Oxford University Hospitals NHS Foundation Trust is one of the centres where the trial will be conducted, and where patients will be recruited. Research at Oxford into Crohn’s disease and other inflammatory bowel conditions is supported by the NIHR Oxford Biomedical Research Centre.
Crohn’s disease is a painful and chronic intestinal disease which affects at least 115,000 people in the UK. The condition causes inflammation of the lining of the digestive system, and results in diarrhoea, abdominal pain, extreme tiredness and other symptoms that significantly affect quality of life.
Current treatments include drugs to reduce inflammation but these have varying results, and surgery is often needed to remove the affected part of the bowel. In extreme cases, after multiple operations over the years, patients may require a final operation to divert the bowel from the anus to an opening in the stomach, called a stoma, where stools are collected in a pouch.
The study, led by Queen Mary University of London and Barts Health NHS trust, is funded with £2m from a Medical Research Council and National Institute for Health Research partnership. As well as Oxford, patients will be recruited in Cambridge, Edinburgh, Liverpool, London, Nottingham, and Sheffield. The trial is coordinated through the Clinical Trials Unit at the University of Sheffield.
Professor Simon Travis (pictured above right), the consultant gastroenterologist who will be leading the study at OUH, said: “Many patients do not respond to the new drugs that have been introduced to tackle Crohn’s disease. Surgery and stomas allow some patients to resume a normal life, but they are not appropriate for all patients.”
“We’re hoping that we can alter the course of this disease by completely ‘resetting’ a patient’s immune system through a stem cell transplant. Rather than being a cure, this approach may allow some patients to respond to drugs that had previously been ineffectual for them.
Helen Bartlett, a Crohn’s disease patient who had stem cell therapy at Oxford’s John Radcliffe Hospital as part of an earlier trial, said: “Living with Crohn’s is a daily struggle. You go the toilet so often, you bleed a lot and it’s incredibly tiring. You also always need to be careful about where you go. I’ve had to get off trains before because there’s been no toilet, and I needed to go there and then.
“When offered the stem cell transplant, it was a complete no brainer as I didn’t want to go through yet more failed operations. I cannot describe how much better I feel since the treatment. I still have problems and I’m always going to have problems, but I’m not in that constant pain,” Helen, pictured left) said.
The use of stem cell transplants to wipe out and replace patients’ immune systems has recently been found to be successful in treating multiple sclerosis. This new trial will investigate whether a similar treatment could reduce gut inflammation and offer hope to people with Crohn’s disease.
In the trial, patients undergo chemotherapy and hormone treatment to mobilise their stem cells, which are then harvested from their blood. Further chemotherapy is then used to wipe out their faulty immune system. When the stem cells are re-introduced back into the body, they develop into new immune cells which give the patient a fresh immune system.
In theory, the new immune system will then no longer react adversely to the patient’s own gut to cause inflammation, and it will also not act on drug compounds to remove them from their gut before they have had a chance to work.
Professor Tom Walley, Director of the NIHR Evaluation, Trials and Studies programmes, which funded the trial, said: “Stem cell therapies are an important, active and growing area of research with great potential. There are early findings showing a role for stem cells in replacing damaged tissue. In Crohn’s disease this approach could offer real benefits for the clinical care and long term health of patients.”
The current clinical trial, called ‘ASTIClite’, is a follow up to the team’s 2015 ‘ASTIC’ trial, which investigated a similar stem cell therapy. Although the therapy in the original trial did not cure the disease, the team found that many patients did see benefit from the treatment, justifying a further clinical trial.
Prof Travis, Professor of Clinical Gastroenterology in the University of Oxford’s Nuffield Department of Medicine, said: “The previous ASTIC study showed that haematopoietic stem cell transplantation was effective in some patients, especially those for whom other treatment options had been exhausted. However, we could not say with confidence that it was better than any current standard treatment.
“One of the main issues with the original trial was the toxicity of the treatment, because of the high doses used. We are hopeful that the lower-intensity treatment being used in this trial will minimise those risks ate translate into real benefits for patients.”
The study was funded by a Medical Research Council and NIHR partnership created to support the evaluation of interventions with potential to make a step-change in the promotion of health, treatment of disease and improvement of rehabilitation or long-term care.