There are about 25435 clinical studies being (or have been) conducted in United Kingdom. The country of the clinical trial is determined by the location of where the clinical research is being studied. Most studies are often held in multiple locations & countries.
This study is being undertaken in order to enhance our understanding how human airways are being constricted in healthy people and in individuals with asthma. There is an unmet need for identification of new pathways (mediators) related to enhanced constriction of the asthmatic airways that would reveal new targets for therapy. Sphingosine-1-phosphate (S1P) is a naturally occurring bioactive lipid molecule that has been suggested to play an important role in asthma. Physiologically, S1P can be detected in human blood but local tissue concentrations (for example in the lung) are very low. Upon activation many cells can secrete S1P. Increased concentrations of S1P have been detected in airways of asthmatic subjects after allergen inhalation. When studied in animal models, S1P did not cause contraction of airways in healthy animals but contracted airways in animal with pulmonary inflammation. In laboratory experiments S1P has been shown to be a potent constrictor of cells responsible for contraction of human airways. As yet, however, we lack evidence that S1P actually causes constriction of airways in real life. Establishing S1P as a molecule capable of causing airway constriction in humans and perhaps specifically in asthmatics will have important implications for our understanding of physiological and pathophysiological responses in human airways and could open new windows for therapeutic strategies in diseases like asthma.
There has been little improvement in outcome for patients with osteosarcoma (OS) over the last 20 years. There have been only a few clinical trials of new treatments and no major new therapies introduced recently. This is in part because there is no good understanding of the biology of osteosarcoma, but also trials have only included subgroups of patients. The more that is understood about how and why osteosarcoma arises and grows the better clinicians will be able to decide what treatments are most likely to work best. The purpose of this project is to collect high quality clinical data about patients of all ages with osteosarcoma, such as information about the size of the disease, how it was diagnosed and where it is at diagnosis, what treatments were given and how the disease responded the treatments. Blood and tissue samples will also be collected for analysis in research laboratories. By looking at the results of the laboratory findings and the clinical data together, the questions will start to be answered about why osteosarcomas arise and grow, what makes it spread, and why some patients respond to treatment better than others. As time goes on, this information is planned to be used to develop clinical trials of new treatments. Alongside this, the aim is to find out more about how osteosarcoma and its treatments affect the lives of those living with this disease. This information will help provide the most appropriate care and support that will meet the needs of each patient. Ultimately, the aim is to improve the care and treatment of osteosarcoma patients so that they may live longer and better lives.
Constipation remains an important unmet medical need. Patients are currently often dissatisfied with treatment, because of lack of predictability of the laxative, side effects (mainly abdominal pain) and perceived decrease of efficacy with time. A recent systematic review of a range of laxatives reported that bisacodyl increases the number of complete spontaneous bowel movements statistically significant compared to placebo. Recently non-invasive Magnetic Resonance Imaging (MRI) techniques have been developed to assess small intestinal fluid distribution, transit and motility as well as colonic fluid, volumes and motility in healthy volunteers and constipated subjects. Other laxatives such as movecol and ispaghula have been investigated using this methodology. This study will use these novel techniques to further characterize bisacodyl's mode of action. This study is intended to assess the effect of a single-dose of bisacodyl on the gut motor function and its effect on water distribution within the small and large intestine in subjects with occasional constipation by MRI. It may allow better understanding of the relative importance of both the secretory and the prokinetic effect of bisacodyl. Since bisacodyl is often used by self-medicating people with constipation it is proposed to study subjects suffering from occasional constipation. As such subjects often take the drug intermittently it would be of interest to study both the acute response after single dose and the response after several days of treatment to see if this alters the response. The current study will be performed as a cross-over with 2-period and 2-treatment (bisacodyl/placebo), for assessing the effects over of a single-dose of 5mg bisacodyl. Evaluations will be performed after one single dose of bisacodyl or placebo in two different time periods, separated by a 2 week washout period between end of period 1 and start of period 2. The study will recruit individuals ≥18yrs from the general public who consider themselves as suffering from occasional constipation and who self-medicate with an occasional over-the counter (OTC) laxative, not more than once a week. Up to 18 adult healthy subjects will be recruited to ensure 10 evaluable subjects. An evaluable subject is defined as participant having the primary endpoint assessed (ascending colon T1 300, 375, and 450 minutes correctly evaluated) for the two periods of the crossover.
