University Hospitals Bristol NHS Foundation Trust, University of Bristol and Barth Syndrome UK Initiate Phase 2 Study of Bezafibrate in Barth Syndrome

Share Article

Barth Syndrome Foundation and Barth Syndrome UK announce the beginning of a clinical trial evaluating the use of bezafibrate for people with ultra-rare mitochondrial disorder Barth syndrome. The trial takes place in Bristol, UK and is made possible by global partnerships and collaborations.

“It’s an equation of collaboration. UHB and UoB brought the academic experts; we found the families. We firmly believe that clinical trials in rare diseases such as Barth syndrome require cross-sector partnership.” -- Michaela Damin, Barth Syndrome UK Founder

University Hospitals Bristol NHS Foundation Trust (UHB), University of Bristol (UoB), Barth Syndrome UK and Barth Syndrome Foundation (BSF) recently announced the opening of CARDIOMAN, a Phase II trial evaluating bezafibrate in individuals affected by Barth syndrome, a rare, life-threatening mitochondrial disease caused by a mutation in the tafazzin (TAZ) gene. The trial, funded by an MRC and NIHR Partnership, is a randomized, placebo-controlled pilot trial to assess the efficacy and safety of bezafibrate to increase mitochondrial biogenesis and potentially modify the cellular ratio of monolysocardiolipin to L4- cardiolipin, a biomarker of Barth syndrome. The trial has been designed in collaboration with the UKCRC-registered Bristol Clinical Trials and Evaluation Unit (part of the Bristol Trials Centre), which has managed the conduct of the study throughout.

Barth syndrome is a multi-system, complex disorder with symptoms that vary in severity and incidence. Individuals with Barth syndrome commonly present with heart muscle weakness (cardiomyopathy), cardiac arrhythmias, low white blood cell count (neutropenia) which can lead to serious infection, skeletal muscle weakness, delayed growth, fatigue and varying degrees of physical disability. There are presently no approved pharmacological therapies to treat Barth syndrome.

Bezafibrate is a lipid-lowering drug that has been safely and broadly used to treat hypercholesterolemia since approval in 1978. Many patients with Barth syndrome experience metabolic consequences related to impaired fat metabolism at the cellular level. CARDIOMAN aims to investigate the efficacy of bezafibrate on lipid metabolism and subsequent heart function in boys and young men with Barth syndrome. Peak oxygen consumption is measured at baseline and the final week of treatment. It also includes the direct assessment of heart function of participants during exercise stress by cardiac ultrasound imaging, a methodology developed for children by a research group of the Chief Investigator, Dr. Guido Pieles, in collaboration with international elite sports academies and the cardiac imaging partner of the University of Bristol, Canon Medical Systems. “This is one of the first drug trials ever performed for children and young people affected by a genetic heart muscle disease and would not have been possible without NIHR and the international Barth syndrome community’s enthusiasm and support.”

Notably, CARDIOMAN’s genesis is owed to the long-standing collaboration between Barth Syndrome UK and UHB to generate critical mass to hit enrolment targets. With incidence estimated at 1 in 300,000, identifying eligible and willing patients in the Barth syndrome community has been a critical role of both organisations to ensure the clinical trial can proceed. Michaela Damin, Barth Syndrome UK’s visionary founder, believes, “It’s an equation of collaboration. UHB and UoB brought the academic experts; we found the families. We firmly believe that clinical trials in rare diseases such as Barth syndrome require cross-sector partnership.”

CARDIOMAN marks the second trial in Barth syndrome and first in Europe. “Five years ago, a clinical trial in Barth syndrome seemed elusive. We are now on the advent of multiple trials that have built on the innovation and scientific network that BSF has seeded over the years across the globe,” says Emily Milligan, Executive Director of BSF.

Presently, there are two clinics worldwide that specifically serve the Barth syndrome community, one of which is the Barth Syndrome Service (BSS) at the University Hospitals Bristol NHS Foundation Trust. Emeritus Professor Colin Steward, founder of the BSS and laboratory lead for the CARDIOMAN study, has been instrumental in bringing this important work to fruition for the Barth syndrome community with whom he has worked for over 20 years. “Bezafibrate offers hope that we may discover a safe and effective therapy to fight this debilitating disease in children and adults with Barth Syndrome and end the suffering and loss of life.”

