Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01625663
Other study ID # Pro00105474
Secondary ID
Status Completed
Phase
First received
Last updated
Start date June 2012
Est. completion date March 31, 2020

Study information

Verified date May 2020
Source Duke University
Contact n/a
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

Barth syndrome (BTHS) is an X-linked disorder caused by abnormal cardiolipin metabolism and is characterized by skeletal and cardiomyopathy and high mortality rates. Through clinical metabolism and imaging studies and pluripotent stem cell induction and molecular techniques on skin biopsy samples, this project will produce novel translational information regarding the pathogenesis of BTHS, reveal potential targets for interventions and provide unique data regarding nutrient metabolism and abnormal cardiolipin and mitochondrial function. This project has the potential to provide information that could significantly improve morbidity and mortality in children and young adults with BTHS and may have relevance to other non-BTHS related conditions such as aging and adult heart failure.


Description:

Barth syndrome (BTHS) is an X-linked disorder characterized by abnormal cardiolipin metabolism, mitochondrial dysfunction, muscle wasting and heart failure. BTHS is a particularly significant disease as it is often fatal in childhood and there are no approved therapies for BTHS other than the standard treatment of heart failure. Therefore novel areas of research and platforms in which to test new therapies are highly needed. Through state-of-the-art and innovative methodologies, this project will focus on the novel role of skeletal muscle and heart nutrient (glucose, fatty acid, and amino acid) metabolism in the pathogenesis of BTHS. Phenotypic information regarding skeletal muscle and heart nutrient metabolism in BTHS and how it may relate to energy production and function of these organs is lacking and is significant as this may advance our understanding of the underlying pathogenesis of BTHS. With this understanding, safe and efficacious therapies can be targeted for BTHS. The investigators' overall hypothesis is that impaired fatty acid metabolism in skeletal muscle and the heart produces a fuel deficit in these organs leading to impaired energy production, exercise intolerance and heart failure. Further, as a consequence of impaired fatty acid metabolism in skeletal muscle and the heart, protein breakdown (wasting) in skeletal muscle and the heart occurs to provide amino acids as compensation for this inadequate fatty acid energy supply, thereby worsening heart and skeletal muscle function in BTHS. The investigators' aims to address this hypothesis in 30 young adults and children with BTHS and 30 healthy, age, puberty stage and activity level matched controls ages 8-35 years are:

1) To characterize skeletal muscle and heart nutrient metabolism and 2) To examine the relationship between skeletal muscle and heart nutrient metabolism, energy production and function (exercise tolerance and heart function). As an exploratory aim, we will examine mechanistic molecular pathways of nutrient metabolism; specifically protein breakdown, mitochondrial function and fatty acid metabolism, in human myocytes derived from inducible pluripotent stem cells (from skin fibroblasts) obtained from adults and children with BTHS and from adult controls. Skeletal muscle nutrient metabolism will be quantified by stable-isotope tracer methodology and mass spectrometry, heart nutrient metabolism using radio-isotope tracer methodology and PET imaging, skeletal muscle and heart energy production using magnetic resonance spectroscopy, skeletal muscle function by graded exercise testing and indirect calorimetry, heart function by echocardiography, and myocyte nutrient pathway mechanism examination by pluripotent stem cell induction and protein and RNA expression analyses.


Recruitment information / eligibility

Status Completed
Enrollment 64
Est. completion date March 31, 2020
Est. primary completion date March 31, 2020
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Male
Age group 8 Years to 35 Years
Eligibility Inclusion Criteria:

1. confirmed diagnosis of BTHS or healthy control

2. age 8-35 years

3. sedentary (physically active less than 2x/wk)

4. stable on medications for = 3 months including ß-blockers, ACE inhibitors, digoxin

5. lives in North America, the UK, Europe, South Africa or other locations feasible for travel to the US

Exclusion Criteria:

1. current unstable heart disease

2. diabetes or other known concurrent disease that may affect nutrient metabolism

Study Design


Related Conditions & MeSH terms


Locations

Country Name City State
United States Washington University Saint Louis Missouri

Sponsors (2)

Lead Sponsor Collaborator
Duke University University of Florida

Country where clinical trial is conducted

United States, 

References & Publications (2)

Bashir A, Bohnert KL, Reeds DN, Peterson LR, Bittel AJ, de Las Fuentes L, Pacak CA, Byrne BJ, Cade WT. Impaired cardiac and skeletal muscle bioenergetics in children, adolescents, and young adults with Barth syndrome. Physiol Rep. 2017 Feb;5(3). pii: e131 — View Citation

Cade WT, Bohnert KL, Peterson LR, Patterson BW, Bittel AJ, Okunade AL, de Las Fuentes L, Steger-May K, Bashir A, Schweitzer GG, Chacko SK, Wanders RJ, Pacak CA, Byrne BJ, Reeds DN. Blunted fat oxidation upon submaximal exercise is partially compensated by — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Whole-body fatty acid oxidation rate Whole-body fatty acid oxidation rate will be measured by 13C-labeled fatty acid stable isotope tracer infusion and mass spectrometry baseline
Secondary whole-body amino acid oxidation rate whole-body amino acid oxidation rate will be measured by 13C leucine stable isotope tracer infusion and mass spectrometry baseline
Secondary cardiac energetics cardiac energetics will be measured by 31P magnetic resonance spectroscopy of the heart baseline
Secondary skeletal muscle energetics skeletal muscle energetics will be measured by 31P magnetic resonance spectroscopy baseline
Secondary Myocardial fatty acid oxidation rate Myocardial fatty acid oxidation rate will be measured by radio-isotope tracer infusion and PET imaging baseline
Secondary left ventricular systolic strain Left ventricular systolic strain will be measured by tissue Doppler echocardiography baseline
See also
  Status Clinical Trial Phase
Enrolling by invitation NCT03655223 - Early Check: Expanded Screening in Newborns
Completed NCT01629459 - Resistance Exercise in Barth Syndrome N/A
Completed NCT03098797 - A Trial to Evaluate Safety, Tolerability and Efficacy of Elamipretide in Subjects With Barth Syndrome Phase 2/Phase 3
Completed NCT01194141 - Exercise Training in Barth Syndrome N/A
Recruiting NCT05554835 - Global Registry and Natural History Study for Mitochondrial Disorders
Available NCT04689360 - An Intermediate Size Expanded Access Protocol of Elamipretide
No longer available NCT01461304 - Compassionate Use of Triheptanoin (C7) for Inherited Disorders of Energy Metabolism