Conservative Management in Traumatic Pneumothoraces in the Emergency Department (CoMiTED): A Randomised Controlled Trial.

Injury is the leading caused of death among adults ages 45 and over. Traumatic pneumothoraces (lung collapse) are present in 1 in 5 victims of severe trauma. In 2019, over 50,000 patients were diagnosed with traumatic pneumothoraces in hospitals in England and Wales. It is a condition that affects not only victims of accidents such as motor vehicle crashes but also a diverse range of underserved groups including young victims of knife crime and older patients who suffer chest injuries after falls.

We estimate from our prior observational and survey work that around half of patients admitted to hospital with traumatic pneumothoraces will be treated with the insertion of a tube into the chest. Current guidelines advise chest drain insertion for any traumatic pneumothorax, although very small pneumothoraces can be managed with observation at the treating physician’s discretion. For some patients with very large pneumothoraces, chest drain placement can reduce the risk of cardiorespiratory compromise. However, there remains a large proportion of patients in whom there is clinical uncertainty as to whether an immediate chest drain is required. Insertion is usually done in the emergency department and is one of the most invasive procedures undertaken outside of an operating theatre. Chest drains carry a high-risk of complications such as bleeding and infection in 15-30% of patients. There is no robust evidence to inform practice, and the default to invasive treatment may cause potentially avoidable patient pain, distress, and complications.

In our analysis of 600 (+) patients with traumatic pneumothoraces from TARN data, 90% of patients treated without a chest drain did not require subsequent intervention, suggesting a potential role for conservative management. However, in this analysis, a remaining 50% of patients were initially treated with a chest drain and there was a considerable clinical variation in those selected for this invasive procedure. We have also conducted an international survey of 222 emergency physicians utilising vignettes of larger traumatic pneumothoraces, and over 60% of clinicians would elect to insert a chest drain in ED, even without clinical compromise.

Therefore, based on the observational studies and lack of robust data, we propose a randomised controlled trial (RCT) to assess the clinical and cost-effectiveness of an initial conservative approach to the management of patients with traumatic pneumothoraces. If we demonstrate that this approach is effective, it will reduce the use of a painful, invasive, and potentially harmful management strategy.

Chief Investigator – Professor Edward Carlton

Principle Investigator – Professor Edward Carlton

Our aim is to understand how best to investigate acute severe headaches, which are suggestive of a condition called subarachnoid haemorrhage (SAH). SAH is a potentially severe cause of headache in the UK and requires urgent identification and treatment. It is defined as the presence of blood within one of the layers of the brain. At its most serious, it can cause death and severe disability.

We want to understand the accuracy of CT brain scanning in the Emergency Department (ED) and how this accuracy changes with time.

We will collect data on patients presenting to the Emergency department that have headaches reaching peak intensity within one hour. These are the classic headache patterns that raise concern with clinicians about the possibility of SAH. We will use this data to try and validate recently proposed clinical rules, and CT brain strategies, which suggest they can exclude the possibility of SAH with a high degree of precision.

With this information, we will be able to inform clinicians how accurate CT brain scans are safely excluding SAH. Further to this, we will highlight how this accuracy changes depending on the timing of the scan, using hourly intervals from onset of the headache. We will also evaluate the accuracy of clinical decision rules (without any brain scans) to exclude the condition of SAH.

Project Details
Principal Investigator: TBC
Planned End Date: TBC
Local Ref: 4761

Multi-centre open label randomised controlled trial of immediate enhanced ambulatory ECG monitoring versus standard monitoring in acute unexplained syncope patients: The ASPIRED study.

Syncope (or blackout) is common; 650,000 patients present to UK Emergency Departments every year. The 3 underlying causes are vasovagal (simple faint), postural hypertension (blood pressure fall on standing) and cardiac disease. Diagnosis is difficult and is not apparent in 50% of patients after assessment. Whilst vasovagal and postural syncope are relatively benign, serious pathology include dysrhythmia (an abnormal heart rhythm). When cardiac dysrhythmia are detected, they are most commonly asystolic pauses, reflex bradycardia or advanced atrioventricular block, with tachycardia being the minority. The difficulty in the ED is to differentiate between the causes of syncope and identify patients at higher risk. This can be complicated as many patients have fully recovered on ED arrival and their examination and presenting Electrocardiogram (ECG) may both be normal. The lack of efficacy and availability of commonly used monitoring devices means most high and medium risk patients are admitted to hospital for observation and telemetry, with escalating costs. Unfortunately, many still end up being discharged without a diagnosis.

In general, syncope reoccurs in around 50% of patients within a year. Recurring episodes impact upon number of hospital admissions, health costs and importantly the quality of life patients. Whilst there is a wide variation in the literature with respect to the number of syncope episodes and recurrence rates pre and post treatment once a cardiac dysrhythmia diagnosis is made and treatment initiated, around only 10% of patients will have a 1-year recurrence and syncope episodes will drop by over 90%. Pacing, the most specific treatment studied shows a syncopal recurrence rate during follow up of 0-20% versus 20-60% in untreated patients.

The studies primary objective is to determine whether immediate, enhanced ambulatory ECG monitoring decreases the number of self-reported episodes of syncope at one year compared to standard care monitoring in acute unexplained syncope patients.

