787
records
Rare Diseases Research Landscape Project
DATA_SOURCE | FUNDER_PROGRAMME | FUNDER_REF | TITLE | ABSTRACT | SUMMARY | MRC_AIMSANDOBJS | MRC_KEYWORDS | NIHR_CALLTEXT | RESEARCH_ORGANSIATION | RO_POSTCODE | RO_COUNTRY | STARTDATE | ENDDATE | AWARD_VALUE | HRCS_HEALTH CATEGORY | HRCS_RAC | CON_TI_RDcount | CON_TI_RDlist | CON_TIAB_RDcount | CON_TIAB_RDlist | INDI_TI_RDcount | INDI_TI_RDlist | INDI_TIAB_RDcount | INDI_TIAB_RDlist | SUM_TIAB | ORPHANET_GROUPING | NIHR_PROGRAMMESTREAM | MRC_Grant Category | MRC_Grant type | MRC_Funding Mode | MRC Strategic Criteria | MRC_Call | INCLUDED_ IN_5_YEAR_ANALYSIS |
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DATA_SOURCE | FUNDER_PROGRAMME | FUNDER_REF | TITLE | ABSTRACT | SUMMARY | MRC_AIMSANDOBJS | MRC_KEYWORDS | NIHR_CALLTEXT | RESEARCH_ORGANSIATION | RO_POSTCODE | RO_COUNTRY | STARTDATE | ENDDATE | AWARD_VALUE | HRCS_HEALTH CATEGORY | HRCS_RAC | CON_TI_RDcount | CON_TI_RDlist | CON_TIAB_RDcount | CON_TIAB_RDlist | INDI_TI_RDcount | INDI_TI_RDlist | INDI_TIAB_RDcount | INDI_TIAB_RDlist | SUM_TIAB | ORPHANET_GROUPING | NIHR_PROGRAMMESTREAM | MRC_Grant Category | MRC_Grant type | MRC_Funding Mode | MRC Strategic Criteria | MRC_Call | INCLUDED_ IN_5_YEAR_ANALYSIS | |
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1 | NIHR PROG | Health Technology Assessment | 07/89/01 | FIAT (Fistula-in-ano trial) comparing Surgisis® anal fistula plug versus surgeon's preference (advancement flap, fistulotomy, cutting seton) for transsphincteric fistula-in-ano | Anal fistula is a common surgical condition yet the treatment remains controversial. This is particularly so for high transsphincteric fistula which involve a substantial proportion of the anal sphincter muscle. Traditional surgical methods of laying the fistula open (fistulotomy) by necessity cut that portion of the sphincter muscle involved in the fistula and put the patient at risk of permanent faecal incontinence. Faecal incontinence is a distressing condition that severely impacts on quality of life. In an attempt to overcome the problem of postoperative incontinence, a variety of novel procedures have been advocated, however, none have achieved universally acceptable results in terms of high healing rates combined with a low incidence of incontinence. The most recent innovation in this field is the Surgisis® anal fistula plug. The fistula plug has the advantages that it is simple to insert, with minimal patient discomfort or morbidity. In addition, the integrity of the anal sp | Design: Prospective, randomised, multicentre trial of Surgisis® anal fistula plug versus surgeon's preference (fistulotomy, advancement flap, or cutting seton) in the treatment of high transsphincteric anal fistulae.It is not practicably possible to perform a blinded comparison given the nature of the procedures and the specifics of the postoperative care
Setting: Teaching and District General Hospitals in the United Kingdom. Participating surgeons will be members of the Association of Coloproctology of GB&I
Target Population: Inclusion and exclusion criteria are based on current recommendations regarding patient suitability and details of operative technique(6).
Inclusion Criteria
1.Clinical diagnosis of high transsphincteric cryptoglandular fistula-in-ano. A high transsphincteric fistula is defined as a fistula involving 1/3 or more of the external anal sphincter muscle as assessed by clinical examination or radiological imaging.
2.Patients must have undergone a prior examination un | Management of high anal fistulae | University of Leeds | LS2 9JT | England | 12 January 2010 | 31 August 2017 | £1,566,928 | Oral and Gastrointestinal; | 6.4 Surgery; | 0 | 0 | 1 | anal fistula | 1 | anal fistula | 1 | Rare gastroenterologic disease | Commissioned | Yes | |||||||||
2 | NIHR PROG | Efficacy and Mechanism Evaluation | 11/14/33 | Low-dose Intravenous Immunoglobulin Treatment for Complex Regional Pain Syndrome (‘LIPS’) Randomised Controlled Trial. | Complex Regional Pain Syndrome (CRPS) arises after injury to a limb. Patients experience ongoing, severe pain, out of proportion to the injury. The pain can eventually get better. However, unfortunately in every 7th patient (15%) the pain is unrelenting even after one year. If the pain lasts that long it is less likely to get better later. The quality of life of these patients is very poor. They cannot use the affected limb, and only a few can return to work. Unfortunately, we do not know why CRPS occurs. There are currently few treatments, and for many patients no treatment works.We propose to test a new treatment. We have recently shown in a small study, that a drug called intravenous immunoglobulin (IVIG) can profoundly reduce pain from CRPS. IVIG had only few side effects. IVIG treats the immune system. Our study only had 13 participants. We now wish to find out with more confidence whether IVIG is indeed effective, and how effective it is. This information is needed so that IVIG-t | Research design: Randomised, double-blinded, placebo controlled parallel trial with an open single- dose extension. Study Population: Adult patients with Complex Regional Pain Syndrome of 1-5 years duration, and a pain intensity of >4 on an 11-point numeric rating scale (NRS). Excluded are patients with other significant chronic pains, unstable medical conditions, rare IVIG contraindications, or who are pregnant or breastfeeding. Planned interventions: Patients are randomised (online block-randomisation with stratification to study site and pain intensity) to receive either 0.5g/kg intravenous immunoglobulin (IVIG), or an equal volume of placebo (0.1% Albumin in Normal Saline), with a second infusion three weeks later. After six weeks, patients can choose to receive a one off dose of 0.5g/kg IVIG openly. Proposed outcome measures: Primary outcome: NRS 24h average pain intensity over 37 days (study days 6 - 42); secondary outcomes: pain interference and quality of life; additional explo | 0 | University of Liverpool | L69 7ZX | England | 12 January 2012 | 31 July 2016 | £644,378 | Injuries and Accidents; Neurological; | 6.1 Pharmaceuticals; | 0 | 0 | 1 | complex regional pain syndrome | 1 | complex regional pain syndrome | 1 | Rare neurologic disease | Researcher Led | Yes | |||||||||
3 | NIHR PROG | Efficacy and Mechanism Evaluation | 12/205/28 | COHESIVE - COrticosteroids in HErpes SImplex Virus Encephalitis | 1. THE PROBLEM: Encephalitis means inflammation (swelling) of the brain, often caused by a virus. In the UK Herpes simplex virus (HSV) is the most important cause, affecting 1 per 250,000-500,000 people. Although classed as a “very rare” disease, it has a significant impact because survivors are incapacitated with severe disability, with estimated costs of £3-5 million per severe case. Inflammation and swelling occurs as part of the body’s defence against infection. However in the brain it can cause damage, because the brain is in a fixed space (the skull) with no room for swelling. In herpes encephalitis the temporal lobes of the brain are especially affected. These lobes are very important for memory. Thus verbal memory is especially badly affected in herpes encephalitis. Verbal memory is the ability to remember the names of objects and people, and to listen to and recall spoken information
Brain magnetic resonance imaging (MRI) scans can be used to assess brain swelling. Doctors so | Herpes simplex virus (HSV) encephalitis is a rare but devastating brain infection, with temporal lobe swelling and severe memory impairment in survivors, particularly verbal memory. The swelling appears to respond to corticosteroid treatment, though some clinicians worry about uncontrolled viral replication.
PRIMARY HYPOTHESIS: In HSV encephalitis treatment with the corticosteroid dexamethasone is associated with an improvement in verbal memory, assessed at 6 months.
DESIGN: A multicentre observer-blind trial of corticosteroids in 90 adults with HSV encephalitis.
SETTING: Recruitment through NHS Hospital Trusts in the Brain Infections UK Network: up to 90 sites
TARGET POPULATION: Adults with HSV encephalitis, proven by PCR of the cerebrospinal fluid (CSF).
INTERVENTION: Patients will be randomised to dexamethasone 40 mg intravenously every 24 hours for 4 days, or no dexamethasone; in addition all will receive standard antiviral treatment: 10 mg/kg aciclovir 8 hourly for 14 da | 12/205 Very Rare Diseases | University of Liverpool | L69 7ZX | England | 6 January 2015 | 28 February 2023 | £1,305,463 | Infection; Neurological; | 5.1 Pharmaceuticals; 6.1 Pharmaceuticals; | 0 | 1 | rare disease | 2 | herpes simplex virus encephalitis|encephalitis | 3 | herpes simplex virus encephalitis|hsv encephalitis|encephalitis | 4 | Rare infectious disease; Rare neurologic disease | Commissioned | Yes | ||||||||
4 | NIHR PROG | Health and Social Care Delivery Research | 13/54/25 | Transitions from paediatric to adult services for sickle cell disease (SCD): a prospective qualitative study examining young adult patients’ experiences | Transitions from paediatric to adult services cause problems worldwide. Sickle Cell Disease (SCD) - a chronic debilitating condition that causes cumulative damage to multiple organ systems and acute pain episodes - provides an excellent case study for examining transitions: it is complex and growing rapidly in the UK, and there is a lack of UK-based research on this topic. Over 15,000 people live with SCD in the UK; it is the fastest growing genetic blood disorder. In England, SCD-related hospital admissions increased more than 50% between 2001/02 and 2009/10 with the highest rates of emergency admissions among those who had recently transitioned to adult care, suggesting there is an urgent need for improvement in SCD care, particularly during transition.
Poorly-managed transitions have high economic and social costs to patients, their families and health services. Many young adults with SCD reach the transition period without appropriate education or support. Our research will bring | Transitions from paediatric to adult services cause problems worldwide, particularly among patients with chronic disease and complex health needs requiring integrated care. Transitional care is a key area within the NHS and sickle Cell Disease (SCD) provides an excellent case study for examining transitions. SCD is complex and growing rapidly in the UK, and there is little UK-based research on this topic. In the UK, over 15,000 people live with SCD, 2/3 of them in London. It is the fastest-growing genetic blood disorder in England with increasing associated mortality and morbidity: between 2001/2 – 2009/10, SCD-related hospital admissions increased more than 50%. The highest rates of emergency admissions were among those who recently transitioned from paediatric to adult care, suggesting an urgent need for improvement in transitional care. Yet we lack empirical evidence about the support patients need during such transitions. Transition is a time of increased medical vulnerability and | 0 | London School of Hygiene & Tropical Medicine | WC1E 7HT | England | 4 January 2015 | 30 April 2019 | £444,924 | Blood; | 7.1 Individual care needs; 8.1 Organisation and delivery of services; | 0 | 0 | 1 | sickle cell | 1 | sickle cell | 1 | Rare hematologic disease | Researcher Led | Yes | |||||||||
5 | NIHR PROG | Health Technology Assessment | 07/51/01 | Torpedo-CF: Trial of optimal therapy for pseudomonas eradication in cystic fibrosis | Children and adults with cystic fibrosis are prone to chest infections and these infections can cause long term damage to the lungs, which can affect the health and long term survival of the patient.