There is growing evidence for the benefits of music for individuals living with dementia but there has been limited research looking specifically at personalised music. Methodologies have not yet been developed to generate and play personalised music playlists quickly and cost effectively. The research team proposes a feasibility study to develop effective methodologies for: i. efficient creation and delivery of personalised playlists for people with mild to moderate dementia in care homes; and ii. assessing their responses to this music. A long-list of personalised music (about 100 tracks) will be created by asking residents and their carers about the resident's musical tastes and background (particularly from their teenage years). A refined personalised playlist (of 10-20 tracks) will be created by playing excerpts from these tracks to the resident and gauging their responses including through direct feedback from the resident and their carer(s) plus observations of changes in facial expression, together with directly observed movements of hands, feet and/ or head, and changes in pulse rate (a monitor worn on the wrist to measure movement and pulse and the investigators will ask to film sessions). Care home staff and informal carers will use these playlists within the residents' care and the research team will use feedback from residents and carers to assess responses and explore whether factors such as the timing of listening or delivery methodology appear to affect the resident's well-being over time. The findings from this study will be used to develop automated approaches to playlist creation (e.g. an App) and to inform further feasibility studies to: test and refine methodologies for use with participants with more advanced dementia; and explore more systematically the benefits of personalised music and factors that affect this, ultimately to inform the design of a subsequent larger scale intervention study. Two substantial amendments were approved to this existing feasibility study on October 23, 2020. The two substantial amendments are: 1. To extend the main study to include participants who may lack capacity to consent. 2. A sub-study using fMRI to explore the mechanisms underlying reported beneficial effects of personalised music listening on behavioural and psychological symptoms in people living with dementia. A further amendment was approved in January 2021, to recruit 1000 families affected by dementia, living at home or in the community, to use our recently developed WebApp to create a personalised playlist for their loved one living with dementia and provide their perceptions of how the music has impacted the well-being of the person with dementia.
The study hypothesises that the variability in relief of air hunger with inhaled furosemide that is reported in previous studies can be explained by the breathing pattern adopted during the inhalation and the droplet size in the aerosol, both of which would influence the site of deposition of the aerosol in the lungs
There has been growing interest in the relationship between reward processing and clinical symptoms of depression such as anhedonia (loss of interest and response to pleasurable activities). The aim of the study is to investigate the acute effects of a single dose of selegiline (an irreversible monoamine oxidase B inhibitor) on reward and emotional processing in healthy volunteers.
Constipation remains an important unmet medical need. Patients are currently often dissatisfied with treatment, because of lack of predictability of the laxative, side effects (mainly abdominal pain) and perceived decrease of efficacy with time. A recent systematic review1 of a range of laxatives reported that bisacodyl increases the number of complete spontaneous bowel movements statistically significant compared to placebo. Recently non-invasive Magnetic Resonance Imaging (MRI) techniques have been developed to assess small intestinal fluid distribution, transit and motility as well as colonic fluid, volumes and motility in healthy volunteers and constipated subjects. Other laxatives such as movecol and ispaghula have been investigated using this methodology. This study will use these novel techniques to further characterize bisacodyl's mode of action. This study is intended to assess the effect of multiple doses of bisacodyl on the gut motor function and its effect on water distribution within the small and large intestine in subjects with occasional constipation by MRI. It may allow better understanding of the relative importance of both the secretory and the prokinetic effect of bisacodyl. Since bisacodyl, is often used by self-medicating people with constipation it is proposed to study subjects suffering from occasional constipation. As such subjects often take the drug intermittently it would be of interest to study both the acute response after single dose and the response after several days of treatment to see if this alters the response. The current study will be performed as a cross-over with 2-period and 2-treatment (bisacodyl/placebo), for assessing the effects over of multiple doses of 5mg bisacodyl. Evaluations will be performed after multiple doses of bisacodyl or placebo in two different time periods, separated by a 2 week washout period between end of period 1 and start of period 2. The study will recruit individuals ≥18yrs from the general public who consider themselves as suffering from occasional constipation and who self-medicate with an occasional over-the counter (OTC) laxative, not more than once a week. Up to 18 adult healthy subjects will be recruited to ensure 10 evaluable subjects. An evaluable subject is defined as participant having the primary endpoint assessed (ascending colon T1 300, 375, and 450 minutes correctly evaluated) for the two periods of the crossover.
