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Resistance Exercise in Barth Syndrome

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ClinicalTrials.gov Identifier: NCT01629459
Recruitment Status : Completed
First Posted : June 27, 2012
Last Update Posted : May 13, 2020
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine

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.

Condition or disease Intervention/treatment Phase
Barth Syndrome Behavioral: Resistance exercise and protein supplementation Not Applicable

Detailed Description:
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 pilot/feasibility/proof-of-concept proposal is to collect preliminary data on the following hypothesis: Supervised RET (3x/wk, 45min, 12 wks) with diet standardization (meeting at least minimum RDA recommendations for adolescents/young adults- 52-56 g protein/day) and protein supplementation (whey protein isolate, 42 g/day, Unjury Medical Quality Protein, Reston, VA ) will improve exercise tolerance, left ventricular function, muscle strength and quality of life, and will be found safe in adolescents and young adults with BTHS. In addition, our preliminary data suggest there is impaired protein metabolism and skeletal muscle atrophy in BTHS. Typically, in other populations, whole-body and skeletal muscle protein synthesis increases with RET; however, this is unclear in BTHS. Thus, as a secondary aim, we will examine the effect of RET on whole-body protein metabolism in BTHS. We aim to address these hypotheses through left ventricular function, skeletal muscle strength, body composition, exercise tolerance, and whole-body protein metabolism measurements at baseline and following a 3 month supervised RET program in 3 participants with BTHS (ages 15-30 yrs). Supervised RET programs will be uniformly designed, but individualized and performed at a physical therapy or cardiac rehabilitation facility near the participant's home. Protein supplementation (whey protein isolate, 42 g/day) will be ingested by the participants in conjunction with the RET program. Nutritional status will be evaluated at baseline, mid-training (6-weeks) and post-training through plasma levels of pre-albumin and amino acid profile. Left ventricular function will be examined using 2-D, Doppler and tissue Doppler echocardiography, skeletal muscle strength will be measured using isotonic and isokinetic dynamometry, body composition using dual energy x-ray absorptiometry, exercise tolerance will be measured using graded exercise testing and indirect calorimetry, whole-body protein metabolism by stable-isotope tracer methodology and mass spectrometry, and quality of life will be measured by the Minnesota Living with Heart Failure Questionnaire. We expect to find that RET is safe in BTHS, and effectively improves cardiac function, skeletal muscle strength and mass, whole-body protein synthesis and quality of life. Preliminary data from this proposal will be used in larger federal or association grant applications examining the cardiovascular, musculoskeletal and protein metabolic effects of RET in BTHS.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Resistance exercise training
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effects of Resistance Exercise Training on Cardiac, Metabolic and Muscle Function and Quality of Life in Barth Syndrome
Actual Study Start Date : June 2012
Actual Primary Completion Date : June 30, 2019
Actual Study Completion Date : June 30, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Resistance exercise training
Participants will undergo resistance exercise training 3x/wk for 12 weeks at a physical therapy or cardiac rehabilitation facility near the participant's home.
Behavioral: Resistance exercise and protein supplementation
Resistance exercise training will occur 3x/wk for 12 wks at a physical therapy or cardiac rehabilitation facility near the participant's home. Participant will take 42 grams of supplementation protein daily.




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   15 Years to 35 Years   (Child, Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Age 15-35 years
  2. Sedentary (exercises less than 2x/wk)
  3. Motivated to exercise (BTHS only)
  4. Stable on medications for ≥ 3 months (BTHS only)
  5. Lives in North America
  6. Lives in the St. Louis area (Controls only)

Exclusion Criteria:

  1. Unstable heart disease
  2. 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 ClinicalTrials.gov identifier (NCT number): NCT01629459


Locations
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United States, Missouri
Washington University
Saint Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
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Principal Investigator: William T Cade, PT, PhD Washington University School of Medicine
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Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01629459    
Other Study ID Numbers: 201205024
First Posted: June 27, 2012    Key Record Dates
Last Update Posted: May 13, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Washington University School of Medicine:
exercise
strength
training
barth syndrome
mitochondria
amino acid
protein
Additional relevant MeSH terms:
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Barth Syndrome
Syndrome
Disease
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