Chief Investigator – Dr Matt Reed

Principal Investigator – Professor Edward Carlton

The Second Bedside Evaluation of Sensitive Troponin (BEST-2) Study.

Approximately 3% of patients who attend an Emergency Department have chest pain that the clinician who treats them initially suspects may have been caused by an acute coronary syndrome. Most of these patients are admitted to hospital for further investigation, meaning that chest pain is the most common reason for emergency hospital admission. However, tests will later identify that only a minority of those patients has an acute coronary syndrome. If better investigations had been available at the time of arrival in the ED, many of these hospital admissions could have been avoided, which would lead to earlier reassurance for patients and more efficient use of healthcare resources.

It is often difficult to tell quickly if a patient has pain from a heart problem or from something less serious like a muscle strain. At the moment, we rely on testing blood samples in the hospital’s main laboratory for signs of heart damage. It can take up to two hours for the results of each test to be available. If is now possible to do the blood tests for signs of heart damage using small machines that can be used at the bedside. We call these machines ‘point of care’ devices. These devices can usually give results in just 15-20 minutes after taking blood.

In this research study, we want to find out whether the results that we get from such tests are as accurate as the results that we get from the hospital laboratory for diagnosing chest pain related to a heart attack. We hope that this research will enable us to provide faster and better care to patients in the future.

Chief Investigator – Professor Richard Body

Principal Investigator – Professor Edward Carlton

Lower urinary tract infection with SARS COV2 infection.

It is increasingly recognised that non-respiratory problems can appear as damage in other organs/tissues due to COVID-19. Later on in the pandemic, small studies reported patients with SARS-CoV-2 infection develop new lower urinary tract symptoms (LUTS). More research is required to understand the short and long-term effects of COVID-19 on LUT function.

In the elderly, LUTS and incontinence are also associated with other health problems and are often the reason for needing residential or nursing home care. So, early detection of these patients and proactively treating symptoms, would have an enormous benefit. The objective is to conduct long-term studies in hospitalized patients who have received a diagnosis of COVID-19 compared with a control cohort with no history or current SARS-CoV-2 infection. The study uses validated questionnaires at baseline and after six months, to measure symptoms of LUTS.

Project Details

Principal Investigator: Nikki Cotterill

Planned End Date: 01/03/2023

Local Ref: 5052

Increasing physical activity levels using e-bikes to enhance prostate cancer survival – a randomised pilot study

Exercise has been identified as having numerous health benefits in cancer survivors, specifically among prostate cancer survivors, leading to improvements in quality of life and physical function.

The National Institute of Health Research in the UK and the European Association of Urology (EAU) now recommend that all men diagnosed with prostate cancer participate in supervised exercise training as part of standard treatment. However, delivering supervised exercise programs is rarely achievable in clinical care due to time constraints and training.

Exercise uptake amongst cancer survivors remains low throughout their cancer journey, therefore finding new and accessible ways to increase physical activity for this population is a priority. Electrically assisted bicycles (e-bikes) have been highlighted as a way to increase physical activity enough to achieve significant health outcomes, providing electrical assistance only when the rider is pedalling, through sensors which detect pedalling speed and force. There is also the added benefit of being more environmentally friendly than cars. This study aims to determine if we can recruit individuals to e-cycling from oncology clinics and if so, when in the treatment pathway is most appropriate to offer men an e-cycling intervention.

Project Details

Principal Investigator: Jonathan Aning 

Recruitment End Date: 30/09/22

Local Ref: 5166

A Retrospective study for prostate cancer diagnosis support

Prostate cancer is the most common cancer among men in the UK. It is estimated that 120,000 men go through diagnosis, 47,000 are diagnosed with prostate cancer, and 11,000 die from the disease each year. Magnetic resonance imaging (MRI) scans have recently been introduced to help reduce biopsy rates and improve detection of clinically significant cancer that requires treatment. The interpretation of prostate MRI scans needs proper training and experience.

Prostate cancer is being missed or found late, even with the new MRI pathway. Given the importance of the role of MRI in diagnosis, accurate reporting is crucial in the multidisciplinary management of prostate cancer. There is a growing interest in the potential to apply artificial intelligence (AI) computer software to improve and streamline the process.

Lucida Medical has developed AI software called Prostate Intelligence, Pi™, to support prostate cancer diagnosis. Preliminary results suggest that this prototype performs well compared to radiologists and alternative AI systems. This should help low-risk patients avoid unnecessary biopsies (and the related possible complications), and detect significant cancers with equal or better performance than world-leading hospitals. Consequently, it could reduce healthcare inequality, reduce the burden on the NHS, and give patients confident early diagnosis.

Project Details

Principal Investigator: Jonathan Aning

Recruitment End Date: September 2022

Local Ref: 5085

Virtual 3D modelling for improved surgical planning of robotic assisted partial nephrectomy

Surgery is the mainstay treatment for abdominal cancer, resulting in over 50,000 surgeries annually in the UK, with 10% of those being for kidney cancer. Preoperative surgery planning decisions are made by radiologists and surgeons upon viewing CT (Computed Tomography) and MRI (Magnetic Resonance Imaging) scans.

The challenge is to mentally reconstruct the patient’s 3D anatomy from these 2D image slices, including tumour location and its relationship to nearby structures such as critical vessels. This process is time consuming and difficult, often resulting in human error and suboptimal decision-making.

