Trial Name: The clinical and cost effectiveness of oraL vErsus intrAmuscular glucocorticoiDs in rhEumatoid aRthritis

Chief Investigator: Dr James Bluett

Trial Description: Interventional assessor blinded randomized parallel group-controlled trial

Background: Rheumatoid Arthritis (RA) causes joint pain and swelling affecting people’s daily activities and quality of life. The National Institute for Health and Care Excellence advise treatment with drugs called anti-rheumatic medicines, but they can take up to 6 months to work. Whilst waiting for these medicines to take effect, patients are offered another type of drug, steroids, which act quickly to control symptoms. Unfortunately, steroids have long-term side effects such as diabetes, weight gain and skin changes, so should only be used for short periods of time.

Main Outcomes:  Steroids can be given as an injection into the muscle or as a daily tablet. Doctors currently do not know whether it matters which of these and what dose has the best balance between side effects and rapid symptom relief.
The LEADER trial aims to find the most effective and safest way of using steroids for patients with uncontrolled RA who are starting a new anti-rheumatic medicine.

Funder: NIHR

Registration: ISRCTN32090559

Further Information:  https://www.isrctn.com/ISRCTN32090559?q=leader%20james%20bluett&filters=&sort=&offset=1&totalResults=1&page=1&pageSize=10

Trial Name: The Role of ATP in Chronic Cough. Identifying those who may benefit from new anti-cough medications by assessing cough response to ATP and by measuring blood ATP levels

Chief Investigator: Jaclyn Smith 

Trial Description: Single centre randomized controlled single blinded three way crossover study

Background: Refractory Chronic Cough (RCC) is cough that does not respond to treatment. It can have a profound effect on its sufferer's lives with patients coughing 100s of times a day without any relief. Previous studies have shown that blocking receptors on airway nerves called P2X3 can dramatically reduce cough. The exact mechanism of this is unknown but these receptors are activated by ATP. 

Main Outcomes:  This study aims to find out if inhaled hypo-osmolar solutions and ATP shown to promote ATP release in pre-clinical studies cause coughing in patients with refractory chronic cough compared to healthy volunteers. It also aims to see if RCC patients have elevated systemic levels of ATP and breakdown products in blood compared to healthy volunteers.

Funder: Wellcome Trust (UK)

Registration:  ISRCTN11791599

Further Information:  https://www.isrctn.com/ISRCTN11791599?q=ISRCTN11791599&filters=&sort=&offset=1&totalResults=1&page=1&pageSize=10

Trial Name: ENRICH: ENhancing efficacy of Radiotherapy to Improve Care for glioblastoma patients capitalizing on the mitotic enrichment Hypothesis

Chief Investigator: Dr Gerben Borst

Trial Description: 

Background: Glioblastoma (GBM) is an incurable type of brain cancer with a dismal prognosis of about 15.4 months. The standard treatment of care (SoC) for patients diagnosed with a GBM is surgical resection followed (chemo)radiotherapy. Unfortunately, complete resection of the tumor is not possible, and radiotherapy is only controlling the tumor, emphasizing the unmet need for better treatment strategies.

Main Outcomes: The overarching goal is to implement ABT-751 (now renamed MITX-101) as a new combinational drug with radiotherapy for GBM patients. Following our promising preclinical data, we hypothesize that MITX-101 will radiosensitize GBM tumors in patients when given approximately 8 h prior to radiation. This strategy will be tested in combination with the current SoC treatment but is potentially implementable in all future treatment strategies involving radiotherapy. The aim of this proof-of-concept study is to assess if 100 mg/m² of oral MITX-101 causes mitotic enrichment and can be safely added to the SoC of patients with MGMT-unmethylated tumors.

Recruitment Target: 18

Trial Name: Screen and Treat with Aspirin to Reduce Pre-eclampsia (STARshiP)

Chief Investigator: Professor Jenny Myers

Trial Description: Multi-centre, stepped-wedge cluster randomised study with an internal pilot phase and parallel economic evaluation.

