̽��ֱ�� of Cambridge - clinical trial

Dementia patients and their carers to be asked about direction of drug research

cjb250 — Wed, 19 Mar 2025 07:00:07 +0000

Today sees the launch of the POrtal for Patient and Public Engagement in Dementia Research (POPPED) website, where anyone can give their feedback on dementia research projects.

Dementia affects 50 million people worldwide and 1 million people in the UK. Current treatments are limited, but research has led to some significant recent advances. For example, the first drugs which slow down the disease are now licensed in the UK and potential dementia blood tests are being trialled.

Scientists are also turning to existing drugs to see if they may be repurposed to treat dementia. As the safety profile of these drugs is already known, the move to clinical trials can be accelerated significantly. Researchers want to ask members of the public which drugs they would like to see prioritised for these clinical trials.

Dr Ben Underwood, from the Department of Psychiatry at the ̽��ֱ�� of Cambridge and Cambridgeshire and Peterborough NHS Foundation Trust, said: “One thing that always improves research into medical conditions is the involvement of people with experience of them – in many respects, you are the experts, rather than us.

“As dementia is common, almost everyone has some experience of it, either through family, friends, work or meeting people with dementia in general life. It’s a problem across society and we want a wide range of opinions for the best way to tackle it.”

Dr Underwood has teamed up with Linda Pointon, a Programme Manager at the Department of Psychiatry, to create a website where everyone can give their feedback on dementia research projects. Linda herself has experience of caring for her mother-in-law, who had frontotemporal dementia and passed away in 2020.

Linda said: “We’re launching our website because we want as many people as possible to share their views and help us guide the direction of our research. It’s a great opportunity for all of us who have been affected by dementia, either directly or caring for a friend or relative, to help researchers understand what aspects of these potential treatments are important and meaningful, both in terms of benefits and side-effects.”

̽��ֱ��information collected by the POPPED team will be used to help inform AD-SMART, a trial to be led by Imperial College London, which will test several existing drugs alongside a placebo to quickly determine if any can slow early Alzheimer’s progression.

Dr Underwood added: “Instead of asking a few people what might be helpful, our website gives us the opportunity to ask thousands of people. ̽��ֱ��more people who use it, the more powerful it will be, so I’d encourage everyone to visit the site and tell us what they think. We can use it to work together to beat dementia, a condition whose effects I see in my clinic every day.”

Cambridge researchers are seeking the views of people with lived experience of dementia – patients and their friends and families – on which existing drugs should be repurposed for clinical trials to see whether they can slow or halt the progress of dementia.

One thing that always improves research into medical conditions is the involvement of people with experience of them – in many ways, they are the experts, not us

Ben Underwood

Toa55 (Getty Images)

Elderly woman putting pills into pill box for the week - stock photo

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Training a new breed of clinical triallist

skbf2 — Thu, 03 Feb 2022 11:48:27 +0000

Cambridge's Experimental Medicine Initiative, working with AstraZeneca and GSK, is training specialists who can work out at an earlier stage of clinical trials if a treatment is likely to succeed.

Cambridge leads trial to see if tapeworm drug can boost protection from COVID-19 among vulnerable

cjb250 — Mon, 22 Mar 2021 08:16:58 +0000

If the trial is successful, it may pave the way for a new treatment to prevent or alleviate the impact of COVID-19 in people on dialysis, people who have had a kidney transplant, and people with auto-immune diseases affecting the kidneys such as vasculitis who require treatment to suppress their immune system. ̽��ֱ��treatment will last up to nine months.

Led by scientists from the Cambridge ̽��ֱ�� Hospitals NHS Trust and the ̽��ֱ�� of Cambridge, the PROphylaxis for vulnerable paTiEnts at risk of COVID-19 infecTion (PROTECT-V) trial will start in Cambridge with a plan to expand to other UK healthcare centres. It will recruit at least 1,500 kidney patients, who will be randomised to receive either a placebo (or dummy) drug, or UNI911 (niclosamide) as a nasal spray, both provided by the manufacturer UNION therapeutics, in addition to all their usual treatments. Participants can receive the vaccine and still take part in this trial, which will identify whether niclosamide can protect people from the virus either on its own, or in combination with any of the vaccines currently available.

