Gwo-tzer Ho (Consultant Gastroenterologist and Researcher)
I look after patients with IBD at the Western General Hospital and I lead a group of scientists in the University of Edinburgh that are doing research to understand why people develop these conditions. I have worked in science for more than 20 years, ever since my first spark of interest, having completed my PhD in 2003 in Edinburgh!
The ultimate aim of any person in my field is to bring about new knowledge of science into direct improvement in our patients. How do the results of our experiments in the lab ultimately help our patients in the clinic? This journey can be often long and challenging (and many times unfruitful!).
Figure 1: Mitochondria (‘Batteries’ or ‘Powerstations’) in the gut lining cells (yellow arrows). All cells have mitochondria, which are descended from ancient bacteria 3 billion years ago. Mitochondria produce energy for cells but are also important for many other functions including in controlling immune and inflammation responses. Electron micrograph with magnification of >100 times.
The bottom panel is a zoomed-in version of the top panel.
In 2010, I made the observation that there were high levels of mitochondrial damage (damage to the ‘batteries’ of the cell, see figure 1) in the gut lining of mouse IBD models (mice that scientists use in the lab to better understand the biology of IBD.) More recently, we have also observed this in humans. Not much was known about this then, but it has now been shown that damaged mitochondria can cause inflammation. Following work funded by MRC and Crohn’s & Colitis UK, we came up with the idea that treating the damaged mitochondria might be beneficial for Ulcerative Colitis (UC).
But the idea was the easy part!
It was only in 2021 that we finally opened our clinical trial (www.marvelstudy.uk), more than 10 years after making that initial observation! During that time, we learned from scratch all the fundamentals about clinical trials, worked with experts and regulatory bodies, and got through the challenging pandemic period. We are now delighted to be recruiting participants across hospitals in the UK.
We aim to complete the study in 2025 and report the final results. Then, using evidence from our trial, we will plan the next steps for this work.
What is a clinical trial?
In order to find out if a new treatment works in IBD, a researcher has to compare this treatment in a group of patients who receives it with one that don’t (a placebo group).
If the tested treatment works, one would expect many more people in the treatment group to get better compared to the placebo group. Sometimes, if the difference is expected to be small – a trial has to be carried out in large numbers of patients.
The best trials are carried out when neither the participant nor researcher know whether they are getting the drug or placebo (what we call ‘double-blinded’ study).
We usually find out the results when all the patients have been enrolled and finish their follow-up in the study.
Since there are many more treatments available in IBD, many new clinical trials are carried out alongside with standard NHS treatments.
Patient safety is most important. That is why all clinical trials need approval from an independent ethical review committee and also pass all the rigorous safeguards by the regulatory bodies such as the MHRA.
Clinical trials are vital to find new and better ways to treat IBD. Even if a study is negative, it provides a lot of knowledge that can help shape future research and studies.
Figure 2: Phoebe Lau, our research scientist working on cells from our patients in our lab, at the Centre for Inflammation Research, University of Edinburgh
Figure 3: Our team at Western General Hospital, Edinburgh after recruiting the first participant for MARVEL UC study in June 2022, more than 12 years after the initial scientific research work. Left to right: Dr Gwo-tzer Ho (CI), Ms Jackie Moloney, Ms Katie Mungall (both Endoscopy Nurses), Dr Shaun Chuah, Dr Rebecca Hall (clinical research fellows) and Ms Athena Oddy (research nurse)
Jon Rysdale (Patient Involvement and Engagement in the Edinburgh IBD Science Group)
I first began to show the signs and symptoms of UC in my late twenties although it was more than a decade before I was actually diagnosed with the condition. Over the years I was treated with many different medications without ever achieving a long-term remission. My symptoms waxed and waned over the years progressively getting more and more debilitating until, in my fifties, I had an operation to remove my colon.
A colectomy is a life changing operation that has many pros and cons. It certainly cured my symptoms of colitis.
Having lived with quite difficult symptoms of UC for many years, I wanted to see if there were opportunities to help with research to further understand and improve treatment in IBD.
Since 2018, myself and several other patients collaborate with Gwo-Tzer and his team from a patient engagement perspective. What does this mean?
Firstly, we help to provide the patient’s perspective into the research and in this case, the clinical trial. Sometimes, clever clinicians just don’t see simple practical things that can make things better for the patients!
Examples include helping to improve the design of clinical studies to suit and benefit the patient. Reviewing and making the Patient Information Sheets that patients read when considering to take part in our studies, easier to read. Also, making sure we capture and improve the patients’ experience when they do take part in research.
From a personal viewpoint, I feel that we are still some way off from finding a cure for IBD but with your help and participation in clinical research I am hopeful that one day we will get there.
Figure 4: Jon Rysdale (from North Berwick), our patient public engagement volunteer in the Edinburgh IBD Science group
Lisa Derr (Trial Manager for MARVEL)
I have worked in research for over 10 years now. I started my research career as a research nurse in 2013 and then moved into trial management in 2018. I have worked on the MARVEL study since 2019.
Perhaps people don’t know this – but we are extremely fortunate that we have a good system in place to allow trials to be carried out in the UK, safely and with the patients’ best interest at heart.
Running a drug trial especially, is very complex and challenging! Particularly coordinating everything from all the regulatory approvals to opening new hospital sites.
Currently, I am coordinating the study from 7 different hospitals across the UK.
Trial management provides a lot of variety and opportunity to work with many different people.
I love the people aspect of the job! I get a lot of satisfaction knowing that I am contributing to evidence-based medicine and ultimately improving the care pathways for patients.
Figure 5: Gwo-tzer Ho with Lisa Derr (MARVEL trial manager) and Alix Macdonald (miniMARVEL trial manager, the paediatric arm of MARVEL study). Trial managers ensure the smooth running of studies often involving many hospitals and patients from across UK.
Concluding Remarks
Although science can be challenging and equally rewarding, no translational research can be successful without our patients. We are very grateful to all our patients and also Crohn’s & Colitis UK. The Charity has supported not only our work but many other studies, both in terms of funding and increasing awareness of all our work.
Footnote:
MARVEL is a Phase 2b double-blinded randomised controlled trial in UC comparing oral mitochondrial antioxidant therapy with placebo in patients treated with oral prednisolone for a flare of UC. This study is ethically approved by South East Scotland Ethics Committee, sponsored by NHS Lothian and University of Edinburgh; and funded by Jon Moulton Foundation. You can follow the progress of MARVEL study on Twitter at @Marveltrial.
Want to follow progress of MARVEL study?
You can do so by following their Twitter account.