Better surgical planning tools are essential to improve patient outcome and reduce the cost. To address this, dedicated software has transformed the 2D images into 3D images. The main research question to be addressed in the present study is, whether surgical planning using virtual 3D modelling (Innersight 3D) , improves the outcome and cost-effectiveness of surgery with many potential benefits for patients and surgeons.

The study will compare current surgical planning method to planning with the addition of virtual 3D models in randomised patient groups.

Project Details

Principal Investigator: Ahmed Mahrous

Recruitment End Date: December 2023

Local Ref: 5212

Many men, particularly those who are older are experiencing problems passing urine. They may need to pass urine more frequently than usual, find their sleep interrupted by having to go to the toilet during the night, slower urine flow rate or even a loss of bladder control. These problems are grouped into what we call Lower Urinary Tract Symptoms (LUTS), which can be particularly unpleasant for men, impacting on their work and social life, and usually prompting a visit to the GP for treatment.

GPs have no easy way of identifying common causes of LUTS, or the best options to relieve symptoms. This means that men are usually referred to hospital for specialist urology tests, and often have treatment that could have been given out by the GP, such as medication and lifestyle changes.

The aims of the PriMUS study is to create a ‘decision aid’ to help GPs find out the most likely cause of patients’ urinary symptoms, so that together they can choose the best management. The decision aid will be a programme on a computer, where the GP will enter patient information and test results. The software will then display the most likely cause of symptoms and suggested management options.

In order to create the decision aid, we need all men taking part to have simple index tests, as well as a more invasive test called ‘urodynamics’, which is the gold standard test to determine the cause of urinary symptoms. We can then work out how the less invasive tests above relate to results from urodynamics, so that in the future only the less invasive tests are needed.

We believe that this will have many benefits such as getting to the right treatment sooner, avoiding unnecessary hospital visits, and getting those who need to be treated by a specialist there more quickly.

Project Details
Principal Investigator: Prof Marcus Drake
Planned End Date: 30/11/2021
Local Ref: 4131

Localised prostate cancer is common but can usually be cured with surgery, however, this often leads to a loss of erections and urinary incontinence due to nerve damage. Nerve sparing, where the outer layers of the prostate are peeled off, increases post-operative potency, but increases the risk of cancer being left behind and the need for radiotherapy, which renders the men impotent, even if they had nerve sparing surgery. A new technique called NeuroSAFE has been developed to promote nerve sparing without compromising cancer control. With the NeuroSAFE technique, during surgery, a pathologist examines the prostate near the nerves to check for exposed cancer. If cancer is found, the nerve tissue is removed so the recurrence risk is similar to when cancer cells are not exposed.

This study will compare NeuroSAFE with current UK practice (non- NeuroSAFE, where nerve sparing is based on an MRI scan and biopsy results and clinical examination before the operation, rather than an examination by a pathologist during the operation). Men will be randomly allocated, to either NeuroSAFE or robotic prostatectomy without NeuroSAFE. The main measure of effectiveness will be the proportion of men who have erections and cancer control at 1 year post surgery. We will also evaluate quality of life, including patient recorded outcome measures and analyse the cost/benefit of the procedure.

This study is needed because we are treating larger and more aggressive cancers. Information about nerve sparing is based on limited evidence from studies where the risk of treatment failure is lower. Adoption of nerve sparing without scientific evaluation puts UK men at risk of disease recurrence and extra treatment.

Project Details
Principal Investigator: Prof Rajendra AR Persad
Planned End Date: 31/07/2022
Local Ref: 4320

Outcomes in patients with high-risk prostate cancer who undergo radical prostatectomy (surgery which aims to remove the whole prostate, and the cancer cells inside it) as a primary therapy have not significantly improved with time. Early prostate cancer is highly responsive to hormonal blockade. Therefore, androgen (a steroid hormone) blockade prior to and after prostate surgery could decrease tumour burden, increase the likelihood of complete resection and improve objective outcomes such as metastasis-free survival (MFS – time without the cancer spreading) and overall survival (OS).

The purpose of this study is to determine whether 6 months of treatment with apalutamide (an antagonist of the androgen receptor), with or without abiraterone acetate and prednisone (AAP), and in combination with androgen deprivation therapy (ADT), improves the pathological complete response rate and MFS rates in patients with high risk localised prostate cancer that are indicated to undergo a radical prostatectomy, compared to patients receiving ADT and a placebo.

The study will consist of a screening period of up to 35 days, after which participants will be randomised (randomly selected) to receive either apalutamide (with or without AAP) and ADT or receive ADT and a placebo. Participants will then receive 6 months of treatment in 28 day treatment cycles, before undergoing a radical prostatectomy. They will then receive a further 6 months of treatment. Following the treatment phase, participants will enter a post treatment phase in which they will be followed up until death, the cancer spreads, they withdraw from the study or they are lost to follow-up.

Project Details
Principal Investigator: Mr Jonathan Aning
Planned End Date: 02/05/2023
Local Ref: 4398

The Proper Understanding of Recurrent Stress Urinary Incontinence Treatment (PURSUIT) study is a trial of endoscopic versus surgical treatment for women.

Primary Stress Urinary Incontinence (SUI) affects 16-35% of women. It can arise due to abnormal urethral mobility (‘hypermobility’) after pregnancy.

