NIHRDataInsights/HRCSData huggingface dataset:
Title: Development and clinical evaluation of a new dual purpose insole used for ulcer prevention and balance-enhancement in neuropathic individuals with diabetes
Funder: Department of Health (England)

Abstract: Neuropathy (nerve damage) commonly affects the feet of people with diabetes and can lead to foot problems and falls. Insoles are commonly provided to protect diabetic feet. This project aims to improve and extend the usefulness of insoles by designing and testing a new dual purpose insole to protect feet and enhance balance. First people with diabetes who wear insoles will be asked for their views. Once designed, high-tech laboratory based equipment will be used to study balance and test the new insole. Finally an exploratory study will compare new and traditional insoles to see which is best at improving the balance of people with diabetes.The study design maximises clinical impact by transferring new knowledge directly to clinical practice. Each fall and related injury prevented could save a person from long term disability, increased dependence on others, loss of earnings, premature institutionalisation, social isolation and reduced quality of life.


Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS;5.3 MEDICAL DEVICES
Health categories: MUSCULOSKELETAL;METABOLIC AND ENDOCRINE
Title: Childhood vitamin D deficiency in the UK: diagnosis, treatment and healthcare costs in primary and secondary care
Funder: Department of Health (England)

Abstract: Reports suggest that rickets, caused by vitamin D deficiency and preventable by dietary supplementation, has re-emerged among UK children. However, there is a paucity of data available to quantify these concerns. Using routinely collected data in large primary and secondary care clinical databases, we will investigate rates and trends in the diagnosis of vitamin D deficiency in UK children, approaches to its treatment, and associated healthcare costs for the NHS. The study will further our understanding of the health burden caused by this preventable condition, and will facilitate evaluation of current public health policy directed towards preventing childhood rickets.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION;8.2 HEALTH AND WELFARE ECONOMICS
Health categories: MUSCULOSKELETAL;METABOLIC AND ENDOCRINE
Title: Highly accelerated quantitative MRI of skeletal and cardiac muscle in muscular dystrophy and type 2 diabetes
Funder: Medical Research Council

Abstract: Research Objectives: To accelerate magnetic resonance imaging (MRI) evaluation of cardiac and skeletal muscle using a novel acquisition and reconstruction technique. This will enhance the use of MRI in clinical trials and scientific studies with higher patient compliance and lower cost. This will be achieved by applying a form of mathematical reconstruction called compressed sensing which exploits the redundancy in transformed images to reduce the amount of data that needs to be acquired. We will evaluate its validity in muscular dystrophy and type 2 diabetes patients. The overall aim is to reduce what is presently a two hour examination for muscular dystrophy to take no longer than 40 minutes, a significant advantage for all patients, particularly young children. The project has two aims: Aim 1 : To accelerate the acquisition of quantitative fat mapping in skeletal muscle of patients with muscular dystrophy and in the liver and pancreas of patients with type 2 diabetes. Aim 2 : To accelerate the acquisition of cardiac cine imaging and tagging, a technique which sensitively measures cardiac strain and torsion and has been found to be altered in the muscular dystrophies. This will substantially reduce the acquisition time and the number of breath holds required. Respiratory muscles are often compromised and breath-holding is time consuming for this patient group. Aim 1 will be achieved by: (1) optimising the compressed acquisition by building a computer model and testing it on our library of previously acquired data; (2) programming, testing and validating the optimum pulse sequence to acquire the compressed data on the MRI scanner, and (3) performing pilot studies in 10 healthy subjects and 10 adults with muscular dystrophy, analyzing 9 muscle groups and performing a Bland-Altman analysis of the accelerated technique to determine repeatability and bias. It will also be validated for pancreas and liver fat measurements in 10 subjects with type 2 diabetes and 10 healthy controls. Aim 2 will be achieved by: (1) using previously acquired cardiac tagging data to optimise the compressed acquisition, (2) programming, testing and validating the optimum pulse sequence, (3) performing in vivo validation in 10 healthy volunteers and 10 adult muscular dystrophy patients, using Bland-Altman analysis. The research will be exploited in peer-reviewed journals, international and national conferences and results presented directly to patient groups. Subsequently the acquisition and processing algorithms developed by the research will be made publicly available.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: MUSCULOSKELETAL;METABOLIC AND ENDOCRINE
Title: Type 2 Diabetes Mellitus and frozen shoulder: risk, prognosis, and influence on treatment outcomes
Funder: Versus Arthritis

