Resistance Exercise in Barth Syndrome

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Washington University School of Medicine
Sponsor:
Information provided by (Responsible Party):
W. Todd Cade, Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01629459
First received: June 20, 2012
Last updated: December 18, 2013
Last verified: December 2013
  Purpose

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 Intervention Phase
Barth Syndrome
Behavioral: Resistance exercise
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Change in exercise tolerance [ Time Frame: Enrollment, 3 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    This study will examine the effect of resistance exercise training on left ventricular systolic strain measured by tissue Doppler echocardiography


Secondary Outcome Measures:
  • Change in muscle strength [ Time Frame: Enrollment, 3 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 12
Study Start Date: June 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Resistance exercise training will occur 3x/wk for 12 wks at a physical therapy or cardiac rehabilitation facility near the participant's home

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) 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. 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.

  Eligibility

Ages Eligible for Study:   15 Years to 30 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Age 15-30 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01629459

Contacts
Contact: William T Cade, PT, PhD 314-286-1432 tcade@wustl.edu
Contact: Kathryn Bohnert, MS 314-362-2407 bohnertk@wusm.wustl.edu

Locations
United States, Missouri
Washington University Recruiting
St. Louis, Missouri, United States, 63110
Principal Investigator: William T Cade, PT, PhD         
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: William T Cade, PT, PhD Washington University Early Recognition Center
  More Information

No publications provided

Responsible Party: W. Todd Cade, Assistant Professor of Physical Therapy and Medicine, Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01629459     History of Changes
Other Study ID Numbers: 201205024
Study First Received: June 20, 2012
Last Updated: December 18, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Washington University School of Medicine:
exercise
strength
training
barth syndrome
mitochondria
amino acid

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

ClinicalTrials.gov processed this record on October 30, 2014