Tag: Clinical research

A deep dive into 30 years of progress and challenges

Professor Jonathan Valabhji

Diabetes now affects over half a billion people globally, including 3.8 million people in England. Type 2 diabetes, which accounts for 90-95% of all cases, has obesity as its primary modifiable risk factor. Expanding waistlines, both nationally and globally, have driven a steady increase in type 2 diabetes rates in recent decades. To mark World Diabetes Day, Professor Jonathan Valabhji OBE, from the Department of Metabolism, Digestion and Reproduction, reflects on his 30 years of experience in the field, in clinical practice, in national leadership, and in clinical and epidemiological research.  

My background in Diabetes research and clinical practice 

I qualified as a doctor in 1990 from St Bartholomew’s Hospital Medical College, London. I undertook specialist training in diabetes, endocrinology, and general medicine in North-West London, and landed at Imperial College in 1997 to undertake my MD (Doctor of Medicine degree) as a British Heart Foundation Junior Research Fellow. In those early years, I was interested in cardiovascular disease in diabetes, which at that point was responsible for the majority of deaths in people with diabetes. My work centred on understanding the paradox in type 1 diabetes: although patients often displayed healthy cholesterol profiles, they were at elevated risk of heart attacks and strokes. I spent 3 years in a lipid laboratory, using ultracentrifugation (a technique used to separate and isolate particles based on their density) to isolate high-density lipoprotein (HDL) cholesterol particles from blood samples, to try to disentangle the paradox.  

Population-level progress in cardiovascular health  

While I like to think that some of that early research advanced the field a little, it was other epidemiological and societal factors that saw cardiovascular disease fall in people with diabetes over the next two decades. Public health initiatives, such as reduced smoking rates, and improved management of blood glucose, blood pressure, and cholesterol, have collectively driven a marked decrease in cardiovascular complications, resulting in longer lifespans for people with diabetes. However, with this success came new challenges, as other and multiple long-term conditions (MLTCs) have increasingly become leading causes of illness and death. This has complicated care for patients, healthcare professionals, and the NHS.  At the same time, obesity has driven younger onset of type 2 diabetes, contributing to accelerated development of MLTCs at younger ages. 

(more…)

The Fleming Centre: Driving the fight against antimicrobial resistance.

Prof Ara Darzi, Chair, The Fleming Centre Initiative 

In the relentless pursuit of global health, few adversaries loom as large as antimicrobial resistance (AMR). AMR poses a pervasive threat to both different disease areas and public health as a whole. It has the potential to undermine modern medicine, as previously treatable common infections and injuries may once again become life-threatening. As the gravity of this crisis intensifies, The Fleming Centre will stand at the forefront of a burgeoning global movement to combat AMR. On World Antimicrobial Awareness Week,  Professor Ara Darzi, Chair of The Fleming Centre Initiative, writes about the pivotal role this centre will play in the fight against AMR and the far-reaching impact it promises to deliver.  

AMR poses a significant threat to global health, making it one of the most pressing challenges of our time. Drug-resistant infections occur when the bacteria responsible for the adaption and evolution of infections, gain the capacity to withstand drugs intended to kill them. The overuse and misuse of antimicrobial drugs, such as antibiotics and antifungals, in both humans and animals is only accelerating this process. As a result, AMR has been linked to more than one million deaths worldwide each year; a sign common infections are becoming increasingly difficult to treat as the medicines we all rely on become less effective. With people across the globe already dying from drug-resistant infections, the threat of more drugs losing their potency, will put more lives at risk.  

Deaths attributed to AMR every year
Source: Wellcome Trust (https://wellcome.org/sites/default/files/wellcome-global-response-amr-report.pdf)

(more…)

A new dawn for disease modelling and precision medicine at Imperial College London

Tamas Korcsmaros

In a ground-breaking stride towards advancing medical research, earlier this year, the NIHR Imperial Biomedical Research Centre (BRC) proudly inaugurated the state-of-the-art Organoid Facility. This monumental achievement is the result of years of meticulous planning and the outstanding contributions of researchers like Tamir Rashid, Gary Frost, Nick Powell, and Harry Leitch, who laid the foundation for what promises to be a revolutionary venture in the field of organoid science. Generously backed by five years of strategic funding from the NIHR, the Organoid Facility is poised to become a pivotal resource, not just within Imperial College but across the academic community. Dr. Tamas Korcsmaros, Senior Lecturer in Intestinal Epithelial Biology for the Department of Metabolism, Digestion and Reproduction shares more about the launch of the Facility and how they hope to transform precision medicine.