Background: Pre‑eclampsia (PE) is a hypertensive disorder of pregnancy that typically develops after 20 weeks’ gestation and is a major driver of iatrogenic preterm birth (PTB). It carries substantial risks to both mother (e.g. end‑organ damage, future cardiovascular disease) and baby (e.g. neonatal intensive care, long‑term neurodevelopmental impairment) and imposes very high short‑ and long‑term health‑care costs. Low‑dose aspirin (LDA) begun before 16 weeks’ gestation is proven to reduce preterm PE, but current UK NICE screening—based on maternal history alone—detects only ~40 % of those who will develop preterm PE. A first‑trimester multimodal algorithm from the Fetal Medicine Foundation (FMF)—incorporating maternal risk factors, mean arterial pressure, uterine artery Doppler, and placental growth factor—has been shown in trials (e.g. ASPRE) to double detection of preterm PE and, when coupled with LDA, to reduce its incidence by ~60 % relative (from ~4.3 % to ~1.6 %).

Main Outcomes: Implementation of first‑trimester FMF screening with targeted low‑dose aspirin is projected to reduce iatrogenic preterm birth rates from approximately 2.2 percent to 1.9 percent (an absolute reduction of 0.3 percent), accompanied by declines in maternal complications (such as postpartum hemorrhage and high‑dependency care) and neonatal morbidities (including NICU admissions, respiratory support needs, and perinatal mortality). Although the FMF protocol incurs an initial cost of roughly £177,000 per 4,500 births, these expenses are expected to be offset by savings from avoided intensive‑care utilization and long‑term disability care, resulting in a favourable cost‑per‑QALY (quality‑adjusted life year) profile. A concurrent implementation evaluation will document practical barriers and facilitators and assess acceptability among patients and staff, thereby informing potential wider adoption within NHS maternity services.

Recruitment Target: 224,000

Trial Name: Acceptability of radiofrequency assessment of breast density

Chief Investigator: Sasha Howell

Trial Description: Multicentre, non‑randomised, single‑arm, observational cross‑sectional cohort study with embedded qualitative focus‑group and semi‑structured interview evaluation

Background: Breast cancer affects 1 in every 7 women in the UK and is the most common cause of death in women aged 35 to 49 years old. Younger women who are more likely to develop breast cancer may be identified earlier by having a breast cancer risk assessment. This means they could be offered earlier screening and prevention measures to increase their chance of survival. One of the strongest risk factors for breast cancer is called breast density. This is measured using mammograms (breast X-rays), which are used in breast cancer screening. One problem with using mammograms as part of breast cancer screening is that women need to have a second appointment at a specialist centre. However, women in this age group are likely to be employed, have children and other care responsibilities. This presents a barrier to attending screening in this group. Previous research has found that women would prefer risk assessments to be completed in a single appointment. 

Main Outcomes:  A company called Micrima Ltd. have developed a desktop device to assess breast density. This device offers a painless, simple and quick density score for women without needing a mammogram. This study plans to assess the acceptability of the Mi~Scan® device to patients and healthcare professionals. The study will also conduct interviews with healthcare professionals to explore their views regarding the acceptability and usability of the Mi~Scan® device.

Recruitment Target: 240

Funder: Wellcome Trust (UK)

Registration:  ISRCTN48626243

Further Information:  https://www.isrctn.com/ISRCTN48626243

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: 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: 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: 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: 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: 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: 1064

Status: Active - recruiting

CTU: N/A

Funder: NIHR

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

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

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

Registration: https://www.clinicaltrials.gov/study/NCT06952777?term=Measurement%20and%20Validation%20of%20Fetal%20Heart%20and%20Fetal%20Movement%20Signals%20Detected%20via%20Non-adhesive%20Sensors&rank=1 

Trial Name: First in Human (FIH) clinical investigation of safety and feasibility of a novel graphene micro-electrocorticography array for brain mapping in neuro-oncology

Short title: FIH Clinical Investigation of Graphene Electrodes for Brain Mapping

Chief Investigator: Mr. David J. Coope

Trial Description: Pilot stage, prospective, interventional, non-randomised, single arm, single site

Background: During surgical operations within the brain such as the removal of a tumor, electrodes are commonly used to map specific brain functions or monitor brain activity. These are most commonly flexible plastic devices with embedded metallic contacts that allow electrical activity in the brain to be detected and measured. They may also be used to stimulate precise areas of the brain to either trigger or block a response such as the contraction of a muscle. This allows the surgeon to define which regions of the brain are involved in controlling critical functions such as movement or speech so that these areas can be protected during the operation.

