Clinical trials

The goal of this clinical trial is to evaluate the capacity of implantable/remote technology for early evaluation of drug therapies in patients with pulmonary arterial hypertension (PAH). The main question it aims to answer is whether structured changes in clinical therapy will be detectable using implanted regulatory approved devices. Participants will will be implanted with approved medical devices and will enter into a study of approved drugs to assess physiology, activity and patient reported quality-of-life (QoL) outcomes. Researchers will compare two therapeutic strategies in each individual patient to see if the study design provides enough evidence to personalise drug treatment plans

Recently, concerns have been raised by regulators that there is little data about the long-term safety of rectal hydrogel spacers for use in conjunction with radiotherapy treatment for prostate cancer. To address this, this study will collect data about the short-term side-effects and long-term safety of SpaceOAR and SpaceOAR Vue rectal hydrogel spacers in men who receive them in the UK and France. Men who have agreed to receive these spacers as part of their standard medical care will be asked to take part in the study whereby data about their treatment and health will be collected from their medical records and from members of the clinical team who deliver their treatment. Additionally, men will be asked to consent to completing questionnaires about their experiences of side effects from their treatment. Further information will be collected about their clinical characteristics before they receive a spacer, the physician-rated clinical performance of the spacer insertion procedure, their radiotherapy treatment plan and details of the other treatments they are also receiving which could influence the types and extent of side effects they experience. Data collection will span eight time points: pre-spacer insertion, spacer insertion, the start of radiotherapy, post-radiotherapy follow-up, 6-month follow-up, 12-month follow-up, 24-month follow-up \& 36-month follow-ups. Outside of these timepoints treatment-related adverse event data will be concurrently reported and collated. Participants' treatments will not be changed as a result of their participation in this study. Data from this study will be used to summarise the characteristics of this study population, physicians' perceptions of the spacer implantation procedure, the radiotherapy treatments plans made, and the types, extent and timing of treatment-related adverse events and side effects.

This research study is looking at new ways of measuring the function of the lungs in patients with cystic fibrosis. This study is using the most advanced methods for measuring lung function including 2 tests called hyperpolarised gas magnetic resonance imaging (HP MRI) and multiple breath washout (MBW), to better understand changes in the lungs over time. HP MRI involves taking pictures of the air in your lungs after breathing in a harmless gas (xenon). MBW is a breathing test used to calculate something called the lung clearance index (LCI). By measuring these tests on the same day, alongside standard lung function tests, we aim to understand lung function in greater detail than ever before.

After a subarachnoid haemorrhage, complications are common and increase the overall rate of disability and death from the condition. Despite some advances in preventing, detecting and treating these complications, the rates of complications and associated risks remain high. Further research into ways to reduce complications of subarachnoid haemorrhage. Transcutaneous vagus nerve stimulation (tVNS) is a technique where a small handheld device is attached to an earpiece which stimulates the nerves to the ear. This is given for short periods and may help improve blood flow and reduce inflammation in the brain. The intervention has been safely used and licensed in seizures, headache and severe depression. This study will look to see if it is feasible and tolerable to have tVNS twice daily for 5 days after subarachnoid haemorrhage, and whether it can help reduce the risk of complications from subarachnoid haemorrhage. The participant will be randomly allocated to receive either tVNS or a dummy intervention, known as sham. The researchers will collect some personal and clinical details such as diagnosis, medications, age, blood test results, as well as some details about the subarachnoid haemorrhage. The researchers will also complete brief questionnaires with the participant to assess symptoms. They will take measurements of heart rate, pupil response, and brain activity using a cap. The participant will then be randomly allocated to either receive the tVNS or sham intervention. Next, the research team will apply the earpiece to their ear twice a day for 45 minutes, for a total of 5 days. At the end of the 5-day study period, the intervention will be complete. The researchers will arrange a follow-up meeting on discharge and at 6 weeks, to assess the participants symptoms and recovery. Previous studies have shown that tVNS is safe and well tolerated, including a recent review of tVNS studies which evaluated the side effects experienced by 1322 patients receiving tVNS. The main side effects include localised tingling/numbness/pain/redness around the ear (17%), headaches (3%), dizziness (1%), facial droop (1%), nausea (1%), nasal discharge (2%). Rarely, palpitations or a slow heart rate may occur. They will continue to receive full medical treatment and observation alongside the study. They are free to withdraw from this study if they find it too demanding on top of their other activities.

