Trial Name: Effect of Perioperative AntiHER-2 therapy on Early Breast Cancer Study – Biological phase

Chief Investigator: Professor Nigel Bundred

Trial Description: A multicentre, three group, randomised controlled trial conducted in two parts

Background: Her2 overexpression in breast cancer is associated with poorer overall survival. Anti Her2 therapy may prove vital to improving disease outcome. Trastuzumab, a monoclonal antibody and lapatinib, a dual kinase inhibitor both target Her2. This trial will determine the effects of these agents independently and in combination, alongside a control arm.

Main Outcomes: To determine the biological efficacy of perioperative anti Her2 therapies, specifically in relation to the inhibition of proliferation and/or increase in apoptosis in primary Her2 positive breast cancer patients.

Recruitment Target: 250

Status: Closed to recruitment - in follow up

CTU: The Institute of Cancer Research Clinical Trials and Statistics Unit (ICR-CTSU)

Funder: Cancer Research UK and GlaxoSmithKline/Novartis

Registration: https://www.isrctn.com/ISRCTN15004993  

Further Information: http://www.icr.ac.uk/our-research/our-research-centres/clinical-trials-and-statistics-unit

Trial Name: Evaluation of the safety of CEdiranib in the prevention of Bowel perforation in platinum-resistant Ovarian Cancer

Chief Investigator: Gordon Jayson

Trial Description: This is a single arm, phase II trial of cediranib 20mg/day with weekly paclitaxel 70mg/m2/week in patients with recurrent platinum-resistant ovarian cancer and clinical and/or radiological features indicating an increased risk of developing subacute bowel obstruction.

Background: In the UK, ovarian cancer is the fourth most common cause of female cancer death and the commonest cause of gynaecological cancer death accounting for 4,000 lives a year in the UK. The principal cause of death in ovarian cancer is malignant bowel obstruction. Because the disease causes multi-site obstruction of the bowel, surgery is seldom possible and there is a critical need to develop new treatments to stop development of bowel obstruction as effectively and safely as possible. CEBOC is the first trial that has been developed specifically to address the management of malignant bowel obstruction. CEBOC aims to take advantage of the additive effects of combining a VEGF inhibitor, cediranib, with an effective chemotherapeutic regimen, weekly paclitaxel. Subsequently, the patient can continue cediranib with the addition of an additional drug, olaparib at the point of progression.

Main Outcomes: The main objective of the trial is to determine the safety of combining cediranib with paclitaxel. Safety will be assessed by monitoring the frequency of two serious adverse events, bowel perforation and fistula. The trial will also summarise the side-effects of the treatments and how well the treatment works in terms of controlling the disease and preventing bowel obstruction.

Recruitment Target: 30

Status: Closed to recruitment and follow-up

CTU: Cardiff CTU

Funder: AstraZeneca

Registration: https://www.isrctn.com/ISRCTN38690336

Further Information: Study Contact Clare Freestone CEBOC@cardiff.ac.uk

Trial Name: A 3-Arm Randomised Phase II Evaluation of Cediranib in Combination with Weekly Paclitaxel or Olaparib Versus Weekly Paclitaxel Chemotherapy as Second-Line Therapy for Advanced/ Metastatic Endometrial Carcinoma or for disease relapse within 12 months of adjuvant carboplatin-paclitaxel chemotherapy

Chief Investigator: Gordon Jayson

Trial Description: A randomised, controlled, 3-arm, open-label, parallel group, multi-arm-multi-stage trial.

Background: In the UK there has been a 50% increase over the last 20 years in the number of women developing endometrial cancer. Most of these women are cured by surgery to remove the womb and ovaries. However, in some cases, the cancer recurs or is at an advanced stage when it is first diagnosed. In these women, chemotherapy treatment to control the endometrial cancer is often recommended. The benefits from this initial chemotherapy are often limited and more treatment may be required. Currently, there has been little research looking at new drug treatments for recurrent endometrial cancer. The COPELIA trial is evaluating 2 new tablet medications in endometrial cancer for the first time.

Main Outcomes: To determine whether the two new treatments, cediranib-paclitaxel (Arm 2) and cediranib-olaparib (Arm 3) are more effective at controlling endometrial cancer than standard paclitaxel chemotherapy (Arm 1). In addition, assess whether the two new treatment cause more or fewer side-effects than standard chemotherapy and how each of these treatments impact on the daily life of women receiving the treatment by asking trial participants to regularly complete quality-of-life questionnaires.

Recruitment Target: 129

Status: Closed to recruitment and follow-up

CTU: Cardiff CTU

Funder: AstraZeneca

Registration: https://www.isrctn.com/ISRCTN16320634

Further Information: Study Contact Clare Freestone CEBOC@cardiff.ac.uk

Trial Name: Home monitoring of creatinine in cancer patients: assessing acceptability and clinical benefit

Chief Investigator: Leanne Ogden

Trial Description: This is a single-centre, single-arm trial.

Background: Current research suggests that people with reduced kidney function may have an increased risk of cancer, for reasons that are not clear. When patients with reduced kidney function develop cancer, the treatment options can be limited due to concerns over causing more damage to already damaged kidneys and because cancer drugs haven’t been tested in this type of person. Currently, cancer clinical trials exclude people with reduced kidney function from taking part. This can lead to further reduction in treatment options for people with reduced kidney function and cancer. This study aims to see if monitoring kidney function more frequently in people receiving anti-cancer treatments (that can affect the kidneys) picks up problems with the kidneys quicker and whether it is acceptable to patients to monitor their kidney function in this way at home.