There remain limitations with the design and physical characteristics of commercially available electrodes for use during brain operations. These include the limited ability of conventional materials to fold over the complex shape of the brain and the need to use comparatively large metallic contacts to detect the tiny electrical signals.

Main Outcomes:  This study will be the first to introduce a new generation of electrodes which have been designed to overcome these limitations. They are extremely thin and flexible allowing them to follow the surface of the brain and to be used in locations within and around the brain for which the standard electrodes are unsuitable. The contact surfaces that detect electrical activity and enable and stimulate the brain have been replaced with graphene which is a novel carbon-based material. The use of graphene allows electrodes to be made that are more sensitive to the tiny electrical signals of the brain. This means that they can be much smaller and closer together providing increased detail in the recording and potentially enabling signals to be detected that would previously have required such long recordings that they could not be used to guide decision making during surgery.

Recruitment Target: 10

Funder: European Union Graphene Flagship

Registration:  https://clinicaltrials.gov/study/NCT06368310#study-overview

Trial Name: Transforming outpatient consultations by integrating regular symptom tracking into clinical care: the Remote Monitoring of Rheumatoid Arthritis (REMORA2)

Chief Investigator: Professor William Dixon

Trial Description: Randomized; Both; Design type: Process of Care, Device, Management of Care, Active Monitoring, Cross-sectional

Background: Rheumatoid arthritis (RA) is managed by specialists at infrequent outpatient consultations. Treatment decisions are informed by asking “how have you been in the last six months?”. However, patients find it difficult to give accurate information, which can negatively affect treatment decisions and outcomes. We have shown that patients with RA and their clinicians can use a daily smartphone symptom tracker integrated into their electronic health record. Patients used the app regularly, and patients and clinicians thought graphical summaries at consultations improved care. There is, however, currently no evidence that integrated symptom tracking improves health outcomes.

Main Outcomes:  The programme aims to determine whether integrating daily patient‑reported symptom tracking via a smartphone app into routine rheumatology care can improve disease control and quality of life for people with rheumatoid arthritis, while also generating practical guidance on how to embed patient‑generated data into NHS workflows. Across four workstreams it will refine implementation materials, test the impact of symptom tracking versus usual care on disease activity (DAS28), quality of life, disability, shared decision‑making, self‑management and satisfaction in a 500‑patient stepped‑wedge trial, assess its cost‑effectiveness, explore barriers to both clinician/patient uptake and digital inclusion, and co‑design governance and e‑consent processes.

Recruitment Target: 931

Funder: NIHR

Registration: https://www.isrctn.com/ISRCTN51539448

Further Information: https://fundingawards.nihr.ac.uk/award/NIHR202030

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

Chief Investigator: Professor 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 (500v500)

CTU: Manchester Clinical Trials Unit

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

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: Timing of Primary Surgery for Cleft Palate

Chief Investigator: Professor 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.

Main Outcomes: The National Institute of Dental and Craniofacial Research (NIDCR), a branch of the U.S. National Institutes of Health, has contributed the follow-up grant ($7.6 million) for the TOPS (Timing of Primary Surgery for Cleft Palate) clinical trial.

The money will allow the team of researchers, led by Honorary Professor William Shaw and Honorary Senior Lecturer, Dr Gunvor Semb, to complete the TOPS trial over the next five years.

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.

More than 550 infants with cleft palate were recruited at 23 sites in the UK, Denmark, Norway, Sweden and Brazil between September 2010 and July 2015, with a grant that the NIDCR previously awarded. Babies who participated in the trial received surgery using the same technique (Sommerlad technique) and were randomly assigned to have their surgery when they are either aged 6 months or 12 months. There was a 50:50 chance of infants being in either group.

After surgery, children taking part will be followed up at age 12 months, three years and five years when speech, hearing and physical development will be reviewed.

Patients recruited: 558

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)

Further Information: https://clinicaltrials.gov/study/NCT00993551?term=NCT00993551&rank=1

Website: http://www.tops-trial.org.uk/

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: 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 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: 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: 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: 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

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: 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: 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