CARDIOMAN
Treatment of Barth Syndrome by CARDIOlipin MANipulation
(CARDIOMAN): A randomised placebo controlled pilot trial conducted
by the nationally commissioned Barth Syndrome Service
Chief Investigator
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Institution
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Dates
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Funding Stream
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Grant Ref
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Amount
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Steward, Dr Colin
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University of Bristol
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01/04/2015-31/07/2017
(28 months)
+ 18 months
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NIHR Efficacy and Mechanism Evaluation (EME)
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12/205/56
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£528,070
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Summary
Barth Syndrome is a life threatening genetic disease which
affects young males. It is caused by abnormal fats (lipids) in the
powerhouses of cells (mitochondria). Those affected may be
stillborn or develop heart failure, bacterial infections, poor
growth or feeding problems during childhood. 22 males are alive
with the disease in the UK.
This disease carries many risks and problems for its sufferers,
as well as major healthcare costs. 7 in 10 people require frequent
drug injections to boost their white blood count. Almost half have
been considered for heart transplantation, but only half of these
survive. Even those who have not received transplants can develop
life-threatening heart rhythm disturbances.
Boys/men living with the disease have severe exercise
intolerance, lethargy and fatigue which affect their daily life;
many use wheelchairs intermittently to aid mobility. Furthermore,
children continue to die from this disease, which has claimed the
lives of 4 of the 5 boys born since the start of the national Barth
Syndrome Service (BSS).
Scientific research has shown that several treatments can
improve the fat abnormalities in cells affected by Barth Syndrome
in mice or humans. One is a drug (bezafibrate) which is already
used in children to lower blood fats as well as in adults with a
muscle disease resulting from mitochondrial problems and the other
is a food supplement (resveratrol). These treatments have also
shown promising effects in a mouse that has heart problems like
those seen in Barth Syndrome.
The purpose of this project is to see if the more tried and
tested of these treatments (bezafibrate) can be given safely and
effectively to people with Barth Syndrome in a blinded randomised
trial.
Bezafibrate or an inactive (placebo) treatment, would be given
for 4 months at a time with a one month break between the two
phases. Tests would be performed after each treatment period,
looking for benefit in blood cells, exercise capacity, heart
function or quality of life. These potential treatments would run
alongside laboratory work at Bristol University and Great Ormond St
Hospital to see the effect of each drug on their cells and
mitochondria (powerful electron microscopes show that these are
abnormal in Barth Syndrome). This is to see whether we can predict
any improvement in symptoms in order to tell us which patients
would benefit from this treatment in future.
We wish to study up to 18 Barth Syndrome boys/men, all of those
with Barth Syndrome in the UK aged 6 years or over. We would use a
national children's research network and local GPs to perform
monthly blood tests in order to minimise the amount of travel to
Bristol. These studies will only be performed with appropriate
permissions from relevant ethics and regulatory committees and
safety will be monitored by an independent committee with the
authority to recommend stoppage if obvious problems are seen.
Costs have been calculated to cover the staff running the
trial/testing procedures, laboratory costs, time on testing
machines, blood sampling, data collection, analysis, and writing up
for public journals, as well as overnight hotel costs for patients
where stays are necessary. If promising results are obtained with
either or both drugs, we would share this information with
American/European teams so that this work will have worldwide
benefit. For this, we have the complete backing of our patients,
their families and the respective UK and USA charities.
Links to further information
Protocol: http://cteu.bris.ac.uk/our-studies/?trialType=Rare-diseases