Main Outcomes: To assess the feasibility and acceptance of patients measuring at home. To understand the potential for earlier diagnosis of changes in renal function through intensive home-monitoring.

Recruitment Target: 72

Status: Active - recruiting

CTU: The Christie NHS Foundation Trust

Funder: University of Manchester; Cancer Research UK

Registration: https://www.isrctn.com/ISRCTN11076307

Further Information: https://digitalecmt.org/2020/01/taking-clinical-trial-patient-home-trial-recruits-first-patient/

Trial Name: A randomised controlled trial to measure the effects and costs of a dental caries prevention regime for young children attending primary care dental services

Chief Investigator: Martin Tickle

Trial Description: A Phase IV, multicentre randomised controlled trial

Background: Dental caries have become a public health problem, with little change to the incidence amongst children in the last two decades. With fluoride-based interventions highlighted as a possible solution, this trial aims to compare standard practices with regular attendance at primary care services, on the occurrence of dental caries and the associated costs.

Main Outcomes: To assess the number of children that are dental caries free to the proportion of children who become dental caries active following the relative interventions.

Recruitment Target: 1200

Status: Completed

CTU: Belfast CTU

Funder: National Institute for Health Research (Health Technology Assessment)

Registration: https://trialsearch.who.int/?TrialID=ISRCTN36180119

Further Information: HTA Final Report: http://www.journalslibrary.nihr.ac.uk/hta/volume-20/issue-71#abstract  

Winner of the 2016 International Association for Dental Research AUBREY SHEIHAM AWARD FOR DISTINGUISHED RESEARCH IN DENTAL PUBLIC HEALTH SCIENCES

(http://www.dentalresearch.org/i4a/pages/index.cfm?pageid=3654#.WRsKmTvYaLs)

Trial Name: Mesoangioblast-mediated exon skipping for genetic correction of exon 51 mutation, based upon a single injection in individual skeletal muscles of five non ambulant patients affected by Duchenne Muscular Dystrophy: a non-randomized, open label, phase I/IIa study

Chief Investigator: Giulio Cossu, Imelda Hughes

Trial Description: A Phase I/IIa, non-randomized, open label study

Background: There are currently limited treatments available for Duchenne Muscular Dystrophy patients. This study uses a lentiviral vector to transduce, differentiate and inject patient mesoangioblasts (MABS) to genetically correct exon 51, potentially inducing synthesis of dystrophin in the injected muscle.

Main Outcomes: To determine the safety of injected autologous MABS after genetic modification and their subsequent ability to engraft and induce dystrophin synthesis.

Recruitment Target: 5

Status: Set-up

CTU: N/A

Funder: Wellcome Trust

Registration: https://trialsearch.who.int/Trial2.aspx?TrialID=EUCTR2019-001825-28-GB

Trial Name: The use of Granulocyte Transfusions after Umbilical Cord Blood Transplant for Leukaemia: A prospective, non-randomised, single-centre study to evaluate safety and immune reconstitution

Chief Investigator: Robert Wynn

Trial Description: A single-centre, single-arm, early-phase safety trial 

Background: Although most children with leukaemia are cured using drugs (chemotherapy) alone, for some children additional treatments are needed. Stem cell transplant can cure children where chemotherapy and other drugs have failed. Cord blood collected from the placenta of unrelated babies is often used. The immune cells of the donor attack the leukaemia cells of the patient, and this appears to work well at controlling leukaemia and is less likely to cause complications, such as when the immune cells also mistakenly attack healthy tissues (called graft versus host disease, GVHD).

The investigators have noticed that during cord blood transplant, the donor immune system appears to recover more quickly and not be associated with GVHD, when a type of blood transfusion containing white cells (granulocytes) are also given to the patient. The additional white cells appear to stimulate the donor immune cells to expand much more than usual.

The investigators will study this immune cell expansion during cord blood transplant in children with difficult-to-cure leukaemia who also receive a transfusion of granulocyte white cells. The investigators will assess the safety of the white cell transfusions, immune cell expansion, the outcomes on the patient's leukaemia, and whether there is GVHD or not.

Main Outcomes: Is it feasible and safe to administer a course of pooled, donor granulocytes after a cord blood transplant in a child with high-risk leukaemia?

What is the safety profile of the granulocyte infusions after T-replete, unrelated donor, cord blood HSCT in children?

Recruitment Target: 10

Status: Active – recruiting

CTU: None

Funder: Patient parent funds, Bone Marrow Fund, NHS Blood and Transplant, Manchester Foundation Trust

Registration: https://clinicaltrials.gov/ct2/show/NCT05425043

Trial Name: A Phase I/II, study of autologous CD34+ haematopoietic stem cells transduced ex vivo with CD11B lentiviral vector encoding human IDS tagged with ApoEII in patients with neuronopathic mucopolysaccharidosis type II (nMPS II, Hunters syndrome)