NICE recommends pelvic floor muscle training and, if this fails, surgery is an option. At least 6% of women have persisting or recurrent SUI (rSUI) after surgery, which may reflect persistent hypermobility or emergence of sphincter deficiency. rSUI affects quality of life, ability to work, and has substantial cost impact. Up to 17% of women undergo a second operation for SUI within 10 years.

The James Lind Alliance, a group of healthcare professionals and patients, identified rSUI as a top 10 research priority in urinary incontinence. Women with rSUI commonly express desire to return to normal life, but they also wish to minimise the severity of surgery or complications.

Project Details
Principal Investigator: Mr Hashim Hashim
Planned End Date: 31/03/2025
Local Ref: 4404

End-stage kidney disease (ESKD) affects ~55,000 people in the UK, with ~7,000 newly affected people each year. It ranks among the most severe of the chronic non-communicable diseases. Morbidity is high, with dialysis patients in the UK admitted to hospital on average ~1.5-2.0 times per year and spending ~15 days in hospital per year. Quality of life on dialysis is also well below that of the general population. There is therefore an unmet and urgent need to improve ESKD patient treatment.

Renal replacement therapy (dialysis or transplantation) is necessary when patients become symptomatic of ESKD. Currently ~90% of dialysis patients are on some form of haemodialysis (HD) or haemodiafiltration (HDF). Although HD and HDF can be performed at home, the majority is performed in-centre.

Treating the 25,000 people on HD costs around £500m of NHS spending each year, with a further £75m spent on hospital admissions and £50m on transport to and from dialysis. Half of patients now starting dialysis are 65 years or older and less likely to be fit for kidney transplantation and in the general population this group is predicted to increase by 60% (from 10.3m to 16.9m) by 2035. While preventing ESKD in the first place should remain a priority, the optimal form of dialysis will remain highly relevant to the NHS.

This study aims to establish the effectiveness and cost-effectiveness of high-volume HDF compared with high-flux HD in adult patients with ESKD on maintenance thrice weekly in-centre HD. We will do this by running a randomised controlled trial using non-cancer mortality or hospital admission due a cardiovascular event or infection as our primary outcome.

For more information about this study, please visit the H4RT website.

Project Details
Principal Investigator: Dr Fergus Caskey
Planned End Date: 30/09/2025
Local Ref: 3859

When kidney function drops to 15% of normal, symptoms such as tiredness, loss of appetite and sickness usually develop. At this stage, dialysis or kidney transplantation is considered. Not all patients are suitable for a kidney transplant so the following treatment options may be being considered:

• To prepare for renal dialysis if things progress – this involves visiting the hospital for 4 hours of treatment 3 times a week, or flushing fluid in and out of the body through the abdomen 4 times a day every day at home.
• To have all supportive treatment and care, but not plan to start renal dialysis even if things progress – this focuses on controlling symptoms with medication and aims to minimise hospital clinic visits and admissions. 

Surprisingly, for people over 65 with other health problems, survival and quality of life seem to be similar with these options. As a result, doctors and nurses seem to give quite different advice to their patients and the treatment people choose depends a lot on which renal unit they attend. More evidence is needed, therefore, to help patients and their families make an informed decision about the right treatment for them.

 The Prepare study is a randomised controlled trial which aims to provide far better evidence to help patients and their families reach the best decision for them and influence NHS policy on care for this group of patients.

For more information about this study, please visit the Prepare for Kidney Care website.

Project Details
Principal Investigator: Dr Fergus Caskey
Planned Recruitment End Date: May 2024
Report findings to NIHR August 2025

Local Ref: 3858a

Vitamin D deficiency is common in kidney failure and is a strong predictor of death from cardiovascular disease, infections and cancer. Dialysis patients typically receive pre-activated vitamin D, since it used to be thought that only the kidneys activate vitamin D. However, this increases blood calcium concentrations and may paradoxically make vitamin D deficiency worse. International treatment guidelines now recommend that kidney patients receive inactive vitamin D (known as cholecalciferol), since we now know that every organ activates vitamin D as required, even in kidney failure. However, this approach has not yet been tested in a trial. We will test whether supplementation with cholecalciferol increases survival in UK dialysis patients.

We will randomly assign adult UK dialysis patients to cholecalciferol or standard care.

We will determine the number of deaths over time in the two groups, to establish whether cholecalciferol improves survival. Whether patients are alive or dead at the end of the study will be determined from the national deaths register. We will also measure any differences in survival free from cardiovascular events, infections and cancers, the three leading causes of death in those on dialysis. We will use questionnaires to compare the quality of life of those in the two groups.

Currently only 68% of patients survive 3 years or more on dialysis. Assuming that this will be the case in the control group, we would need to witness 2200 deaths during the study to determine with a sufficient degree of certainty whether cholecalciferol improves survival. We estimate that this would require the inclusion of 4200 patients, followed for a total study duration of approximately 7 years. Put differently, this trial is designed to detect whether cholecalciferol has a clinically relevant effect by saving 4 or more lives for every 100 patients treated.

