Extrait

Background and study aims Cystic fibrosis (CF) is a common genetically inherited disease caused by mutations in the CFTR gene. Mutations in this gene lead to thick sticky mucus clogging the lungs, infection, inflammation and eventually irreversible lung damage. There is currently no treatment that stops the natural progression of the disease; all available successful treatments merely slow the rate of decline in clinical condition. Gene therapy is a promising new treatment for CF where the faulty CFTR gene is replaced with a working one. The aim of this study is to assess whether CFTR gene therapy can lead to clinical improvement. Who can participate? Children aged 12 and above and adults with CF. What does the study involve? Participants are randomly allocated to inhale (breathe in) doses of either the gene therapy or a placebo (dummy) treatment every 4 weeks over a 48-week period. A subgroup of at least 20 patients is asked to undergo dosing with a nasal spray. Another subgroup of at least 24 patients is asked to undergo a bronchoscopy, a procedure that allows your doctor to look at your airway through a thin viewing instrument called a bronchoscope. What are the possible benefits and risks of participating? If the treatment is effective, the benefits will likely include an increased ability to clear mucus from the lungs, reduced inflammation, improvements in lung function and reduced symptoms. At higher doses, the gene therapy can lead to a systemic inflammatory response (fever), but the side effects are low with the dose used in this study. There is a risk of the side effects increasing with repeated dosing. To ensure that we identify any side effects early, a group of 20 patients will receive three doses before the rest of the group and will be intensively monitored. If there are side effects we will lower the dose for the rest of the study and if there are significant safety concerns the study will be stopped early. As with any treatment, there is a possibility that certain patients may be intolerant or allergic to the treatment. It is possible that there will be an immune response to the treatment but we have seen no evidence for this to date. All dosing will be conducted in hospital with full resuscitation facilities. There is a theoretical risk that the gene therapy could be released into the environment either during dosing or by patient exhalation (breathing out). All dosing will therefore be conducted in hospital within state of the art, purpose-built rooms. The bronchoscopy will be performed under general anaesthetic. The chance of fever following the procedure will be reduced by using antibiotics. Where is the study run from? The Royal Brompton & Harefield, London; The Western General Hospital, Edinburgh and The Hospital for Sick Children, Edinburgh (UK). When is the study starting and how long is it expected to run for? March 2012 to March 2014. Who is funding the study? National Institute for Health Research (NIHR) and the Medical Research Council (MRC) through the Efficacy and Mechanism Evaluation programme. Who is the main contact? Prof. Eric Alton [email protected]

Critère d'inclusion

• Cystic fibrosis

Liens

• ictrp
• isrctn