All Clinical Trials in United Kingdom

The main objective of the study is to determine whether fully closed-loop insulin delivery using ultra-rapid acting insulin lispro will improve glucose control compared to standard lispro under conditions mimicking missed meal bolus. Ultra-rapid acting lispro (Lyumjev) is a novel formulation of insulin lispro in which two additional excipients (citrate and trepostinil) have been added, resulting in accelerated initial absorption and more than double the glucose lowering effect in the first 30 minutes after subcutaneous administration using insulin pump. To date, no randomised controlled trial involving fully closed-loop in type 1 diabetes has been performed to evaluate the benefit of Lyumjev over standard lispro. This is an open-label, single-centre, two-period, randomised, crossover study. The study involves two 12-hour in-patient stays at the clinical research facility during which glucose levels will be controlled by the Cambridge closed-loop system with either Lyumjev or standard lispro. Up to 26 adults with type 1 diabetes treated with insulin pump will be recruited at Manchester Royal Infirmary, aiming for 19 completed participants. During the study days, closed-loop will automatically modulate insulin infusion rate based on real-time glucose sensor measurements. Participants will receive standardised meals with no meal bolus for the lunch time meal during each study day. Primary outcome is the time spent in sensor glucose range (3.9-10.0mmol/l) between 11:00 - 17:00 hrs. Secondary outcomes are the time spent with glucose levels above and below target, and other sensor-based metrics. Safety evaluation comprises assessment of the frequency of hypo and hyperglycaemic episodes. Read Less

Analysis of circulating tumour DNA (ctDNA) found in a patient's peripheral blood can identify cancer progression and predict a patient's response to therapy. By using ctDNA analysis and imaging techniques, the FAIM trial aims to determine whether the addition of the experimental drug ipatasertib to a standard combination of the hormone treatment fulvestrant and the targeted agent palbociclib increases progression free survival (PFS) for patients with hormone-receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer. Read Less

ORBITA-COSMIC is a randomised, double-blinded, placebo controlled trial of the coronary sinus reducer (CSR). The investigators will compare the effects of CSR versus placebo on myocardial perfusion on MRI, exercise time and symptoms in 50 participants with refractory angina and ischaemia. Read Less

PIONEER-IV is a prospective, single-blind (patient), randomized, 1:1, controlled, multi-center study comparing clinical outcomes between angiography-derived physiology guidance to LRDP and usual care in an all-comers patient population (including patients with high bleeding risk, HBR) undergoing PCI with unrestrictive use of the HT Supreme sirolimus-eluting stent. Patients will be randomized to either angio-based physiology guidance angio-FFR (Quantitative Flow Ratio and coronary angiography-derived FFR, caFFR) or local routine diagnostic procedure (LRDP) and usual care. Patients will be treated with 1-year P2Y12 inhibitor monotherapy after 1-month of dual-antiplatelet therapy in approximately 2540 (2\*1270) patients. All patients (both cohorts) must receive dual anti-platelet therapy, being aspirin (ASA) and ticagrelor for 1 month, followed by 11 months of ticagrelor only (i.e. monotherapy). At 1 year, ticagrelor monotherapy is replaced by aspirin monotherapy or left to the discretion of the operator. Read Less

Sepsis, or systemic infection, is a common reason for ICU admission and death throughout the world. Despite advances in the way we treat this condition, it remains a significant economic and healthcare burden. A key part of the treatment of sepsis is the administration of IV fluids and blood pressure medication. However, there is huge uncertainty around dosing of these drugs in an individual patient. A tool to personalise these medications could improve patient survival. The study team has developed a new method to automatically and continuously review and recommend the correct medication doses to doctors, which was created using artificial intelligence (AI) techniques applied to large medical databases. The researchers' previous work has shown it has the potential to improve patient survival rates. The tool will be capable of processing patient data within the electronic patient record of NHS hospitals in real-time to suggest a course of action. This tool will be evaluated and refined in simulation studies and then be tested in two NHS Trusts in "shadow mode" (results not provided to duty clinicians). This will allow comparison of actual decisions made and recommended decisions from the AI system. The second stage of this clinical evaluation will display the recommendations to clinicians to assess the acceptability of the tool and confirm technical feasibility to inform future clinical trials. The long-term expected benefits of this project are numerous: improved patient survival, reduced use of precious intensive care resources and reduction in healthcare costs. Read Less

This study aims to investigate the role of IL-5 in suppressing anti-viral immune responses in bronchial epithelial cells (BECs) and in peripheral blood mononuclear cells (PBMCs) from 5 people with asthma. Read Less

Patients are admitted to wards at all times of day and night and in various states of ill health. As this research is non interventional and does not impact on patient safety, the guidance from the ethics committee was reviewed and agreed that it would be appropriate to enrol every admission into the 2 bed bays and gain consent within 24 hours of admission.All data collected within the trial using the smart tablets will be associated to a study number, no patient details will be stored on the smart tablet and therefore the cloud data store.It has been discussed with the trust information governance and this complies with their regulations. Any patient identifiable data will be kept by the research team. All data will be archived and stored as per the Sponsors policy. The novel nurse call system has been designed to be user friendly to all patients regardless of age, learning ability and first language used. By using colours, images and words in the hope that this will be accessible to all. The nursing staff on the ward advised on the main reasons for the nurse call system activation and therefore the icons used in the novel system were adapted from this. This trial was discussed in the patient and public involvement group. As this is a pilot trial, any adaptions that need to be made will be made before the large scale trial. Read Less