Abstract: Background Frozen shoulder is a common and debilitating condition that is more severe and prevalent (27.5%) in patients who have diabetes mellitus (DM) compared to the general population (5%). Frozen shoulder may also indicate the presence of type II DM in undiagnosed patients. However, evidence for DM as risk factor, prognostic factor, or predictor of treatment outcome in patients with frozen shoulder is unclear.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION;7.3 MANAGEMENT AND DECISION MAKING
Health categories: MUSCULOSKELETAL;METABOLIC AND ENDOCRINE
Title: Defining the Role of the Human Lipodystrophy Protein Seipin in Adipose Tissue Development and Metabolic Disease.
Funder: Medical Research Council

Abstract: The incidence of obesity has increased dramatically and is linked to the development of conditions such as diabetes and cardiovascular disease. Adipocyte dysfunction is believed to significantly contribute to the development of metabolic disease in obesity. Hence, understanding how metabolically active adipocytes form may suggest new ways to beneficially manipulate newly generated or pre-existing adipocytes. As 10% of adipocytes in the human body are renewed each year, just targeting these newly developing cells could improve metabolic health. The overall aim of this study is to increase our understanding of adipocyte development and function and identify potential new therapeutic targets. Our approach is to focus on a protein called seipin, encoded by the gene BSCL2. Disruption of seipin causes a near complete absence of fat tissue in affected individuals, representing the most severe and selective form of this rare condition. Despite its critical role in fat development we know relatively little about what seipin does in developing adipocytes. If we can define how it regulates this process this could suggest novel future therapeutic targets. Using cutting edge inducible knockout technologies we will define when during development seipin plays its critical role in fat development. We will also determine whether seipin is required for normal adipocyte turnover in adults and/or is needed to increase the number of adipocytes during obesity. In all cases we will define the metabolic consequences of losing seipin at these different developmental stages. Finally we will investigate the molecular mechanisms via which seipin may regulate adipogenesis. Together this will provide novel fundamental insights into the processes controlling fat cell development. It will also demonstrate whether altering the function of seipin, or the pathways it regulates, could be therapeutically useful for treating obesity related metabolic disease.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MUSCULOSKELETAL;METABOLIC AND ENDOCRINE
Title: Determining the function of the transcriptional co-repressor RIP140 in skeletal muscle metabolic adaptation to exercise and insulin resistance.
Funder: Wellcome Trust

Abstract: Obesity and its associated diseases are now recognized as a worldwide epidemic, found among the top five risk factors for global deaths. Different environmental cues promote the development of obesity, but physical inactivity is thought to be among the leading causes. Particularly, deterioration of skeletal muscle metabolic fitness is a common hallmark of obesity and insulin resistance. The development of therapies for these pathologies has been limited, in part, due to the lack of knowledge of the molecular mechanisms regulating muscle adaptation. Interestingly, the protein RIP140 has been found to exert a negative effect on energy metabolism and glucose uptake, yet its therapeutic potential for human metabolic disease has not been studied. This project aims to define the molecular mechanisms by which RIP140 regulates skeletal muscle energy metabolism and to identify how exercise regulates RIP140 activity. This project will undertake a translational approach initially using cell based genetic studies before translational exercise studies in healthy and obese-insulin resistant individuals. Therefore, this study will provide novel examination into the potential role of RIP140 in the development of human metabolic diseases and, importantly, the therapeutic potential of exercise to improve metabolic capacity in obese and insulin resistant skeletal muscle.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MUSCULOSKELETAL;METABOLIC AND ENDOCRINE
Title: A preclinical feasibility study using recombinant homogentisic acid dehydrogenase as an enzyme replacement therapy for alkaptonuria
Funder: Wellcome Trust

Abstract: There are over 6000 known rare diseases and most are of genetic origin. One such condition is alkaptonuria (AKU), which is caused by a faulty enzyme. This means patients produce a chemical called homogentisic acid (HGA). Some HGA leaves the body in urine. The rest builds up in body tissues, eventually causing serious health problems Some of this HGA is converted into a black pigment. Over time this black pigment stains joint tissues, including bone and cartilage, causing early onset, severe arthritis. This is why AKU is also known as black bone disease'. Patients also suffer severe pain and heart disease. Most AKU patients become severely disabled as life progresses and many of them end up wheelchair-bound. There is no known cure for AKU and current treatment relies on pain management and joint replacement. This project's key objective is to test the idea of enzyme replacement therapy (ERT). We will make human enzyme in bacteria (as a method of manufacture) and then test it in mice with AKU. If this reduces the effects of AKU in the mice, then it might be possible to treat this debilitating disease for the first time.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: MUSCULOSKELETAL;METABOLIC AND ENDOCRINE
Title: Discovery of P2Y14 antagonists for the treatment of osteoarthritic pain
Funder: Innovate UK

