Rapamycin and Crohns Disease: open label phase I-II trial

• Research type

  Research Study

• Full title

  A phase I-II prospective, non-randomized open label proof of concept trial of the use of sirolimus (rapamycin) in the treatment of patients with Crohn’s disease

• IRAS ID

  6096

• Sponsor organisation

  Cambridge University Hospitals NHS Foundation Trust

• Eudract number

  2008-005023-28

• ISRCTN Number

  N/A

• Clinicaltrials.gov Identifier

  N/A

• Research summary

  This study investigates using the drug sirolimus (rapamycin) to treat patients with Crohn??s disease. Crohn??s disease is an aggressive inflammation of the intestine that causes pain, diarrhoea and malnutrition. Around 1 in 500 people are affected in the UK and the peak incidence is in young adults. The mainstay of treatment is immune suppressive drugs, although more than 80% of patients require surgery during the course of their disease for complications such as intractable bowel inflammation, bowel scarring and perforation. There is increasing evidence that Crohn??s disease is driven by infection of intestinal cells with bacteria from the gut, leading to an over-active immune and inflammatory response. Sirolimus (rapamycin) is an immune-suppressant drug licensed for use in renal transplantation to prevent organ rejection and has been shown experimentally to enhance cell killing of invasive bacteria. There are also reports that it reduces the formation of scar tissue. Sirolimus is an attractive candidate drug for treating Crohn??s disease given its antibacterial, anti-inflammatory and anti-scarring properties. Our centre has successfully used sirolimus to treat one patient with severe Crohn's disease, who had lost response to all forms of conventional drug therapy (case report in press), but there are no other clinical data on the use of sirolimus in Crohn??s disease. We propose a small-scale study of using sirolimus to treat 30 patients with active Crohn??s disease. We will choose adults who are losing response/unresponsive to 1st and 2nd line treatments and give them Sirolimus tablets for 12 weeks. Our primary end-point is of safety and tolerability of the drug. Our secondary end-point is of response of Crohn??s disease and this will be assessed using a variety of validated modalities: endoscopic examination with scoring intestinal inflammatory activity at the beginning and end of the trial, quality of life questionnaire, symptom diaries and the Crohn??s Disease Inflammatory Index (CDAI). This study will be conducted across 2 centres, in Cambridge and Edinburgh.

• REC name

  East of England - Cambridge East Research Ethics Committee

• REC reference

  08/H0304/105

• Date of REC Opinion

  6 Jan 2009

• REC opinion

  Further Information Favourable Opinion