Chief Investigator: Robert Wynn

Trial Description: Phase 1-2, non-randomised, single-arm, open-label

Background: Mucopolysaccharidosis Type II is also referred to as MPS II or Hunter Syndrome. This is one of a family of diseases referred to as lysosomal storage diseases. MPS II is an x-linked inherited disease that means the person affected is missing a gene which codes for a specific enzyme (iduronate-2-sulphastase [IDS]). Without this enzyme, two waste products build up in cells in the body causing the symptoms seen in MPS II – delayed development, progressive deteriorating mental status and behavioural problems. Currently, enzyme replacement therapy (ERT) is the only approved treatment available for patients diagnosed with MPSII. However, ERT is a supportive therapy and is intended to alleviate symptoms and improve patient quality of life, rather than addressing the pathogenic mechanisms of the disease. To date, there is no effective disease-modifying treatment. In children with other MPS conditions it has been shown that it is possible to provide enzyme to cells in the body by a bone marrow transplant – transplanted cells from a donor, able to make the absent enzyme and secrete to other cells through the blood, however, in MPS II a bone marrow transplant does not seem to deliver enough enzyme to the cells to get rid of the waste product. The treatment proposed hopes to deliver increased amounts of the enzyme to the cells by genetic manipulation of the patient's own cells to include the missing IDS gene.

Main Outcomes: Safety of the IMP, including engraftment, absence of significant regimen-related toxicity, absence of short-term infusion reactions and of long-term vector related integration events. Safety and tolerability will be assessed throughout the full 2 years of the study from IMP administration by evaluating adverse events (AEs), clinical laboratory test results (haematology, chemistry, and urinalysis), vital signs measurements, electrocardiogram (ECG), physical examination results, and concomitant medication usage.

Recruitment Target: 5

Status: Active - recruiting

CTU: N/A

Funder: AvroBio

Registration: https://www.isrctn.com/ISRCTN12458940

Trial Name:A Phase I-II, Study of Autologous CD34+ Haematopoietic Stem Cells Transduced ex Vivo With CD11b Lentiviral Vector Encoding for Human SGSH in Patients With Mucopolysaccharidosis Type IIIA (MPS IIIa, Sanfilippo Syndrome Type A)

Chief Investigator: Robert Wynn

Trial Description: This is a single-centre, single-arm, phase I-II trial

Background: Patients with MPSIIIA have a clinical disorder marked by severe and progressive brain disease and neurological symptoms, due to the accumulation of undigested glycosaminoglycans in all cells of the body.

This study will be the first in human clinical trial to explore the safety, tolerability, and clinical efficacy of ex vivo gene therapy (autologous CD34+ cells transduced with a lentiviral vector containing the human SGSH gene) in MPSIIIA patients. Following treatment with the gene therapy patients will be followed up for a minimum of 3 years.

Main Outcomes: To evaluate tolerability of the treatment in MPS IIIA patients; to evaluate biological efficacy post-treatment; to assess safety of the treatment in MPS IIIA patients.

Recruitment Target: 5

Status: Active – recruiting

CTU: CTI (https://www.ctifacts.com/)

Funder: Orchard Therapeutics

Registration: https://clinicaltrials.gov/ct2/show/NCT04201405

Trial Name:BiomArker-guided Duration of Antibiotic treatment in hospitalised PaTients with moderate to severe Sepsis

Chief Investigator: Paul Dark

Trial Description: A Phase IV, randomised, multicentre study

Background: Sepsis is linked to long term illness and unavoidable deaths, with the NHS providing a generic antibiotic treatment plan. Increases in the biomarkers C-reactive protein (CRP) and procalcitonin (PCT) are linked with sepsis, providing an opportunity for a targeted, antibiotic duration plan to reduce patient side effects and overall antibiotic usage.

Main Outcomes: To determine whether monitoring of CRP or PCT as a treatment plan reduces the duration of guided antibiotic therapy in patients with moderate to severe sepsis compared to standard care.

Recruitment Target: 2760

Status: Recruiting

CTU: Warwick CTU

Funder: National Institute for Health Research (Health Technology Assessment)

Registration: https://www.isrctn.com/ISRCTN47473244

Further Information: adaptsepsistrial@warwick.ac.uk

Trial Name: A Phase II Randomised Controlled Study of Oral Prednisolone in Early Diffuse Cutaneous Systemic Sclerosis

Chief Investigator: Ariane Herrick

Trial Description: A Phase II, randomised, double blind, multicentre, placebo-controlled trial

Background: Diffuse cutaneous systemic sclerosis (dcSSc) is a devastating illness with a very major impact on quality of life as well as on survival.  Affected patients typically experience rapid progression of skin thickening, commencing distally but going on to involve proximal limb and/or trunk, often with early involvement of internal organs.  Early dcSSc is characterised by pain, stiffness, disability, disfigurement, fatigue, intractable itch, and a feeling of helplessness, where patients find themselves unable to cope with the simple tasks of everyday living.  Currently there is no cure.  The major impact on quality of life in patients with early dcSSc is in the context of a 10-year survival rate of only 52 to 62%. 

Several aspects of the disease have a major impact upon patients’ day-to-day lives, namely the pain and itch from their skin, fatigue, and loss of function due to a combination of early contractures (especially of the fingers) and musculoskeletal involvement.  Many of these early features which severely impact on quality of life have an inflammatory component and are potentially treatable with steroid therapy.  However, corticosteroids are much less frequently prescribed in patients with systemic sclerosis compared with patients with other connective tissue diseases due to the risk of renal crisis associated with steroid treatment in this subset of patients.  The purpose of this study is to evaluate the efficacy and safety of moderate dose oral prednisolone in providing therapeutic benefit to patients with early dcSSc.