Coeliac Disease (CD) is a lifelong autoimmune condition where eating gluten (a protein found in wheat, barley, and rye) causes damage to the small intestine. It affects around 1 in 100 people. Most individuals feel better and their gut heals after switching to a strict gluten-free diet. However, up to 1 in 5 people with coeliac disease continue to experience unpleasant gut symptoms-such as bloating, pain, and diarrhoea-despite following the diet and having a healed intestine. These ongoing symptoms can be very distressing and impact daily life. This study investigates whether a food supplement called Symprove, a probiotic drink containing live good bacteria, can help relieve these ongoing symptoms. Scientists believe that in some people with coeliac disease, the community of bacteria in the gut (called the microbiota) becomes unbalanced, even after going gluten-free. This imbalance (known as dysbiosis) may lead to inflammation, irritation, and symptoms similar to irritable bowel syndrome (IBS). The aim of this study is to test whether Symprove can help correct this imbalance and reduce symptoms. Participants will take Symprove daily and their symptoms, quality of life, and gut bacteria (measured from stool samples) will be monitored over time. The study hopes to answer three key questions: Can Symprove reduce gut symptoms in people with coeliac disease who are in remission? Does it work by restoring a healthy balance of gut bacteria? Are people with more severe imbalance (dysbiosis) more likely to have symptoms? If successful, this research could offer a safe, non-drug option to improve life for coeliac patients who continue to suffer symptoms despite avoiding gluten. It could also help suggest that gut bacteria play a role in ongoing symptoms and are a target for future treatment.

This clinical study is exploring whether a pre-recorded, on-demand webinar led by specialist dietitians can be as effective as traditional one-on-one appointments in helping people newly diagnosed with coeliac disease learn to follow a gluten-free diet. Coeliac disease is a serious, life-long condition where eating even tiny amounts of gluten, a substance found in wheat, barley, and rye, can cause damaging symptoms and long-term health problems. The only current treatment is sticking to a strict gluten-free diet, which can be difficult without proper support and guidance from dietitians. The number of people being diagnosed with coeliac disease in the UK is growing, and this is placing extra pressure on NHS dietetic services, which are already stretched. Many patients currently face long waits or do not get any dietetic support at all. To address this, the research team at Sheffield Teaching Hospitals has developed an on-demand, first-appointment webinar to provide immediate access to trusted dietary information, with the aim of improving patient care and saving NHS resources. In this study, adults newly diagnosed with coeliac disease at Sheffield Teaching Hospitals will be asked to join one of two groups: one group will receive their first dietitian appointment through the new on-demand webinar, while the other group will have a traditional face-to-face or phone appointment with a dietitian. Both groups will complete short questionnaires to measure their knowledge about the gluten-free diet, their symptoms, how well they are following the diet, and their quality of life, both before and after receiving their dietary support, and again after six months. Blood tests will also be used to monitor health markers. The main goal of the research is to find out if the first-appointment webinar is just as effective as traditional appointments in helping patients understand and follow a gluten-free diet, feel satisfied with the support they receive, and achieve good health outcomes. If the study shows that the webinar approach is as good as traditional care, it could mean quicker, easier, and more consistent access to essential dietary support for people with coeliac disease, both locally and across the UK. Hypothesis: The study hypothesis is that a dietitian-led, on-demand, pre-recorded webinar for a first appointment is as effective as traditional one-to-one consultations (face-to-face or by phone) in helping newly diagnosed coeliac patients achieve the same standard health outcomes, dietary knowledge, and satisfaction with care.