Niclosamide has been re-formulated into a nasal spray so it can be delivered directly to the lining of the nasal cavity, like a hayfever spray. In the trial, people will take one puff up each nostril twice a day, as this is the part of the body where the virus can take hold. This ‘local’ drug delivery is likely to reduce the chances of people experiencing any side effects.

Usually used to treat intestinal worms and taken as a tablet, niclosamide has shown real promise in the lab. Early tests revealed niclosamide could stop SARS-CoV-2 multiplying and entering cells of the upper airways.

Dr Rona Smith, senior research associate at the ̽��ֱ�� of Cambridge and honorary consultant nephrologist at Addenbrooke’s Hospital, who is leading the UK study, said: “It is vital that we find a way to protect patients on haemodialysis and other high-risk kidney patients from catching SARS-CoV-2 and developing COVID-19. If they get it, they are more likely to fall seriously ill or die, and we need to find a way to change that.

“We believe testing niclosamide is particularly important for people who are immunosuppressed and have kidney disease, because their immune responses to vaccines can sometimes be less effective. While the vaccine will offer a level of protection, niclosamide may provide further protection against COVID-19 that doesn’t rely on the immune system mounting a response.

“If successful, our innovative trial could mean that the treatment becomes available to kidney patients more widely within months. It would mean they could receive their regular life-saving dialysis or take their immunosuppressant drugs without additional worry. And if it’s successful it could even be rolled out more widely – and benefit more vulnerable people.”

̽��ֱ��trial involves researchers and patients from across the UK. It is funded by LifeArc, Kidney Research UK, the Addenbrooke’s Charitable Trust and UNION therapeutics and is supported by the NIHR Cambridge Biomedical Research Centre. UNION therapeutics is supplying the drug.

Professor Jeremy Hughes, kidney doctor and chair of trustees at Kidney Research UK, said: “Sadly, one in five kidney patients receiving dialysis in hospital or who have a kidney transplant and tested positive for the virus died within four weeks. Many of those on dialysis are having to put themselves at risk and attend their renal unit for life-saving dialysis treatment several times each week. And those who have had a kidney transplant must continue taking their immunosuppressant drugs, despite these making them more susceptible to infection.”

“Repurposing already available drugs or those in the late stage of development offers the fastest route to bring benefit to patients at this critical time,” said Melanie Lee, CEO of LifeArc.

Announcing the PROTECT-V trial, Matt Hancock, Health and Social Care Secretary, said: “Since the beginning of the pandemic, we have worked to find the best treatments the world has to offer for COVID-19.

“We have been clear from the outset that it will be a combination of safe and effective vaccines, testing and therapeutics that will bring an end to this pandemic, and we will not rest until every individual in the country is protected against this awful disease.”

Kidney patients who would like to take part in the PROTECT-V trial should speak to their nephrologist in their local centre to find out if their centre is participating in the trial and if they are eligible to take part.

Adapted from a press release by Kidney Research UK.

UK researchers are launching a clinical trial to investigate if the drug niclosamide, usually used to treat tapeworms, can prevent COVID-19 infection in vulnerable, high risk kidney patients and reduce the number of people who become seriously ill or die from it.

It is vital that we find a way to protect patients on haemodialysis and other high-risk kidney patients from catching SARS-CoV-2 and developing COVID-19

Rona Smith

BarocoF

Coronavirus

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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How machine learning can help to future-proof clinical trials in the era of COVID-19

Anonymous — Wed, 23 Sep 2020 16:41:38 +0000

In an article published in Statistics in Biopharmaceutical Research, an international collaboration of data scientists and pharmaceutical industry experts – led by the Director of the Cambridge Centre for AI in Medicine, Professor Mihaela van der Schaar of the ̽��ֱ�� of Cambridge – describes the impact that COVID-19 is having on clinical trials, and reveals how the latest machine learning (ML) approaches can help to overcome challenges that the pandemic presents.

̽��ֱ��paper covers three areas of clinical trials in which ML can make contributions: in trials for repurposing drugs to treat COVID-19, trials for new drugs to treat COVID-19, and ongoing clinical trials for drugs unrelated to COVID-19.