Abstract: The primary objective of the project is to identify novel antagonists of the receptor P2Y14 for the treatment of osteoarthritis. P2Y14 has been linked to immune functions but its role in disease is poorly understood. Convergence Pharmaceuticals has obtained novel genomic and target validation data linking P2Y14 with pain behaviour in models of chronic pain and also with responses to NGF. The role of NGF is at the cutting edge of modern pain research and identification of new ways to modulate NGF signalling in chronic pain offer the hope of therapies with significant improvement in efficacy. Convergence scientists have identified a series of quality hit and lead antagonists to P2Y14 for the initiation of a drug discovery campaign. This proposal encompasses the selection of key lead series, lead optimisation for the discovery of drug candidates, the selection of a drug candidate and completion of non-GLP safety pharmacology and toxicology across two species.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: MUSCULOSKELETAL;NEUROLOGICAL
Title: A failure of neuroprotective redox signalling from skeletal muscle to motor neurons leads to loss of motor units with ageing
Funder: Biotechnology and Biological Sciences Research Council

Abstract: Age-related loss of skeletal muscle mass and function is a major factor leading to the physical frailty seen in the elderly. The age-related decline in skeletal muscle mass is due to loss of muscle fibres and weakness of the remaining fibres. This is associated with loss of the motor nerves (neurons) that normally innervate those fibres. It is currently unknown whether the loss of the motor neurons precedes, and leads to, loss of the muscle fibres or whether the reverse occurs. Damage to tissues by highly reactive free radicals or reactive oxygen species (ROS) appears to contribute to the age-related loss of muscle fibres and is in part due to an age-related failure of homeostatic mechanisms that regulate ROS activities. Exercise or contractile activity of muscle upregulates protective systems in the muscle that help maintain ROS homeostasis, but it is unclear whether similar processes occur in the motor neurons. This project will use a combination of cell culture and mouse models to determine: (i) whether contracting skeletal muscles release substances that act on motor neurons to upregulate defences against ROS and other cytoprotective proteins, (ii) whether ageing leads to a decline in this cytoprotective signalling process potentially leading to an increased susceptibility of the motor neuron to damage during ageing, (iii) whether interventions known to improve the ability of skeletal muscle to generate ROS that signal adaptations prevent the age-related loss of motor neurons, and (iv) whether substances released from muscle oxidise proteins in the peripheral nerve axons and whether these oxidised proteins signal the upregulation of defences against ROS and other cytoprotective proteins in the motor neuron cell body. If sucessful this project may indicate novel approaches to maintaining motor neuron numbers in the ageing neuromuscular system.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: MUSCULOSKELETAL;NEUROLOGICAL
Title: To explore falls and balance impairments in people with neuromuscular diseases (NMD), particularly Charcot-Marie-Tooth disease (CMT) and distal myopathy (DM).
Funder: Department of Health (England)

Abstract: Falls are a common problem for people with neurological problems, leading to significant consequences such as injury and avoidance of activities. Falls in people with neuromuscular disorders (NMDs) have received scant attention but are a problem identified by people with Charcot-Marie-Disease in a recent focus group study. This programme of research aims to investigate the incidence and circumstances in which people fall using a questionnaire survey. This will lead on to a laboratory based study using 3D motion and force analysis to characterise static balance, dynamic balance and gait in people with distal NMDs. A battery of clinical measures, e.g. strength and sensation, will be collected to ascertain the relationship between balance and impairments. Prospective falls diaries will also be instigated for the participants. The results of these studies will be used to develop a pilot balance intervention study with a view to inform further research after the lectureship period.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MUSCULOSKELETAL;NEUROLOGICAL
Title: Carpal Tunnel Syndrome: an investigation of the impact of neuropathic pain and somatosensory phenotype on postoperative outcome
Funder: Department of Health (England)

Abstract: Carpal Tunnel Syndrome (CTS) results from a trapped nerve in the wrist. It is common, causes pain and numbness of the hand, and makes everyday tasks difficult. Many patients with CTS have neuropathic pain however individual symptoms vary. This observational study uses repeated measures to investigate how neuropathic pain affects outcome following carpal tunnel surgery. We will correlate measures of neuropathic pain and sensory function with surgical outcome to determine what traits relate to poor outcome. We will then develop a screening tool to identify CTS patients at risk of poor outcome and develop new patient pathways to improve outcome.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;7.3 MANAGEMENT AND DECISION MAKING
Health categories: MUSCULOSKELETAL;NEUROLOGICAL
Title: Development of a Functional Electrical Stimulation System for Bone Health Maintenance in Spinal Cord Injury Patients
Funder: Engineering and Physical Sciences Research Council

