Clinical trials

Cystic fibrosis (CF) is a disease that affects over 11,000 people in the UK. It is a genetic condition that affects many organs including the lungs, pancreas, kidneys and liver. New drugs called "modulators" have meant people with CF are now living much longer. Until recently, heart disease was rare in CF, but with the new modulators there are increasing concerns that heart disease may become a big problem in the future. This is partly to do with the drugs causing weight gain and higher blood pressure, which are risk factors for heart disease. My PhD project aims to find out whether the blood vessels and hearts of people with CF are healthy or diseased. I will then find out how the blood vessels are changing over time and work out what things are driving those changes. I will measure the health of the blood vessels and heart using an ultrasound machine to understand what the pattern of disease is like and who might be at the highest risk for heart disease in the future. I will then repeat these measurements a year later. I will compare people of different ages and with different types of disease to understand what things may help us identify heart disease as soon as possible. In the general population, doctors often use medical prediction tools to find out who is at the highest risk for heart disease. We do not know if these work for people with CF, so I will also find out whether those prediction tools are useful in CF. It is vital to understand who may be at risk for heart disease, as one of the most effective ways of treating heart disease is to prevent it from happening. This work may pave the way for future studies to test early treatment for heart disease in those people we identify might be at high risk. Early prevention treatment could reduce the risk of heart disease and ultimately improve the length and quality of life of people living with CF. This is particularly important given people with CF already have a much shorter life expectancy than the general population. In summary, this PhD project will help improve our understanding of heart disease in CF and help identify the best way forward to prevent heart disease causing health problems related to heart disease for these individuals in the future.

Around 8-12 in every 1000 babies are born with an abnormal heart, known as a congenital heart defect (CHD). Thanks to major advances in medical and surgical care, most babies born with CHD now live into adulthood. As people with CHD get older, many need repeated heart operations. It is known from other areas of medicine that "prehabilitation" - a short, structured exercise programme completed before surgery - can improve fitness and help patients cope better with major operations. However, this approach has never been tested in adults with CHD. The investigators are running a randomised controlled trial to find out whether a prehabilitation programme can improve physical fitness before heart surgery in adults with CHD. Participants will be randomly assigned to usual care or a prehabilitation group. Those in the prehabilitation group will follow a tailored, supervised exercise plan for several weeks before surgery. All patients undergoing cardiac surgery routinely complete a cardiopulmonary exercise test (CPET) as part of their standard pre-operative assessment. CPET is a well-established test that shows how the heart and lungs respond to increasing levels of exercise. During the test, participants exercise on a bike while their breathing, heart rate, and overall physiological response are continuously monitored. The results of each participant's routine CPET will be used to guide the individualised exercise programme in the intervention group. Exercise levels prescribed in the study will not exceed the intensity already safely achieved during the routine CPET, ensuring that activity remains within clinically assessed limits. Participants in the trial will complete an additional second CPET following the trial period. The key question is whether a tailored exercise programme can improve fitness in adults with CHD before heart surgery, and whether this approach is feasible, acceptable and practical to deliver, including successful recruitment and measurable physiological improvements.

Ventricular tachycardia (VT) is a life-threatening heart rhythm disorder and one of the commonest causes of heart-related sudden death. It often affects people who have had a heart attack or other structural heart damage. VT occurs when abnormal electrical circuits develop within and around scar tissue in the heart. People at risk are usually offered an implantable cardiac defibrillator (ICD), a device that can detect VT and deliver a lifesaving shock. While effective, these shocks can be sudden, painful and distressing. Medications such as amiodarone can also help, but they are often unsuitable for long-term use due to their potential side effects on the liver, lungs and thyroid gland. An alternative is catheter ablation. Thin tubes (catheters) are threaded from a blood vessel in the groin to the heart, allowing the cardiologist to identify scar tissue and abnormal electrical circuits, which can be destroyed using heat, freezing or electrical energy. Although ablation can help many patients, VT can return in up to one in three people after the procedure. This is because it can be difficult to precisely identify the scar and surrounding tissue that sustain the abnormal circuits, making it challenging to know exactly where to apply ablation treatment. Dynamic Voltage Mapping, is a technique which the investigators believe can more accurately identify scar and the critical bordering tissue during ablation. Initial data collected suggests that the approach accurately predicts the VT circuit and helps guide ablation. In this study, the investigators wish to recruit 40 participants undergoing VT ablation to determine how effective Dynamic Voltage Mapping is in real-world procedures.

The diagnosis of either asthma or chronic obstructive pulmonary disease (COPD) is currently based on a combination of symptoms, different lung tests and sometimes a 'trial by treatment'. Both COPD and Asthma tests currently include forced breathing using a test known as spirometry which can be difficult and uncomfortable for people to perform and needs expert interpretation. Asthma can require multiple tests in sequence which can make the process of diagnosis long and inconvenient for patients. In the UK, there have been challenges providing enough testing for COPD and asthma, in part because the tests are challenging to provide in the community to everyone who needs one. The STARDUST study aims to test and develop new ways of diagnosing asthma and COPD that are quick, accurate and easy for patient and healthcare professionals to perform. People who have been referred for routine lung testing will breathe normally in and out into a handheld device called the N-Tidal Handset for 75 seconds. This device measures how the level of carbon dioxide (CO2) changes in the breath as people breath through it. The information gathered on the N-Tidal Handsets, called breath records or capnograms, will not be used to alter the diagnosis of any participants in the study. After the capnograms have been collected, the research team will test 'algorithms' that have been developed using artificial intelligence, to see if they can accurately identify the correct diagnosis. Information collected in the study will also be used to make improvements in these algorithms. If confirmed to be accurate, these algorithms could be used in clinical practice to help healthcare professionals make faster, more accessible and accurate diagnoses, especially in settings like GP clinics in the community where access to specialist tests may be limited.

Doctors and nurses who perform heart procedures using X-ray guidance are exposed to radiation, which can be harmful over time. This exposure increases the risk of certain health problems, including cancers, eye damage (cataracts), and DNA damage. Although protective lead clothing is used to reduce exposure, it is heavy, uncomfortable, and can cause muscle and joint problems for those who wear it daily. A new radiation protection device, called RAMPART, may help reduce radiation exposure for heart specialists and their teams. It could also allow them to wear lighter protective gear-or none at all-making their work safer and more comfortable. This study will compare the radiation levels received by doctors and nurses during heart procedures when using RAMPART versus standard protection. By doing so, we hope to find out if this new device can better protect medical teams from radiation, improving both their safety and well-being.