Heart failure with preserved ejection fraction (HFpEF) causes symptoms of breathlessness and leg swelling. It is associated with significant number of hospital admissions and could lead to the patient's death. In HFpEF, the pumping function of the heart is normal but the heart is too stiff to fill properly. The first line investigation is an ultrasound of the heart (echocardiography). A number of parameters are assessed that indicate stiffness within the heart or raised pressures within the heart. However, most of these parameters lack sensitivity which can make HFpEF difficult to diagnose. The best test is to invasively measure the pressures in the heart at rest and with exercise in a procedure called heart catheterisation. However, this is invasive and not readily available. As a result, HFpEF is significantly under diagnosed meaning many patients do not get access to disease specific treatment that may improve symptoms and quality of life. There are a number of new imaging techniques that may help us to better identify HFpEF . However, it is not currently known how to best apply them in clinical practice. In this study, the investigators will recruit patients presenting to the HF clinic at Sheffield Teaching Hospitals who have symptoms of HFpEF but whose diagnosis remains unclear after initial assessment. The impact of their symptoms will be assessed with the use of a quality of life (QoL) questionnaires and a six-minute walk test (6MWT). They will undergo advanced imaging with a specialist echocardiogram and a cardiac MRI scan. If they are found to have features of HFpEF, they will be started on disease specific treatment. All patients will be followed up after six months to see if they have any symptomatic or functional improvement. They will also undergo repeat imaging to see if there has been any change in the imaging parameters.

Physiological cardiovascular stress test plays a crucial role in the assessment of patients with suspected heart disease. There are several methods of cardiac physiological stress tests and each of them offer varied insight into cardiac physiological adaptation: passive leg raise, intra-venous fluid challenge, pharmacological stressors and physical exercise stress test. Echocardiography, which is the mainstay for the non-invasive rest/stress assessment of the left ventricular (LV) haemodynamics has several limitations. Novel methods of CMR imaging allow to map intra-cardiac flow in three-dimension using novel flow acquisitions. These novel flow acquisitions are called four-dimensional flow CMR, where the fourth dimension is time. Additionally, traditional cine CMR imaging for functional assessment can now be done without breath-holds using advanced acceleration methods, allowing them to be used during exercise. A comprehensive understanding of functional-flow coupling at rest, during increased pre-load (fluid challenge) to the heart or during exercise, is lacking in the literature. There is an important need to validate these novel CMR methods for developing mechanistic insight into physiological cardiac adaptation to increased pre-load or to exercise in health and how it alters in heart disease.

This research project is investigating the impact of sleep quality on cognitive and laparoscopic surgical performance. The background to this study is the growing recognition that factors beyond technical skill, such as sleep, can significantly influence a surgeon's performance. The aim is to understand how sleep patterns affect surgeons' ability to perform surgical tasks, both technically and cognitively. After this, we will aim to see if a targeted sleep intervention has a positive impact on technical skills and cognitive performance. This is a preliminary feasibility study and is part of ongoing research by the research team.

Aphasia is an acquired language disorder. Stroke is the most common cause of aphasia, which affects 30% of stroke survivors. Speech and Language Therapy (SLT) can help people with aphasia but it may not be provided at the required intensity. Access to therapy is often limited after the first few months following stroke. People with aphasia can improve with therapy many years after stroke but these benefits have not been found to translate to day to day conversation. Transcutaneous Vagus Nerve Stimulation (tVNS) is a non-invasive technique which involves stimulating a branch of the vagus nerve through the skin of the ear, using a small earpiece. This technique is safe and has been approved for use in headache. There is promising evidence that tVNS can improve motor rehabilitation in chronic stroke. This technique may be helpful in aiding language recovery in individuals with chronic aphasia. The current pilot study will primarily assess the feasibility, safety and tolerability of self-directed tVNS paired with computer-based SLT, in individuals with chronic stroke-related aphasia. Secondly, the study aims to explore the effect of the intervention on word-finding ability and to explore potential mechanisms of action. Participants will be randomly allocated to an active or sham tVNS group. Participants will be asked to use the stimulation device at home for 6 weeks, whilst completing computer-based SLT. To date, there are no published studies exploring the use of tVNS in aphasia. An indication of study feasibility may support the development of a larger RCT to explore treatment efficacy.