̽��ֱ��team, which includes scientists from pharmaceutical companies such as Novartis, notes that ‘the pandemic provides an opportunity to apply novel approaches that can be used in this challenging situation.’ They highlight the latest advances in reinforcement learning, causal inference and Bayesian approaches applied to clinical trial data.

̽��ֱ��researchers considered it important to present the current state of the art in ML and to signpost how they used ML not only to address challenges presented by COVID-19 but also to take clinical trials in general to the next level, making them more efficient, robust and flexible.

In their paper, the researchers say that COVID-19 is:

Reducing the ability/willingness of trial subjects and staff to access clinical sites, disrupting timely data collection or necessitating a move to virtual data collection.
In some situations, causing delays or halting of clinical trials altogether.
Revealing how the standard approach to clinical trials – time-consuming and inflexible randomised controlled trials in distinct trial phases – is inefficient, and not sufficient in a crisis such as this.

However, they say that machine learning can:

Support in the creation of ‘virtual’ control groups. By integrating data across hospitals, data-driven methods can identify patients who have received standard treatments but are otherwise similar to patients who have received experimental treatments.
Extract knowledge from the data of clinical trials suspended as a result of the pandemic to adjust design elements such as recruitment plans, sample sizes and treatment allocations.
Improve the design, execution and evaluation of large, adaptive clinical trials for evaluating repurposed medications for COVID-19. Trials such as Solidarity (WHO 2020) and RECOVERY (Oxford 2020), which are underway, recruit patients at a multitude of sites randomly assigned across available treatment arms.
Play an important role in finding patterns and signatures in COVID-19’s biomolecular behaviour, facilitating the identification and repurposing of existing drugs, as well as validating, in silico, whether new medicines may be effective.
Exploit the large body of data generated by the experimental and compassionate use of drugs to treat COVID-19 to select future drug target for further clinical trials. ML methods for causal inference from observational data are especially well-suited to this task.
Break the multi-phase paradigm of standard RCTs and convert the trial process into a more efficient, continuous and adaptive trial-collection-retrial loop. Use ML methodologies to learn simultaneously about toxicity and efficacy of a new drug, reducing learning time, making it particularly useful for time-sensitive clinical trials of COVID-19 treatments.

“ ̽��ֱ��coronavirus pandemic represents the greatest global healthcare challenge of our generation,” said van der Schaar. “Now, and in the immediate future, the need is to identify, approve and distribute treatments and vaccines for COVID-19. Our recent work in machine learning for clinical trials has shown enormous promise. And while many of the technical issues discussed in our paper are particularly acute in the context of a pandemic, they are also highly relevant to ongoing clinical practice. It is my hope that machine learning will not only improve the execution and evaluation of clinical trials in the COVID-19 era, but also well beyond that.”

“Artificial intelligence is already making significant impact in several areas of medicine,” said co-author Professor Frank Bretz from Novartis. “Machine learning algorithms have proven to be equivalent or superior to expert clinicians in interpreting X-ray and MRI images and slides, for example. This new work aims to bridge the gap between the machine learning community and the data scientists who are engaged in clinical trials that are affected by or related to COVID-19. Adopting these new methods is critical to the pharmaceutical industry well beyond the current pandemic. What we learn in this effort will yield benefits that affect the entire future course of drug development and change the lives of patients across the world.”

Reference:
William R. Zame et al. 'Machine Learning for Clinical Trials in the Era of COVID-19.' Statistics in Biopharmaceutical Research (2020). DOI: 10.1080/19466315.2020.1797867

̽��ֱ��COVID-19 pandemic is the greatest global healthcare crisis of our generation, presenting enormous challenges to medical research, including clinical trials. Advances in machine learning are providing an opportunity to adapt clinical trials and lay the groundwork for smarter, faster and more flexible clinical trials in the future.

It is my hope that machine learning will not only improve the execution and evaluation of clinical trials in the COVID-19 era, but also well beyond that

Mihaela van der Schaar

Image by PIRO4D from Pixabay

Coronavirus

Yes

‘Pill on a string’ test to transform oesophageal cancer diagnosis

Anonymous — Thu, 30 Jul 2020 22:30:00 +0000

̽��ֱ��test, which can be carried out by a nurse in a GP surgery, is also better at picking up abnormal cells and potentially early-stage cancer.

