Bile salt manipulation in Crohn’s disease

• Research type

  Research Study

• Full title

  Bile salt manipulation as a novel treatment for Crohn’s disease: a single centre open label pilot study of atorvastatin and colesevalam in patients with active terminal ileal Crohn’s disease [BISMAC]

• IRAS ID

  12330

• Sponsor organisation

  University College London

• Eudract number

  2009-010163-16

• ISRCTN Number

  ISRCTN77283008

• Research summary

  Research has shown that bile salts produced by the liver necessary for digestion may cause mucosal damage and/or increase permeability of the small bowel causing dysfunction of the intestinal barrier. Should this occur bacteria and antigenic material may penetrate the bowel wall causing acute inflammation. We have shown that people with Crohn??s disease inflammatory have a defect in the way they respond to acute inflammation: their neutrophils do not arrive at the site of inflammation quickly enough and this allows the inflammation to persist and become chronic. We therefore hypothesise that damage by bile salts may act as a trigger for the development of small bowel Crohn??s disease and that altering the composition of bile that arrives in the small bowel may reduce the damage and enable healing.The combination of a statin (a commonly used class of drugs which inhibit the manufacture of cholesterol and are used for prevention of coronary heart disease) with a bile acid binding resin (used for the treatment of high lipid levels and also bile salt malabsorption) should result in a decreased concentration of bile acids in the small bowel and it is proposed that a trial of this novel treatment approach in subjects with small bowel Crohn??s disease be undertaken to determine whether this can bring about clinical benefit.Thirteen subjects with active Crohn??s disease affecting the small bowel will all receive both 10 mg Atorvastatin once daily and 1875 mg Colesevelam hydrochloride twice daily orally for six weeks. Efficacy will be assessed by comparison of their disease activity score (Crohn??s Disease Activity Index) and markers of inflammation (faecal calprotectin and serum C-reactive protein) at the end of treatment with that at baseline. Should benefit be demonstrated a larger randomised trial would be planned to further assess this potential treatment modality.

• REC name

  East Midlands - Leicester Central Research Ethics Committee

• REC reference

  09/H0406/63

• Date of REC Opinion

  5 Jun 2009

• REC opinion

  Further Information Favourable Opinion