Main Outcomes: To determine the efficacy of moderate dose prednisolone in reducing pain and disability, and improving skin score in patients with early dcSSc. To determine whether moderate dose prednisolone is a safe therapy in patients with early dcSSc, with particular reference to renal function.  

Recruitment Target: 72 (36 patients in 2 experimental arms)

Status: Closed to recruitment and follow-up

CTU: Manchester Academic Health Science Centre Trials Co-ordination Unit

Funder: Arthritis Research UK

Registration: https://www.isrctn.com/ISRCTN75313566

Further Information: www.predss.org

Trial Name: JAK 1/2 Inhibitor, Baricitinib, in the Treatment of Adult IIM

Chief Investigator: Hector Chinoy

Trial Description: This is a randomised, two-arm, treatment-delayed, multicentre trial

Background: This study aims to investigate the clinical efficacy of baricitinib in patients with adult idiopathic inflammatory myositis (IIM). Half of the patients enrolled onto the study will receive 24 weeks of baricitinib from the baseline visit with a 12 week follow-up period. The other half of patients will receive 24 weeks of barcitinib treatment after an initial 12-week delay with a 4 week follow up period for safety.

Main Outcomes: Assess the clinical response across treatment arms after 24 weeks of active treatment. Time Frame: Immediate-start arm: 24 weeks after baseline visit; Delayed-start arm: 36 weeks after baseline visit 

Recruitment Target: 25

Status: Recruiting

CTU: Manchester CTU

Funder: Eli Lilly

Registration: https://clinicaltrials.gov/ct2/show/NCT04208464

Trial Name: The Effect of a Subcutaneous Injection of Denosumab on Pain and Bone Marrow Lesions in Men and Women with Symptomatic Knee Osteoarthritis: A Randomised Double-Blind Placebo Controlled Clinical Trial

Chief Investigator: Terence O’Neill

Trial Description: A Phase III, randomised, double-blind, placebo-controlled trial

Background: Knee osteoarthritis is associated with substantial pain and disability. Evidence suggests bone marrow lesions are an important source of knee pain and act as an indicator of disease progression. Denosumab, a potent anti resorptive, is being trialled as a targeted therapy, proposed to reduce pain and specifically reduce bone marrow lesions through structural modification.

Main Outcomes: To determine the effect of a single, subcutaneous dose of Denosumab on knee pain and total bone marrow lesion area.

Recruitment Target: 167

Status: Closed to recruitment and follow-up

CTU: Manchester Academic Health Science Centre Trials Co-ordination Unit

Funder: Arthritis Research UK

Registration: https://www.isrctn.com/ISRCTN96920058

Further Information: www.manchester.ac.uk/roam

Trial Name: Validation and Reliability of Iris Recognition and InfraRed Cameras using Bespoke Image Analysis  Software for the Quantification of Corneal Opacification in Mucopolysaccharidoses

Chief Investigator: Jane Ashworth

Trial Name: Feasibility of a multispectral macular imaging (MMI) system for detecting and monitoring morphological features of the macula

Chief Investigator: Tariq Aslam

Trial Description: Single centre, non-randomised, single-arm trial

Background: The most common causes of vision loss in the western world are from age-related macular degeneration and diabetes. The number of people with age-related macular degeneration globally is projected to increase to 288 million in 2040. Great advances have been made in treating these patients in recent years by injection of anti-vascular endothelial growth factors (anti-VEGF) into the eye leading to global reductions in prevalence of blindness. An estimated 300-500,000 patients in the UK alone are currently under anti-VEGF therapy and the need to diagnose, monitor and treat these patients expediently is a challenge to health services. There is an urgent need for an efficient, sensitive and effective system of home monitoring that would appropriately assess patients in their own homes and detect those patients who require hospital care.

As part of ongoing research and development funded by NIHR grants, the GiveVision team has developed a means of imaging the retina to allow for reliable multispectral (more than one wavelength of light) macular imaging (MMI). The system has been engineered to be able to safely and accurately image volunteers’ eyes in a general adult population. In its current form the MMI system involves Surface mount RGB-IR light sources that are independently controllable to achieve this. The software will control the light sources independently, allowing for a red, green and blue image in quick succession (a few milliseconds apart). The infrared light source will be used to align the patient without causing a blink reflex or pupil constriction. The system will therefore result in 3 or 4 images of the same area, one in red, green and blue and infrared. It requires imaging of the subject to be performed by an expert human user at this stage.

Main Outcomes: To demonstrate of the feasibility of applying image analysis to the images obtained to determine some measure reflecting macular thickness and significant change in macular morphology. The validity will be presented in the form of scatter plots and regression analyses comparing the MMI system macular thickness with true macular thickness. The reliability of the system will be demonstrated with Bland Altman plots and reliability coefficients.

Recruitment Target: 50

Status: Active - recruiting

CTU: N/A

Funder: NIHR

FEHEMO

Trial Name: Measurement and Validation of Fetal Heart and Fetal Movement Signals Detected via Non-adhesive Sensors

Chief Investigator: Alexander Heazell

Trial Description: Single centre, non-randomised, single-arm trial

Background: Current technologies to objectively assess fetal wellbeing including fetal movement counting using “kick charts” and intermittent cardiotocography have little or no effect on reducing perinatal mortality, even in high-risk populations.1-3 Despite this, they are commonly used in clinical practice, particularly for pregnancies at high-risk of adverse pregnancy outcome. One reason for the use of these technologies is that there are no more effective alternatives. There is limited evidence that computerised analysis of the fetal heart rate trace, in high-risk pregnancies, is associated with a reduction in stillbirth.3 This suggests that computerised analysis can detect abnormalities which are not detected by visual analysis of the heart rate trace.

