Treatment of Barth Syndrome by CARDIOlipin MANipulation (CARDIOMAN): A randomised placebo controlled pilot trial conducted by the nationally commissioned Barth Syndrome Service

Sponsor: University Hospitals Bristol NHS Foundation Trust

Status: In Follow Up

Funding: National Institute for Health Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme and the Barth Syndrome Foundation USA.

Barth syndrome is a rare, life threatening, genetic disease which affects young males. It is caused by abnormal fats (lipids) in the powerhouses of cells (mitochondria) and those who suffer with it often develop heart failure, heart rhythm abnormalities, bacterial infections, poor growth or feeding, weak muscles, developmental delay, severe exercise intolerance, lethargy and fatigue; all of which affect their daily life. Low white blood cell counts occur frequently due to intermittent or persistent reduction in numbers of the neutrophils that are responsible for fighting bacterial infections. This requires expensive and distressing injections to stimulate the bone marrow to produce more neutrophils. In addition, approximately one third of all males living with this disease in the UK have required heart transplantation.

Scientific research has shown that several treatments can improve the fat abnormalities in cells affected by Barth syndrome from either mice or humans; one of which is a drug called bezafibrate. Bezafibrate is particularly attractive as it has been safely administered for over 20 years in the UK to both adults and children for the treatment of high blood fats. The purpose of this study is to see if bezafibrate can be given safely and effectively to boys and men with Barth syndrome in a blinded randomised trial.

Bezafibrate or an inactive (placebo) treatment will be given to patients for 4 months, followed by a one month break, and then followed by 4 months of the alternate treatment (e.g. if bezafibrate is given for the first 4 months, a placebo will be given for the second 4 months) . Half of the participants will take bezafibrate first, the other half will take placebo first. Participants and research staff will not know which order the treatments are given in (double-blind trial).

Tests will be performed when patients enrol onto the study and at the end of each 4 month treatment period. The tests will investigate the effects bezafibrate on blood cells, exercise capacity, heart function and quality of life. The laboratory work performed at Bristol University and Great Ormond St Hospital will test the effect of bezafibrate on participant’s cells and mitochondria (which have been shown to be 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. Laboratory work will also be carried out on participant’s cells using another drug called resveratrol, which has also shown promise in laboratory tests, to see if this could provide an alternative treatment.

We wish to study up to 18 boys and young men with Barth syndrome in the UK, aged 6 years or over. In order to minimise travel to Bristol for participants, we will use local GPs and hospitals to perform monthly blood tests. Safety will be monitored by an independent Data Monitoring and Safety Committee.

Results from this study will be shared with our American and European colleagues so that this work will have worldwide benefit.

NIHR Award Information

Contact information

Chief Investigator: Professor Colin Steward

Study Coordinator: Lucy Dabner