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: Analysis

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.

 

Contact information

Chief Investigator: Professor Colin Steward

Study Coordinator: Lucy Dabner

Email: Cardioman-trial@bristol.ac.uk

 

 

The incidence of chronic thoracic aortic aneurysm (CTTAA) is rising as the UK population ages and will therefore pose an increasing challenge to healthcare providers and policy makers.  These patients are at risk of both fatal and non-fatal complications of the condition and the subsequent treatment costs for these patients are high.  The risk of rupture or dissection is related to size and rate of growth of the aneurysm, but these two factors alone are not sufficient to predict risk of rupture, dissection or death.  Both Endovascular Stent Grafting (ESG) and Open Surgical Repair (OSR) are known to be effective treatments but each has limitations and cannot always be offered to all patients. There is limited research in this area; the ETTAA study is designed to overcome existing deficiencies in the body of evidence.  It is a prospective observational cohort study that will collect data from the point of referral through to secondary care, aiming for 3 years median follow-up of patients with CTTAA. The results will enable clinicians to make a more informed decision about which treatment option will be best for individual patients.

  •          Study arms are Watchful Waiting (WW), ESG, OSR, and Conservative Management (CM)
  •          Patients consented and followed up over the telephone
  •          25 centres currently taking part

Aims:

  •          Understand the growth rate of aneurysms and identify which factors influence growth rate
  •          Understand how quality of life changes, following surgical procedures
  •          Estimate cost-effectiveness of different treatment options, by measuring changes in survival and quality of life of patients, compared to the cost of treatment and post-op patient care.
  •          Create a risk score that will help specialists determine which intervention (stenting or surgery) is best suited to a given patient, and when this treatment should be offered
 

Benefit to patients and the NHS of cardiac magnetic resonance imaging (CMR) after Primary percutaneous coronary Intervention (PPCI) Pathway Activation

Sponsor: University of Bristol 

REC Number: 12/SW/0326

Status: Analysis

Cardiac magnetic resonance imaging (CMR) can be used to provide detailed pictures of the heart and is used by cardiologists to assess heart function and guide treatment in people who had, or were suspected of having, a heart attack.  We want to set up a multicentre registry by making use of data collected by NHS hospitals in the course of providing usual care for those patients.  Such a registry will provide information on CMR use and how CMR influences patient management. 

The PIPA study is determining whether it is feasible to set up such a registry, for example, whether hospitals can retrieve the data we need and whether we can merge data from different sources (for example, data from the Emergency Department and ward, data describing blood and imaging test results) for a particular patient.  We have finished recruiting patients with suspected heart attacks from four hospitals in the UK (Bristol, Leeds Cardiff and Swansea), two with and two without CMR readily available.  We are assembling a database containing information on patient characteristics, details of interventions and clinical outcomes, and whether CMR has been used or not.  We are requesting hospital activity data from NHS Digital on all patients who participated in the study so that we can add information about future hospital care to the database. We are also requesting data from the Office of National Statistics (ONS) where all births and deaths are recorded. Please contact the study teamif you do not wish us to include information about you from NHS Digital or ONS on the database. 

We will provide regular updates about how the study is progressing and the final conclusion about whether or not the registry is feasible and will be extended to all UK centres that deal with emergency or suspected heart attacks.

 

 

Contact Information

Chief Investigator: Prof Barney Reeves

Study coordinator: Dr Rachel Brierley 

E-mailpipa-study@bristol.ac.uk

 

Progenitor cell response after Myocardial Infarction Study

Sponsor: University Hospitals Bristol

REC Number: 09/H0104/58

After a heart attack, stem cells produced in bone marrow are released in large amounts into the blood and travel to the heart to promote the growth of new blood vessels and repair the damage caused by the heart attack.  In people with diabetes this process may be impaired, resulting in less efficient repair and poorer clinical outcomes after a heart attack.

The Promis study is studying patients with and without diabetes who have had a heart attack.  We are collecting blood samples after the heart attack to determine how many stem cells are released in the blood and how these stem cells behave.