There are a number of different organisms that cause these infections, one of the most important of which is known as Pseudomonas aeruginosa (there is no lay term for this organism). Pseudomonas is treated with oral (by mouth), intravenous (directly into the blood) and nebulised antibiotics (inhaled as an aerosol), usually in combination. Sometimes doctors choose to treat the patient in the community with three months of oral and at least three months of nebulised antibiotics and sometimes choose to admit the patient to hospital and treat for 10-14 days with intravenous treatment as well as continuing the same nebulised treatment for three months.
Despite there being substantial differences to the patient and family in terms of what these two treatment choices offer, at present it is | Design
Multi-centre parallel group, randomised controlled trial comparing ten days of intravenous therapy to three months of oral therapy.
Setting
Multicentre (Paediatric and Adult centres) UK study coordinated via the Medicines for Children Research Network Clinical Trials Unit
Target Population
All cystic fibrosis patients who have isolated P.aeruginosa and fulfil the inclusion criteria from participating centres will be considered eligible to take part in the trial.
Health Technologies Being Assessed
This trial aims to examine whether ten days intravenous ceftazidime with tobramycin is superior to oral ciprofloxacin Both treatment arms will receive three months of nebulised colistin in conjunction to the randomised treatment.
Measurement of cost and outcomes
The primary outcome measure will be successful eradication of P.aeruginosa infection at three months post randomisation, and remaining infection free through to 15 months post randomisation. Secondary outcomes will i | Pseudomonas aeruginosa in cystic fibrosis patients | University Hospitals Bristol and Weston NHS Foundation Trust | BS1 3NU | England | 12 January 2009 | 31 December 2018 | £1,256,659 | Congenital Disorders; Infection; | 6.1 Pharmaceuticals; | 0 | 0 | 1 | cystic fibrosis | 1 | cystic fibrosis | 1 | Rare respiratory disease | Commissioned | Yes | |||||||||
6 | NIHR PROG | Health Technology Assessment | 11/129/261 | Short course daily prednisolone therapy at the time of upper respiratory tract infection in children with relapsing steroid sensitive nephrotic syndrome; the PREDNOS 2 study. | Steroid sensitive nephrotic syndrome (SSNS) is the commonest kidney disease of childhood. Large amounts of protein are leaked into the urine resulting in generalised oedema (swelling). Treatment is with high dose oral prednisolone, a steroid drug which is effective, though associated with a number of serious side-effects including weight gain, behavioural change, diabetes, high blood pressure, poor growth and weak bones. Another HTA funded study that we are conducting (PREDNOS) is currently investigating whether giving a longer course of prednisolone at presentation results in better long-term outcomes. Following successful initial treatment, 70-80% of children develop relapses where leakage of protein into the urine recurs. These are associated with a risk of significant complications, including infection, blood clots, high cholesterol levels and malnutrition. Treatment of relapse of nephrotic syndrome is with a further course of high dose prednisolone, further increasing the risk of | Design: Phase III randomised parallel group, double-blind, placebo-controlled trial.
Setting: The 13 UK Paediatric Nephrology centres, plus additional teaching hospitals and district hospitals led by Consultant Paediatricians with a special interest in Paediatric Nephrology. All of these centres are currently participating in the ongoing PREDNOS study (HTA 08/53/31).
Target population: Children with relapsing steroid sensitive nephrotic syndrome (SSNS). The prevalence of SSNS was reported to be 16/100,000 children in the 1960s, though since then there has been a significant rise in the number of children of South Asian origin in the UK; these children have a sixfold increased risk of developing SSNS compared with white children. There are estimated to be more than 2000 children currently under follow-up with SSNS in the UK.
Health Technologies Being Assessed: Current practice is for no change to be made to immunosuppressive therapy at the time of development of an upper respiratory tra | 0 | Manchester University NHS Foundation Trust | M13 9WL | England | 10 January 2012 | 31 July 2020 | £1,023,064 | Renal and Urogenital; | 6.1 Pharmaceuticals; | 0 | 0 | 0 | 0 | 0 | Researcher Led | Yes | ||||||||||||
7 | NIHR PROG | Evidence Synthesis Programme | 13/89/12 | Evidence-based care for preterm or sick newborn infants and their families: Cochrane partnership programme | Although outcomes for preterm or sick newborn infants have improved substantially over the past 30 years, major morbidities associated with the need for prolonged intensive or invasive care have emerged. These include extra-uterine growth and developmental faltering secondary to nutritional deficiency, necrotising enterocolitis (NEC), and late-onset (hospital-acquired) invasive infection. Attributable mortality for NEC and severe infection is more than 20% and these are now the most common causes of death beyond the early neonatal period for very preterm infants. NEC, infection, and nutritional insufficiency are also associated with neuro-disability, longer durations of hospital stay, and higher (life-long) health service costs. Families and clinicians need to access high-quality evidence to guide care practices, highlight uncertainties, and inform priority setting for further research to prevent and treat these conditions.
This programme focuses on two related themes identified as st | Babies who are born too early (preterm), and particularly very preterm babies who are born before about 32 weeks of pregnancy, often require intensive care for several weeks after birth. Advances in care have improved survival and outcomes for preterm and sick infants substantially over the past 30 years. However, partly because of this increase in the chances of survival, infants now encounter problems associated with the need to prolonged periods of intensive care. The main problems include infections and severe bowel disorders (mainly “necrotising enterocolitis”), and these are associated with reduced intake of nutrition and problems with growth and development which may persist in the long term.
The Cochrane Collaboration’s Neonatal Review Group [see http://neonatal.cochrane.org/] aims to provide clinicians, and parents and their families, with reliable and useful summaries of the best evidence to guide care and further research to reduce the burden of harm due to infection and n | 0 | University of York | YO10 5DD | England | 8 January 2014 | 30 September 2017 | £356,731 | Reproductive Health and Childbirth, | 7.3 Management and decision making, | 0 | 0 | 0 | 2 | parenteral nutrition-associated cholestasis|necrotising enterocolitis | 2 | Rare hepatic disease; Rare gastroenterologic disease | Researcher Led | Yes | ||||||||||
8 | NIHR PROG | Efficacy and Mechanism Evaluation | 12/164/16 | PITCHES: Phase II trial in IntrahepaTic CHolestasis of pregnancy (ICP) to evaluate Efficacy of urSodeoxycholic acid (UDCA) in improving perinatal outcomes with parallel biobank collection for mechanistic studies. | Intrahepatic cholestasis of pregnancy (ICP) is the commonest liver disease in pregnancy. Affected women itch and have abnormal liver blood tests. It is important to diagnose ICP because it is associated with risks for the unborn baby. Blood tests in the mother may show high levels of bile acids, which can increase the risk of the baby being born early and, in severe cases, being stillborn.
At present the main drug used to treat ICP is ursodeoxycholic acid (UDCA). Our pilot study showed that women with ICP are willing to take part in a trial comparing UDCA with a placebo (an identical tablet not containing the drug). Our trial also suggested that UDCA may protect the unborn baby from poor outcomes, but the study was not large enough to be certain. A recent study that combined the results of several similar trials also showed that UDCA may improve the outcome for the baby in ICP. However, the current guideline from the Royal College of Obstetricians and Gynaecologists (RCOG) states, “W | Background: Intrahepatic cholestasis of pregnancy (ICP), defined as gestational pruritus in association with raised maternal serum bile acids, affects approximately 1 in 150 pregnancies and is associated with increased rates of preterm labour, stillbirth and neonatal unit admission. Ursodeoxycholic acid (UDCA) is the most commonly used drug treatment for ICP. We and others have shown that UDCA improves maternal pruritus and biochemical abnormalities in ICP but there has been no adequately powered study to address the potential benefit of UDCA treatment in reducing adverse perinatal outcomes; this remains a novel research question.
Aims: To evaluate the efficacy of ursodeoxycholic acid (UDCA) treatment on reduction of perinatal death, preterm delivery and neonatal unit admission in women with ICP, with the goal of establishing the potential benefit to the fetus.
The secondary aim is to obtain samples in order to perform embedded studies to determine the mechanism(s) by which UDCA thera | 12/164 Disorders of pregnancy | King's College London | SE1 8WA | England | 3 January 2015 | 28 February 2019 | £1,242,610 | Reproductive Health and Childbirth; | 5.1 Pharmaceuticals; 6.1 Pharmaceuticals; | 0 | 0 | 1 | intrahepatic cholestasis of pregnancy | 1 | intrahepatic cholestasis of pregnancy | 1 | Rare hepatic disease | Commissioned | Yes | |||||||||
9 | NIHR PROG | Health Technology Assessment | 14/167/01 | Steroid Induction Regimen for Juvenile Idiopathic Arthritis (JIA) | What is JIA?
JIA stands for Juvenile Idiopathic Arthritis. Arthritis means inflammation in the joints leading to pain, stiffness, swelling and warmth. It can cause damage and reduced movement in affected joints. The term JIA covers several types of arthritis that start under the age of 17 and for which there is no known cause. It is a chronic disease meaning that it can cause trouble for many years. Approximately half of young people will continue to suffer from arthritis as adults.
Treatment:
There are many good treatments for JIA including anti-inflammatory drugs, disease modifying drugs, and new ‘biologic’ drugs. They block the inflammation. Although these newer drugs are good, they are powerful and expensive and sometimes not effective enough. Patients often still need steroids at the start of treatment to induce remission of arthritis and if the arthritis flares up again. A short course of steroids can stop the flare and reduce increases in other treatments.
There are four w | Design: A UK-wide feasibility study
Setting: NHS Trusts with Paediatric Rheumatology services
Strategy for literature review: A review of recent literature, review of the latest revision of the European Medicines Agemcy (EMA) guideline on JIA trial design, review of the outcomes of the Single Hub Access for Rheumatology in Europe (SHARE) conclusions.
Target populations: Patients <16 years with Juvenile Idiopathic Arthritis requiring Corticosteroid (CS) Treatment
Health technologies assessed: The feasibility study will explore four CS delivery regimens (intra-articular corticosteroid injections (IACI), oral, intravenous (IV) pulsed, or depot intramuscular (IM) injections or a combination) for induction of treatment response and remission in patients with newly diagnosed or flaring JIA. The study will determine from HCP and PPI perspectives as well as from current practise, which modalities would be compared in a future RCT.