Liver stiffness is a marker for scarring of the liver, which occurs after damage from various liver conditions. Scarring prevents normal liver function and can lead to liver failure. Fatty liver is a common cause of liver damage and can contribute to scarring. Currently, liver biopsy serves as the 'gold standard' for assessing the degree of liver scarring and fatty infiltration, guiding treatment decisions. However, liver biopsy poses a significant risk of death and unpleasant side effects, including internal bleeding and pain. Moreover, due to the small sample of liver tissue obtained during the biopsy, the results can be misleading and may not provide an accurate overview of the liver's health. Therefore, there is an unmet need for a non-invasive method of measuring liver stiffness and fat content. Ultrasound-based methods utilize various properties of ultrasound waves to assess liver stiffness and fat levels. This study aims to recruit 100-120 patients with chronic liver disease. The investigators will assess liver stiffness and fat levels during patients' hospital visits for routine scans, biopsies, or clinic appointments. The resulting measurements of liver stiffness and fat obtained through ultrasound-based methods will be compared to patients' routine liver biopsies, routine FibroScan results (another non-invasive method routinely used in clinical care to assess patients' liver stiffness), and other non-invasive severity scores (calculated from results obtained from patients' routine blood tests, providing an overview of the extent of liver damage). Read Less

1.4% of babies have a very premature birth (PTB) (less than 32 weeks of pregnancy). This can result in severe life-long complications including cerebral palsy, learning and behavioural difficulties and breathing problems. This has significant cost implications for the NHS, education services and immeasurable human costs for the child and their family. Early delivery may result from maternal infection or poor attachment of the placenta to the womb, which may also cause abnormal brain and lung development. Even where obvious signs of infection are not present in the mother, subtle infection is often present in the baby. Currently there is no test routinely used to see if there is an infection of the baby inside the womb, and it is unknown how the placenta develops in babies that subsequently deliver preterm. Using MRI, the investigators will assess the baby's thymus and placenta for signs of infection and assess how the lungs and brain are developing whilst still in the womb. Machine learning techniques, where computers analyze all the results together, will then be used to see if these scans can identify babies that do poorly after birth. 137 pregnant women at high risk of PTB (between 16-32 weeks of pregnancy) and 183 women with uncomplicated pregnancies will be invited to participate. Women will have an MRI scan of the fetus assessing the lung, brain, thymus and placenta. Where high risk women do not deliver, repeat imaging will be offered every two weeks (maximum 3). After birth the investigators will see if infection was present by analysing the placenta under a microscope, and see how the baby does. All the information from scans and after birth will be put into a computer, to predict which babies do poorly after birth. Health records of the child will be accessed up to two years of age. Read Less

The primary objective of this study will explore whether circulating acyl-ghrelin (AG) and unacylated-ghrelin (UAG) are reduced in neurodegenerative disease associated with cognitive impairment. It will focus on validating pilot data generated following the analysis of Parkinson's disease (PD), Parkinson's disease dementia (PDD) and healthy cohorts (IRAS project ID: 250933). In addition to the advantages of study replication we will extend the analysis to include two further patient groups that are associated with cognitive impairments, namely, Alzheimer's dementia (AD) and dementia with Lewy bodies (DLB). This study will increase confidence in the replication of our findings. This will be a cross-sectional study using peripheral venous blood. Read Less

The human immune response to bacterial blood stream infection (sepsis) and systemic viral infection are fairly well understood, but we lack details on the most early phases. Better knowledge of these events would be important for the prevention and treatment of severe bacterial or viral disease. From models of infection, we have data showing that bacteria replicate in a specific type of cells in the spleen from where the bacteria then seed to the blood to cause blood stream infection. In order to gain more relevant data for humans, we have developed a spleen perfusion model using pig organs. This model confirms our previous work and most importantly will now allow us to study these events in human organs. In order to move novel treatment strategies into human trials, we propose to test early events during infection using human spleens and the cells and tissues derived thereof. This research is expected to provide data on the relevance of the early events in bacterial and viral disease, in particular on the role of immune cells. The research includes work with human cells and tissue obtained from human spleens. In these settings, we will test pharmacological prevention and treatment of severe bacterial or viral infection (sepsis). The expected outcome of this work on human organs and tissue is expected to provide evidence that allows to move new treatment options into clinical trial. This study is a preclinical research project and does not involve any intervention on patients, but it involves human tissue. The source of the human splenic tissue for our research will be spleen tissue removed during radical surgery. The present application relates exclusively to the ethical approval for the use of spleen tissue removed during radical surgery and discarded. The utilisation of the spleen or splenic tissue for research purposes does not alter in any way the surgical procedures at any stage and importantly the research will involve only anonymity samples. Read Less

A multicentre, international case-control study to develop a biobank of sera from 150 cases of serotype III GBS disease and associated clinical information from seven countries (Malawi, Uganda, UK, the Netherlands, Italy and France), with 3:1 (450) serotype matched healthy controls. Read Less