Barrett’s oesophagus is a condition that can lead to oesophageal cancer in a small number of people. It’s usually diagnosed in hospital by endoscopy – passing a camera down into the stomach – following a GP referral for longstanding heartburn symptoms.

̽��ֱ��Cytosponge test, developed by researchers at the ̽��ֱ�� of Cambridge, is a small pill with a thread attached that the patient swallows, which expands into a small sponge when it reaches the stomach. This is quickly pulled back up the throat by a nurse, collecting cells from the oesophagus for analysis using a laboratory marker called TFF3.

̽��ֱ��pill is a quick, simple and well tolerated test that can be performed in a GP surgery and helps tell doctors who needs an endoscopy. This can spare many people from having potentially unnecessary endoscopies.

In a study funded by Cancer Research UK, the researchers studied 13,222 participants who were randomly allocated to the sponge test or were looked after by a GP in the usual way. Over the course of a year, the odds of detecting Barrett’s were ten times higher in those offered the Cytosponge with 140 cases diagnosed compared to 13 in usual care. In addition, the Cytosponge diagnosed five cases of early cancer (stage 1 and 2), whereas only one case of early cancer was detected in the GP group.

Alongside better detection, the test means cancer patients can benefit from less severe treatment options if their cancer is caught at a much earlier stage.

“It’s taken almost a decade of research and testing thousands of patients to show that we’ve developed a better route to diagnosing Barrett’s oesophagus,” said Professor Rebecca Fitzgerald from the Medical Research Council Cancer Unit at the ̽��ֱ�� of Cambridge, who led the research. “And the sponge could also be a game-changer in how we diagnose and ensure more people survive oesophageal cancer. Compared with endoscopies performed in hospital, the Cytosponge causes minimal discomfort and is a quick, simple test that can be done by a GP. Our test is already being piloted around the country, so we hope more people across the UK could benefit from it.”

Because COVID-19 has reduced the number of endoscopies that can be carried out by the NHS, Addenbrooke’s Hospital in Cambridge has already fast-tracked the Cytosponge into use in order to help identify priority cases with suspected cancer who need further tests urgently.

̽��ֱ��researchers are currently putting the Cytosponge test through an economic evaluation and hope that it will be rolled out within GP practices within three to five years. It’s expected that the Cytosponge will be offered by GPs to patients on medication for acid reflux symptoms.

Professor Peter Sasieni, whose King’s College London team have been leading the clinical evaluation of the Cytosponge over the last decade, said: “ ̽��ֱ��results of this trial exceeded my most optimistic expectations. Use of Professor Fitzgerald’s simple invention will hopefully lead to a significant reduction in the number of people dying from oesophageal cancer over the next 20 years. This trial found that both patients and staff were happy with the Cytosponge test and it is practical to consider rolling it out within the NHS.”

“It’s great news for patients that there’s proven benefit to taking the Cytosponge test, and they won’t have to undergo a potentially uncomfortable endoscopy unless it’s needed,” said Dr Julie Sharp, Cancer Research UK’s head of health and patient information. “We hope that people will be able to access the Cytosponge from their GP as soon as possible. It will also help doctors enormously, as it will allow them to more accurately predict if someone is at risk of oesophageal cancer.

Around 9,200 people are diagnosed with oesophageal cancer in the UK each year and around 7,900 sadly die. Early diagnosis is crucial to patients’ survival and a shift in stage can have a large impact on outcomes. 85% of people diagnosed with the earliest stage of oesophageal cancer in England survive their cancer for 1 year or more. This figure drops to 21% if the cancer is diagnosed at the most advanced stage.

Liz Chipchase, a retired scientist from Cambridge, was one of the people who took part in the Cytosponge clinical trial. She felt in good health, but abnormalities were discovered and she was referred for further tests. Not only did she have Barrett’s oesophagus, she also had cancer.

“If I hadn’t been invited and gone on the trial, I would’ve had no idea that I needed treatment for an early stage cancer. And I’m also aware that the survival rate for oesophageal cancer isn’t good, so the fact I am clear of cancer is wonderful.

