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 Phase 2, Randomized, Double-Blind, Placebo-Controlled Study is intended to evaluate the Efficacy, Safety, and Tolerability and PK of INCB000928 administered to participants with a clinical diagnosis of fibrodysplasia ossificans progressiva (FOP).
Participants will undergo preoperative baseline screening and will be randomised to either normal postoperative care or a 12-week supervised exercise programme comprising of both an aerobic and resistance component They will be assessed prior to surgery which will include cardiopulmonary exercise testing (CPET). This is a well-established method of assessing aerobic exercise response and is widely used in the perioperative period for assessment of cancer patients with co-morbidity. The assessment days will also include: - muscle ultrasound (vastus lateralis) to ascertain muscle structure (thickness, pennation angle and fascicle length), - blood tests, - functional composite scores, - quality of life questionnaires, The assessment days will be carried out at four time points during the study; prior to surgery, before commencement of the exercise program, halfway through the intervention (6 weeks post commencement of exercise) and at the end of the study. In the week before the assessment days patients will wear a physical activity monitor to characterise their daily movements. The control group will also be assessed at the same time points and wear the activity monitors but will not take part in the exercise program. All participants will have a physical activity monitor placed onto the right thigh in the midline at postoperative day 1 until discharge or day 7, whichever is sooner. This is a non-invasive measure of activity and can discriminate between whether a patient is lying, sitting, standing or walking. Once participants self-report feeling able to start exercising again post-discharge, they will commence the 12 week programme. The intervention will consist of 2 resistance training (RET) sessions per week and 75 minutes of vigorous or 150 minutes of moderate aerobic exercise per week (can be split according to patient preference). They will receive a diary to log their sessions and will be monitored via twice weekly virtual follow-up (either telephone or video calling) and for the first 6 weeks weekly visits to ensure that they are adherent to the exercise protocol and provide any support/advice. Satisfactory compliance with the programme will be considered to be the completion of at least 27 sessions over the 12 week period, with a minimum of 13 out of 18 and 14 out of 18 sessions completed in the first and last 6 weeks, respectively.
The rationale for this study is to use immune molecule-specific drug treatment to leverage a mechanistic understanding of the brain changes that drive sickness behaviour. This will combine current therapy with innovative neuroimaging technologies to obtain data in humans that has hitherto only been available in animal studies. Data supporting the role of inflammatory molecules in sickness behaviours and other cognitive disorders are increasingly compelling. A putative mechanism linking inflammatory proteins to sickness behaviour is Tumour Necrosis Factor (TNF)-driven increases in extracellular glutamate leading to changes in neural function and brain network integrity and ultimately to sickness behaviour. Investigators hypothesise that TNF antagonism will effect changes in brain network connectivity and sickness behaviour score, that Rheumatoid Arthritis (RA) patients will show changes in brain network connectivity and glutamate quantification in the brain and that RA patients will show changes in monocyte infiltration into the brain that are correlated with changes in sickness behaviours. This is a randomised, placebo-controlled waiting list study. All patients will be eligible for anti-TNF treatment i.e. moderate to severe active disease as defined by Physician. Participants will be randomised to immediate (fast tracked) treatment or to treatment after 6-8 weeks (the routine waiting time). The latter group will receive placebo during the treatment phase.
The psychological health of frontline healthcare workers, caring for critically ill patients with COVID-19, has deteriorated during the pandemic. Nurses appear to be most seriously affected. Despite the availability of supportive interventions, uptake is poor, and none have been found beneficial in randomised controlled trials. The investigators have developed a two-pronged approach (combining the FLASH technique and Guided Imagery) that aims to reduce existing symptoms of distress and provide participants with techniques to help them cope with future stressful events. This approach has been developed with experienced psychological practitioners, and staff members. The FLASH technique is a recently developed therapy which aims to reduce psychological distress following traumatic events. It allows participants to process traumatic memories without feeling distress. Using guided imagery, a trained psychological practitioner helps participants to direct attention from distressing or intrusive memories, by evoking or generating positive mental images, sounds, tastes, smells and movement. Emerging evidence suggests that both techniques are safe and effective. PROACTIVE will investigate the feasibility and acceptability of this two-pronged approach to address existing traumatic symptoms and enhance future resilience for intensive care nurses. Findings will inform the design of a larger trial which tests intervention effectiveness.