Project Details
Principal Investigator: Dr James Bushnell
Planned End Date: 01/03/2023
Local Ref: 4021

A study to correlate the epidemiological and clinical features of Steroid Resistance Nephrotic Syndrome including FSGS (Focal Segmental GlomeruloSclerosis) in childhood and Adulthood, in the UK, with genotype and to develop biomarkers of disease activity post-transplant.

Project Details
Principal Investigator: Dr Simon Satchell
Planned End Date: 31/12/2021
Local Ref: 2854

The National Registry of Rare Kidney Diseases (RaDaR) is a research initiative by UK kidney specialists (the Renal Association and the UK Renal Registry). It is designed to gather information from patients who have rare kidney diseases. This will give a much better understanding of how these illnesses affect people. It will help to improve treatment and identify possible causes of these rare diseases.

As patient information is entered into the database, researchers will be able to analyse whether certain aspects of their condition (e.g. laboratory results or treatments) are associated with specific benefits or complications. By allowing the research team to link this data with that gathered from other clinical studies, researchers will also be able to study the long-term outcome of these rare conditions and any treatments they may receive.

Project Details
Principal Investigator: Dr Albert Power
Planned End Date: 09/10/2024
Local Ref: 2962

Primary systemic vasculitidies (PSV), encompassing Anti-Neutrophil Cytoplasmic Antibody (ANCA) associated vasculitis and medium vessel vasculitis, are relatively uncommon diseases, but have a propensity for renal involvement and account for a significant number of patients with both acute and chronic kidney disease. The aetiology of PSV is unknown and current therapies are non-specific and associated with major side effects. Outcome data for such patients have comprised small cohort studies from single centres. Understanding the factors that influence disease outcome and the impact different therapies have outside of clinical trials can only be achieved using a larger number of patients, accrued from multiple different units.

We propose to establish the first pan-UK PSV dataset, which will collect regular returns regarding patient recruitment and outcome from all participating centres. This will facilitate investigation of disease associations, outcomes and demographic trends for the UK PSV population. We will test the hypothesis that disease incidence is increasing in Indo-Asians and why the outcome may be different among different ethnic groups, as well as investigating contemporary outcomes with modern immunosuppressive protocols. In addition, we will combine clinical phenotype with genetic studies. Specifically we will investigate genetic variation between ethnic groups by looking at variations in DNA sequences that can help to explain differences in disease susceptibility. These are investigated using many DNA specific markers, called single-nucleotide polymorphisms (SNPs) whose expression will be compared between patients from different ethnic groups.

Finally, we will be able to record the outcome of all patients treated with novel therapeutics, thus eliminating the significant reporting bias that exists. This will allow individual investigators to carry out particular projects mining the dataset.

Project Details
Principal Investigator: Dr Albert Power
Planned End Date: 28/02/2022
Local Ref: 3724

Calciphylaxis is a rare condition which results in small arteries becoming calcified. This results in painful ulceration of the skin which in turn can result in infection and further damage to tissue. It is associated with a high mortality rate (60–80%).

Consequently, research into this area is important. The aims of this study are to determine the following:

• What is the natural history of the disease?
• What risk factors are associated with development and progression of calciphylaxis?
• Which treatments currently in clinical practice confer a favourable outcome?
• What are the underlying disease processes?

These aims will be achieved by collecting information on medications, clinical parameters, local laboratory tests, measuring specific proteins and molecules in blood and tissue as well as studying patient’s DNA profiles.

Project Details
Principal Investigator: Mrs Saira Risdale
Planned End Date: 01/09/2021
Local Ref: 2970

This application relates to Phase 2 of the UNPACK study. Phase 1 - a qualitative interview study - informed Phase 2: a discrete choice experiment. Phase 2 uses the same screening and recruitment processes as in Phase 1. This application covers piloting of the study at a single site. It is our intention to expand to more sites following an amendment. This application will be submitted to the Research Ethics Committee that reviewed Phase 1.

Individuals at risk of kidney failure must choose between transplantation, dialysis, and non-dialysis care (also known as ‘comprehensive conservative care’ - CCC). Older people are rarely medically suitable for transplantation and are more likely to choose CCC than younger people. This may be because they don’t want intrusive treatment and are willing to live shorter lives to avoid it. Dialysis is particularly burdensome for them, with marginal survival benefit. People close to them, such as family members, are also involved in decision-making, but may be less willing to consider reduced survival to avoid treatment burden.

The trade-offs that older UK patients and those close to them are prepared to make have never before been quantified. Phase 1 of the UNPACK study used qualitative interviews to identify they treatment attributes and outcomes important to older people with kidney disease and those close to them when deciding between dialysis or CCC.

The discrete choice experiment is a questionnaire based on hypothetical treatment scenarios that measures treatment preferences of older people at risk of kidney failure and those close to them. The process will quantify and compare the importance of the treatment attributes (location and frequency) and outcomes (quality and quantity of life) identified in Phase 1. The results of this process will be used to inform the development of kidney services that fit better with the preferences of individuals using them.

Project Details
Principal Investigator: Dr Albert Power
Planned End Date: 31/10/2022
Local Ref: 4764

Researchers want to find out if the drug bardoxolone methyl can improve the disease ADPKD (autosomal dominant polycystic kidney disease).

Bardoxolone methyl is an investigational (experimental) drug that is being tested and is currently not approved by any regulatory agency for sale. It is a semi-synthetic (man-made) substance based on the scaffold of the natural product oleanolic acid. Bardoxolone methyl was shown to inhibit inflammation-mediated processes and to improve parameters of kidney function in multiple clinical studies.