A multidisciplinary team of a doctor and engineers have developed a new sensor that will be able to detect mothers’ and babies’ heartbeat and babies movements in late pregnancy. This sensor can be placed in contact with the mothers’ skin over the pregnant uterus without having to be stuck down. We anticipate that this sensor would allow us to monitor babies for longer periods of time which might help us to better identify babies who are being deprived of oxygen during pregnancy. We need to test these sensors on women in late pregnancy for two reasons. Firstly, we need to ensure they reliably measure mother and babies heart rates without interference from movement or other electrical equipment. Secondly we need to ensure that the information they provide is accurate (compared to current measurement techniques).

Main Outcomes: The primary aim of this project is to conduct initial studies using non-adhesive sensors to determine whether they are able to consistently detect the mother's and baby's heart rate and whether this can be distinguished from background electrical noise.

Recruitment Target: 69

Status: Active - recruiting

CTU: N/A

Funder: Tommy’s, EPSRC

Trial Name: Metformin impact on maternal and infant cardiometabolic health

Chief Investigator: Jenny Myers

Trial Description: This is an open label, two-arm, randomised, controlled, phase III trial

Background: Gestational diabetes mellitus is high blood sugar (glucose) that develops during pregnancy and usually disappears after giving birth.
The prevalence of diabetes in pregnancy is increasing rapidly. Women with a combination of diabetes and vascular disease are six times more likely to develop foetal growth restriction. This means that whilst foetal overgrowth remains a common problem in women with hyperglycaemia, a very important minority of women (~3%) will develop placental disease leading to a small-for-gestational-age infant.
Metformin is known to reduce foetal growth in pregnancies complicated by diabetes.
Current practice is to offer metformin to all women with diabetes (type 2 and gestational) irrespective of potential risk factors for placental disease. The effect of metformin on placental function and foetal growth is poorly understood.

Main Outcomes: Assessing foetal growth at 20-26 weeks, and then at birth in women treated either with standard care (diet and lifestyle changes and insulin and/or metformin if indicated), or with the intervention (diet and lifestyle changes and insulin if indicated).

Recruitment Target: 225

Status: Active- recruiting

CTU: None

Funder: Consolidator Award

Registration: https://www.isrctn.com/ISRCTN13866189

Trial Name: Reduced Foetal Movement Intervention Trial

Chief Investigator: Alexander Heazell

Trial Description: A multicentre, randomised controlled pilot trial of standard care informed by results of an additional placental factor blood test versus standard care in women presenting with reduced foetal movement at or after 36⁺⁰ weeks gestation

Background: In the UK, 1 in 220 babies are stillborn, which describes a baby born with no signs of life after 24 weeks of pregnancy. Forty percent of babies who are stillborn born die after 36 weeks of pregnancy and have no lethal structural abnormality. If these babies could be identified and delivered earlier, lives could be saved. The association between a woman’s perception of a reduction in her baby’s movement and stillbirth is well documented. Reduced fetal movement is thought to be a symptom of nutrient or oxygen restriction and is related to changes in placental structure and function. Currently, it is not known which tests are best at predicting whether women with reduced fetal movements are at increased risk of pregnancy complications. This trial will involve women having an additional blood test to measure how well their placenta is working. The results of the blood test will help clinicians decide how to treat women with reduced fetal movement compared with standard care.

Main Outcomes:

Feasibility outcomes:

• Number of potentially eligible women at each site and number of women recruited at each site
• Proportion lost to follow-up after discharge from hospital and reasons for loss to follow-up
• Spectrum of clinical characteristics of women at randomisation (frequency of small for gestational age (SGA) fetuses, obstetric history, nulliparous)
• Reasons for non-recruitment, if available
• Compliance with the trial interventions and reasons for non-compliance
• Completeness of data collection for planned outcomes in the main trial including that needed for health economic analyses
• Views of women about participation collected ~6 weeks after birth using a Participant Views questionnaire
• A sub-group of participants will be interviewed ~16 weeks after birth to gain further insight into their views of the trial using a semi-structured interview guide
• Views of clinicians on the trial collected 9-12 months after site initiation using a Health Professional Views questionnaire

2) Proof of concept outcomes:

• Frequency of induction of labour or planned caesarean and reasons for these procedures
• Neonatal outcome including:
  • Stillbirths and deaths before discharge
  • Five minute Apgar score of <7
  • Umbilical artery pH <7.05
  • Admission to neonatal unit for >48 hours with hypoglycaemia, hypothermia, seizures or complications of fetal growth restriction (FGR)
  • SGA (<10^th centile on customised birthweight chart)
  • Use of therapeutic cooling
  • Length of stay in hospital
• Maternal hypertensive disorders defined as development of gestational hypertension or pre-eclampsia
• Change in Generalised Anxiety Disorder 2 (GAD-2) scale measured at enrolment and ~6 weeks after birth
• Quantifiable impact on costs and outcomes incurred by delivering the intervention from a National Health Service (NHS) perspective and as assessed by the SF-12™ Health Survey measured at enrolment and ~6 weeks after birth along with a Health Resource Use questionnaire measured ~6 weeks after birth.
• The diagnostic performance of the placental factor test in participants allocated to the control arm of the trial

