1310849 / 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. 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. Treatment of relapse of nephrotic syndrome is with a further course of high dose prednisolone, further increasing the risk of side-effects. Children are kept off school, resulting in educational impairment and parental absence from work. Around 50% of children suffer frequent relapses (4 or more per year). In this situation, attempts are made to reduce prednisolone exposure using other more potent drugs e.g. ciclosporin and cyclophosphamide, which are associated with other significant side effects. It is therefore logical to attempt to reduce the frequency of relapses.
There is known to be a strong link between viral upper respiratory tract infection (URTI the common cold) and the development of relapse of nephrotic syndrome. Three previous small studies have suggested that the use of a short course of daily prednisolone at the time of URTI reduces the rate of disease relapse. The PREDNOS 2 study aims to determine whether the use of such therapy effectively and safely reduces the rate of relapse in a large population of UK children.
We will randomise 300 children with relapsing SSNS to receive either 6 days of daily prednisolone or continue unchanged on their existing therapy (the current standard of care) each time they develop a URTI over a 12 month period. We will assess the incidence of URTI related relapse of nephrotic syndrome in both study arms and look carefully for side effects of treatment. (Study due to close 31/10/2019)
1409987 / The long-term Safety and Efficacy of Biologic Therapies in Children with Rheumatic Diseases
This prospective observational cohort study aims to recruit all children with Juvenile Idiopathic Arthritis who are starting therapy with a biologic drug. A parallel cohort of children starting Methotrexate will also be collected. Recruitment and data collection will be facilitated by research nurses established in a number of key paediatric centres across the UK and in particular through collaboration with the MCRN/CLRN and its Local Research Networks (LRN). All children will be followed for a minimum of 5 years. The response to treatment will be assessed at regular intervals using the American College of Rheumatology (ACR) JIA core outcome variables, including active and joint counts, inflammatory markers, pain and disability levels. The rates of serious adverse events, defined as events resulting in death, hospitalisation, disability, or are otherwise life-threatening,will be compared with those observed in a cohort of patients receiving Methotrexate. (Study due to close 01/01/2020)
1412022 / TrialNet (LIFT)
The aim of this study is to provide long term follow up information on people who have previously taken part in a TrialNet study. Participants will be invited to join this study at the end of an intervention trial or when they are diagnosed with diabetes in either the TrialNet Natural History study or another TrialNet intervention study. The long term effects of receiving an intervention or of being diagnosed with diabetes at an early point in the disease process will be studied.
This will help fill the gaps in knowledge about what changes occur around the time of diagnosis of type 1 diabetes and beyond, and the impact of prediabetes values to post diagnosis clinical course. Study visits will be either annual or semi annual and will involve a Mixed Meal tolerance test or an oral glucose tolerance test depending on participant cpeptide and diabetes status on entry to the study. As the study is designed to give long term follow up information an end date has not been set and participants can stay in follow up as long as LIFT continues. (Study due to close 30/09/2019)
1502055 / FADES
Children with Down’s Syndrome (DS) have increased risk of autoimmune conditions where the body’s immune system attacks its own cells, such as thyroid problems, diabetes and coeliac disease (causing problems absorbing food). In DS autoimmunity is likely to be related to inherent defects in the immune system. The increased risk of diabetesrelated autoimmunity is despite a reduced prevalence of the usual genes that are seen in people who develop diabetes. Infant feeding practice has been linked to diabetes and coeliac risk with some evidence that prolonged breastfeeding is protective. We hypothesise that in infants with DS, already at increased risk, early feeding practices may be related to the development of autoimmunity. Children with DS may have difficulties with breastfeeding leading to rapid introduction of formula feeds.
There will be an initial phase (Phase 1) where we will pilot the stool collection kit.
In Phase 2, the main study, we aim to create a cohort of infants with DS recruited through the Down’s Syndrome Association (DSA) and Down’s Syndrome Scotland (DSS) to study the association between early infant feeding, infections and the development of autoimmunity. We anticipate that we will recruit 100 patients per year.
Parents will be asked to complete questionnaires at baseline detailing family history, birth history, weight, medical problems and early feeding. They will have further feeding questionnaires at 7 months and 12 months, and medical questionnaires annually until the age of 5 years. Samples would be collected at baseline including faeces, a brushing from the infant’s cheek for genotyping (looking at their DNA), a blood sample to look at autoantibody production (antibodies which act against their own cells), and a urine specimen to detect development of diabetes.