In this study, bardoxolone methyl will be given to participants as a capsule (pill).

The study has two main purposes:

• To see if bardoxolone methyl pills are safe and well tolerated in patients with ADPKD
• To see if bardoxolone methyl pills improve the estimated glomerular filtration rate (eGFR), a measure of kidney function

The study plans to enrol approximately 300 patients with ADPKD who are between the age of 18 and 70 years at up to 100 global study centres.

Project Details
Principal Investigator: Dr Albert Power
Planned End Date: 31/12/2021
Local Ref: 4870

The ALIGN clinical trial is looking into a new tablet and it’s effectiveness in treating IgA Nephropathy, a disease which affects the tiny filters in the kidneys and their ability to remove ‘waste’ from the body which can lead to End Stage Kidney Disease and the need for Dialysis. Atrasentan has been developed by Chinook Therapeutics and has previously shown positive results in over 5000 people with diabetic kidney disease. In this study the tablet is taken once a day for 2.5 years. The trial is placebo-controlled meaning there is a 50/50 chance of receiving the trial drug or an inactive placebo, and to reduce bias, neither participants or their Doctors will know which they receive. 

A dedicated study team of nurses and doctors will care for participants during their time on the study, in partnership with their usual kidney doctors, and will see the participants in clinic approx. every 12 weeks, after a few weekly visits initially.

IgA Nephropathy currently has no approved treatments other than generic blood-pressure control and doctors are excited about the prospect of a treatment to delay the progression of this disease.

Principal Investigator: Dr Albert Power

Planned End Date: March 2023

Internal Reference: 5160

Individuals on dialysis are at risk of developing heart problems such as heart attacks and heart failure as well as high blood pressure. There is an urgent need for treatments that reduce the risk of heart problems in patients that require dialysis. Spironolactone is a tablet that is approved in the UK and has been used for over 50 years to treat heart problems in patients that do not require dialysis. Spironolactone belongs to a class of medicines called mineralocorticoid receptor antagonists (MRAs) and works by blocking a hormone called aldosterone in the body that can damage the heart.

Although spironolactone is very effective in patients that do not require dialysis, it is not known if spironolactone is effective in dialysis patients. We hope that this study will help determine if spironolactone works in dialysis patients. The purpose of this study is to determine if taking spironolactone will reduce death or hospitalization for heart failure and to see if it is well tolerated in patients that require dialysis.

Eligible participants will be asked to take spironolactone for 7-14 weeks to make sure it is safe for them. This is done by checking potassium results on weeks 1,2,3 and 7.  In the next part of the study, the participant will either be assigned to take the spironolactone tablet or a placebo (a tablet with no active medication) once a day.

Project Details
Principal Investigator: Dr Albert Power
Planned End Date: 31 Dec 2023
Local Ref: 4891

There is a great shortage of kidneys for transplantation. All kidneys from deceased donors carry risk to the recipient (risk of not working, or of disease transmission), but donor age is strongly associated with poor function and early failure of the kidney transplant. This is important, because the majority of the pool of potential UK deceased donors are now over 60 years old. Thus, if we can improve our identification of kidneys from older donors that are better ‘quality’, we can maximise numbers of transplants performed without compromising transplant outcomes.

The use of urgent kidney biopsy (analysis of a small portion under the microscope) to identify age-related damage has been reported to aid selection of those kidneys from older donors that are good enough ‘quality’ for transplantation. This approach has not been widely adopted in the UK, because the exact impact that the extra information provided by biopsy has on transplant numbers and on transplant outcomes is not clear, and its cost effectiveness remains unproven.

Our study will evaluate whether providing an urgent 24 hour National Biopsy Service increases the number and function of kidneys transplanted from donors aged over 60 years. The study is a national trial: every four months a randomly-chosen group of UK kidney transplant centres will be offered access to the National Biopsy Service (a ‘stepped-wedge cluster randomised trial’). By the end of the trial, all UK centres will have access, and we will then compare results for each centre from before and after the biopsy service was made available as well as evaluating the cost of providing the service. We anticipate that this comparison will show that biopsy availability increases the use of kidneys from elderly donors by about 10%, which equates to an additional 180 kidney transplants performed in the UK per year.

Project Details
Principal Investigator: Dr Samuel Turner
Planned End Date: 31/01/2022
Local Ref: 4119

Enroll-HD is a prospective observational multicentre multi-national cohort study to be conducted in multiple native languages. Study visits will take place yearly and may occur at the time of the participant’s routine clinical care visit, where possible. The goal of Enroll-HD is to build a large and rich database of clinical information and biospecimens that will serve as a basis for future studies aimed at developing tools and biomarkers for progression and prognosis, identifying clinically relevant phenotypic characteristics, and establishing clearly defined endpoints for interventional studies.

Principal Investigator: Dr Elizabeth Couthard
Planned End Date: Open ended
Local Ref: 3553

Enroll-HD (study explained above) is also a clinical research platform that supports other HD studies. Anyone participating in Enroll-HD study who have been confirmed to have the HD gene expansion are invited to take part in HDClairity.