Recruitment Target: 750

Status: Completed

CTU: Nottingham CTU

Funder: National Institute for Health Research

Registration: https://clinicaltrials.gov/ct2/show/NCT04754594

Further Information: http://documents.manchester.ac.uk/display.aspx?DocID=39950

Trial Name: Communication-centred parent-mediated treatment for autism spectrum disorder in South Asia

Chief Investigator: Jonathan Green

Trial Description: Two-centre, two-arm, single (rater) blinded random allocation parallel-group study

Background: Eighty percent of the world's children with Autism Spectrum Disorders (ASD) live in low resource settings. Recent evidence from high-income countries supports the effectiveness of targeted parent-mediated interventions for the early treatment of children with ASD. Interventions that are delivered through parents have the additional advantages of improving parental knowledge and morale, potentially promoting the social empowerment of mothers, generalising into improvements in the family environment for the child and thus potentially conferring long-term impacts on the social context, the child's environment, and functional outcomes. The Pre-school Autism Communication Therapy (PACT) trial conducted in the UK is the largest yet trial of this kind. It is targeted at getting parents to recognize their child's social communication difficulties and to create an environment which gives the child a space and time to communicate at their own pace. This intervention uses video feedback techniques to work with parents to enhance their understanding and responsiveness to the atypical communications of young children with autism. The trial showed that children with ASD who received this treatment benefited from the enriched communication environment that their parents were able to create; this in turn had a positive impact on the social interactions the children initiated. More importantly these changes in parent-child interaction and independent communication from the child were sustained in a follow-up study after six years which demonstrated a decrease in autism symptoms in children who received the intervention. The intervention has now been successfully adapted for use in South Asia, including relevant cultural adaptation to enhance parental acceptability, developing a supervision and training cascade to allow the intervention to be delivered by community-based non-specialist workers, and delivery of the intervention at home. Most children with ASD in India and other low resource settings do not receive evidence-based care, which the proposal investigators have shown can reduce the symptoms of ASD, and is feasible and acceptable for delivery in the proposed study setting. The intervention will be delivered through existing health system frontline workers. COMPASS will be the largest trial of its kind for ASD in any low resource setting and the evidence generated will have an impact not only health policy and practice in India, home to over 5 million children with ASD, but also other low resource settings in the region.

Main Outcomes: To evaluate the effectiveness at scale of a parent-mediated intervention for Autism Spectrum Disorders in South Asia, delivered by non-specialists in community health settings, to investigate the cost-effectiveness of the intervention, to generate tools and evidence for policy makers to guide the scale up the intervention.

Recruitment Target: 240

Status: Active- recruiting

CTU: Kings College London CTU

Funder: Joint Global Health Trials Programme; Medical Research Council, Department for International Development, National Institute for Health Research, and the Wellcome Trust

Registration: https://www.isrctn.com/ISRCTN21454676

Further Information: https://gtr.ukri.org/project/093F0DB7-DF1A-4502-9483-88A627CC5E94

Trial Name: Lumi Nova - a digital intervention supporting 7-12 year olds who experience difficulties with anxiety. An implementation study in Greater Manchester to optimise for economically disadvantaged children.

Chief Investigator: Paula Whelan

Trial Description: Non-randomised interventional trial

Background: Half of all mental disorders start by the age of 14 years, yet up to 70% of children and young people don’t get access to timely, appropriate support. The demand for support has increased by 50% in the last 10 years leaving services under tremendous pressure. Anxiety, and other mood disorders, are the most common problem affecting children.

In the UK, there were 4.3 million children living in poverty in 2019/20; children living in households in the lowest 20% income bracket are 2-3 times more likely to experience mental illness compared to those in the highest income bracket. Yet they also face the biggest barriers to accessing treatment.

Lumi Nova is a therapeutic mobile game that delivers timely access to elements of Cognitive Behavioural Therapy (graded exposures), in a child-led, non-stigmatising way. The game supports dialogue with parents, whilst providing professionals with recognised outcome scales to monitor progress remotely. Lumi Nova was initially built to appeal to the broadest range of children with anxiety; now, there is an opportunity to tailor Lumi Nova to meet the needs of disadvantaged children - specifically those living in poverty.

This implementation study intends to understand the barriers to take-up and usage for the most economically disadvantaged children in Greater Manchester, and use the findings to optimise Lumi Nova, and how its deployed, so that it can better serve these patients.

