NIHRDataInsights/HRCSData huggingface dataset:
Title: Small Vessel Disease - Spotlight on Symptoms (SVD-SOS) - Improving recognition of symptoms and signs of progressing cerebral small vessel disease-related brain damage to prevent cognitive decline, dementia and stroke
Funder: Stroke Association

Abstract: Cerebral small vessel disease (SVD) diagnosed on brain scan causes up to 45% of dementias and 25% of strokes. SVD changes develop gradually and usually unnoticed. Patients or doctors may be dismissing important unconventional symptoms (common after stroke) that indicate SVD progression. In August 2018, we started a longitudinal clinical study of SVD (target sample n=300) in patients with ischaemic SVD (lacunar) or minor cortical (control) stroke, assessing medical, cognitive, physical function and performing structural and dynamic magnetic resonance imaging (MRI). We repeat these assessments at 6 and 12 months. In a pilot phase we invited patients for additional assessments (including MRI) at monthly intervals. We were surprised that so many participants (18/28, 64%) agreed and there was a high rate of new SVD lesions in patients scanned so far (6/12, 50%). To address this important observation properly, we seek additional funding (adding value to and benefiting from the existing project) to assess 120 of these patients at 6-8 weekly intervals for a year. At each visit, we will assess symptoms including unconventional symptoms, cognition, physical function and structural MRI to test a) whether subtle symptoms correspond with new lesions on MRI, and b) document risk factors for lesion progression.

Lay abstract: Cerebral small vessel disease (SVD) diagnosed on brain scan causes up to 45% of dementias and 25% of strokes. SVD changes develop gradually and usually unnoticed. Patients or doctors may be dismissing important unconventional symptoms (common after stroke) that indicate SVD progression. In August 2018, we started a longitudinal clinical study of SVD (target sample n=300) in patients with ischaemic SVD (lacunar) or minor cortical (control) stroke, assessing medical, cognitive, physical function and performing structural and dynamic magnetic resonance imaging (MRI). We repeat these assessments at 6 and 12 months. In a pilot phase we invited patients for additional assessments (including MRI) at monthly intervals. We were surprised that so many participants (18/28, 64%) agreed and there was a high rate of new SVD lesions in patients scanned so far (6/12, 50%). To address this important observation properly, we seek additional funding (adding value to and benefiting from the existing project) to assess 120 of these patients at 6-8 weekly intervals for a year. At each visit, we will assess symptoms including unconventional symptoms, cognition, physical function and structural MRI to test a) whether subtle symptoms correspond with new lesions on MRI, and b) document risk factors for lesion progression.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: NEUROLOGICAL;STROKE
Title: Brain Computer Interface driven rehabilitation of upper limb weakness of stroke survivors - (NeuRestore)
Funder: Innovate UK

Abstract: Stroke is the leading cause of acquired disability in adults, and as such occupies a special place amongst the different types of brain injuries. Problems with arm function (upper limb impairments) are very common after a stroke. Existing advanced neurorehabilitation techniques (physiotherapy being comparatively limited and subjective) share a range of limitations including limited understanding of the underlying mechanisms. The NHS spends 4-6% of overall budget on stroke rehabilitation. Upper limb "circulatory" disorders account for 9% of primary care consultations and present a 55-90% admission rate to hospitals. The **NeuRestore** project proposes to significantly address these limitations by exploring a unique non-invasive brain-computer interfaces (BCIs) approach to exploit electroencephalogram (EEG) patterns to trigger feedback or an action output from an exoskeleton. **NeuRestore** achieves this at a cost of £98k/licenced unit/year (just under the average salary of 2x NHS Advanced-Physiotherapist), while crucially reducing physio waiting times (and resources can be spent elsewhere).


Research activity codes: 5.3 MEDICAL DEVICES
Health categories: NEUROLOGICAL;STROKE
Title: Phase III programme for alicaforsen enema in the orphan disease pouchitis
Funder: Innovate UK

Abstract: Atlantic Healthcare is focused on the development and commercialisation of niche profitable specialist drugs meeting unmet clinical needs of patients managed in the hospital and specialist care environments in Europe and the US, neglected by larger international pharmaceutical companies. Alicaforsen, Atlantic's first product, is a novel ICAM-1 inhibitor and a first in class drug for the treatment of Inflammatory Bowel Disease (IBD). This is a $3.5bn pa market growing at 10% pa, driven by the need for new & effective therapies. Alicaforsen has completed Ph2 development and been granted orphan designation and a letter of fast track for Europe and the US for the treatment of pouchitis, a rare disease for which there is no approved treatment. Atlantic Healthcare has obtained agreement from international regulators that only a small single pivotal placebo controlled Ph3 is necessary for marketing approval for Europe/US.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: ORAL AND GASTROINTESTINAL
Title: OrganOx Phase 2 Clinical Investigation
Funder: Innovate UK