HDClarity is looking at the biomarker, Cerebrospinal fluid (CSF). A biomarker is a biological measure that captures what is happening in a cell or organism at that given moment. These play an important role in understanding biological processes and understanding relationships between environment exposure, human biology and disease. CSF is an extremely useful biosample since it directly surrounds the brain and so likely reflects what is happening there throughout the course of disease. HDClarity is an open-ended study (no set end date) with CSF collection encouraged every year.
 

Principal Investigator: Dr Elizabeth Couthard
Planned End Date: 01/04/2026
Local Ref: 3817

European project title European eHealth Care Model for Rare Neurodegenerative Diseases: Development of HD-specific outcome measures UK study title Development and validation of multilingual, multinational HD specific need-based quality of life assessment tools: HD value assessment study.

This study is for anyone who is HD gene positive or companions of an individual who is HD gene positive. The aim is to find out more about their wishes, needs and expectations about living with Huntington’s Disease. From this, a questionnaire will be developed that can assess the quality of life for other individuals impacted by HD, in other countries too. 

PI : Ms Natalie Rosewell

Planned end Date: 01/09/2023

Local Ref: 4950
 

Longitudinal Adaptive Study of Molecular Pathology and Neuronal Networks in Huntington’s Disease Gene Expansion Carriers (HDGECs) and Healthy Controls using Positron Emission Tomography and Multi-modal Magnetic Resonance Imaging

Anyone participating in Enroll-HD study who has been confirmed to have the HD gene expansion are invited to take part in iMarkHD.

The study will compare PET and MRI scan measurements at different stages of the disease, with healthy control participants. This will look for changes which may influence the development of symptoms and disease progression. It may also lead to the identification of disease progression markers that characterise and predict symptom development which may be used in the future as outcome measures
 

PI: Dr Elizabeth Coulthard

Planned end date: 30/09/2024

Local Ref: 5213

​​​​​DRN 552 is a database collecting data from newly diagnosed patients with Type 1 diabetes, which may lead to progression onto other studies. It will characterisation of people with new-onset Type 1 diabetes (<6 months duration) and their siblings who are free from diabetes, with participants providing their consent to be contacted about other Type 1 diabetes research.

Project Details
Principal Investigator: Dr Danijela Tatovic
Planned End Date: 31/12/2022
Local Ref: 2969

This study aims to evaluate the decline in endogenous insulin secretion (measured using C-peptide) in a robustly defined cohort with Type 1 diabetes. We will recruit 164 participants who have been clinically diagnosed with Type 1 diabetes in the previous 100 days (113 diagnosed at over 30 years of age and 51 diagnosed at age 18-30 years). At the baseline visit we will take blood tests and perform a mixed meal tolerance test (repeat blood sampling after consumption of a liquid meal replacement). We will also ask volunteers to be fitted with a continuous glucose monitor to measure a participant’s daily glucose. This is a device worn on the upper arm and remains in place for 14 days.

We will repeat this mixed meal tolerance test after 6 months and 1 year to examine how quickly participant’s insulin secretion falls as well the continuous glucose monitoring.

We will also ask volunteers to do a home dried blood spot test (DBS) to measure insulin secretion at their own homes at baseline, 3, 6, 9 and 12 months. This is to see if a simple test which participants can do at home can be used to easily identify those with rapidly decreasing insulin secretion. We will compare how quickly participants lose their own insulin secretion in each age group and also examine how we can best identify older participants who will rapidly progress.

Project Details
Principal Investigator: Dr Angus Jones
Planned End Date: 31/12/2022
Local Ref: 4627

This study has been set up within the framework of the INNODIA network. INNODIA is a global partnership between 27 academic institutions, 4 industrial partners, a small sized enterprise and 2 patient organisations, bringing their knowledge and experience together with one common goal: "To fight type 1 diabetes".

The overall aim of INNODIA is to advance in a decisive way how to predict, stage, evaluate and prevent the onset and progression of type 1 diabetes (T1D). For this, INNODIA has established a comprehensive and interdisciplinary network of clinical and basic scientists, who are leading experts in the field of T1D research in Europe and the UK, with complementary expertise from the areas of immunology, Beta-cell biology, biomarker research and T1D therapy, joining forces in a coordinated fashion with industry partners and two foundations, as well as with all major stakeholders in the process, including regulatory bodies and patients with Type 1 Diabetes and their families.

Type 1 diabetes (T1D) occurs when a person's own immune system attacks their insulin producing cells. When newly diagnosed, many T1D patients still have 10-20% of their insulin-producing cells still functioning. The study is a multicentre, randomized, double-blind, placebo-controlled study in volunteers with newly diagnosed diabetes mellitus type 1 (within 6 weeks after diagnosis).

The purpose of the clinical trial (Ver-A-T1D) is to confirm the effect of 360mg Verapamil sustained release (SR) administered orally once daily (titrated over the first 3 months from 120 mg to 360 mg) on the preservation of beta-cell function measured as stimulated C-peptide after 12 months compared to placebo.

The study has a cross-over design and a duration of approximately 24 months, consisting of 3 telephone visits and 7 visits at the trial site. The duration of the treatment phase with verapamil is 12 months, and an additional (optional) follow-up visit will be carried out 12 months after completion of the study. The study procedures are identical in all 20 clinical centres across Europe and the UK.