Measurements of costs and outcomes
1 Costs: Determin | 14/167 Steroid induction regimen for juvenile idiopathic arthritis (JIA) | Alder Hey Children's NHS Foundation Trust | L12 2AP | England | 1 January 2016 | 31 December 2018 | £269,526 | Inflammatory and Immune System; | 6.1 Pharmaceuticals; 7.1 Individual care needs; 7.3 Management and decision making; | 0 | 0 | 1 | juvenile idiopathic arthritis | 1 | juvenile idiopathic arthritis | 1 | Rare systemic or rheumatologic disease | Commissioned | Yes | |||||||||
10 | NIHR PROG | Efficacy and Mechanism Evaluation | 12/205/56 | Treatment of Barth Syndrome by CARDIOlipin MANipulation (CARDIOMAN): A randomised placebo-controlled pilot trial conducted by the Nationally Commissioned Barth Syndrome Service | Barth Syndrome is a life threatening genetic disease which affects young males. It is caused by abnormal fats (lipids) in the powerhouses of cells (mitochondria). Those affected may be stillborn or develop heart failure, bacterial infections, poor growth or feeding problems during childhood. 26 males are alive with the disease in the UK.
This disease carries many risks and problems for its sufferers, as well as major healthcare costs. 7 in 10 people require frequent drug injections to boost their white blood cell count. Almost half have been considered for heart transplantation, but only half of these survive. Even those who have not received transplants can develop life-threatening heart rhythm disturbances.
Boys/men living with the disease have severe exercise intolerance, lethargy and fatigue which affect their daily life; many use wheelchairs intermittently to aid mobility. Furthermore, children continue to die from this disease, which has claimed the lives of 4 of the 5 boys bor | HYPOTHESIS & AIMS
Barth Syndrome patients show a deficiency of L4-cardiolipin (L4-CL) and excess of monolysocardiolipin (MLCL) in their inner mitochondrial membranes. In vitro studies on mouse and human fibroblasts show that the lipid lowering drug bezafibrate can produce major improvement in the abnormal MLCL/L4-CL ratio and has proven clinical efficacy in mitochondrial myopathy. We seek to examine the effect of bezafibrate in boys/young men with Barth Syndrome, looking at peak skeletal muscle oxygen consumption on bicycle exercise testing and a range of secondary outcome measures, including biochemical cardiolipin levels and Quality of Life (QOL). This will be run in parallel with in vitro testing of transformed lymphoblasts, using both bezafibrate and another potentially effective drug called resveratrol, to look for confirmation of biological activity in each patient and predictive correlates of treatment response. In addition we will use qualitative methods to evaluate trial desig | 12/205 Very Rare Diseases | University Hospitals Bristol and Weston NHS Foundation Trust | BS1 3NU | England | 4 January 2015 | 31 January 2021 | £528,070 | Congenital Disorders; Metabolic and Endocrine; | 5.1 Pharmaceuticals; 6.1 Pharmaceuticals; | 0 | 1 | rare disease | 1 | barth syndrome | 2 | barth syndrome|mitochondrial myopathy | 3 | Rare inborn errors of metabolism; Rare neurologic disease | Commissioned | Yes | ||||||||
11 | NIHR PROG | Efficacy and Mechanism Evaluation | 14/187/01 | A blinded randomised controlled trial investigating the efficacy of morphine analgesia for procedural pain in infants. | Pain in babies has negative consequences, both immediately and in the longer-term. As babies cannot describe their pain the measurement and treatment of pain is difficult and, compared to adults and older children, pain is under-treated in this group. In the late 1980s, surgery was routinely performed on babies without providing adequate pain relief. The assumption that babies do not feel pain is still present in clinical practice. It is remarkable that 2015 UK NHS Choices guidelines for tongue-tie surgery state that “in small babies, being cuddled and fed is more important than painkillers”. In part, the acceptance that pain relief in babies is not necessary has arisen because so few clinical trials have tested whether different types of medication provide effective pain relief in babies. Given that a baby requiring intensive care will experience an average of 10 painful procedures per day and, the youngest and sickest babies may experience 50 painful procedures per day, this is a ser | While infant pain is recognised to have immediate and long-term consequences, it is still drastically under-treated. In the late 1980s surgery was routinely performed on infants without the provision of adequate analgesia. While this practice has now changed, the historical misconception that infants do not feel pain still prevails in clinical practice.
In part, the under-treatment of infant pain has arisen because so few trials have been conducted to test whether pharmacological analgesics are effective in this population. Consequently, comfort measures (such as non-nutritive sucking and swaddling) are often recommended as an alternative to pharmacological analgesia. Given that an infant requiring intensive care will experience an average of 10 painful procedures per day, and the youngest and sickest infants may experience 50 painful procedures per day, this is a serious clinical issue.
The aim of this study is to test whether morphine can provide effective pain relief for procedu | 0 | University of Oxford | OX1 2JD | England | 9 January 2015 | 30 June 2018 | £419,722 | Neurological; | 5.1 Pharmaceuticals; 5.5 Radiotherapy; 6.1 Pharmaceuticals; | 0 | 0 | 0 | 1 | retinopathy of prematurity | 1 | Rare ophthalmic disorder | Researcher Led | Yes | ||||||||||
12 | NIHR PROG | Efficacy and Mechanism Evaluation | 12/212/15 | Intravenous immunoglobulin in the management of encephalitis in children | Viral infections and inflammation of the brain caused by the immune system, both of which are described by the term “encephalitis”, are important causes of brain injury and death in childhood, with 7% of those affected dying and up to 50% of survivors reporting problems. A treatment for these conditions using a preparation of natural antibodies made from blood donations (intravenous immunoglobulin, IVIG), has been shown to improve the outcome of a number of inflammatory conditions of the brain and nerves, but has not been widely used in the treatment of viral brain infections and is usually given after some delay in the immune-mediated cases due to the time it takes to establish the diagnosis. There is evidence to support the view that IVIG is beneficial irrespective of the cause of encephalitis.
In this study, we plan to test whether use of intravenous immunoglobulin (IVIG), given soon after a child presents to hospital with signs of encephalitis, will improve outcomes. The rest of | Infectious and immune-mediated encephalitides are important but under-recognised
causes of neurological morbidity and mortality in childhood, with 7% mortality and up to 50% of survivors reporting deficits after prolonged follow up. There is theoretical and empirical evidence for a beneficial response to intravenous immunoglobulin (IVIG) for both viral and auto-immune aetiologies of childhood encephalitis, but (a) use of this therapy has remained limited in infectious cases (mainly used for outbreaks of enterovirus 71 in the Far East and in the immunocompromised) and (b) it has only been used after inevitable delay (by weeks in some cases) in the immune-mediated conditions while alternative diagnoses are being excluded or a definitive diagnosis is obtained. It is currently unknown whether wider use of IVIG in infectious encephalitis and earlier use in immune-mediated encephalitis could alter the outcome of this group of conditions with a similar clinical presentation.
AIMS
To determi | 12/212 Interventions in Paediatrics | University of Oxford | OX1 2JD | England | 1 January 2015 | 30 April 2019 | £766,773 | Infection; Neurological; | 6.1 Pharmaceuticals; | 0 | 0 | 1 | encephalitis | 2 | encephalitis|infectious encephalitis | 2 | Rare neurologic disease | Commissioned | Yes | |||||||||
13 | NIHR PROG | Health Technology Assessment | 14/22/23 | The cystic fibrosis (CF) anti-staphylococcal antibiotic prophylaxis trial (CF START); a randomised registry trial to assess the safety and efficacy of flucloxacillin as a longterm prophylaxis agent for infants with CF | The aim of the CF START study is to determine the safest and most effective antibiotic strategy for infants diagnosed with cystic fibrosis. Cystic fibrosis (or CF) is an inherited genetic condition. Infants with CF in the UK are most often diagnosed following a positive newborn screening test. They may appear quite well initially but quickly develop significant chest infections, which if untreated will cause lung damage and early death. For many years, physicians in the UK have prescribed children with CF long-term antibiotics that they take every day. Most often this is an antibiotic called flucloxacillin. The aim of this strategy is to prevent lung infection with Staphylococcus, which is known to be a common bug causing infection for people with CF.
Physicians in other countries have been more reticent to use this approach and have tended to only prescribe antibiotics when the infant has a cough or grows a bug from a cough (or throat) swab. The reason they use this more targe | Design; multi-centre randomised open label registry trial (with internal pilot study)
Setting; multi-disciplinary care setting (UK Paediatric CF clinics)
Literature and background; Systematic review confirms that long-term flucloxacillin treatment results in reduction in Staphylococcus aureus (SA) airway infection but possibly at the expense of earlier Pseudomonas aeruginosa (PsA) airway infection. This limited evidence base has resulted in varied interpretation with diverse practice across the globe. Recent UK registry data suggest an increase prevalence of PsA infection in patients on flucloxacillin, making UK physicians and patient advocacy groups anxious about the validity of this management strategy for infants with CF. Determining that long-term flucloxacillin is safe and effective is a priority research area in the field of Paediatrics, illustrated by the repeated prioritisation of this topic by the NIHR CRN: Children's Respiratory and CF Clinical Studies Group.
Target popul | 0 | Alder Hey Children's NHS Foundation Trust | L12 2AP | England | 8 January 2016 | 31 July 2028 | £1,842,732 | Congenital Disorders; | 6.1 Pharmaceuticals; 7.1 Individual care needs; | 0 | 0 | 1 | cystic fibrosis | 1 | cystic fibrosis | 1 | Rare respiratory disease | Researcher Led | Yes | |||||||||
14 | NIHR PROG | Health Technology Assessment | 16/111/106 | AZithromycin ThErapy for Chronic lung disease (AZTEC): A randomised, placebo controlled trial of azithromycin for the prevention of chronic lung disease of prematurity in preterm infants | Ten per cent of the world’s babies are born prematurely. Those born extremely prematurely may not survive and many of the survivors develop the lung disease called Chronic Lung Disease of Prematurity (CLD, often also called BPD or bronchopulmonary dysplasia). CLD develops due to underdeveloped lungs and also because they may need breathing machines (mechanical ventilators) and oxygen to keep them alive. CLD is variously defined but most commonly as needing oxygen at 28 days of age or at 36 weeks “corrected” gestation. Most babies will come off their oxygen therapy as their lungs continue to grow at least for the first 2-3 years of age. Some babies go home on oxygen placing enormous burden on the parents. Babies with CLD also have many hospital admissions and chest infections in childhood.
We have noted that inflammation (redness or soreness) of the lungs is often seen in babies who develop CLD. In addition, we believe that the germ called Ureaplasma is found more frequently in the lun | Design/setting: We plan a randomised, placebo controlled, double-blind trial of azithromycin to show improvement in survival without CLD (defined as oxygen dependency at 36 weeks’ postmenstrual age) in preterm-born infants <30 weeks completed gestation who are cared for in Level III neonatal units in the UK.