Main Outcomes: The barriers and enablers to the usage and engagement of Lumi Nova within an economically-disadvantaged group of children and young people, assessed using interviews on completion of the intervention. Stakeholders’ views on a primary outcome for a future trial, assessed using interviews throughout the study

Recruitment Target: 120

Status: Active - recruiting

CTU: N/A

Funder: SRBI

Registration: https://www.isrctn.com/ISRCTN11131689

Further Information: https://www.gmmh.nhs.uk/lumi-nova/

Trial Name: Remote psychosocial interventions to prevent avoidable psychiatric hospital admissions in people with serious mental health problems: a multi-arm multi-stage trial

Chief Investigator: Anthony Morrison

Trial Description: Multicentre, multi-arm, multi-stage, randomised controlled interventional trial

Background: People with serious mental health problems (SMHP) are more likely to be admitted to psychiatric hospital following contact with crisis services. Pressure on hospital beds is made worse by the extra impact on crisis care, and hospital admissions can be traumatic; because of COVID-19 admitting someone to hospital can be additionally problematic. People with SMHP are vulnerable to COVID-19 due to increased risk of underlying physical health problems, medication effects and engagement with services. There is an urgent need for treatments to address suicidal thoughts/behaviours and reduce avoidable hospital admissions. We will conduct a multi-site trial to find out which brief and remotely delivered treatments are helpful for people with SMHP with recent suicidal thoughts/suicide attempt. The main question is whether the treatments are more effective in reducing hospital admissions over a 6-month period compared to usual treatment (TAU), and if these treatments provide value for money. We will assess the impact on suicidal thoughts and behaviour, hope, recovery, anxiety, and depression.

Main Outcomes: Psychiatric hospital admission (yes/no) over a 6-month period measured using patient records

Recruitment Target: 1235

Status: Active - recruiting

CTU: N/A

Funder: NIHR

Registration: https://www.isrctn.com/ISRCTN33079589

Further Information: https://www.psychosisresearch.com

Trial Name: Investigation of a digital health solution providing real-time inhaler technique guidance

Chief Investigator: Prof. Clare Murray

Trial Description: Single centre, two-arm, interventional randomised controlled trial

Background: Most medicines for asthma are given by inhaler so that medicine can directly reach the lungs and work better. However, we know it’s difficult to use an inhaler properly and mistakes are often made. Poor inhaler technique has been linked to increased asthma symptoms, hospital admission and the need for more asthma medicines. To be certain patients are using their inhaler correctly, it is necessary for patients to be trained regularly; showing someone once is not enough! However, patients and their health care professionals are busy and opportunities to check and refresh inhaler technique are often limited.

Clip-Tone is a small device fitted to the top of the patients’ inhaler which makes a very quiet whistle when used properly. This is used with the Clip-Tone Buddy app which detects the specific sound of the Clip-Tone along with the sound of the inhaler being pressed and provides real time feedback on the screen on how to improve inhaler technique. Together the device and app are known as the Clip-Tone System, CTS.
The study aim is to assess whether a new tool can help people to learn how to use their asthma inhaler better.

Main Outcomes:  Inhaler technique measured using an inhaler technique checklist (based on UK Inhaler Group standards) at baseline, 1 month, 3 months, and 6 months

Recruitment Target: 126

Status: Active - recruiting

CTU: N/A

Funder: NIHR

Registration: https://www.isrctn.com/ISRCTN14411274

Further Information: www.Clin-e-cal.com/Clip-Tone-study

Trial Name: TRial of Atorvastatin for the primary prevention of Cardiovascular Events in Rheumatoid Arthritis

Chief Investigator: George Kitas

Trial Description: Multi-centre, randomised, double blind, placebo-controlled trial

Background: Rheumatoid Arthritis (RA) is a severe, progressive disorder associated with increased and premature cardiovascular mortality. This study aims to assess if the statin Atrovastin will protect RA patients from atherosclerotic events.

Main Outcomes: To determine the effects of Atrovastatin on cardiovascular events and mortality in RA patients.

Recruitment Target: 3808

Status: Completed

CTU: N/A

Funder: Arthritis Research Campaign and the British Heart Foundation

Registration: https://trialsearch.who.int/Trial2.aspx?TrialID=EUCTR2006-006032-22-GB

Further Information: g.d.kitas@bham.ac.uk

Trial Name: Does Interleukin-1 Receptor Antagonist Improve Outcome following aneurysmal Subarachnoid Haemorrhage (aSAH)?

Chief Investigator: Andrew King

Trial Description: A Phase III, randomised, double blind, multicentre, placebo controlled trial

Background: Despite many aneurysmal subarachnoid haemorrhage (aSAH) patients surviving the initial bleed, the risk of further neurological damage is prevalent. Following on from our Phase II trial that demonstrated Kineret (IL-1 receptor antagonist) reduced plasma inflammation, we aim to increase understanding of the mechanism between this induced inflammation reduction and clinical outcome.

Main Outcomes: To determine if treatment with subcutaneous Kineret to patients with aSAH will improve clinical outcome.

Recruitment Target: 1000 (500 per trial arm)

Status: Recruiting

CTU: Manchester CTU

Funder: Medical Research Council/National Institute for Health Research (Efficacy and Mechanism Evaluation)

Registration: https://www.isrctn.com/ISRCTN12961797

Further Information: SCIL@manchester.ac.uk

Trial Name: Phase II Trial of Interleukin-1 Receptor Antagonist in Intracerebral Haemorrhage: BLOcking the Cytokine IL-1 in ICH

Chief Investigator: Adrian Parry-Jones

Trial Description: This is a two-arm, double-blinded, randomised, placebo controlled, phase II trial.

Background: This trial will help inform the development of a new treatment for intracerebral haemorrhage (ICH; also known as haemorrhagic stroke). ICH is a type of stroke caused by spontaneous bleeding into the brain. In the hours to days after bleeding occurs, inflammation develops in the brain around the haematoma (collection of blood in the brain). Inflammation is the body's natural response to injury, however when it continues unchecked there is a risk that the brain tissue around the haematoma will become swollen. This type of swelling can worsen existing stroke symptoms or cause new deficits such as speech disturbance and limb weakness, which can lead to long term disability.