Project Details
Principal Investigator: Prof Colin Dayan
Planned End Date: 31/05/2023
Local Ref: 4680

ONWARDS 6 is a clinical study seeking to compare a new weekly insulin, insulin icodec, and a known insulin, insulin degludec, both in combination with mealtime insulin in people with Type 1 diabetes.

This is an international study of around 580 people in approximately 12 countries around the world. It is expected that about 45 participants will be from the United Kingdom.

Project Details
Principal Investigator: Dr Georgina Russell
Planned End Date: 28/10/2021
Local Ref: 4936

Bariatric surgery has substantial evidence demonstrating its safety and efficacy as a treatment for obesity and type 2 diabetes mellitus. However, there are a proportion of patients who do not demonstrate an improvement in diabetes control and another subset who will see the metabolic effects of surgery diminish with time. This study aims to see if continuing intensive multimodal therapy for type 2 diabetes mellitus following surgery would be beneficial in improving long term outcomes.

Participants will be followed up at 4 weeks, 3, 6, 12 months and then yearly thereafter for 5 years, medications will be titrated to help participants achieve targets for HbA1c, blood pressure and cholesterol levels.

Project Details
Principal Investigator: Dimitri Pournaras
Planned End Date: 01/10/2026
Local Ref: 4868

The study aims to assess risk and identify (if any) medication classes and/or individual medications for which absorption is likely to be significantly altered post-surgery, as well as determining medication information needs in this population.

Project Details
Principal Investigator: Danielle Wigg
Planned End Date: 14/06/2023
Local Ref: 5021

The profound improvement in glucose control after Roux-en-Y-gastric bypass (RYGB) has led to the recognition of the intestine as a major player in glucose regulation. The optimal length of each of the three limbs (alimentary, biliopancreatic and common) remains controversial. This is further complicated by the differences in total small intestinal length in humans (ranging between 3.5-10.5 meters).

Anatomical arrangements of RYGB results in three segments or 'limbs':

• Alimentary limb: Through which food enters the small intestine through a gastric pouch (the remnant of the stomach)
• Biliopancreatic limb: Includes the bypassed segments of the duodenum (first section of the small intestine) and proximal jejunum (second section) through which the biliopancreatic (bile acids from the gall bladder and pancreatic) secretions flow and
• Common limb: In which the food and biliopancreatic secretions mix.

Current evidence supports the hypothesis that a 'modified' RYGB with a long alimentary limb and short common limb may optimize glucose control. There have not been any clinical trials comparing 'modified' and 'standard' RYGB with glucose control as primary outcome.

In this study, we propose to recruit 80 patients with type 2 diabetes mellitus (DM) and obesity who are eligible for metabolic surgery and currently on the waiting list for bariatric surgery at North Bristol NHS Trust obesity service. Randomisation will take place intra-operatively in patients with a total small intestinal length < 5.5 meters. The surgeon will contact the randomiser who will make the allocation to either 'modified' or 'standard' RYGB before continuing with the surgery.

Participants will attend 5 visits in total (baseline, day 10, 3, 6 and 12 months post operatively) for anthropometric measurements, blood tests, urine pregnancy test, assessment of number of glucose lowering medications and adverse event profile.

Project Details
Principal Investigator: Dimitri Pournaras
Planned End Date: 01/06/2022
Local Ref: 5007

The metabolomics study aims to find out the impact of weight change and bariatric surgery on the levels of certain blood components.  The study involves donating a small sample of blood before your surgery and again one year later. Your blood samples will be used to measure changes in specific blood components after surgery and during weight loss.

Project Details
Principal Investigator: James Hopkins
Planned End Date: 01/03/2023
Local Ref: 4096

The sunflower study is for people who have gallstones. Some patients who are waiting for gallbladder surgery may also have gallstones that have moved into the bile duct. Currently, it is uncertain whether testing for bile duct stones, by doing an additional scan, is necessary. This study will find out whether it is necessary to test for bile duct stones in patients waiting for gallbladder surgery. By following up operation outcomes using medical notes, this study will compare what happens to patients who are tested for bile duct stones with patients who are not.

Project Details
Principal Investigator: James Hopkins
Planned End Date: 30/11/2022
Local Ref: 4262

COmBining memantine and cholinesterase inhibitors in Lewy body dementia Treatment trial

The COBALT Trial aims to find out if adding Memantine to AChEI treatment improves overall health and functioning for people with Lewy Body Dementia (DLB) or Parkinson's Disease Dementia (PDD).
A 150 patients with DLB and 150 patients with PDD, from across the UK will  take part in this trial. Participation will consist of a few visits over 52 weeks to the site for cognitive assessments, telephone follow ups and monitored use of either the placebo or Memantine. 

PI Dr Elizabeth Coulthard

Recruitment end date:01 April 2025

Local Ref: R&D 5195

Our research group and others have found links between Alzheimer’s and gum disease. Gum disease occurs when certain bacteria thrive under the gum line causing inflammation and bleeding. There is good evidence these bacteria pass into the bloodstream and speed up, or cause development of other diseases (such as diabetes and heart disease). This study monitors Alzheimer’s patients treated for gum disease for 12 months to see if this also slows their rate of memory loss. We're looking for 50 participants. 

PI: Dr Elizabeth Coulthard

Planned end Date: May 2025

Local Ref: R&D 5319