Target population: In- and out-born <30 completed weeks’ gestational age at birth who require respiratory support for at least 2 hours during the first 72 hours of life. Babies with a realistic chance of survival; no exposure to other macrolide antibiotics (not maternal) before enrolment; no major surgical or congenital abnormalities.
Health technology: Azithromycin or placebo will be commenced within 72 hours (20mg/kg once daily iv for 3 days then 10 mg/kg once daily iv for 7 days). The dosage and duration are based on achieving therapeutic levels of the drug to eradicate Ureaplasma colonisation and to utilise the drug’s anti - inflammatory activities on pulmonary inflammation th | 0 | Cardiff University | CF10 3AT | Wales | 1 January 2018 | 30 June 2023 | £2,361,018 | Infection; Reproductive Health and Childbirth; | 6.1 Pharmaceuticals; | 0 | 0 | 0 | 2 | bronchopulmonary dysplasia|cystic fibrosis | 2 | Rare respiratory disease | Researcher Led | Yes | ||||||||||
15 | NIHR PROG | Technology Assessment Review | 15/64/07 | Adalimumab and dexamethasone for treating non-infectious uveitis [ID763] | This review will assess the clinical and cost-effectiveness of adalimumab subcutaneous injection and dexamethasone intravitreal implant within their marketing authorisations for treating non-infectious, intermediate, posterior or pan uveitis. | Uveitis is an inflammation of the uveal tract of the eye, which consists of the iris, the ciliary body and the choroid. It is usually caused by an underlying autoimmune disorder or trauma to the eye. In some people the cause is unknown. Uveitis is classified according to the main location of inflammation. Anterior uveitis is inflammation of the iris. Intermediate uveitis affects the posterior part of the ciliary body and the vitreous humour. Posterior uveitis affects the back of the eye, including the retina and the choroid. Panuveitis is inflammation of the whole of the uveal tract (front and back of the eye). Symptoms include pain and redness in the eye, blurred vision, sensitivity to light, loss of peripheral vision and headaches. One or both eyes may be affected.
Intermediate, posterior and panuveitis are less common than anterior uveitis (they account for around 1 in 4 uveitis diagnoses1 but are more severe and more likely to cause vision loss. Consequences of uveitis include gla | Batch 42 | The University of Sheffield | S1 4DA | England | 1 July 2016 | 4 December 2017 | £175,000 | Eye, | 6.1 Pharmaceuticals, | 0 | 0 | 1 | uveitis | 5 | intermediate uveitis|anterior uveitis|panuveitis|posterior uveitis|uveitis | 5 | Rare ophthalmic disorder | Commissioned | Yes | |||||||||
16 | NIHR PROG | Technology Assessment Review | 15/64/13 | Aflibercept for treating visual impairment due to macular oedema secondary to branch retinal vein occlusion [ID844] | To appraise the clinical and cost effectiveness of aflibercept within its marketing authorisation for treating visual impairment caused by macular oedema secondary to branch retinal vein occlusion. | The macula is the central part of the retina responsible for colour vision and perception of fine detail. Macular oedema is the accumulation of fluid within the retina at the macular area, which can lead to severe visual impairment in the affected eye.
Retinal vein occlusion (RVO) is a common cause of reduced vision. It is classified into central retinal vein occlusion and branch retinal vein occlusion (BRVO). BRVO is caused by a blood clot in the small veins in the retina. Blockages in the retinal veins increase the pressure in the retinal capillaries, which can lead to blood and plasma leaking into the macula. These changes trigger vascular endothelial growth factor (VEGF) to be released, which increases the permeability of the blood vessels and causes new vessels to grow.
The impact of vision loss associated with RVO can have a profound effect on vision-related quality of life. Patients may struggle with daily tasks, lose confidence, and become increasingly dependent on family and c | Batch 42 | University of Aberdeen | AB24 3FX | Scotland | 2 August 2016 | 5 November 2016 | £65,625 | Eye, | 6.1 Pharmaceuticals, | 0 | 0 | 0 | 1 | central retinal vein occlusion | 1 | Rare ophthalmic disorder | Commissioned | Yes | ||||||||||
17 | NIHR PROG | Technology Assessment Review | 16/27/01 | Strimvelis for treating severe combined immunodeficiency caused by adenosine deaminase deficiency [ID926] | To evaluate the benefits and costs of Strimvelis within its licensed indication for treating severe combined immunodeficiency caused by adenosine deaminase deficiency for national commissioning by NHS England. | Immunodeficiency is caused by failure of a component of the immune system
and results in increased susceptibility to infections. Severe combined immunodeficiency caused by
adenosine deaminase deficiency (ADA-SCID) is a disease in which the body cannot make functional
lymphocytes (a type of white blood cell) and, as a result, patients have a severely impaired immune
system. A faulty gene inherited from both parents impairs production of an essential protein called
adenosine deaminase, which is particularly important for the formation of lymphocytes and a
functioning immune system. This deficiency usually results in the onset of serious infections
within the first few months of life. The symptoms of ADA-SCID include an increased susceptibility
to infections and failure to thrive; ADA-SCID also has non- immunological manifestations, including
neurological and developmental effects. ADA-SCID is chronically debilitating and life-threatening.
ADA-SCID accounts for about 10–15% of al | Highly Specialised Technologies 2016 | University of York | YO10 5DD | England | 7 April 2017 | 28 September 2017 | £87,281 | Inflammatory and Immune System, | 6.2 Cellular and gene therapies, | 0 | 2 | highly specialised technolog|orphanet | 1 | severe combined immunodeficiency | 1 | severe combined immunodeficiency | 3 | Rare immune disease | Commissioned | Yes | ||||||||
18 | NIHR PROG | Efficacy and Mechanism Evaluation | 17/60/67 | Enceph-IG - Intravenous Immunoglobulin in Autoimmune Encephalitis in Adults: A Randomised Double-Blind Placebo-Controlled Trial | Background
Autoimmune encephalitis is inflammation and swelling of the brain caused by the body’s own immune defence system. It affects about 1 in 100,000 people per year in the UK. The symptoms can include abnormal behaviour, memory problems and seizures (fits). Some patients recover completely, but in others it causes death or severe disability.
Autoimmune encephalitis is treated with steroids, which reduce inflammation and swelling. If patients are not improving intravenous immunoglobulin (IVIG) is often also given, usually after a couple of weeks. IVIG is a protein product extracted from the blood of healthy donors. It is given by a drip into a vein each day for five days, and is used for other similar diseases.
Some doctors think that if IVIG is used from the start of treatment, patients may recover more quickly and have better outcomes. We are therefore faced with a dilemma: on the one hand IVIG may help patients; on the other it is expensive, can have side effects, includin | Research question
In adults with autoimmune encephalitis, does the addition of early intravenous immunoglobulin (IVIG) to the standard corticosteroid treatment give a different recovery time to improve the outcome, and if so, by what mechanism?
Background
Autoimmune encephalitis, inflammation and swelling of the brain caused by the body’s own immune defence system, affects about 1 in 100,000 people per year in the UK. It is sometimes associated with anti-neuronal antibodies, and is being recognised increasingly. Some patients recover completely, but in others it causes death or severe disability. The disease is treated with steroids. If patients are not improving IVIG is often added, usually after a couple of weeks, but its efficacy is unknown. IVIG is expensive, and can have side effects, including blood clots or allergic reactions. There is currently clinical equipoise about its use.
Aims and objectives
The AIM of this research is to determine whether in adults with autoimmune e | 0 | University of Liverpool | L69 7ZX | England | 4 January 2020 | 30 April 2026 | £2,731,532 | Inflammatory and Immune System; | 5.1 Pharmaceuticals; 6.1 Pharmaceuticals; | 0 | 0 | 1 | encephalitis | 1 | encephalitis | 1 | Rare neurologic disease | Researcher Led | Yes | |||||||||
19 | NIHR PROG | Health and Social Care Delivery Research | 16/52/25 | Rethinking Strategies for Positive Newborn Screening Result Delivery (ReSPoND): a process evaluation of co-designing interventions to minimise impact on parental emotional well-being and stress | Each year about 800,000 babies in the UK have a blood test taken to screen for specific conditions, which if treated early will improve the child’s health and well-being (known as newborn screening (NBS)). In 2014-15, over 10,000 babies were identified as being affected or healthy carriers of a gene for one of the conditions screened for, which include sickle cell disease, cystic fibrosis, metabolic diseases and hypothyroidism.
Parents’ agree to the blood test at the time of birth but many never expect a positive result. When a positive result occurs, a variety of ways are used to deliver the result but many parents complain about the manner in which the information is communicated to them. With the expansion of NBS in England, the importance of delivering this information appropriately to minimise any long-term negative health and psychological consequences is vital.
Our Aim: For parents and health professionals to work together to design interventions to facilitate effective commu | Background: Annually, circa 10,000 parents of babies born in the United Kingdom (UK) are given a positive newborn screening (NBS+) result 2-8 weeks after birth(1,2). Despite guidance(3), NBS+ results are inconsistently delivered across UK-regions(4-7) and many parents are dissatisfied with how NBS+ results are communicated(5-12). Expansion of UK NBS to include nine conditions means added pressure for a cost effective approach to communication of NBS+ results.