The level of inflammation in the blood is high after ICH. The investigators want to examine whether blocking this inflammation can improve overall recovery. The investigators’ research group has extensively investigated the use of a well-established anti-inflammatory drug, Kineret® in trials with patients who have suffered a stroke or brain haemorrhage. Kineret® is similar to a naturally produced protein called interleukin-1 receptor antagonist (IL-1Ra) and is already licensed to treat patients with rheumatoid arthritis. The investigators have evidence from these previous studies that Kineret® reduced levels of inflammation in the blood after ischaemic stroke (caused by a blockage in an artery). However, to develop Kineret® as a treatment for ICH, the investigators need to know if it reduces levels of inflammation present in the blood following ICH and if it reduces swelling in the brain.

Main Outcomes: Does an anti-inflammatory drug (IL-1Ra) reduce inflammation after brain haemorrhage when given as an injection into the skin? If IL-1Ra reduces inflammation after brain haemorrhage, does this improve recovery? Is IL-1Ra given as an injection into the skin for 3 days after brain haemorrhage safe?

Recruitment Target: 25

Status: Closed

CTU: Manchester CTU

Funder: NIHR

Registration: https://clinicaltrials.gov/ct2/show/NCT03737344

Further Information: https://sites.manchester.ac.uk/bloc-ich/

Trial Name: A diagnostic accuracy study comparing the use of the Rapid Rhythm System to 12-Lead ECG to identify atrial fibrillation in over 65s in primary care

Chief Investigator: Pete Bower

Trial Description: A diagnostic, non-randomised, multicentre study

Background: The 12-lead ECG device is currently the gold standard for diagnosis of atrial fibrillation (AF). This study aims to compare 12-lead ECG readings to the Rapid Rhythm Handset, a novel device taking readings from the trunk, that hopes to provide a rapid and simple way to perform an ECG.

Main Outcomes: The study will compare the performance of the 12-lead and Rapid Rhythm system in diagnosing AF.

Recruitment Target: 1000

Status: Completed

CTU: N/A

Funder: National Institute for Health Research (Invention for Innovation)

Registration:  https://www.isrctn.com/ISRCTN12144707?q=&filters=conditionCategory:Circulatory%20System&sort=&offset=75&totalResults=1532&page=2&pageSize=50&searchType=basic-search

Further Information: jonathan.lamb@manchester.ac.uk

Trial Name: A Phase I study of a novel synthetic polymer nerve conduit ‘Polynerve’ in patients with sensory digital nerve injury

Chief Investigator: Adam Reid

Trial Description: Medical Device Intervention

Background: Surgical reconstruction is required following peripheral nerve injury. Standard procedures involve the use of a patient’s own nerve tissue, that carries with it fundamental problems. This feasibility study uses a biodegradable conduit to determine improved nerve function, while assessing this composition as a clinically relevant biomaterial.

Participants with a traumatic sensory nerve injury in the hand will be recruited to the study. Participants found to have a nerve gap of at least 5 mm and no greater than 20mm will undergo repair with the Polynerve. Participants will be followed up regularly, observed for device-related complications and to assess the return of sensory innervation.

Main Outcomes: This study aims to determine if a novel synthetic nerve conduit is a viable, safe biomaterial to improve nerve repair and regeneration following peripheral nerve injury.

Recruitment Target: 12

Status: Closed to recruitment and follow-up

CTU: Manchester Academic Health Science Centre Trials Co-ordination Unit

Funder: National Institute for Health Research

Registration: https://clinicaltrials.gov/ct2/show/NCT02970864

Further Information: adam.reid@manchester.ac.uk

Trial Name: Timing of Primary Surgery for Cleft Palate

Chief Investigator: Bill Shaw

Trial Description: A multicentre, randomised controlled trial

Background: Cleft palate/lip is a common birth anomaly, leading to serious developmental and social issues. Primary surgery often determines downstream success but the effect of when this intervention should occur is unknown. The aim of this study is to address the timing of primary surgery for cleft palate.

The international TOPS study is looking into the timing of surgery for cleft palate in infants and compares the results of surgery performed at either 6 or 12 months. It involves data over a wide range of disciplines such as clinical genetics, speech and language pathology, audiology and orthodontics. 

A review of surgical practice across the UK and Scandinavia identified differences in the timing of primary surgery in infants with cleft palate. There is currently no reliable evidence to support that either primary surgery at age 6 months or age 12 months produces better outcomes, however, it is thought that the timing of surgery may influence speech development and for that reason the best possible timing should be assessed.

Main Outcomes: To determine whether surgery for cleft palate, using a Sommerlad technique, at age 6 months, when compared to surgery using the same technique at age 12 months, improves velopharyngeal function at age 5 years. All infants will be followed up at age 12 months, 3 years and five years for the assessment of the primary outcomes (at age 5 years) and secondary outcomes.

Recruitment Target: 558

Status: Closed to recruitment and follow-up

CTU: Clinical Trials Research Centre, University of Liverpool

Funder: National Institute of Dental and Craniofacial Research (NIDCR), a branch of the U.S. National Institutes of Health (NIH)

Registration: https://clinicaltrials.gov/ct2/show/NCT00993551

Further Information: http://www.tops-trial.org.uk/