“I feel so lucky thinking about the chain of events that led to the cancer being caught when it was. To me, this trial saved my life.”

̽��ֱ��BEST3 study was primarily funded by Cancer Research UK (CRUK). ̽��ֱ��National Institute for Health Research (NIHR) covered service support costs and National Health Service commissioners funded excess treatment costs.

Reference:
Fitzgerald RC, et al. ‘A pragmatic randomised, controlled trial of an offer of Cytosponge-TFF3 test compared with usual care to identify Barrett’s oesophagus in primary care.’ ̽��ֱ��Lancet (2020). DOI:

Adapted from a Cancer Research UK press release.

A ‘pill on a string’ test can identify ten times more people with Barrett’s oesophagus than the usual GP route, after results from a 3-year trial were published in the medical journal ̽��ֱ��Lancet.

It’s taken almost a decade of research and testing thousands of patients to show that we’ve developed a better route to diagnosing Barrett’s oesophagus

Rebecca Fitzgerald

Cancer Research UK

Cytosponge

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Drugs: how to pick a winner in clinical trials

lw355 — Mon, 26 Jun 2017 11:00:12 +0000

“Did not meet primary endpoint.”

Prosaic words, but they can mean a billion dollar failure has just happened.

̽��ֱ��average cost of taking a scientific discovery all the way through to a drug on a shelf is enormous – last year it was estimated at $2.6 billion by the Tufts Center for the Study of Drug Development.

One reason the figure is so high is because it also includes the cost of failure. Recent years have seen some very high-profile failures of drug candidates that either did not meet the ‘primary endpoint’ (they didn’t work) or had their trials halted owing to serious side effects.

“It’s only natural that some drugs will fail in clinical trials – the process exists to ensure that treatments are safe and effective for patients,” says Professor Ian Wilkinson, Director of the Cambridge Clinical Trials Unit (CCTU) on the Cambridge Biomedical Campus. “But what’s unexpected is the high number of drugs that fail in phase III. You’d think that by this stage the molecule would be a sufficiently good candidate to make it through.”

He explains that failures in phases I and II – when the drug is tested for safety and dosage in healthy volunteers and patients – are inevitable. However, a great many molecules don’t make it through phase III, the stage at which the drug’s effectiveness is tested in large numbers of patients before regulatory approval is given. In fact only 10–20% of drugs that enter phase I are ultimately licensed.

“ ̽��ֱ��problem with failing at phase III is it’s very expensive – a single drug trial can cost around $500m.”

He continues: “There’s a human impact for the thousands of patients who enrolled on the trial. For patients with cancer, it’s sometimes their last available treatment option,” says Wilkinson. “It’s also really unhelpful economically. Pharma companies have less money to put back into R&D, and it becomes even harder to fund drug development.”

This is why Wilkinson, along with a team of clinicians, scientists and pharmaceutical collaborators, together with statisticians at the Medical Research Council Biostatistics Unit, has been taking a hard look at the early phases of clinical trials. Their aim is to ask what can be done to get an early indication that a potential drug will make it to market.

“Traditionally, clinical trials have been organised to test safety first and efficacy last,” he explains. “It’s a cautious step-by-step approach adopted to ensure that pharma companies can satisfy regulators that the drug is safe.

“For many drugs this has worked well. But we are in a landscape where drug targets are more challenging – think for instance of conditions like psychiatric disorders and dementia. Leaving questions of whether a drug is effective to the final stages is now too risky and expensive.”

On any one day, the CCTU (one of the UK units accredited by the National Institute for Health Research) might be coordinating up to 20 trials in various phases for potential treatments for cancer, stroke, infections, dementia, heart attack, and so on.

Many of the trials are now designed with what Wilkinson calls “added value” built in at very early stages to give indications of whether the drug might work. This could include a biomarker that shows a drug for cirrhosis is reaching the liver, or a drug for heart disease is lowering cholesterol. “These are read-outs. They don’t show the drug works for the disease, but if the results are negative then there’s no point in progressing to later stages.”

̽��ֱ��trials are also run ‘adaptively’. “We look at data for each person as it comes in… once we have enough information to guide us, we make a decision that might change the trial. It’s a quite different approach to the traditional rigidity of trials. It maximises the value of information a trial can yield.”

