Barth SyndromeNCT01625663
Heart and Muscle Metabolism in Barth Syndrome
An observational study of Barth Syndrome, run by Duke University at 1 site in United States.
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… Read more about this study
- Who is it for?
- Ages 8 to 35 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Barth Syndrome
- How many people
- 64 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2012to 31 Mar 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 35 years
- Men only
- Healthy volunteers accepted
- Child, Adult
Study population: Children and adults ages 8-35 yrs with Barth syndrome and healthy controls.
Who may be able to join
- confirmed diagnosis of BTHS or healthy control
- age 8-35 years
- sedentary (physically active less than 2x/wk)
- stable on medications for ≥ 3 months including ß-blockers, ACE inhibitors, digoxin
- lives in North America, the UK, Europe, South Africa or other locations feasible for travel to the US
Who cannot join
- current unstable heart disease
- diabetes or other known concurrent disease that may affect nutrient metabolism
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Heart and Skeletal Muscle Metabolism, Energetics and Function in Barth Syndrome
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.
Read the detailed 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:
- 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.
- Conditions
- Barth Syndrome
- Keywords
- barth syndrome, heart failure, mitochondria, metabolism, amino acid
- Medical subject headings
- Barth Syndrome, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Barth syndrome | Children (8-17 yrs) and adults (18-35 yrs) | |
| Controls | Children (8-15 yrs) and adults (18-35 yrs) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: baseline
Secondary outcomes (5)
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
Measured: baseline
cardiac energetics
cardiac energetics will be measured by 31P magnetic resonance spectroscopy of the heart
Measured: baseline
skeletal muscle energetics
skeletal muscle energetics will be measured by 31P magnetic resonance spectroscopy
Measured: baseline
Myocardial fatty acid oxidation rate
Myocardial fatty acid oxidation rate will be measured by radio-isotope tracer infusion and PET imaging
Measured: baseline
left ventricular systolic strain
Left ventricular systolic strain will be measured by tissue Doppler echocardiography
Measured: baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2012 (estimated)
- Study startJun 2012
- Primary completion31 Mar 2020
- Study completion31 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Barth SyndromeStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- University of Florida
- Responsible party
- Sponsor
- Investigators
- William T Cade, PT, PhD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01625663
- Sponsor's protocol ID
- Pro00105474
- Status last verified
- May 2020
- First submitted
- 19 Jun 2012
- Last updated
- 2 Jun 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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 enhanced glucose metabolism in children, adolescents, and young adults with Barth syndrome. J Inherit Metab Dis. 2019 May;42(3):480-493. doi: 10.1002/jimd.12094. Epub 2019 Apr 11.
PubMed 30924938Bashir 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):e13130. doi: 10.14814/phy2.13130.
PubMed 28196853Cade WT, Laforest R, Bohnert KL, Reeds DN, Bittel AJ, de las Fuentes L, Bashir A, Woodard PK, Pacak CA, Byrne BJ, Gropler RJ, Peterson LR. Myocardial glucose and fatty acid metabolism is altered and associated with lower cardiac function in young adults with Barth syndrome. J Nucl Cardiol. 2021 Aug;28(4):1649-1659. doi: 10.1007/s12350-019-01933-3. Epub 2019 Nov 8.
PubMed 31705425
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Heart and Skeletal Muscle Metabolism, Energetics and Function in Barth Syndrome
- ClinicalTrials.gov ID
- NCT01625663
- Acronym / sponsor ID
- Pro00105474
- Conditions
- Barth Syndrome
- Keywords
- barth syndrome, heart failure, mitochondria, metabolism, amino acid
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- University of Florida
- Study start
- Jun 2012 (actual)
- Primary completion
- 31 Mar 2020 (actual)
- Study completion
- 31 Mar 2020 (actual)
- First posted
- 21 Jun 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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:
- 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.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Barth syndrome | – | –Children (8-17 yrs) and adults (18-35 yrs) |
| Controls | – | –Children (8-15 yrs) and adults (18-35 yrs) |
Who may qualify
- Ages
- 8 to 35 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- Children and adults ages 8-35 yrs with Barth syndrome and healthy controls.
Key inclusion criteria (5 listed)
- confirmed diagnosis of BTHS or healthy control
- age 8-35 years
- sedentary (physically active less than 2x/wk)
- stable on medications for ≥ 3 months including ß-blockers, ACE inhibitors, digoxin
- lives in North America, the UK, Europe, South Africa or other locations feasible for travel to the US
Key exclusion criteria (2 listed)
- current unstable heart disease
- diabetes or other known concurrent disease that may affect nutrient metabolism
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Whole-body fatty acid oxidation rate
Time frame: baseline
Whole-body fatty acid oxidation rate will be measured by 13C-labeled fatty acid stable isotope tracer infusion and mass spectrometry
5 secondary outcomes
whole-body amino acid oxidation rate
Time frame: baseline
cardiac energetics
Time frame: baseline
skeletal muscle energetics
Time frame: baseline
Myocardial fatty acid oxidation rate
Time frame: baseline
left ventricular systolic strain
Time frame: baseline
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2020.
- Results publication: PubMed 30924938Cade 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 enhanced glucose metabolism in children, adolescents, and young adults with Barth syndrome. J Inherit Metab Dis. 2019 May;42(3):480-493. doi: 10.1002/jimd.12094. Epub 2019 Apr 11.
- Results publication: PubMed 28196853Bashir 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):e13130. doi: 10.14814/phy2.13130.
- Derived from this study: PubMed 31705425Cade WT, Laforest R, Bohnert KL, Reeds DN, Bittel AJ, de las Fuentes L, Bashir A, Woodard PK, Pacak CA, Byrne BJ, Gropler RJ, Peterson LR. Myocardial glucose and fatty acid metabolism is altered and associated with lower cardiac function in young adults with Barth syndrome. J Nucl Cardiol. 2021 Aug;28(4):1649-1659. doi: 10.1007/s12350-019-01933-3. Epub 2019 Nov 8.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William T Cade, PT, PhD principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Barth Syndrome, run by Duke University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Whole-body fatty acid oxidation rate (time frame: baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01625663, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2020.