The trial is anticipated to complete by December 2019.


Emeritus Professor Colin Steward of the University of Bristol, the Barth Syndrome Trust UK (the UK charity for the disease) and its founder, Mrs Michaela Damin, jointly obtained funding from NHS Specialised Services to establish a national multidisciplinary service for this disease – the first such service in the World. The NHS Barth Syndrome Service has since provided comprehensive multidisciplinary care and advice for those affected by Barth Syndrome throughout the UK as well as many patients from wider Europe. This is now acting as a bedrock for development of innovative therapies and research.


The study was funded by an MRC and NIHR partnership created to support the evaluation of interventions with potential to make a step-change in the promotion of health, treatment of disease and improvement of rehabilitation or long-term care.

The National Institute for Health Research (NIHR) is the nation's largest funder of health and care research. The NIHR:

  • Funds, supports and delivers high quality research that benefits the NHS, public health and social care
  • Engages and involves patients, carers and the public in order to improve the reach, quality and impact of research
  • Attracts, trains and supports the best researchers to tackle the complex health and care challenges of the future
  • Invests in world-class infrastructure and a skilled delivery workforce to translate discoveries into improved treatments and services
  • Partners with other public funders, charities and industry to maximise the value of research to patients and the economy

The NIHR was established in 2006 to improve the health and wealth of the nation through research, and is funded by the Department of Health and Social Care. In addition to its national role, the NIHR commissions applied health research to benefit the poorest people in low- and middle-income countries, using Official Development Assistance funding.

The Medical Research Council is at the forefront of scientific discovery to improve human health. Founded in 1913 to tackle tuberculosis, the MRC now invests taxpayers’ money in some of the best medical research in the world across every area of health. Thirty-three MRC-funded researchers have won Nobel prizes in a wide range of disciplines, and MRC scientists have been behind such diverse discoveries as vitamins, the structure of DNA and the link between smoking and cancer, as well as achievements such as pioneering the use of randomised controlled trials, the invention of MRI scanning, and the development of a group of antibodies used in the making of some of the most successful drugs ever developed. Today, MRC-funded scientists tackle some of the greatest health problems facing humanity in the 21st century, from the rising tide of chronic diseases associated with ageing to the threats posed by rapidly mutating micro-organisms. The Medical Research Council is part of UK Research and Innovation.

This work uses data provided by patients and collected by the NHS as part of their care and support and would not have been possible without access to this data. The NIHR recognises and values the role of patient data, securely accessed and stored, both in underpinning and leading to improvements in research and care.

Barth Syndrome Foundation ( is the only global network of families, healthcare providers, and researchers solely driven by the mission to save lives through education, advances in treatment and finding a cure for Barth syndrome. In partnership with its affiliates such as Barth Syndrome United Kingdom (, BSF has funded nearly $4.9M USD since 2002 and catalyzed over $21M USD in funding from other agencies to advance global scientific discoveries to end the suffering and loss of life from Barth syndrome. Additionally, BSF provides a lifeline to families and individuals living with Barth syndrome around the world, offering 24/7 individualized support, educational conferences, a robust patient registry and collaborations with specialist healthcare providers to define standards of care, treatment and rapid diagnosis.

Barth syndrome is a rare, life-threatening, genetic mitochondrial disorder primarily affecting boys. Affected individuals may suffer from heart failure, muscle weakness, and infection (caused by neutropenia). Additional characteristics of the syndrome commonly include growth delay, impaired lipid metabolism, fatigue and cardiolipin deficiency. In some individuals affected by Barth syndrome, the symptoms can be very severe, sometimes resulting in heart transplant, potentially lethal infections, and even death.

This project is supported by the National Institute for Health Research (NIHR) Biomedical Research Centre (Cardiovascular Disease). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

Share article on social media or email:

View article via:

Pdf Print

Contact Author

Emily Milligan
Follow >
Barth Syndrome Foundation
Like >
Visit website