Extrait

Background and study aims Crohn's disease is a long-term condition that causes inflammation of the lining of the digestive system. Some patients fail to respond to the best clinical treatment in Crohn's disease and some only experience a temporary benefit, which is why the search for more effective treatments is continuing. Recently, an experimental treatment has been developed for severe Crohn's disease, called 'high dose immunoablation followed by autologous hematopoietic stem cell transplantation'. Hematopoietic blood stem cells are young, undifferentiated blood cells that can develop into differentiated ones, including lymphocytes, and over-reactive lymphocytes are thought to contribute to the development of Crohn's disease. This study involves removing your over-active lymphocytes (immunoablation) and replacing them using blood stem cells that had been taken (harvested) from your body earlier in the study. Conventional medication only temporarily suppresses the over-reactive lymphocytes. At present, about 30 patients suffering from Crohn's disease have been treated with stem cell transplantation worldwide. The results from those studies suggest that the therapy may be effective, but it cannot be concluded yet whether this treatment is better than any best clinical practice. An international collaborative group of medical specialists has agreed that this issue can only be solved by conducting a scientifically sound clinical study in which institutions from all over the world participate. This study is a European collaboration and we aim to treat a total of 48 patients in the different countries that are taking part. Who can participate? Patients aged between 18 and 50 years with severe Crohn's disease who have not responded to immunosuppressant medication. What does the study involve? Participants will have a number of investigations before undergoing stem cell mobilisation. Stem cell mobilisation involves suppressing the bone marrow with a cytotoxic drug (cyclophosphamide) before stimulating it to release large numbers of stem cells into the circulation. These are collected through a tube inserted into a vein and stored until needed. The drug used for mobilisation is also effective against Crohn's disease, thus this phase results in a treatment by itself. Participants are then randomly allocated to undergo bone marrow abolition and stem cell re-infusion either immediately or with a delay of 1 year. Bone marrow abolition involves high doses of cytotoxic drugs to destroy the initial bone marrow. Then the stem cells that were harvested earlier are transplanted (re-infused) into your blood, like a regular blood transfusion thereafter homing into the bone marrow. The re-infused stem cells give rise to a new generation of immune cells, replacing cells of the original 'sick' immune system. Patients are evaluated at intervals and the progress over the first year is compared. Patients are followed up for five years. What are the possible benefits and risks of participating? By comparing the progress of patients who undergo early stem cell transplantation with those who receive late stem cell transplantation, the study will allow the value of immunoablation and stem cell transplantation to be assessed, whilst offering this new procedure to all patients that enter the study. It is possible that the process of mobilisation may give some benefit. The study will allow some assessment of this effect and control for it when assessing transplantation. High dose immunoablation followed by autologous stem cell transplantation is an intensive treatment with risks of severe complications which on rare occasions have been fatal. These complications may require hospitalisation at any time and include: infections, bleeding, heart failure, respiratory insufficiency (breathing difficulties), kidney failure, lymphoma. Less severe, but more frequent (reversible) toxicities include: nausea, fever, alopecia (hair loss), infertility, arthralgia (joint pain), myalgia (muscle pain), menstrual disorders and hematuria (blood in the urine) due to irritation of the lining of the bladder. Of course, the treating physicians will do their utmost to prevent these from occurring and treat them as best as they can when serious complications do occur. The process of stem cell mobilisation can incur similar risks as the high dose immunoablation. There is also a high risk of developing septic complications (severe infections requiring hospitalisation or lengthening your stay in hospital) during the stem cell mobilisation phase of the study and therefore your health will be closely monitored throughout this period. Where is the study run from? Nottingham University Hospital (UK). When is the study starting and how long is it expected to run for? The study started in July 2007 and will run until March 2017. Recruitment has closed but follow-up is ongoing. Who is funding the study? Broad Medical Research Programme (BMRP) (USA). Who is the main contact? Mrs Miranda Clark [email protected]

Critère d'inclusion

• Topic: Oral and Gastrointestinal; Subtopic: Oral and Gastrointestinal (all Subtopics); Disease: Gastrointestinal

Liens

• ictrp
• isrctn