All Clinical Trials in United Kingdom

The goal of this clinical trial is to compare the safety and efficacy of AON-D21 versus placebo, both on top of standard of care, in patients with severe community acquired pneumonia admitted to ICU (or similar unit). The main questions to answer are: * The safety and tolerability of AON-D21 vs placebo. * The efficacy of AON-D21vs placebo. * The pharmacokinetics of AON-D21. * The pharmacodynamics of AON D21. * To identify biomarkers for patient stratification and analyses in future trials. Read Less

This is a Phase 1/2, multicenter, randomized, placebo-controlled, double-blind study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple doses of DNL593 in two parts followed by an optional open-label extension (OLE) period. Part A will evaluate the safety, tolerability, PK, and PD of single doses of DNL593 in healthy male and healthy female participants of nonchildbearing potential. Part B will evaluate the safety, tolerability, PK, and PD of multiple doses of DNL593 in participants with frontotemporal dementia (FTD) over 25 weeks. Part B will be followed by Part C, an optional 18-month OLE period available for all participants who complete Part B. Read Less

The purpose of this Phase 3 study is to determine whether iptacopan (LNP023) is efficacious and safe for the treatment of aHUS in adult patients who are treatment naive to complement inhibitor therapy. Read Less

Interactive electronic devices (IEDs) have become a common part of young children's lives, yet research on this topic remains limited. Most studies utilise cross-sectional designs and present inconsistent evidence regarding the benefits and harms of IED use. Some findings suggest that IEDs may negatively impact sleep quality, be linked to visual impairment, and lead to reduced and more negative interactions between parents and children. However, it might also have a positive effect in helping language learning in young children when IEDs are co-viewed with parents and improving literacy, mathematics and science skills. Due to this conflicting evidence, health guidelines for young children do not provide specific recommendations on using these devices, leading policymakers to request more information in this area. In conversation with parents and nursery practitioners, they told us they were confused about the benefits and hams of using these devices and wanted further guidance. The primary aim of this study is to investigate the long-term association between IED use (duration and mode) and development outcomes in 3-to-5-year-old children. The researchers will also explore the longitudinal association between IED use (duration) and other outcomes, including BMI z-score, movement behaviour, motor skills, parent-child interaction and school readiness. Children and their parents or caregivers from both low, mid and high-income areas in England will be invited to take part. Children can participate if they are between 3 and 4 years old when they join the study, have received consent from their parent or caregiver, and have provided verbal agreement to participate. However, children will not be eligible if their parents or caregivers do not speak or understand English or if the child has been diagnosed with a developmental disorder by a medical professional before the baseline or follow-up measurements. Data collection will occur at the start of the study and one year later when children are 4 to 5 years old. Parents will be asked to download an app called EARS on the smartphone and/or tablet that the child uses. The app will measure how long they use the device (IED duration) and the specific apps accessed during device usage (IED mode). Child development will be assessed through the following measures: 1) working memory, including visual-spatial and phonological aspects; 2) ability to control, referred to as inhibition; 3) the ability to control and redirect attention, defined as shifting; 4) self-regulation; 5) social development; 6) numeracy skills; and 7) expressive vocabulary. Child development will be measured using the Early Years Toolbox app and recorded on an iPad. The researchers will also measure a set of secondary outcomes, including 1) BMI z-score; 2) 24-hour movement behaviour (i.e. physical activity, sedentary behaviour and sleep); 3) motor development (i.e., gross motor skills and fine motor skills); 4) parent-child interaction; 5) school readiness. The researchers will also measure other things that might influence IED use or emerging abilities, such as participants' demographics (i.e., sex, age, ethnicity and caregiver education), parenting styles, parents' smartphone addiction, the presence of screen viewing policy at the early year's settings. To thank the early years settings for participating, each will receive £100 for every data collection session. Parents will receive a £30 high street e-voucher for each data collection session in which they participate. There are no risks of physical injury or harm involved in this study. All researchers entering the nursery will have been subject to an enhanced Disclosure and Barring Service (DBS) check and are permitted to engage in controlled activity. If the research team observes a significant developmental delay in the child while conducting the health and development measures, they will notify the nursery staff, who will then communicate this information to the parents. Parents may feel uncomfortable downloading the app (EARS) onto their electronic devices to track how long the device is being used and the type of apps in use. The app has been designed for research purposes and approved by Sheffield Hallam University Digital Technology Services. Participants will download the app through the official Apple or Google Stores, which offers additional security and convenience. Participants will be advised to delete the app after each data collection point. The investigators will have regular group meetings throughout the project with parents, carers, nursery teachers and policymakers to gather ideas and opinions and share our findings. These discussions will help researchers improve the project. The findings will help inform public health guidance on children's device usage. The researchers will share the knowledge gained from this study with all participants, write policy briefs and scientific papers, and present the findings at conferences. Read Less

Multicenter retrospective and prospective European observational study. At each site, all consecutive patients with a 2016- or 2022 World Health Organization (WHO) confirmed diagnosis of myelofibrosis (MF) established from 01/01/2018 to 31/12/2027 will be enrolled into the study. Yearly follow-up updates will be scheduled until the end of data collection on 31/12/2028 or until the last available patient visit, whichever comes first. At least 1 year of follow-up will be ensured from the last patient enrolled. Read Less