Abstract: According to statistics from charities such as Every Eight Hours and Spinal Research, there are an estimated 40,000 spinal cord injured people in the UK and a new person is injured every eight hours. Many primary causes of death are now no longer direct results of spinal cord injury but are conditions linked to age and inactivity. This means that there are long-term demands on medical support; in particular, treatment of osteoporotic bone fractures often results in lengthy spells in hospital for individuals with spinal cord injury. It is therefore important to minimize the effect of osteoporosis after spinal cord injury; this highlights the need for exercise programmes to target bone health. The proposed research aims to develop effective Functional Electrical Stimulation (FES) induced weight bearing exercises to improve and maintain bone health in the lower extremities of spinal cord injury patients. The type of exercises proposed will be completed using a novel smart standing frame and FES system to cyclically activate different sets of muscles whilst maintaining standing and crouch poses. The hypothesis is that these exercises will induce sufficient joint contact forces to be beneficial for bone health in the ankle, knee and hip joints. Using biomechanical modelling software an optimal combination of these exercises will be sought in order to design a rehabilitation programme to target bone health. To be beneficial to bone health, these exercises need to be repeated several times a week and there is a good chance patients will get bored or frustrated doing the same thing every day. To solve this problem, rehabilitation aids will be developed to keep patients motivated. These aids will use video game technology (based on the Xbox Kinect), to make the sessions more engaging for the patient to encourage compliance and give a sense of achievement. This will also allow the patient and clinician to monitor the progress of a rehabilitation programme and modify it as necessary.


Research activity codes: 5.7 PHYSICAL
Health categories: MUSCULOSKELETAL;NEUROLOGICAL
Title: Participation in physical leisure pursuits and play in children with motor impairments: developing a theory- and evidenc
Funder: Medical Research Council

Abstract: Motor impairments (e.g. difficulties with motor control, muscle tone) affect between 6-9% of children. These children are often diagnosed with conditions such as developmental coordination disorder or cerebral palsy. They experience significant difficulties in participating in everyday life and are at high risk of long-term health and social problems Despite this high burden of disease, interventions to manage these problems have been subject to little systematic research. Current interventions for these children consist of ‘therapeutic activities‘ (e.g. exercises) that aim to increase what the children do in their daily lives. The interventions are poorly defined, lack explicit hypotheses about why or how they might work, and have insufficient evidence to support their effectiveness. The proposed research will identify: The ‘key ingredients‘ of an effective intervention to increase participation in physical leisure pursuits and play in children with motor impairments. How these ingredients can be combined in a feasible and acceptable intervention. Research in stroke and chronic pain has shown that incorporating behaviour change strategies (e.g. confidence-building techniques) into therapeutic interventions significantly improves what patients can do (i.e. activity) and actually do (i.e. participation). Carers have also been shown to have an important role, suggesting that effective interventions should systematically incorporate therapeutic, personal (e.g. child‘s confidence) and environmental (e.g. parents‘ beliefs) components. This project draws on the WHO International Classification of Functioning, Disability and Health - a conceptual framework that integrates biomedical, personal and environmental perspectives on illness and health. The methodology is based on the MRC guidance for developing complex interventions, operationalised into five steps: (1) identify biomedical, personal and environmental factors proposed to predict children‘s participation in leisure pursuits and play; (2) develop an explicit model of the key predictors of participation; (3) select therapeutic and behaviour change strategies to target the proposed predictors; (4) operationalise the strategies in a feasible and acceptable intervention; and (5) model the intervention processes and outcomes within single cases. The primary output will be a detailed protocol for an intervention that is based on empirical evidence and a theoretical model of disability in terms of behaviour (i.e. what children actually do). Such an intervention, if subsequently found to be effective, will support children with motor difficulties in attaining life-long well-being and participation in society. The project will also be an exemplar for the development of non-drug interventions by allied health professionals.


Research activity codes: 8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: MUSCULOSKELETAL;NEUROLOGICAL
Title: Loss of neuromuscular functions of the large bowel during advanced age: characterisation of regionally-dependent mechanisms of action and clinical impact
Funder: Dunhill Medical Trust

Abstract: Chronic constipation is prevalent, markedly increasing with advanced age. Mechanisms are species-/ age-dependent, yet treatments are age-independent. In human colon (>140 people) we observe marked declines in cholinergic function with advanced age in females (70+ years; unrelated to disease/drug use) and males, indicative of progressive neuromuscular weakness. Changes are in proximal, not distal colon. We will address four questions: Q1: To what extent does functional degeneration occur in well-characterised patients (which nerves? both muscle layers? changed muscle functions? comparison with slow-transit constipation in younger adults?), compared with mouse (potential drug development model)? Q2: Do functional changes track neuromuscular degeneration? Q3: Do activities of drugs treating or causing constipation (hyper-tension/ pain treatments) change with age in humans/ mice? Q4: Does aged human colon show evidence of senescence-like phenotype, oxidative damage and changed neurotrophic receptor expression, indicative of regionally-dependent, persistent damage? The answers will strengthen research focus and direct medical practice.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MUSCULOSKELETAL;NEUROLOGICAL