Further stool, urine and blood samples are collected at 6 months, 12 months and yearly thereafter until 5 years of age. (Study due to close 01/01/2020)
1503062 / British Society for Paediatric and Adolescent Rheumatology (BSPAR) Biologics and New Drugs Registry (BNDR) for Juvenile Idiopathic Arthritis (JIA) Patients Treated with Biological Therapies
British Society for Paediatric and Adolescent Rheumatology Etanercpet Cohort Study (BSPAR ECS) (Formerly British Society for Paediatric and Adolescent Rheumatology Biologic and New Drugs Register for Juvenile Idiopathic Arthritis Patients Treated with Biological Therapies (BSPAR BNDR)) (Study due to close 31/12/2018)
1607267 / Outcome After Selective Early Treatment for Closure of Patent Ductus Arteriosus in Pre-term Babies
Babies born prematurely commonly have a condition referred to as Patent Ductus Arteriosus (PDA). This is when the blood vessel (Ductus Arteriosus) that allows blood to bypass the baby’s developing lungs to the mother’s placenta during pregnancy remains open after birth. The word ‘patent’ here means ‘open’.
PDA is associated with a number of very serious and life threatening complications which include neurodevelopmental disability and chronic respiratory problems.
Babies who are born extremely prematurely (less than 29 weeks of pregnancy) are more likely to have a PDA. In the UK, approximately 7,000 babies are born extremely prematurely each year. Of these, 40% will have a PDA. In some the condition will disappear on its own but in others treatment is needed.
The condition can be treated with ibuprofen, but giving extremely premature babies ibuprofen can itself cause serious problems.
Medical opinion is therefore divided on how best to care for extremely premature babies. Some doctors believe it is better to treat all with ibuprofen as a precaution, but others believe it is better to wait until PDA symptoms appear. Treating all babies inevitably means some will be exposed unnecessarily to the potentially harmful side effects of ibuprofen, whilst not treating until symptoms appear may be too late as the condition may have caused irreversible damage.
Our understanding of PDA has improved over the years and it is now possible with developments in ultrasound scanning techniques to identify whether a baby has a PDA within hours of birth and if it is the sort of PDA that is unlikely to close on its own, before symptoms appear.
The aim of this study is to find out whether identifying and treating these babies improves both their short and long term health. (Study due to close 31/12/2020)
1608293 / Improving clinical practice for babies with hearing loss
Childhood hearing loss is a potentially devastating long-term condition. For this reason, all babies get a hearing test soon after birth and hearing aids are now prescribed in infancy. However, there is an urgent need for test procedures that provide information about the necessity for, and appropriateness of, hearing aids in infants. We have completed an exploratory study on 100 normal-hearing babies using a promising solution called ‘Cortical Auditory Evoked Potentials’ (CAEPs). This test measures if sounds are being detected by the brain using recording leads attached to the head. The next step is to turn these findings into a routine clinical procedure for infants with hearing loss. For example, if a CAEP cannot be detected, does this mean that the hearing aid prescription needs to change in order for the infant is hear speech and develop good communication skills?
We will:
1. measure the proportion of infants in whom we can detect a CAEP for different sounds,
2. measure the proportion of infants who complete the CAEP procedure along with how long it takes to make the measurements, and
3. interview parents and invite them to complete a questionnaire in order for us to understand how acceptable they find the procedure.
An innovative aspect of this project is the use of a mobile Hearing Research Van, a bespoke facility purchased especially for this project, because parents tell us that if we visit them, it will make it much easier for them to participate in the study.
Our team is skilled at: (i) undertaking research on infants, and (ii) introducing new developments into clinics.
By reducing the consequences of hearing loss, this project has the real potential to improve clinical practice at an earlier stage in the care pathway for infants with a potentially devastating long-term condition. (Study due to close 31/03/2020)
1705425 / TOPS- UK
In the UK a child injures their brain every 30 minutes through accident or illness. Most survive but this can have a devastating and life-long impact on the child and their family. Brain injury can affect thinking, emotion, behaviour and relationships, which can impair the child’s ability to cope with school, home life, future employment and independence. Families are also more likely to experience mental health difficulties and parental separation, which can further affect how well a child recovers.
Members of the research team have developed an internet-based treatment for children who have survived such brain injuries.This teaches problem-solving skills in response to specific everyday difficulties and is used at home for 10-16 weeks with weekly therapist support. Research on children with traumatic brain injury suggests that those who completed treatment, compared to those who were given general self-help, improved in their ability to plan, organise, problem-solve, and manage mood and behaviour. Families also experienced less stress and better mental health.
These questions remain: will the treatment have similar benefit for all types of brain injury (e.g.stroke, infection, tumour); will it have other benefits (e.g.improved quality of life) and does it offer value for money for the NHS? Before conducting a large multi-site study to answer these questions, we aim to undertake a smaller feasibility study to find out whether we can identify and recruit adolescents and families via the NHS and if they find the treatment and research measures acceptable.
We will recruit 50 adolescents with acquired brain injury and executive function difficulties, and their parents, from four NHS Trusts and randomly allocate them to receive the TOPS-UK online intervention plus usual treatment, or usual treatment only. Study duration for each family is about 9 months, with online questionnaire follow-up for all parents and children and qualitative telephone interviews. (Study due to close 31/07/2018)
1711521 / SPRING
Around 1 in 10 babies are born too early (known as preterm birth). Preterm birth rates have risen sharply in the last few decades. We do not understand why some babies are born preterm. One possibility is that babies’ and/or parents’ genes are involved. Although survival has greatly improved to over 90%, a significant number of those born very preterm (less than 32 weeks of pregnancy) develop a neurodevelopmental disorder (such as attention deficit hyperactivity disorder or autism spectrum disorder) by childhood. These neurodevelopmental disorders are also strongly influenced by genetic inheritance.