Abstract: OrganOx® Ltd. is a company focussed on increasing the quality & supply of organs for transplantation. It’s first product, the OrganOx metra™, a patented liver preservation device, entered a phase I clinical study in Sept 2012 at Kings College Hospital, London. The metra will revolutionise liver transplantation globally by enabling objective assessment of liver viability, planned as opposed to emergency procedures, but most importantly by greatly increasing the supply of livers for transplantation. Globally there were ~18,500 deceased donor liver transplants in 2010. The metra will be launched in Europe Q4 2013. This project will part fund a phase II clinical study in the US to enable an application to the FDA for marketing authorisation. Export of the metra to the US will double the market opportunity thereby delivering increased revenues back to the UK building product pipeline & additional UK job opportunities together with the ability to save thousands of extra lives each year.


Research activity codes: 6.3 MEDICAL DEVICES
Health categories: ORAL AND GASTROINTESTINAL
Title: LiverMultiscan with MRI – replacing liver biopsy
Funder: Innovate UK

Abstract: Chronic liver disease has been termed “the silent killer”: It usually does not cause symtoms until it is too late and most of the liver has been destroyed, at which point life expectancy is short. Furthermore, unlike heart disease or cancer, chronic liver disease will become much more frequent over the next 20 years, mainly because many more people are becoming obese and diabetic, two illnesses which damage the liver. We therefore need better diagnostic tools to recognise patients with liver disease early, to accurately measure the degree of liver damage, and measure both, the progression of liver damage over time, and its improvement with treatment. Currently, the only reliable diagnostic method is biopsy, where liver tissue is obtained by inserting a needle and is then assessed under a microscope. Liver biopsy has serious limitations, is unwelcomed by patients, as it can be painful, and there is a risk of serious complications. Perspectum Diagnostics is a company founded by members of Oxford University, who have developed new magnetic resonance imaging (MRI) technology, LiverMultiscan™, to quickly, accurately and safely measure the degree and extent of liver damage without needles. We believe that our test could replace liver biopsy and become the best way to assess patients over time. We propose to develop our prototype technology into a robust diagnostic product, to be used routinely in patients within 2-3 years. Our vision is to fundamentally change the way liver disease is diagnosed and treated, because our new imaging method will provide risk-free, instant, and accurate assessment of the liver.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: ORAL AND GASTROINTESTINAL
Title: Clinical evaluation of advanced prototype medical device for dental caries assessment
Funder: Innovate UK

Abstract: This project will design, develop, produce and clinically evaluate an advanced prototype of the Calcivis dental caries (decay) activity assessment system. There is a significant unmet need in dentistry to differentiate early dental lesions that are actively demineralising from those which are less likely to progress to cavitation. Calcivis is unique and innovative because it deploys a photoprotein which produces light in the presence of the calcium ions being released from an actively demineralising tooth surface. In combination with a customised intra-oral camera it produces a demineralisation map of the tooth surface. To date, a basic prototype of the camera has been used to demonstrate proof of concept in extracted teeth but this project takes a significant step forward as it enables an advanced prototype reflecting detailed input from dentists to be refined, produced and evaluated in the clinic.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: ORAL AND GASTROINTESTINAL
Title: Use of a Novel Cell Printer to Create, Analyse and Optimise 3D Liver Tissues
Funder: Innovate UK

Abstract: Human liver hepatocytes are extremely valuable cells both for drug development laboratories and for patients whose own livers have become damaged either through viral infections, poor diet and/or long term excessive alcohol consumption. There is already a shortage of donor livers for transplantation and this is set to worsen in the future as liver failure rates continue to increase. It is known that stem cells can be multiplied greatly in culture and changed into hepatocytes to give an endless supply. However, the liver also has other cell types in it which contribute to efficient liver function. In this project we will identify these cell types and their ideal ratios to liver hepatocytes. This should form the basis for further development work towards recreating functional liver tissue from human stem cells.


