A clinical trial to use stem cell transplants to grow new immune systems for people with untreatable Crohn’s disease has begun.
The study, coordinated through the Clinical Trials Unit at the University of Sheffield, is led by Queen Mary University of London and Barts Health NHS trust and is funded with £2 million from a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership.
Patients will be recruited for the trial named ASTIClite (Autologous Stem cell Transplantation In refractory Crohn’s disease – Low-Intensity Therapy Evaluation), from centers in Sheffield, Cambridge, Edinburgh, Liverpool, London, Nottingham, Oxford.
Crohn’s disease is a painful, long-term condition which affects 115,000 people in the UK. It causes inflammation of the lining of the digestive system, and results in diarrhoea, abdominal pain, extreme tiredness and other symptoms that significantly affect the 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 patients may require a final operation to divert the bowel to an opening in the stomach, called a stoma.
“Investigators in the ASTIClite trial hope that by completely resetting the patient’s immune system through a stem cell transplant, it might be possible to radically alter the course of the disease. Stem cell transplant alone may not provide a cure, but it may allow some patients to start responding to drugs which had not worked previously," says Lizzie Swaby, Study Manager for the ASTIClite trial from the School of Health and Related Research (ScHARR) at the University of Sheffield.
“Although there are multiple treatment options available for patients with Crohn’s Disease, in many cases these do not work, with patients’ either not responding, or suffering unpleasant side effects. Surgery can be an option, which may allow patients to return to their normal daily activities, but this is not always suitable, and some patients may not wish to consider surgery,” she says.
“Living with Crohn’s is a daily struggle. You go the toilet so often, you bleed a lot and it’s very tiring. I’ve been in and out of a hospital for the last 20 years, operation after operation, drug after drug, to try to beat this disease. It’s frustrating, it’s depressing and you just feel so low," says Helen Bartlett, a Crohn’s disease patient who had stem cell treatment.
“When I was 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 constant pain”, she says.
The use of stem cell transplants to 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.
“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”, says professor Tom Walley, director of the NIHR Evaluation, Trials and Studies programmes.
The current clinical trial 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. There were also some side effects from the doses of drugs used, so this follow-up trial will be using a lower dose of the treatment to minimise risks due to toxicity.
The trial will involve academics from the universities of Sheffield, Manchester, Nottingham, Edinburgh, Oxford, Nottingham Trent as well as Queen Mary University of London.
The study was funded by a MRC 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.