In recent years, pharmaceutical companies like GSK and AstraZeneca (AZ) have championed the need for rigorous trial design to weed out likely failures earlier in the process.

GSK has its only trials unit in the UK in the same building as the CCTU. There, GSK researchers work alongside Cambridge clinicians and scientists on first-in-man studies. A more targeted approach to testing medicines in patients is a key component of a Strategic Partnership between GSK, the ̽��ֱ�� of Cambridge and Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust (CUH), which has the long-term ambition of jointly delivering new medicines to patients in the next five to ten years.

A few years ago, AZ analysed its drug pipeline before embarking on a major revision of its R&D strategy to increase the chance of successful transition to phase III and beyond. One area AZ identified as being crucial to success is to identify a causal relationship between target and disease. This might seem obvious but so-called mistaken causation has led to late failures right across the drugs industry. ̽��ֱ��usual cause is confounding – where a factor that does not itself cause a disease is associated with factors that do increase disease risk.

Professor John Danesh and colleagues at the Department of Public Health and Primary Care have pioneered a new way of finding evidence for causality before a patient is ever involved. Called ‘Mendelian randomisation’, it’s akin to a trial carried out by nature itself.

“Misinterpreting correlation as causation is a big problem,” explains Dr James Peters, who works with Danesh. “An increase in a protein biomarker in patients with atherosclerosis might suggest it’s important in the disease, but it’s not a valid drug target unless it plays a causal role. ̽��ֱ��conventional way to test this is to block the protein with a drug in a clinical trial, which is expensive, time-consuming and not always ethical.

“In phase III trials, the randomisation of participants helps to average out all differences apart from whether they are receiving the drug. Instead, we take advantage of the natural randomisation of genetic variants that occurs during reproduction.”

Some genetic variants can increase or decrease certain proteins that have been linked to a disease. If these variants can be identified – by computationally analysing enormous genetic datasets – then researchers can compare groups of people to see whether having the variant also increases the risk of a disease.

̽��ֱ��team has used this method to look retrospectively at why two phase III trials for a potential cardiovascular drug failed. “ ̽��ֱ��genetic evidence showed that the drug target was not valid,” says Peters. “We would have advised against taking this drug to a clinical trial.”

But it’s not just about predicting failures, Danesh’s team is picking winners. Evidence for the role of an inflammatory protein in atherosclerosis has now resulted in a clinical trial to see if an arthritis drug can be repurposed for atherosclerosis.

̽��ֱ��researchers are helping industrial collaborators to prioritise potential drug targets and predict side effects. They also hope to expand their capabilities to test large numbers of variants for different potential targets in an automated fashion – a high-throughput approach to therapeutic target prioritisation.

Meanwhile, Wilkinson is planning ahead to avoid a different type of limitation: expertise. “There is a lack of individuals trained to design and deliver innovative clinical trials, and this is now impacting on drug development,” he explains.

Last year, an Experimental Medicine Training Initiative was launched to train medics how to run innovative clinical trials. Wilkinson is its Director and it’s supported by the ̽��ֱ�� in partnership with CUH, Cambridge Biomedical Research Centre, and AZ/MedImmune and GSK.

“We all believe that the failure rate for drug candidates making it through phase III is unacceptably high,” he says. “Less than one in a thousand molecules discovered in the lab make it through to being a drug. We want to be sure that we can answer the billion dollar question of which are most likely to be winners.”

Read more about research on future therapeutics in Research Horizons magazine.

When a drug fails late on in clinical trials it’s a major setback for launching new medicines. It can cost millions, even billions, of research and development funds. Now, an ‘adaptive’ approach to clinical trials and a genetic tool for predicting success are increasing the odds of picking a winner.

We all believe that the failure rate for drug candidates making it through phase III is unacceptably high. We want to be sure that we can answer the billion dollar question of which are most likely to be winners.

