Exercise Training in Barth Syndrome
Condition: Barth Syndrome
MeSH terms: Barth Syndrome; Syndrome
Study type: Interventional

Summary: 
      Barth syndrome (BTHS) is a genetic disease that results in heart failure, muscle weakness and
      exercise intolerance. Several studies in non-BTHS heart failure suggest that endurance
      exercise training is beneficial in improving exercise intolerance, heart function and quality
      of life in young men with BTHS. This study will examine the effects of Endurance (i.e.
      aerobic) exercise training on exercise tolerance, heart function, and quality of life in
      adolescents and young adults with BTHS. We hypothesize that 3 months of endurance training
      will improve exercise tolerance, heart function and quality of life in adolescents and young
      men with BTHS.
    

Detailed description: 
      Barth Syndrome (BTHS) is an X-linked disorder characterized by severe mitochondrial
      dysfunction, skeletal and cardiomyopathy and growth retardation. The investigators have
      recently found severe exercise intolerance in adolescents with BTHS that was mediated by
      impaired skeletal muscle oxygen extraction and utilization. Previous evidence from other
      mitochondrial pathologies demonstrated that chronic aerobic exercise training enhanced
      mitochondrial biogenesis, improved skeletal muscle oxygen extraction/utilization, exercise
      tolerance and quality of life in these individuals. Chronic aerobic exercise training also
      improved left ventricular and cardio-autonomic function and decreased the occurrence of
      arrhythmias in non-Barth heart failure and arrhythmia human and animal models. Currently it
      is unknown if chronic aerobic exercise training is effective in improving left ventricular
      function, skeletal muscle mitochondrial biogenesis and oxygen extraction/utilization,
      exercise tolerance, cardio-autonomic function and quality of life in those with BTHS; a
      condition containing characteristics consistent with both mitochondrial myopathy and heart
      failure. Establishing the safety and efficacy of aerobic exercise training in BTHS could lead
      to clinical recommendations of regular exercise training for the standard of care treatment
      of individuals with BTHS. It may also provide novel mechanistic information about the
      adaptability of muscle mitochondria in BTHS. Therefore, the overall objective of the
      pilot/feasibility/proof-of-concept proposal is to collect preliminary data on the following
      hypothesis: Supervised aerobic exercise training (3x/wk, 20-45 min, 12 wks) will improve
      skeletal muscle oxygen extraction/utilization, left ventricular function, peak exercise
      tolerance, cardio-autonomic function and quality of life, and will be found safe in
      adolescents and young adults with BTHS. The investigators aim to address these hypotheses
      through left ventricular function, skeletal muscle oxygen extraction/utilization, and whole
      body oxygen consumption measurements during a graded exercise test at baseline and following
      a 3 month supervised aerobic exercise training program in 5 BTHS patients (ages 15-30 yrs).
      Cardio-autonomic function will be examined using post-exercise heart rate recovery
      measurements obtained at baseline and after the 12 wk intervention. Supervised exercise
      training programs will be uniformly designed, but individualized and performed at a hospital
      based physical therapy or cardiac rehabilitation facility near the participant's home. Left
      ventricular function will be examined using 2-D, Doppler and Tissue Doppler echocardiography,
      skeletal muscle oxygen extraction/utilization will be measured using near infrared
      spectroscopy, whole body oxygen consumption will be measured using indirect calorimetry,
      cardio-autonomic function will be measured using electrocardiography and quality of life will
      be measured by the Minnesota Living with Heart Failure Questionnaire (MLWHFQ). The
      investigators expect to find that exercise training is safe in BTHS, and effectively improves
      cardiac and skeletal muscle function and quality of life. Preliminary data from this proposal
      will be used in larger federal or association grant applications examining the
      cardiovascular, musculo-skeletal and autonomic effects of chronic aerobic exercise training
      in BTHS.
    

Intervention name(s): Exercise training
Intervention type(s): Behavioral
Intervention description(s): aerobic exercise training, 45-60 minutes, 3x/week, 12 weeks (3-months)
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Barth syndrome; cardiomyopathy; mitochondria; cardiolipin