Exercise Training in Barth Syndrome

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. Identifier: NCT01194141
Recruitment Status : Completed
First Posted : September 2, 2010
Last Update Posted : January 10, 2017
Information provided by (Responsible Party):
W. Todd Cade, Washington University School of Medicine

Brief 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.

Condition or disease Intervention/treatment Phase
Barth Syndrome Behavioral: Exercise training Not Applicable

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety and Efficacy of Aerobic Exercise Training in Barth Syndrome
Study Start Date : July 2010
Actual Primary Completion Date : December 2013
Actual Study Completion Date : December 2013

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Exercise training
Aerobic exercise training 45-60 min/3x/week/12 weeks
Behavioral: Exercise training
aerobic exercise training, 45-60 minutes, 3x/week, 12 weeks (3-months)

Primary Outcome Measures :
  1. Peak oxygen consumption [ Time Frame: Enrollment and 3 months ]
    peak oxygen consumption measured by indirect calorimetry

Secondary Outcome Measures :
  1. Cardiac output [ Time Frame: Enrollment and 3 months ]
    cardiac output measured by echocardiography

  2. muscle oxygen extraction [ Time Frame: Enrollment and 3 months ]
    skeletal muscle oxygen extraction measured by near infrared spectroscopy

Information from the National Library of Medicine

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Ages Eligible for Study:   15 Years to 30 Years   (Child, Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Age 15-30 years
  2. Sedentary (exercises less than 2x/wk)
  3. Motivated to exercise
  4. Stable on medications for ≥ 3 months
  5. Lives in North America.
  6. Planning on attending the Barth Syndrome International Conference in July 2010.

Exclusion Criteria:

  1. Unstable heart disease
  2. Any concurrent disease that may contraindicate exercise testing and training.
  3. Cardiac transplantation

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01194141

Sponsors and Collaborators
Washington University School of Medicine
Principal Investigator: William T Cade, PT, PhD Washington University School of Medicine

Additional Information:
Publications of Results:
Responsible Party: W. Todd Cade, Assisant Professor of Physical Therapy and Medicine, Washington University School of Medicine Identifier: NCT01194141     History of Changes
Other Study ID Numbers: 10-0652
First Posted: September 2, 2010    Key Record Dates
Last Update Posted: January 10, 2017
Last Verified: January 2017

Keywords provided by W. Todd Cade, Washington University School of Medicine:
Barth syndrome

Additional relevant MeSH terms:
Barth Syndrome
Pathologic Processes
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Abnormalities, Multiple
Congenital Abnormalities
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Metabolic Diseases