Ian Wilkinson

Gatis Gribusts

Medication

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Using the internet to boost participation in clinical trials

cjb250 — Mon, 27 Apr 2015 23:00:44 +0000

Type 1 diabetes, the disease that I mainly focus on, is relatively common in the UK – around one in 300 people in the UK alone are affected by it and face multiple daily insulin injections. So one might imagine we would have no problem recruiting patients for the trial of an exciting potential new treatment that could mean an end to those injections in the future.

As you may know already, type 1 diabetes is an autoimmune disease – the immune system mistakes cells in the pancreas as harmful and attacks them. When these cells are damaged the pancreas is unable to produce enough insulin, which plays an essential role in transferring glucose out of the bloodstream and into cells to be converted into energy. This is why patients have to regularly inject themselves with insulin to compensate.

Type 1 diabetes is a genetically complex disease – there is no single gene that causes it, but rather dozens of genes that increase the risk of developing the disease. But we do know of one particular set of genes – interleukin-2, or IL-2 – which plays a prominent role, helping regulate the immune system. We wanted to see whether IL-2 in the form of a drug called aldesleukin could halt the damage to the pancreas in people with newly diagnosed type 1 diabetes and, if so, what dose of the drug gives the best results.

̽��ֱ��problem, of course, is that not everyone with type 1 diabetes is aware of these essential studies and the ability to recruit enough patients can make or break a trial – not enough participants and the trial will be dead in the water before it has even begun. ̽��ֱ��solution is the internet, which provides a direct communication route to individuals with type 1 diabetes allowing them to find out about studies and then immediately with ease connect to the specialist teams running these studies. To get our message out on the web we turned to our funders and the ̽��ֱ�� of Cambridge.

We were very excited at the prospect of trialling this drug – and so, too, were our funders. ̽��ֱ��Wellcome Trust and the ̽��ֱ�� issued a joint press release, which they, together with the JDRF, ran on their websites and promoted through social media. When we looked at the number of people visiting our study website, we could see clear peaks of activity immediately after the stories appeared – and what’s more, this translated into people signing up to the trial: registration increased six- to seven-fold.

Recruitment to the study was also helped massively when Wired.co.uk picked up on the press release and ran a story about the trial – in fact, the single biggest peak of traffic to our site by far came from traffic referred to us from Wired.

Diabetes UK, too, posted an article about the trial. Interestingly, this post increased registrations from clinics and registry sources. We think this is because it stimulated interest from clinicians and research nurses, who then encourage enrolment from their patients.

Overall we found that the internet compared to traditional method of recruitment, to be the most successful and popular method for individuals with type 1 diabetes to find out and participate in the DILT1D study. ̽��ֱ��success of the active internet recruitment strategy campaign meant that we were able to successfully complete our study 11 months ahead of schedule and continue the development of the treatment in our next study.

Dr Frank Waldron-Lynch is Head of Experimental Medicine at the JDRF/Wellcome Trust Diabetes and Inflammation Laboratory in the Cambridge Institute for Medical Research

Reference
Heywood, J et al. Effective recruitment of participants to a phase I study using the internet and publicity releases through charities and patient organisations: analysis of the adaptive study of IL-2 dose on regulatory T cells in type 1 diabetes (DILT1D). Trials; 11 March 2015

̽��ֱ��success of a clinical trial hinges on its ability to recruit enough patients. Dr Frank Waldron-Lynch from the Cambridge Institute for Medical Research explains how the use of the internet to directly contact patients with type 1 diabetes greatly accelerated the recruitment leading to the early completion of his team’s study of a potential new treatment for type 1 diabetes.

̽��ֱ��ability to recruit enough patients can make or break a trial – not enough participants and the trial will be dead in the water before it has even begun

Frank Waldron-Lynch

rachellynnae©

High blood glucose

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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Study of peanut allergy therapy shows 84 per cent success

fpjl2 — Thu, 30 Jan 2014 10:47:30 +0000

Allergy experts have found that 84 and 91 per cent of the two groups of children treated with a new form of immunotherapy could eat at least five peanuts a day.

̽��ֱ��phase 2 trial - the largest of its kind worldwide - used oral immunotherapy (OIT), in which peanut protein is consumed in increasingly larger amounts on a regular basis to build up tolerance. ̽��ֱ��results are published today in ̽��ֱ��Lancet.