We want to understand how genetic inheritance and preterm birth work together to influence development. Some preterm birth studies suggest having biological relatives with a history of psychiatric disorder further adds risk, others suggest it might not. Other research indicates babies who are born preterm might have a pre-existing genetic anomaly. These possibilities can now be directly tested using lab genetics.
To be able to fully understand all these possibilities, we will need to eventually study thousands of babies born very preterm and obtain information about their neurodevelopmental health outcomes in childhood or later.
Here, we propose to begin answering one question and finding out how to set up a future, much larger study that will address more related questions. First, we examine in a sample of 500, if those born very preterm show an increase in rare genetic deletions and duplications (copy number variants) already implicated as neurodevelopmental genetic risks. We will also conduct an investigation with families, UK neonatal units and a broad range of scientific advisors, that will provide information needed to carry out a future, much larger genetic study of those born very preterm that can be linked to later health outcomes. (Study due to close 30/06/2018)
1711522 / ECUSTEC
Shiga Toxin producing Escherichia Coli (STEC) Haemolytic Uraemic Syndrome (HUS) (STEC HUS) follows a gut infection with Shiga-toxin producing E. coli, which causes severe (often bloody) diarrhoea. Around 1000 UK children are infected with STEC each year and ~100 of these develop STEC HUS when a toxin from STEC causes damage to small blood vessels, especially in the kidneys.
About 50-60% of children with STEC HUS need dialysis (artificial kidney support) which may last several weeks. About 2-3% of children with STEC HUS die and about 20-25% get HUS in their brain, causing fits or a stroke. Many make a full recovery, but about 25-30% will have permanent kidney damage or more rarely brain damage. Eculizumab is a drug which blocks part of the immune system called complement. Evidence suggests complement plays a role in STEC HUS, evidence also suggests eculizumab is very effective in a related condition – atypical HUS.
The ECUSTEC study aims to see if eculizumab really does make STEC HUS better. 134 children with STEC HUS will be recruited from children’s kidney units around the UK. They will receive either eculizumab or placebo (inactive medicine) soon after arriving at the unit and a 2nd dose of the same medicine a week later.
For each child we will assess how severely STEC HUS affected them (including how long they needed dialysis, any stomach operations, any heart or brain damage) and turn this into a score (severity score). Mild cases will have a low score and severe cases will have a high score. We will compare the severity score in those who received eculizumab and those who received placebo to see whether eculizumab reduces the severity of STEC HUS and by how much. (Study due to close 30/11/2020)
1802573 / Randomized, Double-Blind, Phase 3B Trial to Evaluate the Safety and Efficacy of 2 Treatment Regimens of Aztreonam 75 mg Powder and Solvent for Nebulizer Solution / Aztreonam for Inhalation Solution (AZLI) in Pediatric Subjects with Cystic Fibrosis (CF) and New Onset Respiratory Tract Pseudomonas aeruginosa (PA) Infection/Colonization
The primary objective of this study is to evaluate the safety and efficacy of a 14-day course versus a 28-day course of aztreonam for inhalation solution (AZLI) in participants with new onset Pseudomonas aeruginosa respiratory tract infection. (Study due to close 31/05/2019)
1802575 / RAACENO
Using Fractional exhaled Nitric Oxide (FeNO) measurements in breathed out air may improve asthma control. In this study we will investigate this in children with asthma. We will recruit children aged 6-16 years with a diagnosis of asthma, who currently use inhaled corticosteroids and who have had an asthma exacerbation in the previous 12 months. (Study due to close 13/10/2019)
1811710 / CF START
CF START is a national UK trial that will determine the safest and most effective antibiotic strategy for infants diagnosed with cystic fibrosis (CF). 480 CF infants will be randomly allocated either flucloxacillin prophylaxis (the current UK standard of care) or antibiotics given in a more targeted manner. The primary outcome will be the age at first growth of Pseudomonas aeruginosa from a respiratory culture (an important safety measure for families).
All outcomes will be recorded on a national CF Registry, including a number of secondary outcomes assessing effectiveness and safety. Finally at 40-48 months, a measure of respiratory function will be undertaken in a central laboratory, which will provide a clearer indication of the effectiveness of these two strategies. (Study due to close 31/01/2020)
806162 / The UK Paediatric ITP Registry
This is a registry for children with acute and chronic immune thrombocytopenia (ITP). The primary aim is to relate the long term consequences of a low platelet count to the frequency and severity of bleeding symptoms, and to the requirement for treatment. The study includes an optional quality of life survey. (Study due to close 01/04/2026)