Successful neurosurgery to remove tumours around the base of the skull, such as a vestibular schwannoma, depends on achieving maximal tumour removal whilst preserving crucial neurological functions such as facial movement, and maintaining quality of life. Current techniques to direct surgery are based on the surgeon's expertise and knowledge of the relevant anatomy, supplemented by the use of electrical recording and stimulation of the facial nerve. However, it is often very difficult to visualise the nerve during surgery and facial nerve paralysis remains a potentially devastating complication of surgery. Advanced imaging methods may be used to visualise important neural connections in the brain and computer-assisted processing can generate tumour maps from MRI and ultrasound scans. This study aims to utilise these technologies to develop a 3D navigation system for skull base surgery. This study aims to develop a system that will combine MRI and intraoperative ultrasound imaging to enhance the surgeon's view of the tumour, facial nerve and other surrounding critical structures during surgery. This information will be made available in the navigation system in the operating room so that operations are more precise resulting in better tumour removal rates and fewer complications. The system will be assessed during the treatment of 20 patients with vestibular schwannoma at the National Hospital for Neurology and Neurosurgery. This feasibility study will validate the different parts of the new system and help us design a future research study to determine its effectiveness in improving patient care. This project will result in safer and more effective neurosurgery, with potential consequent financial savings for the NHS and the UK, in addition to marked improvements in the quality of life of patients and reduced dependency upon others.
Cutaneous T-Cell Lymphoma (CTCL) has a chronic, relapsing course with patients undergoing multiple, consecutive therapies. Treatment aims at the clearance of skin disease, minimization of recurrence, prevention of disease progression and preservation of quality of life. The treatment of CTCL is primarily determined by the disease extent. Prolonged complete remissions have been obtained with skin-directed therapies in early stage Mycosis fungoides (MF) (IA-IIA), whereas advanced stages CTCL (IIB-IVB) are often refractory to treatment and, thus, have an unfavorable prognosis. Currently, there is no standard treatment option for CTCL, especially for advanced stages, and the optimal treatment sequence is still debated with a large variability in the therapeutic approach across countries. Patients with advanced-stage disease or refractory cutaneous CTCL should be treated with systemic therapies and, whenever possible, should be offered to participate in clinical trials. Currently, there is a urgent call for new treatments in CTCL with higher response rate and prolonged time to progression; In this study, we propose a very innovative treatment schedule in which mogamulizumab is used before Total Skin Electron Beam therapy (TSEB) for systemic disease control and as a maintenance treatment after skin-directed therapy. We hypothesize that our regimen will show a more manageable toxicity profile than a combination treatment and allow for a long-term mogamulizumab administration.
The central hypothesis of ROMA:Women is that the use of multiple arterial grafting (MAG) will improve clinical outcomes and quality of life (QOL) compared to single arterial grfating (SAG). The specific aims of ROMA:Women are: Aim 1: Determine the impact of MAG vs SAG on major adverse cardiac and cerebrovascular events in women undergoing coronary artery bypass grfating (CABG). The investigators will compare major adverse cardiac and cerebrovascular events (death, stroke, non-procedural myocardial infarction, repeat revascularization, and hospital readmission for acute coronary syndrome or heart failure) in a cohort of 2,000 women randomized 1:1 to MAG or SAG (690 from the parent ROMA trial + 1,310 from ROMA:Women). Differences by important clinical and surgical subgroups (patients younger or older than 70 years, diabetics, racial and ethnic minorities, on vs off pump CABG, type of arterial grafts used) will also be evaluated. The women enrolled in the ongoing ROMA trial (anticipated to be approximately 690) will be included in ROMA:Women, increasing efficiency and reducing enrollment time. Hypothesis 1.0. MAG will reduce the incidence of major adverse cardiac and cerebrovascular events. Hypothesis 1.1. The improvement with MAG will be consistent across key subgroups. Aim 2: Determine the impact of MAG vs SAG on generic and disease-specific QOL, physical and mental health symptoms in women undergoing CABG. The investigators will compare generic (SF-12, EQ-5D) and disease-specific (Seattle Angina Questionnaire) QOL and physical and mental health symptoms (PROMIS-29) in a sub-cohort of 500 women randomized 1:1 to MAG or SAG (including those enrolled in ROMA:QOL). Differences by important subgroups (as defined above) will also be evaluated. Hypothesis 2.0. MAG will improve generic and disease-specific QOL compared to SAG. Hypothesis 2.1. MAG will improve physical and mental health symptoms compared to SAG. Hypothesis 2.2. The improvement with MAG will be consistent across key subgroups.