Research activity codes: 5.2 CELLULAR AND GENE THERAPIES
Health categories: ORAL AND GASTROINTESTINAL
Title: Non-invasive identification and monitoring of Inflammatory Bowel Disease (IBD)
Funder: Innovate UK

Abstract: This project evaluates the feasibility of a novel, non-invasive diagnosis and monitoring test for crohn’s disease and ulcerative colitis. The test is based on the detection of VOC bio-markers in biological samples using a novel form Ion Mobility technology. Crohn’s disease and ulcerative colitis are particularly unpleasant affecting 1 in 250 of the population. Symptoms range from urgent and bloody diarrhea, pain and continual tiredness to deep ulcers and scarring to the wall of the intestine. Current diagnostic methods are highly invasive; being based on blood tests and endoscopic examinations (camera examination per rectum). The cost to the NHS is set at £500 per procedure with around 180,000 procedures undertaken per annum in the UK. Our innovative step is to replace this with a simple, low-cost (sub £10) urine or stool test based on the detection and analysis of VOC biomarkers released from these biological samples.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: ORAL AND GASTROINTESTINAL
Title: In Vitro Modelling of Biliary Development and Diseases
Funder: SPARKS

Abstract: Cholangiopathies represent a leading cause for liver disease and transplantation. Treatment options are very limited and research in the field is hindered by poor primary tissue access and lack of robust disease models. Alagille Syndrome (AGS) is a monogenic, syndromic infantile cholangiopathy. It is caused by JAG1 or Notch2 gene mutations leading to poor biliary tree development, paucity of bile ducts and hepatic impairment. The pathogenesis of AGS remains elusive and liver transplantation provides the only available therapy. We propose establishing a novel platform for in vitro modelling of biliary diseases, based on a methodology we developed for generating cholangiocytes from patient derived human Induced Pluripotent Stem Cells (hIPSCs). We will validate this platform by developing the first proof-of-principle in vitro model for AGS, towards exploring the role of JAG-Notch signalling in biliary development and disease. The disease phenotype will be reproduced in vitro using AGS-hIPSCs undergoing biliary differentiation and organoid formation in 3D culture conditions. To demonstrate the association between JAG-Notch signalling and our in vitro phenotype, we will correct the JAG mutation in AGS hIPSCs and silence Notch signalling in generic hIPSCs expecting rescue and reproduction of the AGS phenotype respectively. We will then use CHIP assays, genome wide analysis and pathway inducers/inhibitors to characterise the transcriptional network regulated by Notch in biliary development and identify cross-talk with other key pathways. Differentiation of hIPSC to cholangiocytes will increase our insight in biliary development, overcome limitations due to lack of primary tissue and provide large amounts of autologous biliary epithelial cells for the study of cholangiopathies. Modelling AGS in vitro will elucidate the disease pathogenesis, promote the generation of novel prognostic, diagnostic and therapeutic modalities and pioneer in vitro biliary disease modelling. (Lay summary also provided)


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: ORAL AND GASTROINTESTINAL
Title: Electrical Impedance Spectroscopy to detect neoplastic oral lesions
Funder: Innovate UK

Abstract: When found at early stages of development, oral cancers have an 80 - 90 % survival rate. Unfortunately, the majority are found as late stage cancers. This accounts for the very high death rate of ~43% at five years from diagnosis, for all stages combined at time of diagnosis. Zilico Ltd is developing the next generation of cancer diagnostics and proposes to use electrical impedance spectroscopy as a tool to diagnose the presence of oral cancer.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: ORAL AND GASTROINTESTINAL
Title: Body composition and metabolic profile of children with end stage liver disease before and after liver transplant; relations with outcome and cell energy controlling metabolic pathways
Funder: CORE

Abstract: Chronic illnesses have been known to cause wasting and cachexia, leading to worse outcomes. Cachexia is not just a result of poor appetite and malabsorption of nutrients due to the disease, but is the result of altered metabolism. Its mechanism is poorly understood. Children with end stage liver disease suffer from cachexia. It is not unusual for these children to lose weight including fat mass and to have significant muscle wasting. This is associated with glucose intolerance and increased lipid and protein breakdown. At cellular level there are proteins that control these metabolic pathways and therefore control whole body metabolism. A significant body of research is looking into cell energy controlling pathways in a variety of diseases like cancer, cardiomyopathies, obesity, diabetes-type-2 e.g. AMPK, mTOR/S6K1, PI3K/Akt. AMPK is considered the energy masterswitch for the cell and is activated when energy is low. It then stimulates energy production through catabolic pathways, like the breakdown of protein and fat. These energy controlling pathways have not been studied in children with end stage liver disease. The aim of our study is to investigate the mechanism of cachexia in children with chronic liver disease. We will be studying cell energy controlling pathways like AMPK in tissues derived from the patient during the liver transplant operation and associating them to body composition, energy expenditure and outcomes. Linking the alteration of these pathways by liver disease to clinical picture and outcome is particularly exciting: - It would bring us closer to understanding how disease influences metabolism at cellular level and whole body level It could lead to the usage of newer therapeutic strategies, some with substances already existing like amino acids, metformin, thiazolidinediones