̽��ֱ��research involved young people, aged between seven and sixteen, eating daily doses of peanut protein - starting with a tiny dose and slowly building up over four to six months.

After 6 months of OIT, 84–91% of the children could safely tolerate daily ingestion of 800 mg of peanut protein (roughly the equivalent of five peanuts), at least 25 times as much peanut protein as they could before the therapy.

Peanut allergy affects around half a million people in the UK and over 10 million people across the globe. It’s the most common cause of fatal food allergy reactions and, unlike other childhood food allergies such as cow’s milk, peanut allergy rarely goes away. People with peanut allergy risk anaphylactic shock or even death if they become accidentally exposed to peanut.

̽��ֱ��Cambridge allergy research team, led by Dr Andrew Clark and Dr Pamela Ewan from the ̽��ֱ��’s Department of Medicine, have been leading allergy research for more than 20 years.

“Before treatment children and their parents would check every food label and avoiding eating out in restaurants,” said Clark. “Now most of the patients in the trial can safely eat at least five whole peanuts. ̽��ֱ��families involved in this study say that it has changed their lives dramatically.”

“This large study is the first of its kind in the world to have had such a positive outcome, and is an important advance in peanut allergy research,” added Ewan.
“However, further studies in wider populations are needed. It is important to note that OIT is not a treatment people should try on their own and should only be done by medical professionals in specialist settings.”

In the first part of the trial, 99 children with varying severities of peanut allergy were randomly assigned to receive either 26 weeks of OIT or peanut avoidance (the present standard of care). All the children then participated in a double-blind placebo-controlled oral food challenge during which they gradually consumed increasing amounts of peanut protein under medical supervision to determine at what level they experienced allergic symptoms. In the second part, the control group was offered 26 weeks of OIT followed by a final food challenge.

After 6 months of therapy, 24 of 39 children (62%) who received OIT in the first phase passed the challenge and tolerated a daily dose of 1400 mg of peanut protein, roughly equivalent to 10 peanuts (an amount unlikely to be encountered accidentally), compared with none of those in the control group. After the second phase, 54% tolerated the challenge. Food-allergy specific quality of life scores also improved after OIT.

Although a fifth of those receiving OIT reported adverse events, most were mild with oral itching being the most common.

Lena Barden, 11, from Histon in Cambridgeshire, said: “I felt like I had won a prize after I found out I had been picked for the active group. It meant a trip to the hospital every two weeks. A year later I could eat 5 whole peanuts with no reaction at all. ̽��ֱ��trial has been an experience and adventure that has changed my life and I’ve had so much fun. But I still hate peanuts!”

Thomas Baragwanath, 16, from Holbeach, Lincolnshire, said: “ ̽��ֱ��trial has helped me so much. I don’t have to worry when I go out with my friends about what I’m eating and where it’s come from ‘What’s in it? Where’s it been prepared?’ - I don’t have to worry at all.”

̽��ֱ��trial was carried out over five and a half years in the NIHR Wellcome Trust Clinical Research Facility at Addenbrooke’s, part of Cambridge ̽��ֱ�� Hospitals (CUH). It was funded by the MRC-NIHR partnership through the Efficacy and Mechanism Evaluation (EME) Programme. Initial pilot work was funded by the Evelyn Trust, Cambridge.

̽��ֱ��next step is to make peanut immunotherapy widely available to patients. Further investigation and a licensing review will be required to obtain a product licence from the regulatory authorities, which will take several years. In the meantime, Cambridge ̽��ֱ�� Hospitals is planning to open a peanut allergy clinic that would make a range of services, including immunotherapy on a named patient basis, available to patients.

For further information about the development of peanut immunotherapy and when it will become available in clinics, visit www.cambridgeallergytherapy.com.

For more information on this research, please contact Adrian Ient: adrian.ient@addenbrookes.nhs.uk

Inset image: Dr Clark in the allergy clinic at Addenbrooke's Hospital

A new therapy for peanut allergy has been successful in the majority of the 99 children who took part in a clinical trial.

̽��ֱ��trial has been an experience and adventure that has changed my life and I’ve had so much fun. But I still hate peanuts!

Lena Barden, 11, from Histon in Cambridgeshire

Daniella Segura

Peanuts

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