This is a single arm feasibility study of exercise for improving long- course neoadjuvant chemoradiotherapy (NACRT) efficacy in people diagnosed with locally advanced rectal cancer. The study aims to recruit up to 30 patients from the Queen's Centre for Oncology and Haematology of Castle Hill Hospital, Cottingham, diagnosed with locally advanced rectal cancer. Consenting patients will be provided with an 11-week course of structured aerobic exercises and resistance training in the periods before, during and after their chemoradiotherapy treatment. The patients will be followed up for 6 months post long course neoadjuvant chemoradiotherapy (NACRT), with a total of 3 assessment periods. Read Less

This is a single arm feasibility study of exercise for improving short- course neoadjuvant radiotherapy efficacy in people diagnosed with locally advanced rectal cancer. The study aims to recruit up to 30 patients from the Queen's Centre for Oncology and Haematology of Castle Hill Hospital, Cottingham, diagnosed with locally advanced rectal cancer. Consenting patient's will be provided with a 7 weeks course of structured aerobic exercises and resistance training in the periods before, during and after their radiotherapy treatment. The patients will be followed up for 6 months post short course neoadjuvant radiotherapy, with a total of 3 assessment periods. Read Less

Continuous glucose monitoring is a sensor, which monitors glucose levels continuously throughout the day. In people with diabetes, especially those treated with insulin, this sensor helps guide the amount of treatment (such as insulin) required to maintain glucose within target. In dialysis, the glucose levels and insulin needs can change a lot because of the kidney failure and dialysis treatments. The goal of this observational study is to describe the changes in glucose during and in between dialysis sessions over two weeks by using continuous glucose monitoring. The study will also explore whether there is a relationship between the trend of the glucose and fluid level changes during and in between dialysis treatments. Also, the study will assess whether there is a relationship between glucose levels and several long-term outcomes, such as admissions to the hospital, for up to five years. Read Less

This is a multicenter, randomized, open label phase lll trial to assess whether preoperative chemotherapy, as an adjunct to curative-intent surgery, improves the prognosis of high risk DDLPS (dedifferentiated Liposarcoma) and LMS (Leiomyosarcoma) patients as measured by disease free survival. After confirmation of eligibility criteria, patients will be randomized to either the standard arm or experimental arm. Read Less

Background Psychosis is a mental health condition that affects around 3 in 100 people in their lifetime. Most treatments for psychosis target a brain chemical called dopamine but they don't work for everyone and don't address many of the symptoms. People with psychosis and people at risk of developing psychosis show differences in a part of the brain called the hippocampus, such as smaller size and increased activity. This hyperactivity may be associated with cognitive difficulties (thinking and memory). The basis of this hippocampal hyperactivity is thought to be a deficit in excitation and inhibition of brain cells. Excitation causes brain cells to send signals more frequently, and inhibition causes cells to send signals less frequently. A balance between these signals is important for the brain, including the hippocampus, to function properly. Approach Levetiracetam is a medication that is widely used to treat epilepsy and which helps balance excitation-inhibition in the brain. We will use brain imaging, using Magnetic Resonance Imaging (MRI), to test if levetiracetam can help reduce hippocampal hyperactivity, alter connectivity and change levels of brain chemicals in people who are at risk of developing psychosis. Participants (18-40 years), identified as at risk of psychosis through the Outreach and Support in South London (OASIS) teams, will attend an initial visit at the Institute of Psychiatry, Psychology \& Neuroscience. This will involve questions about experiences and feelings, assessment of thinking and memory, and a blood test. They will then attend two scanning visits at the Centre for Neuroimaging Sciences, during which they will take capsules of either levetiracetam or placebo (in a randomised order) before having a 60 mins MRI scan. The MRI scan will look at blood flow to the hippocampus, resting activity, activity during a cognitive task and levels of brain chemicals. A case-control sample of 33 healthy individuals aged 18-40 will be recruited from Greater London. We will recruit a healthy control (HC) sample to establish the presence of hippocampal dysfunction in our CHR-P group by comparing the MRI data for CHR-P under the placebo condition with that of the HC sample. The HC individuals will attend the screening visit and one scanning visit. They will not receive any medication. Funded by the Wellcome Trust and conducted by King's College London researchers, the study spans 2-3 months per participant. Impact Our study will provide important evidence about how levetiracetam affects brain function, and how this relates to cognition. This knowledge may lead to innovative approaches for understanding and treating psychosis early. Read Less

In this project, ocular motor, pupil and gait data in people with Parkinson's disease (PD) will be collected in order to develop machine learning models for the diagnosis and monitoring of PD. With this, the investigators aim to advance the state of the art in PD diagnosis and monitoring. By integrating the principles of machine learning with high-quality sensor data, more accurate and earlier diagnosis could potentially be achieved. Ocular motor and pupil data will be collected with the standard clinical examination and with neos, a medical device approved for objective ocular motor and pupil measurement. Gait will be collected using an IMU sensor and GaitQ senti, a consumer device that allows for an objective and continuous remote gait monitoring. Read Less

The goal of this observational study is to identify prognostic and/or diagnostic signatures (biomarkers) related to microbial keratitis outcomes. We will compare tear and ocular swab samples from participants currently suffering from microbial keratitis to healthy control participants. The primary study objective is to undertake analysis (proteomics and metabolomics) of microbial keratitis patient (and healthy control) ocular samples collected throughout the patient treatment course to better understand the ocular microenvironment and to identify candidate biomarkers for future targeted screening and validation studies. The secondary study objective is to define the microorganisms in patients with microbial keratitis through a better understanding of the ocular surface micro/mycobiome (the resident bacteria and fungi) in health and disease Participants will have their tears collected via capillary tube during their treatment course, and swabs of their conjunctiva collected at their first and final appointments. Read Less