Background Hip fracture affects 70,000 people in the United Kingdom (UK) and costs an estimated £1.1 billion per year to the National Health Service (NHS). Key clinical indicators, such as early surgical repair, have been shown to improve patient outcomes, however morbidity and mortality remain extremely high, reflecting the urgent need for novel therapies to enhance outcomes. Common complications include infection, cardiovascular events, falls and venous thromboembolism. Remote Ischaemic Conditioning (RIC) is a treatment whereby a blood pressure cuff is inflated around an arm or leg to above systolic pressures to occlude blood flow to the limb for short periods of time, that do not result in harm, but trigger innate mechanisms that reduce inflammation, improve organ blood flow and improve bone healing. These may be beneficial effects after hip fracture. Methods This is a single centre, feasibility study; the participants will receive RIC daily for 40 minutes for 10 days during their inpatient stay. Outcome measures relating primarily to safety, tolerability and feasibility will be collected along with compliance with the intervention. Study feasibility will be determined by success criteria based on recruitment, outcome measure assessment compliance with intervention and follow up. Secondary outcomes including inpatient mortality, inpatient complications, length of inpatient stay, blood pressure, serum inflammatory and stress markers and functional recovery will also be collected at discharge and 3 month follow up. Results Data collected on safety, tolerability, and feasibility will be presented descriptively and simple analysis of variance will be undertaken on quantitative data such as blood pressure and serum inflammatory and stress markers between baseline and follow up time points. The study will hopefully establish whether this therapy is feasible to deliver after acute hip fracture.

This project is split into 4 sections: 1. Can improvements be made in the Magnetic resonance imaging sequences used to image the fetus in order to improve diagnostic accuracy? 2. Does 3T improve the quality and diagnostic value of fetal MRI when compared to 1.5T 3. Can fetal MRI be used to image the fetal heart? 4. Can fetal MRI be used to image the fetal Bones?

Prospective, open-label, observational study to evaluate the safety and feasibility of using pulmonary artery pressure (PAP) monitors and wearable activity monitors in patients with pulmonary hypertension (PH).

We wish to use the images a mother would have done as part of her normal medical care and make both 3D animations and 3D models of the baby and it's CDH. This will both help the parents see what the problem is and also allow the surgeons, who will operate on the baby once it has been born, to see the size of the hole and what organs are in the wrong place.

Skin dermatoses are a major health concern around the world, with heavy economic, social, and psychological burdens. Due to their chronic and incurable nature, they are serious diseases that cause physical pain in patients and reduced quality of life. Atopic dermatitis is the most common inflammatory skin disease with a prevalence of almost 20% in children and 10% in adults. Current therapies are designed to control the condition rather than cure it. Therefore, these therapies are lifelong and, when the disease is flaring, must be used intensively to achieve control. Despite the emergence of various therapies, topical corticosteroids (TCS) remains the gold standard therapy generally used as a first-line treatment. However, if used inappropriately, it can act like a double-edged sword. With the beneficial action of TCS comes the potential for undesirable effects, like skin thinning, especially when used long-term or excessively. The objective of this study is to define the normal structural parameters for healthy skin in a diverse cohort, determine the effect of age, sex, and ethnicity and subsequently study how these values differ in clinically abnormal skin resulting from excessive or inappropriate use of topical corticosteroids (TCS). This will be achieved by using optical coherence tomography (OCT) to non-invasively image the skin. By undertaking this study, the investigators will gain real-world insight into the effects of long-term TCS use on the skin.

A cross-sectional retrospective study of a sample of 20 women who completed single agent or multi agent chemotherapy: between 6 weeks and 24 months post treatment involving a semi structured telephone interview. A patient sample of 20 is proposed for the study. These are all the patients who meet the inclusion criteria below and are thus eligible for the study. These patients will be contacted via telephone by the principal investigator to inform them of the study and invite participation. A proposed sample size of 20 is sufficient to generate data to address the central questions and furthermore, this sample size is adequate because the intention is to gain insight into the experiences of patients' perceptions about their psychological experiences. Objectives: * Gaining insight into the emotional impact of GTN post treatment * Ascertaining if health professionals are providing adequate psychological support * Identifying sources of support that patients accessed post completion of treatment * Identifying potential areas of improvement in the follow up support for future patients Criteria for inclusion: * Treated with chemotherapy for a GTN diagnosis * Completed treatment between 6 weeks and 24 months * Are able to provide informed consent * Have no cognitive impairment as judged by the treating clinician Criteria for exclusion * Treatment received less than 6 weeks ago * Treatment received more than 24 months ago * Non-English speaking Outcome measures are not appropriate in this qualitative study. However outputs from this study include increasing knowledge and insight into: * patients' experiences of their psychological experiences post chemotherapy * patients' perspective of the support received after their treatment * potential areas of improvements in care