As most infants will be asymptomatic when parents receive the NBS+ result(1, 2), it is vital that communication is done carefully to avoid potential negative effects on future concordance with treatment and relationships with health professionals(4,5,11-13). Concordance and trust are important(14) to ensure timely uptake of confirmatory diagnostic testing and instigation of necessary treatment to maximise outcomes for the child(1,2). Poor communication can affect parent-child bonding and ongoing parental and social relationship | 0 | City, University of London | EC1V 0HB | England | 10 January 2017 | 30 September 2020 | £425,752 | Reproductive Health and Childbirth; | 8.1 Organisation and delivery of services; | 0 | 0 | 0 | 4 | thalassaemia|cystic fibrosis|sickle cell|sickle-cell | 4 | Rare hematologic disease; Rare respiratory disease | Researcher Led | Yes | ||||||||||
20 | NIHR PROG | Artificial Intelligence | AI_AWARD01815 | A fully automated ultrasound tool to screen for fetal growth restriction in the first trimester | Background: Fetal growth restriction (FGR) secondary to utero-placental insufficiency is the single greatest cause of stillbirth. An effective first-trimester screening test would identify those pregnancies at high-risk thereby targeting NHS ultrasound resources towards those at most risk of FGR, enabling early identification and delivery before stillbirth occurs. FGR can be predicted at 11-13 weeks using placental volume (PlVol) and vascularity but no method is currently available to estimate these metrics which can be used in a population-based screening test. Aim: To generate a prototype OxNNet Toolkit which can automatically generate placental metrics from a 3D-US scan.These can be combined with other known risk factors and blood results to generate a multi-factorial screening test for FGR. Project plan: Producing the OxNNet Toolkit involves three work packages; To incorporate OxNNet, novel vascular metrics and techniques for removal of artefacts into a single software pac | Background Every baby has an inherent growth potential which, with good maternal health and a well-functioning placenta, can usually be achieved. Failing to reach the appropriate size is called Fetal Growth Restriction (FGR ) and it can lead to a very poor outcome for the baby. FGR is the single most common cause of stillbirth, which devastates 8 families a day in the UK, it is also associated with pre-term birth and cerebral palsy. FGR is not currently preventable but spotting it early allows timely delivery thereby preventing the baby from dying before birth. Therefore, identifying pregnancies at risk of FGR should reduce stillbirth. FGR babies usually have small placentas and the placenta is already abnormally small at the time of the dating scan (c.11-13 weeks). We have developed a method that can provide reliable measurements of placental size in the first-trimester as well as estimate the blood flow within it. This can form the basis of a population-based screening test for FG | 0 | University of Oxford | OX1 2JD | England | 10 January 2020 | 31 December 2021 | £142,942 | Reproductive Health and Childbirth; | 4.1 Discovery and preclinical testing of markers and technologies; 7.3 Management and decision making; | 0 | 0 | 0 | 1 | placental insufficiency | 1 | Rare cardiac disease | Researcher Led | Yes | ||||||||||
21 | NIHR PROG | Technology Assessment Review | 17/46/12 | Caplacizumab for treating acquired, acute thrombocytopenic purpura [ID1185] | To appraise the clinical and cost effectiveness of caplacizumab within its marketing authorisation for treating adults experiencing an episode of acquired thrombotic thrombocytopenic purpura. | Thrombotic thrombocytopenic purpura (TTP) is a rare blood disorder that causes blood clots in small blood vessels. These blood clots cause damage to internal organs and red blood cells, by blocking small blood vessels and can result in a very low blood platelet count, breakdown of red blood cells, and organ failure of varying severity. TTP can present as an acute life-threatening disorder requiring prompt diagnosis, early referral and effective immediate management.
TTP is caused by the inactivation of an enzyme called ADAMTS13 which breaks down large von Willebrand factor multimers. When ADAMTS13 levels are very low, the ultra-large von Willebrand factor multimers can cause a thrombotic microangiopathy that is, damage to small blood vessels in vital organs (typically the brain, the heart, and kidneys). If left untreated, acquired TTP can lead to lack of oxygen to tissue in vital organs, loss of function of organs and can be fatal. People who recover from an acquired TTP episode can h | Batch 55 | University of Exeter | EX4 4QJ | England | 10 October 2019 | 13 May 2020 | £65,625 | Blood, | 6.1 Pharmaceuticals, | 0 | 1 | rare blood | 0 | 4 | thrombotic thrombocytopenic purpura|acquired ttp|acquired thrombotic thrombocytopenic purpura|thrombotic microangiopathy | 5 | Rare hematologic disease; Rare circulatory system disease | Commissioned | Yes | |||||||||
22 | NIHR PROG | NIHR Fellowships | DRF-2015-08-065 | Novel applications of magnetic resonance imaging for the evaluation of portal hypertension and liver function | Background Liver-related deaths increased 4-fold in the United Kingdom since 1970, despite all other causes of death declining. Portal hypertension and liver dysfunction are major causes of liver mortality and morbidity, including oesophageal variceal bleeding, ascites and hepatic encephalopathy. Portal pressure is usually measured using invasive venous catheterisation to measure the hepatic venous pressure gradient (HVPG) and oesophageal varices are assessed by gastroscopy. Non-invasive, cheaper, safer methods of assessment are needed. A non-invasive, novel magnetic resonance imaging (MRI) technique created in Oxford accurately evaluates liver fibrosis, fat and iron content, as an alternative to liver biopsy. We propose additionally to develop new candidate predictors of portal hypertension and liver biochemical function. T1 relaxation time is an intrinsic property of tissues affected primarily by extracellular water content. Oxford researchers find that native spleen T1 has excellent | Background Liver-related deaths have increased 4-fold in the United Kingdom since 1970, despite a decline in all other causes of death. Liver disease particularly affects people of working age. Liver disease causes progressive accumulation of scarring in the liver, which in turn leads to increased resistance to blood flow through the liver. This causes congestion and raises the pressure in the veins that carry blood from the gut and spleen to the liver (portal hypertension). Also, as liver disease progresses, more liver cells die, so the liver is not able to carry out its vital biochemical functions properly (liver dysfunction). Liver dysfunction and portal hypertension cause the majority of problems in the later stages of liver disease. Measures of portal hypertension are known to predict liver-related complications and death. To date the most accurate tests to assess portal hypertension require invasive procedures (e.g. passing wires from the neck to the liver vein). These are uncomf | 0 | University of Oxford | OX1 2JD | England | 9 January 2015 | 31 August 2018 | £423,555 | Oral and Gastrointestinal; | 4.2 Evaluation of markers and technologies; | 0 | 0 | 0 | 2 | primary biliary cirrhosis|hepatocellular carcinoma | 2 | Rare hepatic disease; Rare neoplastic disease | Trainee Development | Yes | ||||||||||
23 | NIHR PROG | Integrated Academic Training Programme | CS-2013-13-017 | Improving clinical phenotyping of interstitial lung disease for better diagnosis and disease management | Background: Interstitial lung disease (ILD) is an important cause of morbidity and mortality that results in almost 10 000 hospital admissions and over 5000 deaths in the United Kingdom each year.Whilst approximately two thirds of individuals with fILD fulfil a specific clinical diagnosis (most commonly either idiopathic pulmonary fibrosis (IPF) or connective tissue disease(CTD)). However, a third of patients have either unclassifiable disease or disease of unknown aetiology. For these patients prognosis is difficult to predict and best therapy remains to be defined. This issue is of significant clinical importance following the emergence of specific anti-fibrotic therapies and with the knowledge that immunosuppression is harmful in some patients with ILD (i.e. IPF) Aims: This research will examine strategies for better diagnosing ILD and will deliver a proof of concept study of anti-fibrotic and anti-inflammatory therapy in unclassifiable disease to better define best treatment for th | The interstitial lung diseases (ILDs) are characterised by inflammation or scarring that damages the air sacs in the lung. Current methods of diagnosing ILD are limited and fail to identify the cause of disease in upwards of a third of patients with the condition. Consequently, individuals with unclassifiable disease live with an uncertain prognosis and a lack of available treatments. This study will re-evaluate traditional diagnostic approaches in ILD and, by means of a clinical trial of anti-fibrotic and anti-inflammatory therapy combined with novel molecular research techniques will seek to improve diagnostic approaches and therapeutic strategies for this patient group. | 0 | Imperial College of Science, Technology and Medicine | SW7 2AZ | England | 3 January 2014 | 28 February 2019 | £969,312 | Respiratory; | 4.2 Evaluation of markers and technologies; | 0 | 0 | 1 | interstitial lung disease | 3 | idiopathic pulmonary fibrosis|interstitial lung disease|ctd-ild | 3 | Rare respiratory disease | Trainee Development | Yes | |||||||||
24 | NIHR PROG | NIHR Fellowships | DRF-2015-08-076 | Improving outcomes through development and implementation of Core Outcome Sets in paediatric surgical research | Objectives The ability of paediatric surgeons to counsel parents, obtain informed consent and develop evidence-based management guidelines for key conditions is limited by the paucity of research that has sufficient statistical power and methodological quality to address the impact of interventions on outcomes of interest to patients, parents and service providers(Allin 2014). The objective of this fellowship is to investigate methods for addressing these deficiencies, and in doing so, develop an evidence base for best clinical practice in paediatric surgery in the UK. Key objectives: Increase patient relevance and improve synthesisability in Hirschsprung's disease (HD) and gastroschisis research through development of core outcome sets (COS) to assess surgical treatment of these conditions. Perform a nationwide, multi-centre cohort study investigating the impact of choice of surgical intervention on core outcomes at six years of age in infants with HD. Perform an international, multi- | How can research be improved to help paediatric surgeons deliver the best treatments for children they care for? Paediatric surgeons treat children from birth to age 16 who have a problem that may need an operation, e.g. appendicitis or a hernia. Many of the conditions that they treat however, like Gastroschisis (where the babies are born with their bowels outside their body), and Hirschsprung's disease (where the infants' bowels do not work properly) are rare, and there has been little high-quality research trying to determine the best treatments. Using these conditions as examples, I plan to investigate methods for improving the quality of paediatric surgical research, and in doing so, make sure that every child receives the best possible treatment for their condition. Most research in surgery tries to work out whether one type of treatment is better than another. One way of doing this is to compare children who have had the two different treatments, and look at different things that | 0 | University of Oxford | OX1 2JD | England | 10 January 2015 | 30 September 2018 | £380,002 | Oral and Gastrointestinal; | 6.4 Surgery; 8.4 Research design and methodologies; | 0 | 0 | 0 | 2 | gastroschisis|hirschsprung's disease | 2 | Rare developmental defect during embryogenesis; Rare gastroenterologic disease | Trainee Development | Yes | ||||||||||