Research activity codes: 6.4 SURGERY;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: ORAL AND GASTROINTESTINAL
Title: What is the occurrence and consequence of clinically diagnosed coeliac disease and dermatitis herpetiformis in the UK today? A series of population based cohort studies utilising electronically linked health records
Funder: CORE

Abstract: To plan health services it is crucial to understand the numbers of people affected by coeliac disease and the health consequences. This information also allows clear and precise information to be given to people with coeliac disease and helps clinicians to focus long term follow up upon complications that matter the most and could be prevented. The studies we propose to do aim to provide this information. In terms of occurrence for example, while we have been able to quantify the amount of “undetected coeliac disease” from serology studies we don’t actually know how many people are currently clinically diagnosed and how that varies by age, sex and, perhaps most importantly geographical area and socio-economic status. We know that the diagnosis of coeliac disease can be delayed through inappropriate labelling of irritable bowel syndrome (IBS), but cannot say what proportion of IBS diagnoses this might apply to. Older studies suggest that the risk of coeliac disease in offspring of mothers with coeliac disease is about 10% but we do not know if this is reflected in the real world of general practice today. Moving to the consequences of coeliac disease, it is perhaps surprising that we know that those diagnosed are at increased risk of death, but not what they die from. Equally we do not know how common some of the recognised complications of the disease are, nor how actively the NHS seeks to avoid these. We will therefore examine the certified causes of death of people with coeliac disease. As an example of an avoidable complication we will determine how common pneumococcal diseases are.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: ORAL AND GASTROINTESTINAL
Title: Development Grant - Quantitative Magnetic Resonance Imaging (MRI) Techniques in the Evaluation and Estimation of Portal Hypertension
Funder: CORE

Abstract: Death from chronic liver disease is rising in the United Kingdom. This is largely due to the rise in liver disease from excess alcohol consumption, obesity related fatty liver disease and hepatitis B & C infections. Liver scarring (fibrosis) increases resistance to the circulation which results in raised pressure within the liver called ‘portal hypertension’. This raised pressure leads to the formation of varicose veins within the gullet and stomach; if these rupture it leads to a major blood loss with a high risk of death. We currently measure the pressure within the liver by passing a long catheter through the jugular vein in the neck down into the liver. This is an expensive and invasive test perceived as unpleasant by patients. It is also not available outside specialised liver centres. We aim to develop a non-invasive magnetic resonance (MR) scan to assess the pressure within the liver. We will measure the degree of scarring, changes in the blood flow feeding the liver and delivery of blood into the liver tissue. The combination of these MR markers will reflect the changes in liver pressure. We will recruit 49 patients, who have had invasive liver pressure measurements using a catheter as part of their clinical assessment, to undergo MR scans. We will evaluate the accuracy of our MR parameters in estimating the changes in the pressure within the liver.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: ORAL AND GASTROINTESTINAL
Title: Olympus Fellowship - Evaluation of novel and existing minimally-invasive endoscopic imaging tools to screen for Barrett’s Oesophagus and Oesophageal Varices
Funder: CORE

Abstract: There are certain conditions like Barrett’s Oesophagus (where the normal cell lining of the gullet becomes similar to that of the stomach or small intestine) and Oesophageal Varices (swollen veins in the gullet) that can happen in patients who do not have any symptoms Barrett’s Oesophagus can occasionally lead to complications like ulcers and rarely cancer of the gullet. Similarly, Oesophageal Varices can cause serious bleeding in the gullet. If these conditions are diagnosed and treated early then patients may possibly avoid these complications. Doctors know that certain patients are more likely to develop these conditions, but one of the problems is that there is no suitable test to use in this situation. The standard camera (endoscopy) which is inserted through the mouth is not ideal for testing large numbers of patients. So, a lot of research has been done to find alternative tests (blood tests, scans, very thin cameras which can be inserted through the nose) that are safer, cheaper and more comfortable. Most of these tests can be done at the doctor’s practice, which makes them more convenient. The purpose of this project is first to see whether these existing tests are good enough to replace the standard oral camera. Secondly, to find out if a new model of nasal cameras is as good as the standard oral camera test. Thirdly, to interview some of the patients and identify in more detail what they like and don’t like about each test (nasal and standard camera). And finally, to estimate which tests are affordable for use in the NHS. If the results show that one or more tests are useful and more comfortable to patients, then this will mean that it can potentially be used to diagnose thousands of other patients who may have these two serious conditions and treat them early. This may reduce the chance of complications and improve the quality of life and survival for these patients.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: ORAL AND GASTROINTESTINAL