Clinical Trial: Resistance Exercise in Barth Syndrome

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Effects of Resistance Exercise Training on Cardiac, Metabolic and Muscle Function and Quality of Life in Barth Syndrome

Brief Summary: Barth syndrome (BTHS) is a disorder that is characterized by heart failure, exercise intolerance and skeletal muscle weakness. Preliminary evidence demonstrates that endurance exercise training does not significantly improve exercise tolerance in BTHS. Because endurance exercise training targets a metabolic pathway that is adversely affected by BTHS, the investigators hypothesized that resistance training may improve exercise tolerance in BTHS because this type of training targets a different metabolic pathway than does endurance exercise. Therefore, the overall objective of the pilot/feasibility/proof-of-concept proposal is to collect preliminary data on the following hypothesis: Supervised resistance exercise training (3x/wk, 45min, 12 wks) will improve exercise tolerance, heart function, muscle strength and quality of life, and will be found safe in adolescents and young adults with BTHS.

Detailed Summary: Barth syndrome (BTHS) is an X-linked disorder characterized by severe mitochondrial dysfunction, cardiomyopathy, skeletal muscle weakness and exercise intolerance. Preliminary evidence from our group has demonstrated that a 12-week endurance (i.e. aerobic) exercise training program increases exercise tolerance only modestly (~5%) in participants with BTHS with no effect on heart or skeletal muscle function. Other populations, including non-BTHS heart failure, appear to receive a greater benefit from endurance exercise training (e.g. ~15-25% increase in exercise tolerance) than does BTHS. The blunted effect of endurance exercise training in BTHS may be due to the inherent pathogenesis of BTHS: genetic mitochondrial dysfunction in type I (oxidative>glycolytic capacity) muscle fibers. Endurance exercise training typically results in increased mitochondrial density and enzyme function (primarily in type I muscle fibers) in other populations; however, in BTHS, due to maternally inherited mitochondrial dysfunction, endurance exercise training may result in the generation of more impaired mitochondria thus limiting any beneficial effect of endurance training on exercise tolerance. Thus, it may be more beneficial to target type II (glycolytic>oxidative capacity) muscle fibers with exercise training when attempting to increase exercise tolerance in BTHS. Indeed, previous evidence from non-BTHS heart failure has shown that resistance exercise training (RET) increases exercise tolerance, skeletal muscle strength, and heart function and improves quality of life in these individuals. Currently it is unknown if RET is effective in improving these variables in those with BTHS and is the focus of this proposal. Establishing the safety and efficacy of RET in BTHS could lead to clinical recommendations of regular RET instead of or in combination with endurance exercise training for the standard of care treatment of individuals with BTHS. Therefore, the overall objective of the
Sponsor: Washington University School of Medicine

Current Primary Outcome: Change in exercise tolerance [ Time Frame: Enrollment, 3 months ]

Original Primary Outcome:

• Change in exercise tolerance [ Time Frame: Enrollment, 3 months ]
  This study will examine the effect of resistance exercise training on exercise tolerance: peak oxygen consumption, exercise time and exercise work during graded exercise test on cycle ergometer
• Change in left ventricular systolic strain [ Time Frame: Enrollment, 3 months ]
  This study will examine the effect of resistance exercise training on left ventricular systolic strain measured by tissue Doppler echocardiography

Current Secondary Outcome:

• Change in muscle strength [ Time Frame: Enrollment, 3 months ]
  This study will measure the effect of resistance exercise training on muscle strength measured by 1-repetition maxium testing on universal equipment
• Change in quality of life [ Time Frame: Enrollment, 3 months ]
  This study will examine the effect of resistance exercise training on quality of life measures by Minnesota living with heart failure questionnaire
• Change in left ventricular systolic strain [ Time Frame: Enrollment, 3 months ]
  This study will examine the effect of resistance exercise training on left ventricular systolic strain measured by tissue Doppler echocardiography

Original Secondary Outcome:

• Change in muscle strength [ Time Frame: Enrollment, 3 months ]
  This study will measure the effect of resistance exercise training on muscle strength measured by 1-repetition maxium testing on universal equipment
• Change in quality of life [ Time Frame: Enrollment, 3 months ]
  This study will examine the effect of resistance exercise training on quality of life measures by Minnesota living with heart failure questionnaire
• Change in whole body protein synthesis rate [ Time Frame: Enrollment, 3 months ]
  This study will examine the effect of resistance exercise training on whole-body protein synthesis rate measured by stable isotope labeled leucine and mass spectrometry

Information By: Washington University School of Medicine

Dates:
Date Received: June 20, 2012
Date Started: June 2012
Date Completion: March 2018
Last Updated: January 6, 2017
Last Verified: January 2017