25 | MRC | MRC SIEBEL | G0900887/1 | Antisense nucleic acid splice correction therapy for Duchenne muscular dystrophy and related disorders | Experimental nucleic acid based therapies are being intensively investigated as novel strategies for currently untreatable human disease. This Programme aims to develop a detailed molecular understanding of the chemical biological requirements for long-term, targeted, functional and phenotypic antisense oligonucleotide (AO)-mediated splice correction in mouse models of Duchenne muscular dystrophy (DMD). DMD is a fatal muscle degenerative disease and AO mediated splice correction of the DMD pre-mRNA has the potential to treat approximately 75% of DMD patients and has been shown to be well tolerated with therapeutic efficacy in two recent Phase I clinical trials. A critical challenge now in the development of this approach is the need for long-term, targeted, high efficiency systemic correction of the DMD phenotype. In this Programme beginning with state-of-the-art AO-peptide conjugates (B-PMO and B-MSP-PMO) we will study long-term correction of the muscle and cardiac physiological pheno | Degenerative diseases cause increasing medical and social burdens in aging Western societies. Few of these diseases are treatable and therefore it is vital that new types of therapies are developed. In this research we will study Duchenne muscular dystrophy (DMD), a common, X-linked inherited, degenerative disease of muscle caused by lack of the protein dystrophin, and that is uniformly fatal and currently untreatable, typically leading to the deaths of affected boys in their 20s. We will investigate a new type of gene therapy for DMD, which has already shown promise in two preliminary clinical trials in DMD patients. The therapy, called exon skipping, uses small DNA patches known as antisense oligonucleotides (AOs) to correct the effects of mutations in the dystrophin gene, thereby producing new dystrophin protein of near-normal function and correcting the harmful effects of the disease. The recent clinical trials tested the application of this method in single muscles and therefore o | Mdx Mouse, Morpholino, Peptide-conjugate, Duchenne Muscular Dystrophy, Splice Correction, Exon Skipping, Oligonucleotide | University of Oxford | OX1 2JD | United Kingdom - England | 1 January 2011 | 31 August 2016 | £1,500,712 | Cardiovascular; Musculoskeletal | 5.2 Cellular and gene therapies | 0 | 0 | 2 | duchenne muscular dystrophy|muscular dystrophy | 2 | duchenne muscular dystrophy|muscular dystrophy | 2 | Rare neurologic disease | Research Grant | Programme Grant | Researcher Led | Response Mode | Population and Systems Medicin | Yes | |||||
26 | NIHR PROG | NIHR Fellowships | DRF-2012-05-166 | Vulval Erosive Lichen Planus: Is systemic treatment better than topical alone for long-term disease control? Designing and performing a pilot multi-centre randomised controlled trial. | Training Award | Erosive lichen planus affecting the vulva (ELPV) is a persistent painful condition that is hard to treat. There is no good evidence on which to base treatment. This project will involve patients and clinicians to design and subsequently run a pilot study in preparation for a full randomised controlled trial. The trial will aim to find the most effective and safe tablet treatment for patients with ELPV who haven't responded to creams or ointments. This project will add to existing knowledge, contribute towards the development of evidence-based treatment guidelines and help to improve the quality of life of patients with ELPV. | 0 | University of Nottingham, The | NG7 2RD | England | 10 January 2012 | 31 May 2017 | £318,468 | Inflammatory and Immune System; Skin; | 6.1 Pharmaceuticals; | 0 | 0 | 0 | 0 | 0 | Trainee Development | Yes | ||||||||||||
27 | NIHR PROG | HEE/NIHR Integrated Clinical Academic Programme | ICA-CDRF-2016-02-014 | Dietary intervention to improve glycaemic control in young people with cystic fibrosis and altered glucose handling: A feasibility study. | Cystic fibrosis-related diabetes (CFRD) is an important complication of CF, affecting up to 50% of adults with CF. The combination of diabetes and CF is associated with increased morbidity and mortality and early abnormalities in glucose handling contribute to deterioration in clinical status. A high-fat, high-sugar diet is standard management in CF to maintain weight. However in altered glucose handling, high sugar intakes cause hyperglycaemia, which causes deterioration of lung function and increases mortality. Dietary treatment for CF and diabetes is conflicting. The high-fat, high-sugar CF diet is contrary to the low-sugar, low-fat diet advocated for diabetes management. In practice, this conflict is typically resolved in favour of the standard CF diet, resulting in poor glycaemic control in patients with altered glucose handling. CFRD dietary therapy must control glycaemia and meet the increased energy requirements of CF, but there is limited evidence to guide practice. Manipulati | Cystic fibrosis (CF) is an inherited, life-limiting condition in which the lungs and digestive systems become progressively blocked with thick, sticky mucus. People with CF are living longer due to improvements in the treatments available. However this means that complications caused by CF are being increasingly seen. Most people with CF have some degree of abnormal blood sugar control and this worsens with age, eventually leading to CF-related diabetes. This is a unique type of diabetes that affects up to half of all adults with CF. The combination of CF and diabetes is known to cause worsening lung function, weight loss and ultimately reduces life expectancy.Nutrition is very important in CF and body weight is a predictor of survival. Reduced lung function and chronic infection lead to increased energy requirements. This means an energy dense diet, typically high in fat and sugar, is recommended to maintain weight. However, in individuals with abnormal blood sugar control or CF-relat | 0 | University of Bristol | BS8 1QU | England | 6 January 2017 | 30 November 2021 | £307,747 | Congenital Disorders; | 4.2 Evaluation of markers and technologies; 6.7 Physical; | 0 | 0 | 1 | cystic fibrosis | 1 | cystic fibrosis | 1 | Rare respiratory disease | Trainee Development | Yes | |||||||||
28 | NIHR PROG | NIHR Fellowships | DRF-2015-08-190 | Sarcoidosis and Fatigue: A feasibility study of the treatment of fatigue in sarcoidosis with methyphenidate | Background Fatigue in sarcoidosis is a common and important problem for patients, and a difficult symptom to treat. It occurs independently of disease activity. Fatigue significantly impairs the quality of life of patients, many of whom are of working age. I have conducted a cross-sectional questionnaire study of 76 patients with sarcoidosis in Norwich, which showed that 50.7% had clinically relevant fatigue compared to 8.6% of 76 age-matched controls using the Fatigue Assessment Scale (FAS), and that higher levels of fatigue leads to impaired quality of life. Methylphenidate, a neurostimulant, has been shown to be effective at treating fatigue in HIV and, as evidenced in a Cochrane review, post-chemotherapy for various cancers. Case histories and one small cross-over study have suggested that methylphenidate can improve fatigue in sarcoidosis and is well-tolerated, but data is limited. In order to design a viable RCT investigating methylphenidate in treating sarcoidosis-associated fat | Many patients with sarcoidosis suffer from extreme tiredness for which there is no treatment. This trial investigates whether it will be possible to undertake a large-scale study to tell whether a drug called methylphenidate (Ritalin) is helpful for patients with sarcoidosis suffering from tiredness. Methylphenidate is used to help exhausted patients in other conditions. Patients will receive treatment with methylphenidate or an identical dummy tablets for 6 months. Tiredness and quality of life will be measured using questionnaires, with activitymeasured using a motion sensor and a walking distance test. We will measure how many patients agree to help, whether they finish the study, and whether they are able to complete the assessments. Assessment of increases in activity levels with any improvements in tired ness will also be recorded, and participants will be asked to describe how they have perceived improvements in fatigue through discussionhs held in focus groups at the end of the | 0 | University of East Anglia | NR4 7TJ | England | 10 January 2015 | 30 September 2018 | £350,509 | Inflammatory and Immune System; | 6.1 Pharmaceuticals; | 0 | 0 | 1 | sarcoidosis | 1 | sarcoidosis | 1 | Rare systemic or rheumatologic disease | Trainee Development | Yes | |||||||||
29 | NIHR PROG | HEE/NIHR Integrated Clinical Academic Programme | ICA-CDRF-2018-04-ST2-042 | A mixed methods exploration of early feeding in children with repaired trache-oeosophageal fistula and oesophageal atresia. | Background Trache-oesophageal fistula (TOF) and Oesophageal atresia (OA) are congenital abnormalities affecting 1 in 3500 live births in the UK. Improved surgical techniques have increased survival to over 90%. However, life-long respiratory, gastrointestinal and feeding morbidities exist. Little data exists that informs healthcare practitioners about the exact nature, extent or impact of the feeding difficulties. Aim To characterise feeding and swallowing skills and difficulties in babies and young children with repaired TOF/OA and their impact on parents. Objectives To investigate the nature of pharyngeal and oesophageal stage dysphagia in children under 1 year of age. To identify factors associated with feeding outcome at 1 year of age. To describe parental experiences of establishing feeding and mealtimes in children with TOF/OA. To determine how feeding difficulties associated with TOF/OA impact on parental quality of life and well-being. To inform design of future large-scale | Aims To describe the swallowing abilities of babies born with trache-oesophageal fistula and/or oesophageal atresia. To understand what factors contribute to a baby having feeding difficulties as a result of a trache-oesophageal fistula and/or oesophageal atresia. To understand how parents are impacted by the feeding difficulties of their baby with trache-oesophageal fistula and/or oesophageal atresia. Background A trache-oesophageal fistula (TOF) is an abnormal connection (a fistula) between the windpipe (trachea) and the food pipe (oesophagus). Oesophageal atresia (OA) occurs when the food pipe has not joined properly during foetal development, resulting in a gap between the upper and lower ends.In the UK approximately 300 babies a year are born with TOF and/or OA, 90% are born with both. These conditions are often not identified until the baby is born and starts to feed. As a result of the fistula, swallowed milk can enter from the food pipe into the windpipe and then enter the l | 0 | Great Ormond Street Hospital for Children NHS Foundation Trust | WC1N 1EH | England | 5 January 2019 | 31 July 2024 | £271,160 | Oral and Gastrointestinal; | 7.1 Individual care needs; 8.4 Research design and methodologies; | 0 | 0 | 1 | oesophageal atresia | 1 | oesophageal atresia | 1 | Rare developmental defect during embryogenesis | Trainee Development | Yes | |||||||||
30 | MRC | MRC SIEBEL | G1100236/1 | The International DSD Network (I-DSD) | Disorders of sex development (DSD) include a range of rare diseases that pose a clinical challenge because of poor standardization and understanding of the value of diagnostic investigations, differences in clinical practice and a gap in knowledge about the links between aetiology, clinical practice and long-term clinical outcome. Recent advances in information, clinical and basic sciences coupled with a greater drive for multicentre collaboration have raised the prospects for managing patients with these conditions. However, there is a need to harness all these initiatives so that common goals can be defined and reached. For DSD, this has already started to occur through regional and national networks of clinical and research excellence and more, recently, through the EuroDSD programme of research (www.eurodsd.eu). The European DSD Register funded initially by the European Society of Paediatric Endocrinology (www.eurospe.org), and, subsequently by EUFP7, is a cornerstone of th | Development of the sex organs is a very complicated process and sometimes it does not occur as planned. It is not completely clear as to how often the problem occurs but we think that for every 250 children born there may be one affected child. The severity of the problem varies, with the more severe problems happening much less often. Some may need to undergo tests so that we can find out more about the condition and some may need one or more operations. The need for these procedures may vary from one affected person to another. In addition, these conditions are often managed in slightly different ways in different places and it is not clear whether these differences in practice are important. To improve and maintain the best standard of practice we want to keep a brief and secure record of some of the affected persona??s care and from time to time invite the affected person to take part in studies which have been approved by hospitals. Some conditions are very rare and the only way w | NULL | University of Glasgow | G12 8QQ | United Kingdom - Scotland | 12 May 2011 | 10 April 2017 | £528,128 | Reproductive Health and Childbirth | 2.6 Resources and infrastructure (aetiology); 6.9 Resources and infrastructure (evaluation of treatments) | 0 | 1 | rare disease | 0 | 0 | 1 | Research Grant | Partnership Grant | Researcher Led | Response Mode | Pop & Systems Medicine Board | Yes | |||||||