Patients also have cardiac magnetic resonance imaging (CMR) scans to investigate the extent of damage to the heart after the heart attack.  We will determine whether the number of stem cells released from bone marrow is influenced by the degree of damage to the heart, and whether the relationship between the number of stem cells released and the amount of damage is lost in patients with diabetes.  

  

Contact Information

Chief Investigator: Dr Andreas Baumbach

Study coordinator: Lucy Culliford

E-mailpromis-trial@bristol.ac.uk

 

Determination of the SK channel composition contributing to atrial action potential duration and of predictors of response to treatments in patients with or without atrial fibrillation

Funder: NIHR and British Heart Foundation 

Sponsor: University of Bristol 

Status: Set Up

For the heart to pump blood round the body effectively, the upper and lower heart chambers (atria and ventricles) must beat in a repeated orderly sequence giving rise to what is known as ‘heart rhythm’. Disruptions to normal heart rhythm (‘arrhythmias’) impair blood circulation and can reduce life expectancy. Atrial fibrillation (AF) is the most common arrhythmia and is estimated to effect over 1 million people in the United Kingdom. The SKArF Study aims to understand how this arrhythmia occurs, with a view to developing more effective treatments.

In the SKArF Study we are recruiting adult patients undergoing cardiac surgery with bypass and asking them to donate small pieces of atrial tissue which would usually be discarded of as leftover from surgery. We are recruiting patients both with and without AF, and conducting laboratory experiments on these surplus tissue samples. Chiefly, we are examining the actions of a specific protein which we hypothesise may be an AF specific antiarrhythmic drug target.

The SKArF study is being funded by the British Heart Foundation and is an NIHR Portfolio study. The University of Bristol has overall responsibility for the conduct of the study.

Contact Information

Chief Investigator: Prof Raimondo Ascione

Study coordinator: Madeleine Clout

E-mail:  skarf-study@bristol.ac.uk

 

A Randomised Controlled Trial Investigating the Pharmacodynamic Effect of Ticagrelor Monotherapy on Platelet Reactivity in Patients with Coronary Artery Disease: The TEMPLATE Study

Sponsor: University Hospitals Bristol 

REc Number: 14/SC/1309

Status: Recruiting 

The TEMPLATE study is a single centre, open-label randomised controlled trial of the investigational medicinal product ticagrelor.  Patients with blocked or seriously narrowed coronary arteries are treated with a procedure called Percutaneous Coronary Intervention (PCI) in which a stent is inserted to open up the blockage in the coronary artery.  Patients are usually prescribed Dual Antiplatelet Therapy (DAPT) with aspirin and clopidogrel (ADP blocker) course following their PCI.  The use of two different anti-platelet agents helps ensure that platelets are completely inhibited and thereby, are less likely to contribute to abnormal clot formation in the coronary stent.

A new anti-platelet drug called ticagrelor is now available and is given with aspirin to some patients after a stent procedure.  Ticagrelor is a more powerful and reliable ADP blocker than clopidogrel, and is replacing clopidogrel in some patient groups.  There is emerging evidence from healthy volunteer studies that ticagrelor used alone may be sufficient to strongly inhibit platelets, without the need for additional aspirin.  The TEMPLATE study aims to find out if ticagrelor alone is as good as taking ticagrelor and aspirin together at inhibiting platelets, in patients who have had a PCI.

The study population is patients at the end of a DAPT course with clopidogrel and aspirin following a PCI, and who are due to revert aspirin monotherapy as part of standard clinical care at 6 to 12 months after PCI.  Patients who take part in the trial will be randomised to receive either aspirin and ticagrelor or ticagrelor alone for a 4 week interval prior to reverting to aspirin alone. Blood samples for detailed analysis of the extent of platelet inhibition will be taken at three time-points, whilst patients are receiving different combinations of anti-platelet therapy. The main analysis will compare the extent of platelet inhibition between the patient groups receiving ticagrelor alone compared to those receiving ticagrelor plus aspirin.

Contact Information

Chief Investigator: Dr Andrew Mumford

Study coordinator: Wendy Underwood

E-mail:  cteu-template-trial@bristol.ac.uk