Corticosteroids in IBD neoplasia

• Research type

  Research Study

• Full title

  The role of corticosteroids in the reversal of hypermethylation of WNT inhibitors in inflammatory bowel disease associated neoplasia

• IRAS ID

  30492

• Contact name

  Tariq Iqbal

• Sponsor organisation

  University Hospital Birmingham NHS Foundation Trust

• Eudract number

  2009-015077-12

• ISRCTN Number

  N/A

• Research summary

  Approximately 5% of patients with ulcerative colitis (UC) will develop colorectal (bowel) cancer. The risk of cancer increases with duration of disease and how much of the colon is affected, for instance if the whole colon is involved the risk of cancer may rise as much as 32 times that of the normal population. This risk of cancer is clearly an important consideration and often a significant concern for patients with UC. This study aims to recruit patients at risk of precancerous ??dysplasia? (a pathological change known to predate cancer formation), including those with longstanding ulcerative colitis (>10 years). Currently there is evidence to suggest that cancer in UC develops through a number of genes which are switched off or silenced in the colon lining by a process known as methylation. This process modifies the patients?? DNA which alters the function of these genes. We have also demonstrated that the use of corticosteroids may reverse these changes, which may in turn reduce or even reverse the risks of developing cancer or precancerous dysplasia in these patients. We intend to recruit currently symptomatic patients (n=50) with ulcerative colitis affecting the colon to at least the hepatic flexure (pan-colitis) for more than ten years duration since diagnosis. Age range will be 40 to 60 years, in order to control for age related methylation changes. Patients will have been corticosteroid naive (topical and systemic) for at least 6-months. Patients will be randomised to either receive budenofalk (a topical corticosteroid) per rectum, or no treatment for four weeks. They will receive a flexible sigmoidoscopy (camera) examination of the rectum both before and after this treatment and biopsies (n=4) will be taken. Biopsies will be processed to examine any changes in the DNA methylation status.

• REC name

  West Midlands - Edgbaston Research Ethics Committee

• REC reference

  09/H1208/62

• Date of REC Opinion

  23 Nov 2009

• REC opinion

  Further Information Favourable Opinion