EVIDENT's aim is to test if ex vivo drug screening can predict whether patients with solid cancers will respond, or not respond, to standard care treatments. Patients undergoing standard care surgery to excise their tumour, those undergoing a biopsy, or those having a fluid aspirate of a solid tumour with surplus tissue available after diagnostic use will be eligible for this study. The specimen will then be assessed with ex vivo drug screening utilising all standard therapies and therapies that are more novel and in early stages of development. The results of the ex vivo drug screen will be compared to the cancer's actual response to standard care treatments for those that undergo therapy to determine how effective the test is at predicting treatment response.

The trial is a prospective feasibility trial conducted in Sheffield. Recruitment will include twenty patients receiving first line palliative immunotherapy for advanced, unresectable or metastatic mesothelioma and patients receiving first line systemic anti-cancer treatment for pancreatic cancer. Patients will attend the AWRC for a supervised exercise session once a week to include aerobic exercise along with an unsupervised weekly exercise session for 3 months. Blood samples will be collected at baseline and then monthly for 3 months, pre and post the supervised exercise session. Cytokine, myokine and immune cell concentration will be analysed using cytokine bead-based multiplex immune assays and RNA-seq to full profile changes in gene and protein expression

Dentine hypersensitivity (also known as sensitive teeth) is a common dental condition in which the dentine, a layer of sensitive hard tissue under the enamel of the teeth, becomes exposed making the teeth sensitive to stimuli, such as hot and cold. It poses a significant challenge for clinicians and affects patients' quality of life. The overall aim of the study is to understand if a way of measuring brain activity (electroencephalography \[EEG\]) shows a response to tooth stimulation, and see how these responses may be different in patients with dentine sensitivity. EEG records brain signals and can provide information about how the brain processes painful stimuli. EEG recording is a non-evasive and painless procedure. It involves using a cap with small sensors called electrodes to pick up brain signals. During the EEG assessment appointment, brain signals will be recorded throughout the duration when cold temperatures and short bursts of air are applied to the tooth. Brain signals recorded during tooth stimulation from participants with and without dentine sensitivity will then be compared to explore if there are any differences. The investigators hope that EEG responses could be helpful to objectively assess dentine sensitivity, further the understanding of brain processing of dental pain, and allow the comparison of the effectiveness of different treatment options in the future. This information may help to improve treatments and the quality of life for patients with dentine sensitivity and potentially other types of dental pain.

The underlying disease mechanisms which occur in patients with immune mediation neurological diseases, such as Multiple Sclerosis (MS), are incompletely understood. For such patients, autologous haematopoietic stem cell transplantation (aHSCT) has been increasingly used as a highly successful one-off treatment for some patients. This treatment aims to delete the faulty immune system with a course of chemotherapy and then 'reboot' the immune system using a patients' own stem cells (a cell with the unique ability of being a building block to create many different cells in the body) to stop further damage. Over the last 20 years more than 1800 patients with MS have been treated in Europe with high levels of success. It may be more successful than disease modifying treatment but unfortunately, a small portion of people do not respond to this treatment optimally and continue to accumulate disability. There is a risk of side effects, restricted largely to the time of treatment, which necessitates the need to ensure appropriate patients are treated. Whilst aHSCT is a very effective therapy, it is still in its early phase of development, is not in widespread use, and there is incomplete knowledge regarding how it works and importantly, why it does not work in some patients, and how to monitor response to treatment. Unfortunately, there is no way of detecting which patients will, and will not, benefit from the different treatments available or a way of monitoring the immune system to ensure further treatment is provided before irreversible damage occurs. This study will investigate the immune system which is found in the fluid surrounding the brain and spinal cord, blood and stool of patients undergoing aHSCT and compare it to those receiving disease modifying treatment. This study will therefore further the understanding of biomarkers of aHSCT to develop an awareness of how it can be refined, may improve monitoring of patients following treatment and permit the development of markers which can predict potential treatment success or failure before patients are exposed to the risks.