REFINE-lung will test whether reduced pembrolizumab dose frequency after 6 months of standard treatment is safe and effective. Patients treated with 1st line pembrolizumab who are progression free and otherwise planning to continue therapy at 6 months will be initially randomised to control 6 weekly versus interventional 12 weekly therapy. If an interim analysis shows that the 12 weekly treatment is no less effective, subsequent patients will also be randomised to 9, 15 and 18 weekly treatment frequency arms. Patients who progress on a reduced frequency arm will be offered re-escalation to standard 6 weekly therapy.
Neuropathic pain is very common following a spinal cord injury, estimated to affect 43% of patients after 6 months. A proportion of these patients do not respond to treatment and there remains an unmet need to treat people with refractory spinal injury related neuropathic pain. While neuropathic pain medications, baclofen pumps and spinal cord stimulation work for some patients, a significant number are refractory to these therapies. Chronic pain can contribute to loss of functional ability, mental health problems, and a worse quality of life. Studies of functional neuroimaging have shown that the Anterior Cingulate Cortex (ACC) is a key structure in human pain perception, being part of a central pain neuromatrix or medial pain system, which includes thalamic nuclei and periaqueductal grey matter. A similar neuromatrix also including the insula is involved in the regulation of the autonomic nervous system, which explains the well-recognized interactions between pain and autonomic function. Moreover, it has been shown that the ACC is important for the emotional experience and thus the subjective intensity of pain, and it has a role in cognitive control processes for optimizing behaviour in the presence of pain. Bilateral anterior cingulotomy has been demonstrated to be a safe and effective therapeutic option for patients with otherwise intractable pain syndromes of different origins, e.g., refractory pain due to cancer or stroke. Although, cingulotomy has been shown to be a viable option in intractable pain of different origins, there remains a lack of evidence in patients with spinal cord injury and only scanty data are available in literature. Moreover, the effects of cingulotomy on mood, emotion processing, cognition and autonomic reactivity are not clear.
The purpose of AROC3-1001 is to evaluate the safety, tolerability, pharmacokinetics and/or pharmacodynamics in adult healthy volunteers (HVs) and in adult patients with complement-mediated renal disease (C3 Glomerulopathy [C3G] and IgA Nephropathy [IgAN]). In Part 1 of the study, HVs will receive either one or two doses of ARO-C3 or placebo. In Part 2 of the study, adult patients with C3G/IgAN will receive 3 open-label doses of ARO-C3. Dose levels in Part 2 will be determined based on cumulative safety and pharmacodynamic data from Part 1.
The purpose of this study is to evaluate the pharmacokinetics (PK), efficacy, safety and immunogenicity of ustekinumab and guselkumab in active juvenile psoriatic arthritis (jPsA).
This study aims to build on previous work characterising the PK of penicillin-V to explore the potential impact of probenecid on PK-PD target attainment. Achievement of the aims of this study would provide data to support the design of experimental studies exploring the clinical impact of probenecid on treatment outcomes and also provide a rationale for exploration of probenecid's effects on a larger number of beta-lactam antibiotics. Hypothesis: Addition of probenecid to oral phenoxymethylpenicillin (penicillin-V) has a clinically relevant effect on pharmacokinetic-pharmacodynamic (PK-PD) target attainment.
This is a multi-centre Phase I dose finding and proof-of-concept study of the combination of ASTX660 together with Pembrolizumab with expansion cohorts testing preliminary efficacy in immune-refractory cancers, triple negative breast cancer (TNBC), cervical cancer, and glioblastoma. In contrast to the existing studies combining first-generation cIAP1/2 selective Smac mimetics with immune check point inhibitors, the ASTEROID Phase I clinical trial will be the first trial utilising triple cIAP1/2 and XIAP blockade by ASTX660 as a strategy to maximise immunogenic cell death and the generation of an efficient adaptive immune response. ASTX660 is not simply being used to repeat the data already being acquired with other first generation Smac mimetics. In contrast, we will investigate more in depth the mechanisms by which ASTX660 elicits its therapeutic effects both on tumour and on the host immune system. This will be critical to determine the best strategy to pursue in future later stage tumour specific trials of IAP antagonists in combination with immunotherapy, and to ensure appropriate molecular stratification biomarkers for the greatest benefit to patients.