31 | MRC | MRC LIS | MC_PC_12041 | Low-dose Intravenous Immunoglobulin Treatment for Complex Regional Pain Syndrome (‘LIPS’) Randomised Controlled Trial. | Research design: Randomised, double-blinded, placebo controlled parallel trial with an open single- dose extension. Study Population: Adult patients with Complex Regional Pain Syndrome of 1-5 years duration, and a pain intensity of >4 on an 11-point numeric rating scale (NRS). Excluded are patients with other significant chronic pains, unstable medical conditions, rare IVIG contraindications, or who are pregnant or breastfeeding. Planned interventions: Patients are randomised (online block-randomisation with stratification to study site and pain intensity) to receive either 0.5g/kg intravenous immunoglobulin (IVIG), or an equal volume of placebo (0.1% Albumin in Normal Saline), with a second infusion three weeks later. After six weeks, patients can choose to receive a one off dose of 0.5g/kg IVIG openly. Proposed outcome measures: Primary outcome: NRS 24h average pain intensity over 37 days (study days 6 - 42); secondary outcomes: pain interference and quality of life; additional explo | Complex Regional Pain Syndrome (CRPS) arises after injury to a limb. Patients experience ongoing, severe pain, out of proportion to the injury. The pain can eventually get better. However, unfortunately in every 7th patient (15%) the pain is unrelenting even after one year. If the pain lasts that long it is less likely to get better later. The quality of life of these patients is very poor. They cannot use the affected limb, and only a few can return to work. Unfortunately, we do not know why CRPS occurs. There are currently few treatments, and for many patients no treatment works.We propose to test a new treatment. We have recently shown in a small study, that a drug called intravenous immunoglobulin (IVIG) can profoundly reduce pain from CRPS. IVIG had only few side effects. IVIG treats the immune system. Our study only had 13 participants. We now wish to find out with more confidence whether IVIG is indeed effective, and how effective it is. This information is needed so that IVIG-t | NULL | NULL | University of Liverpool | L69 3BX | United Kingdom - England | 12 January 2012 | 31 July 2016 | £333,851 | Neurological | 6.1 Pharmaceuticals | 0 | 0 | 1 | complex regional pain syndrome | 1 | complex regional pain syndrome | 1 | Rare neurologic disease | P&Cs | Partnership & Contribution | MRC Strategic | Translation | EME | Yes | ||||
32 | MRC | MRC LIS | MC_PC_13052 | Vertebrate Limb Development 2 | Limb defects are the second most common congenital abnormality present in human live births and diseases affecting the musculoskeletal system are a significant clinical problem, particularly in the older population. The goal of our work is to understand how the limbs form normally during embryogenesis and the genesis of limb abnormalities and diseases that affect the musculoskeletal system in humans. ||Limbs are formed from specific regions of the flank of the embryo. At early stages of embryonic development, the forelimb and hindlimb buds are morphologically uniform and indistinguishable from one another. During subsequent steps of development however, dramatic changes take place. Each bud develops to form a network of interconnected limb elements e.g. bones, muscles, and tendons-with morphologies characteristic of either the forelimb or hindlimb. We are using vertebrate animal models to understand the mechanisms that control the initiation of limb bud formation and the subsequent con | Abnormalities in normal heart formation are the most common birth defect, occurring in 1 in 120 live births. If uncorrected, these defects can have serious debilitating effects on quality of life and in severe cases lead to premature death. Other less life-threatening birth defects also dramatically decrease quality of life in affected individuals. Among these, limb defects are the most common. We are interested in studying the causes of two human syndromes that lead to serious abnormalities in normal heart and limb formation. Patients with Holt-Oram Syndrome (HOS) have severely malformed hearts and limbs and those with Ulnar-Mammary Syndrome (UMS) are afflicted with abnormal limb and mammary gland development.|In each syndrome the corruption of the genetic information in a single gene is sufficient to cause all of the associated abnormalities. Armed with this knowledge of the exact genetic cause of each syndrome we propose to investigate the underlying biology of these diseases. Using | NULL | Vertebrate embryonic development, chick, mouse, limb development Tbox genes, transgenic, human congenital defects | King's College London | SE1 3QD | United Kingdom - England | 10 January 2013 | 31 August 2017 | £951,068 | Musculoskeletal; Congenital Disorders | 2.1 Biological and endogenous factors; 1.1 Normal biological development and functioning | 0 | 0 | 0 | 2 | holt-oram syndrome|ulnar-mammary syndrome | 2 | Rare developmental defect during embryogenesis | P&Cs | MRC Institute | MRC Strategic | Institutes | NIMR Transfer | Yes | |||||
33 | NIHR PROG | Invention for Innovation | II-LA-1116-20003 | Xeroderma Pigmentosum: Codesign and testing of a specialised visor for ultraviolet radiation protection | There are four interdependent Work Packages (WP) with discrete deliverables (Appendices 4 Gantt Chart/5 Flowchart). WP1. Co-Design – iterative visor development with patients/parents/clinicians; patient-recorded outcome measures Health Research Authority (HRA) approvals for co-design events and non-UVR exposed patient/surrogate tests. PPI events, supporting WP2. Co-design events/contacts for iterative visor development and the patient-recorded outcomes (TELER methodology). Milestone: HRA approvals for co-design/testing activities (30 month project) (Month 1-6). Milestone: Qualitative data on visor designs; patient-recorded outcome measures, developed with patients, (Month 7-15). Deliverables: 1.1 Co-design report on patient needs and iterative development of the photoprotection visor. 1.2 Patient-recorded outcomes for the visor, developed and validated with the patients/parents using TELER methodology (Appendix 6). Patient-specific cost data will be collected including resource | Xeroderma Pigmentosum (XP) is a rare, inherited, incurable condition affecting approximately one in 250,000 of the general population. People with XP cannot tolerate ultraviolet radiation (UVR) from natural light, not just sunshine. We cannot see or feel UVR, but it can cause normal cells to become cancerous. With XP, miniscule exposure can cause skin and eye cancers from around the age of eight. Life expectancy is around 32 years; skin cancer is the main cause of death. Preventing skin and eye cancers requires absolute protection from UVR. Protective films are applied to car windows, homes, schools, and offices. Outdoor activity requires full cover-up with clothing and headwear, even on a cloudy day. Clothing is purchased. Headwear is homemade. Patients and families say the headwear steams-up, interferes with seeing, talking, and they receive unkind comments on their appearance. Many avoid all of this by not covering up, with disastrous consequences including eye damage/visual impairm | 0 | King's College London | SE1 8WA | England | 12 January 2017 | 30 November 2020 | £753,207 | Cancer and neoplasms; Skin; | 3.2 Interventions to alter physical and biological environmental risks; | 0 | 0 | 1 | xeroderma pigmentosum | 1 | xeroderma pigmentosum | 1 | Rare skin disease | Researcher Led | Yes | |||||||||
34 | MRC | MRC LIS | MC_PC_16036 | Cortical microcircuiltry after traumatic brain injury: molecules to networks | Traumatic brain and spinal cord injury lead to severe motor, sensory and cognitive dysfunctions, which are then followed by a variable recovery in performance. The acute functional deficits depend on the injury severity and extent of neuronal and connectivity loss (deLanerolle et al., 2015). Direct severing of neuronal processes by the mechanical forces set forth detrimental consequences of pathogenic cascades, such as signaling cascades and inflammation. On the other hand, the recovery phase depends on the compensatory and repair responses attributed to the spontaneous circuit connectivity rearrangements that take place after neurotrauma. In a partial spinal cord injury model, sprouting of existing supraspinal and propriospinal connectivity, as well as the formation of new detour connections to input-deprived neurons are fundamental in triggering the recovery of effective locomotor function. Notably, this remodeling of local and long-range connectivity is critically dependent on a spe | Traffic accidents, accidental falls and violent attacks may result in the damage to a person’s brain: the ability to move, feel, speak, form memories and judgments can be lost at once. Repairing this damage is often beyond our current therapeutic abilities. Nerve cells become disconnected following the impact and parts of the brain become unable to communicate with each other. Yet some cells manage to establish new contacts and some level of recovery can arise although it is never complete. Which nerve cells are important for recovery? What happens to those disconnected cells, and why some do some succeed and others fail at making new connections? Are memories, movements, and feelings lost beyond repair, or can we restore lost functions? We have to answer these questions to improve the condition of those patients for whom there are few treatment options. In this project, we will use the most advanced technologies available for visualizing how and when nerve cells lose connections aft | NULL | Neural circuits, traumatic brain injury, Motor circuits, Mouse genetics, Viral vectors | MRC Laboratory of Molecular Biology | CB2 0QH | United Kingdom - England | 2 January 2017 | 30 April 2020 | £151,970 | Neurological | 2.1 Biological and endogenous factors | 0 | 0 | 0 | 1 | spinal cord injury | 1 | Rare neurologic disease | P&Cs | Partnership & Contribution | MRC Strategic | Strategic Calls | MRC ERA-Net | Yes | |||||
35 | MRC | MRC LIS | MC_PC_18030 | ISCF HDRUK DIH Sprint Exemplar: Cloud-based integration of phenotype and genotype data for rare disease research | In depth phenotyping, including pathology and imaging technologies, and innovations in genomics, including whole genome sequencing, have led to remarkable progress in understanding rare diseases. These are commonly genetic and collectively affect around 7% of the population. Maximising the benefits of these advanced technologies requires integration of multi-dimensional data in a secure environment for analysis at scale. Using tools developed by Public Health England for national disease registration and FHIR we will create a clinical, phenotypic and genomic dataset integrated in Microsoft Azure. We will provide proof of principle that can be extended to other datasets by using data from patients with rare diseases recruited to the NIHR BioResource. These patients have consented to be contacted about academic and industry led research studies according to their genotype and phenotype, and for their data to be used in medical research. Two factors limit the power of this resource. Curre | One in 17 people have a rare disease. Rare diseases can be extremely difficult to diagnose, but they often have an unidentified genetic cause. Recent advances in clinical imaging, pathology, and genomic technologies have led to remarkable progress in understanding disease - particularly rare diseases. However, the power of these technologies cannot be fully realised until the immense volume of data generated can be integrated with NHS data, then analysed by researchers in a secure environment that protects the privacy of individuals. Working across the NHS, academia and industry we will use existing tools to transfer data from NHS Trusts to a secure environment that interfaces with the NHS network and shares data with Public Health England. NHS information will then be combined with research data in a cloud-based platform. Initially, we will involve patients with rare diseases recruited to the NIHR BioResource; a national resource of volunteers who have already provided consent that i | The overall goal of this award is to develop the methodology and infrastructure to allow the exchange and integration of routinely collected NHS data and research data, and provide an information ecosystem that supports academia, the NHS and industry. In this exemplar project, proof of principle will be provided for a model that is replicable within the Digital Innovation Hub community and demonstrate its utility. The specific aims are: • to integrate health and research data from patients with rare diseases recruited to the NIHR BioResource, who have their whole genome sequence and Human Phenotype Ontology data held in separate research databases, and have consented for information from their health records to be held in a research database; • to derive NHS data from two sources: (1) NHS Trusts, with an initial focus on digital pathology reports and digital images, and (2) Health Episode Statistics (HES) data from NHS Digital; • to demonstrate proof of principle by initially collec | Cloud computing, rare diseases, phenotyping, genomics, digital innovation, digital healthcare | Cambridge University Hospitals NHS Foundation Trust - HDRUK | CB2 0QQ | United Kingdom - England | 2 January 2019 | 30 November 2019 | £399,400 | Generic Health Relevance | 6.9 Resources and infrastructure (evaluation of treatments); 5.9 Resources and infrastructure (development of treatments); 4.5 Resources and infrastructure (detection); 2.6 Resources and infrastructure (aetiology); 8.5 Resources and infrastructure (health services); 7.4 Resources and infrastructure (disease management) | 1 | rare disease | 2 | rare disease|rare gene | 0 | 1 | pulmonary arterial hypertension | 3 | Rare respiratory disease | P&Cs | Partnership & Contribution | MRC Strategic | Strategic Priorities Fund (SPF) | ISCF D2EDPM Digital Innovation Hub Programme - Sprint Exemplar Projects - HDRUK | Yes | |||