Understanding diseases better and improving how we model them has been the focus of biomedical research for the last couple of decades. Relevant, scalable and useful animal models have been established to understand the basic biology of cellular and mammalian systems in vivo – experiments conducted for research purposes on whole living organism. Rodent models have been used for preclinical and toxicology testing of promising drug molecules. To complement these efforts, immortalised, cancer-related human cell lines have been used to understand in vitro (experiments conducted for research purposes outside of a living organism e.g., test tube) how these systems work in a human cell. However, all these systems possess different limitations: Animal models are often not completely resembling human processes, especially when we are thinking of host-microbe interactions for example, where a mouse gut is very different from a human gut. Human cell lines are often altered due to their immortalization. In addition, many cell types cannot be kept in cell lines, resulting in no data or testing option on key cell types. Around 15 years ago a new technology started to emerge based on isolating and differentiating specific stem cells of an organ. With this approach, a simplified but 3D models of an organ, mostly containing only its epithelial layer can be developed. They are called organoids.

(more…)

Embracing doubt in science

Nana-Marie Lemm, Clinical Research Fellow

Why is ‘doubt’ an important resource in science? How can we support the kind of science that takes intellectual risks – and takes time? Nana-Marie Lemm, Clinical Research Fellow at the Department of Infectious Disease, gives her reflections on the recent Day of Doubt conference, organised by the Good Science Project. 

What are the motivations for becoming a scientist? It might be the search for truth or to understand how things work, or to work towards a greater good. But how does that idea compare to the reality of the day-to day work of science, and the culture of doing science? 

The Day of Doubt was the first conference of its kind at Imperial College London. Organised by The Good Science Project, the conference aimed to reflect on research culture at the university level and beyond. It provided a space for discussion, reflection, and the opportunity to ask fundamental questions.  

So, what is ‘doubt’ and why might it be important in science? The team behind the Good Science Project have helpfully created a thesaurus of doubt and a memo document on the day. In the latter, Dr Anthea Lacchia writes:  

“If we take doubt to be the opposite of complacency, it is associated with pause, with thoughtful hesitation. Yet, this act of questioning, of taking necessary time before making a decision, seems at odds with the push for success, publications, and the need for high impact results. In truth, science is full of conflicts, some internal, some relating to wider culture.”  

On the day, there was the opportunity to take time to engage in the act of questioning. Reflective sessions ranged from questioning concepts such as, ‘public engagement,’ ‘interdisciplinarity,’ ‘excellence,’ ‘expertise,’ to delving into philosophical discussions surrounding the nature of scientific truth. 

A key question to speakers in the first session of the conference that resonated with me was,  “How do you talk about doubt when you don’t come from a position of seniority and confidence?” 

(more…)

Involving critically ill children in research: Is that even possible?

When a young patient’s life hangs in the balance, the last thing on the minds of stressed parents, families and patients would be to get involved in research. Or is it? Despite the turmoil, some brave families and children have volunteered to support clinicians in their research by taking part. Dr Padmanabhan Ramnarayan, Clinical Reader in Paediatric Critical Care in the Department of Surgery and Cancer and Honorary Consultant in Paediatric Intensive Care at Imperial College Healthcare NHS Trust and West London Children’s Healthcare, explains why.  

I have been a children’s intensive care doctor for over 20 years, and for most of that time, I have been leading research that has involved critically ill children. My patients are young, their parents and families are super-stressed, and most of the treatments are given in an emergency – all of which seem like perfectly valid reasons to not involve sick children in research. Despite this, my experience is that parents and families are overwhelmingly in support of research. Why? 

The evidence gap 

Since children’s intensive care is a young speciality, much of our practice is ‘borrowed’ from adult intensive care or newborn intensive care. This is not ideal because our patients range from birth to 18 years of age, with diseases as diverse as asthma, respiratory infections, accidents and trauma, sepsis and brain injury. Without high-quality research to guide care, the treatments provided to sick children may not be the best or the most effective. Doctors and nurses, and parents and families, understand this. By agreeing to include their children in research studies, parents want to improve the care provided to future patients. 

