|Funding||Managed by RLBUHT (Some grants were awarded by Crohn’s and Colitis UK (Currently on a no cost extension from 2016 to December 2019)|
There is strong evidence that Crohn's disease results from an altered response to the intestinal bacteria. There is also growing evidence, supported by at least eight independent studies, that a type of E. Coli bacteria may be particulary involved. These bacteria can invade across the gut lining and can then grow in the tissue within a type of white blood cell called the macrophage. There is now sufficient evidence to justify trials of therapy that target E. Coli within macrophages to see whether this helps to get patients with active Crohn's disease back into remission. Antibiotics are often relatively ineffective at killing bacteria that are "hiding" inside macrophages. In laoratory studies we have found that a drug called hydroxychloroquine substantially increases the ability of antibiotics to kill Crohn's E. Coli isolates that are living inside macrophages. Hydroxychloroquine is a drug that was intiailly developed for treatment of malaria but is now widely used for its anti-inflammatory activities in rheumatoid arthritis. Recently it has also become standard therapy, in combination with antibiotics, in the treatment of two chronic infections: Whipple's disease (an intestinal disease) and Q fever (a more generalised illness that commonly affects the heart) - both conditions that are known to be caused by bacteria that are replicating within macrophages.
We are therefore proposing to conduct a clinical trial that assesses a combination of antibiotics (ciprofloxacin and doxycycline) and hydroxychloroquine designed to attack E. Coli within macrophages for their efficacy to treat active Crohn's disease, in comparison (randomised but without placebo-blinding) with standard therapy with the low absorption coricosteroid budesonide.
Out statistician has advised us that we should study 100 patients to obtain a clear result. We have already received funding (from the National institute of Health Research through the Liverpool Biomedical Research Centre) that allows us to start the trial in Liverpool but the trial would probably take about 5 years to recruit if based on once centre only. We are therefore requesting funding to cover drug costs and research nurse costs for hald the patients (50 with a per capita costing) to allow recruitment at other sites and placement of this trial onto the national CLRN trials portfolio - this will bring substantial added benefit in terms of recruitment speed and will also cover service support costs for Recruiting sites.
We are very hopeful that this could lead quite quickly to a new and relatively safe form of treatment for pations with relapsed Crohn's disease.