36 | NIHR PROG | Invention for Innovation | II-SA-0712-20001 | Development and prototyping of improved surgical devices for management of anal fistula | The project plan derives from a partnership of expert users (colorectal surgeons) and design-engineers (Renfrew Group International). A milestone driven plan will comprise several well-defined stages which will take the product from concept drawings through to handover to high volume production. Stage 1: Diagnosis Observational analysis of current surgical procedures and instruments by team visits to theatres at the Royal London and St Marks' Hospitals. The team will be familiarised with the current problem, initial proposed solutions (as herein contained) and main anatomical and anthropometric data; refinement of the brief on this basis will follow. Further detailed searches of existing IP will be performed and reported and a strategy to avoid infringement agreed. Suppliers of currently used equipment will be contacted if necessary. The defined problem, considering other procedures and instruments, methods for construction of the proposed concept and solutions will be brainstor | An anal fistula is an abnormal connection between the lining on the inside of the anal canal (back passage) and the skin near the anus. Most anal fistulae are caused by an abscess (a collection of pus) just outside the anal canal which then drains away onto the skin on its own or by an operation. A fistula happens when the track, made by the pus on the way to the surface of the skin, stays open. This leads to problems such as pain, persistent discharge and ultimately damage to the anal sphincter muscles. Nearly all treatments for anal fistula involve surgery. Numerous operations exist to try and cure the fistula but these usually require division of some of the anal sphincter muscle with a subsequent risk of incontinence. Thus high fistulae (denoting those which cross a lot of muscle) cannot be safely cured and instead symptoms may be controlled by insertion of a special stitch called a seton which runs through the cleaned fistula track and allows chronic but controlled draina | 0 | Queen Mary University of London | E1 4NS | England | 3 April 2013 | 31 March 2019 | £251,074 | Oral and Gastrointestinal; | 5.3 Medical devices; | 0 | 0 | 1 | anal fistula | 1 | anal fistula | 1 | Rare gastroenterologic disease | Researcher Led | Yes | |||||||||
37 | MRC | MRC LIS | MC_U123192748 | Prion kinetics, toxicity and synthesis and its wider relevance | Prions are lethal pathogens of mammals which occur in multiple biological strains, and yet appear devoid of nucleic acid and composed of aggregated conformational isomers of a host-encoded glycoprotein. Their unique biology, allied with the risks to public health posed by prion zoonoses such as BSE, has focused much attention on understanding the molecular basis of prion propagation and pathogenesis. However, it is clear that the underlying molecular mechanisms, involving aggregation of a misfolded host protein, are of much wider significance and, indeed, analogous protein-based inheritance mechanisms are recognised in yeast and fungi. The common neurodegenerative diseases also involve accumulation of misfolded host proteins and parallels, at multiple levels, in particular with Alzheimers disease, are becoming increasingly apparent. Recent advances suggest that prions themselves are not directly neurotoxic, but rather their propagation involves production of toxic species which may be | Prions are germs that cause fatal brain diseases like CJD in humans and BSE (mad cow disease) in cattle. Unlike bacteria or viruses they do not carry their own genes but are made up of rogue forms of one of our own proteins, which build up in the brain as clumps. This unique biology, together with risks to public health from BSE and other prion diseases, has focused our attention on understanding how prions multiply and cause damage to brain cells. We think it is not the prions themselves that damage the brain, but rather something else that is produced when prions grow and have proposed a theory which tries to bring together and explain all we know about prions; we are now testing this to see if it holds up. To do this we have developed a new way of measuring prions. This has been done in the past by injecting material into mice. Our new method just uses mouse cells and so completely avoids having to do animal experiments. We have automated the test and it is much quicker, cheaper and | NULL | Prion, neurodegeneration, protein misfolding, Alzheimer, neurotoxicity, bioassay, cell culture, animal models, therapeutics | MRC Prion Unit | WC1N 3BG | United Kingdom - England | 4 January 2008 | 31 May 2017 | £13,663,380 | Neurological | 1.1 Normal biological development and functioning; 2.1 Biological and endogenous factors | 0 | 0 | 0 | 0 | 0 | Unit | Unit Programme | Unit Funding | Units | MRC Unit | Yes | |||||||
38 | MRC | MRC LIS | MC_PC_12039 | Rituximab for the Treatment of Fatigue in Primary Biliary Cirrhosis | BACKGROUND: Patients with the primary biliary cirrhosis (PBC) experience profound fatigue for which there is no treatment. Fatigued PBC patients describe impaired muscle function related to abnormality in cellular bioenergetics related to the presence of serum antibodies reactive with pyruvate dehydrogenase (PDH), a key mitochondrial energy generating enzyme. The function of PDH in vitro is inhibited by PDH-reactive antibodies purified from the serum of PBC patients. Proof-of-concept studies have shown that B-cell depleting therapy (Rituximab) reduces fatigue in PBC. HYPOTHESIS & AIMS: We hypothesise that the bioenergetic abnormality underpinning fatigue in PBC is a direct consequence of the in vivo actions of anti-PDH antibody. Our aim is to explore the efficacy of Rituximab in reducing fatigue severity in PBC through reduction in the release of anti-PDH and related antibodies, and associated normalisation of muscle energy generation function. This study will advance both the treatmen | Primary Biliary Cirrhosis (PBC) is a liver disease that predominantly affects females, can present for the first time at any age, and which develops over many years. It is caused by the immune system attacking the body’s own tissues. People with PBC frequently experience profound fatigue or tiredness which they liken to their “batteries running down”, and although people still want to undertake normal activities they simply lack the energy to be able to do them. This reduces quality of life, makes it difficult for people to work, and can end up with them becoming isolated in the community. At present we have no treatment for fatigue in PBC. Finding a treatment for fatigue in PBC is one of the highest research priorities identified by patient groups. We have shown that PBC patients with fatigue have an abnormality in the way they generate energy within their muscles. This appears to be associated with the presence of an antibody in the blood which is directed against an important p | NULL | NULL | Newcastle University | NE1 7RU | United Kingdom - England | 10 January 2012 | 31 December 2016 | £444,784 | Inflammatory and Immune System | 5.1 Pharmaceuticals; 6.1 Pharmaceuticals | 0 | 0 | 1 | primary biliary cirrhosis | 1 | primary biliary cirrhosis | 1 | Rare hepatic disease | P&Cs | Partnership & Contribution | MRC Strategic | Translation | EME | Yes | ||||
39 | MRC | MRC LIS | MC_U142684167 | Disorders of Sex Development | My programme is investigating the mechanisms by which signaling events impact on gene expression using cell fate determination in the embryonic mouse gonad as a model system. The “decision” as to whether an embryo develops as a male or a female is known as sex determination and in mammals this process requires expression of the Y-linked gene SRY in XY embryos to establish commitment of the gonadal primordium, in particular somatic cells, to a testicular fate. In recent years we have established a role for mitogen-activated protein kinase (MAPK) signaling in testis determination. Using a forward genetic screen in mice we identified the boygirl mutant, which causes XY gonadal sex reversal due to loss of the kinase MAP3K4. Analysis of XY gonad development in mutant embryos revealed a reduction in Sry expression at a key stage, leading to ovary development. Our studies in mice became directly disease-relevant when we collaborated with clinical geneticists and identified mutations in MAP3 | The gonads - the testis and ovary - form in the embryo during a process known as organogenesis, a very complex event controlled by a series of changes in which genes are expressed by cells, and their daughters, during development. Disorders in this process cause diseases that are debilitating and costly to our society. This project aims to identify genes functioning during gonad development and offer a way of understanding mechanisms underpinning heritable birth defects at the level of individual molecules. At a more basic level, this programme aims to understand how signaling molecules – proteins which can interpret information and carry it from one part of a cell to another – can regulate the expression of genes in the nucleus of a cell. In order to isolate and study the function of such genes we need to observe the consequences of inactivating them or altering them in a defined manner. Because a complex organ such as a gonad is built by many different types of cell interacting duri | NULL | Sexual development, disorder of sex development (DSD), mouse model, gonad, mesonephros, MAPK signaling, sexual dimorphism, gene expression, mutagenesis, epigenomics, genome editing, developmental, embryo, organogenesis | MRC Mammalian Genetics Unit | OX11 0RD | United Kingdom - England | 10 January 1997 | 31 March 2022 | £11,270,582 | Reproductive Health and Childbirth | 1.1 Normal biological development and functioning | 0 | 0 | 0 | 1 | disorder of sex development | 1 | Rare urogenital disease | Unit | Unit Programme | Unit Funding | Units | MRC Unit | Yes | |||||
40 | MRC | MRC LIS | MC_PC_21010 | Understanding skeletal diseases using human induced pluripotent stem cells | We have generated iPSCs from patients with two closely related rare skeletal dysplasias, multiple epiphyseal dysplasia and pseudoachondroplasia caused by mutations in matrix proteins, Matrilin3 (MATN3) or COMP. We have differentiated these through a mesenchymal stromal cell route to chondrocytes to produce growth plate-like cartilage pellets. Pellets from MATN3 mutant iPSCs are larger than related healthy pellets, with altered expression of cartilage matrix proteins, transcription factors (also for COMP mutants) and increased sensitivity to BMP2 . Building on this we will generate further MATN3 and COMP mutant iPSC lines, then using CRISPR-Cas9 gene editing correct and create the mutations in mutant and healthy iPSC lines respectively, to eliminate molecular changes due to other genetic factors. RNAseq will reveal aberrant molecular pathways of COMP and MATN3 mutant chondrocytes. Mutant cartilage pellets show regional differences from wt; the nature of which will be evaluated by laser | NULL | NULL | NULL | The University of Manchester | M13 9PL | United Kingdom - England | 10 January 2021 | 30 June 2022 | £88,564 | Musculoskeletal | 4.1 Discovery and preclinical testing of markers and technologies | 0 | 1 | rare skeletal | 0 | 3 | pseudoachondroplasia|multiple epiphyseal dysplasia|multiple epiphyseal dysplasia and pseudoachondroplasia | 4 | Rare bone disease | Research Grant | Research Grant | Researcher Led | Response Mode | Research Boards Jan 2018 PSMB | No | ||||
No results