amino acids as compensation for this inadequate fatty acid energy supply, thereby worsening heart and skeletal muscle function in BTHS. The investigators' aims to address this hypothesis in 30 young adults and children with BTHS and 30 healthy, age, puberty stage and activity level matched controls ages 8-35 years are:

1) To characterize skeletal muscle and heart nutrient metabolism and 2) To examine the relationship between skeletal muscle and heart nutrient metabolism, energy production and function (exe
Sponsor: Washington University School of Medicine

Current Primary Outcome: Whole-body fatty acid oxidation rate [ Time Frame: baseline ]

Whole-body fatty acid oxidation rate will be measured by 13C-labeled fatty acid stable isotope tracer infusion and mass spectrometry


Original Primary Outcome:

  • Whole-body fatty acid oxidation rate [ Time Frame: baseline ]
    Whole-body fatty acid oxidation rate will be measured by 13C-labeled fatty acid stable isotope tracer infusion and mass spectrometry
  • Myocardial fatty acid oxidation rate [ Time Frame: baseline ]
    Myocardial fatty acid oxidation rate will be measured by radio-isotope tracer infusion and PET imaging
  • left ventricular systolic strain [ Time Frame: baseline ]
    Left ventricular systolic strain will be measured by tissue Doppler echocardiography


Current Secondary Outcome:

  • whole-body amino acid oxidation rate [ Time Frame: baseline ]
    whole-body amino acid oxidation rate will be measured by 13C leucine stable isotope tracer infusion and mass spectrometry
  • cardiac energetics [ Time Frame: baseline ]
    cardiac energetics will be measured by 31P magnetic resonance spectroscopy of the heart
  • skeletal muscle energetics [ Time Frame: baseline ]
    skeletal muscle energetics will be measured by 31P magnetic resonance spectroscopy
  • Myocardial fatty acid oxidation rate [ Time Frame: baseline ]
    Myocardial fatty acid oxidation rate will be measured by radio-isotope tracer infusion and PET imaging
  • left ventricular systolic strain [ Time Frame: baseline ]
    Left ventricular systolic strain will be measured by tissue Doppler echocardiography


Original Secondary Outcome:

  • whole-body amino acid oxidation rate [ Time Frame: baseline ]
    whole-body amino acid oxidation rate will be measured by 13C leucine stable isotope tracer infusion and mass spectrometry
  • cardiac energetics [ Time Frame: baseline ]
    cardiac energetics will be measured by 31P magnetic resonance spectroscopy of the heart
  • skeletal muscle energetics [ Time Frame: baseline ]
    skeletal muscle energetics will be measured by 31P magnetic resonance spectroscopy


Information By: Washington University School of Medicine

Dates:
Date Received: June 19, 2012
Date Started: June 2012
Date Completion: December 2017
Last Updated: January 10, 2017
Last Verified: January 2017