(more…)

Professor Sir Peter Barnes knighted for excellence: Reflections on his career in respiratory science

Professor Sir Peter Barnes FRS FMedSci, from the National Heart and Lung Institute (NHLI), was made a Knight Bachelor in this year’s King’s Birthday Honours “for services to respiratory science.” Sir Peter is Professor of Thoracic Medicine at the NHLI and he was Head of Respiratory Medicine at Imperial until 2017. Here he writes about his reaction to his award and describes some of the current research projects in chronic obstructive pulmonary disease (COPD).

A surprise! 

My wife opened the letter “On His Majesty’s Service” as she thought it was a tax demand – I was absolutely shocked to see I had been offered a knighthood. Of course, I was and am delighted with the award. It is very good for respiratory science and medicine, which generally receives little public attention. This is surprising as chronic lung diseases are amongst the most common in the UK, affecting one in seven people and the third ranked cause of death. I would like to dedicate this award to all the brilliant students, post-docs, research fellows, visiting scientists and colleagues that I have worked with at Imperial College London over many decades.  

(more…)

How can we manufacture the safest possible challenge agents for human infection studies?

Pipettes in a scientific lab
Dr Emma Smith—HIC-Vac Network Manager—explains how specific guidelines for the provenance and manufacture of challenge agents could make human infection studies even safer.

Human infection studies, also known as human challenge studies, are clinical trials where volunteers are intentionally given a carefully considered dose of a pathogen—known as the challenge agent. These models can be used to study host-pathogen interactions and disease progression; identify and test the efficacy of promising vaccines and drugs in development; or be used as proof-of-concept studies for testing novel medications. In this controlled environment it is possible to study infections in ways that aren’t possible in traditional field studies.

One of the first steps towards establishing a challenge study is the selection, isolation, development and production of the challenge agent. However, unlike medicines, the regulation of challenge agent manufacture varies internationally; an area that the research community has identified as a potential weakness in the field. Although human challenge studies have an excellent safety record—a recent literature review identified just 24 Serious Adverse Events (SAE) and zero deaths or cases of permanent damage among 15,046 participants in 308 studies spanning 1980 to 2021— the lack of specific guidelines for the provenance and manufacture of challenge agents warrants attention.

HIC-Vac—an Imperial-led international network of researchers who are developing human infection challenge studies—has been working with the global charitable foundation Wellcome and the company hVIVO to address this unmet need. Our purpose was to promote volunteer safety whilst maximizing access to challenge agents and challenge models globally. (more…)

A week in the life of a Clinical Research Fellow

Dr Francesca Conway takes us through a typical week as a clinical research fellow and how her previous time at Imperial contributed to her developing an interest in a career in clinical academia.

Monday

6am. I’m awakened by the horrifically jolly alarm tone on my phone. It’s still dark, it’s still raining, and it’s still cold. Hedgehogs have the right idea hibernating over winter, I think, as I haul myself out of bed.  Must consider this hibernation proposition in my next supervisor meeting. 1 shower, 1 yoghurt and 3 smoothies later and I’m in the hospital.

Today I have a patient coming to see if she is eligible to be recruited to the clinical trial which forms part of my PhD. Mrs X has travelled from 300 miles away. She greets me with a smile and tells me how pleased she is to be here. I immediately remember why I love my job, and scrap the idea of hibernation. I offer her a coffee, she gratefully accepts and whispers, could I have an extra shot in that? I assume she means coffee. I wonder what time she woke up, but am pretty sure it was before 6am.

I am researching a potential new treatment for Chronic Cbstructive Pulmonary Disease (COPD) for my PhD. Mrs X suffers with COPD, a disease affecting the lungs most commonly caused by smoking. More than 3 million people die from it each year. Targeted Lung Denervation or “TLD”, is a non-surgical procedure where we deliver energy to the airways using a system made by Nuvaira, a US-based company. The idea is that the energy disrupts the nerve supply to the lungs, so the airways relax and open. With initial data looking promising, we hope that this will lead to improvements in health for patients like Mrs X. More information on the Airflow website. (more…)