OC-003 No clinical benefit of prebiotics in the treatment of active Crohn's disease: a double-blind, randomised, placebo-controlled trial
- J L Benjamin1,
- C R H Hedin1,
- A Koutsoumpas1,
- S C Ng2,
- A L Hart2,
- M A Kamm2,
- J D Sanderson1,
- S C Knight2,
- A Forbes3,
- A J Stagg4,
- K Whelan1,
- J O Lindsay5
- 1Nutritional Sciences Division, King's College London, London, UK
- 2Antigen Presenting Research Group, Imperial College London, UK
- 3Centre for Gastroenterology and Nutrition, University College London, London, UK
- 4The Blizard Institute of Cell and Molecular Science, London, UK
- 5Digestive Disease Clinical Academic Unit, Barts and the London School of Medicine, London, UK
Introduction The intestinal microbiota drive inflammation associated with Crohn's disease.1 The composition of the intestinal microbiota can be influenced by prebiotic's such as fructo-oligosaccharides (FOS). Preliminary data suggest that FOS can increase colonic bifidobacteria and induce immunoregulatory dendritic cell (DC) epithelial responses.2
Methods To assess the impact of a diet supplemented with FOS in patients with active Crohn's disease using an appropriately powered randomised, double-blind, placebo-controlled trial. Patients with active Crohn's disease (CDAI ≥ 220, plus one marker of inflammation) were randomised to receive 15 g/day FOS or placebo for 4 weeks. The primary endpoint was clinical response at week 4 (change in CDAI of −70 in the intention-to-treat (ITT) population). Multiple pre-specified secondary endpoints were analysed, including intracellular cytokine staining assessed by flow cytometry (n=27).
Results In total, 103 patients were randomised to receive FOS (n=54) or placebo (n=49). The mean (SD) baseline CDAI was 283 (61.1) and 286 (61.5) in the FOS and placebo groups, respectively (p=0.79). Significantly more patients receiving FOS (n=14.26%) than placebo (n=4.8%) withdrew before the 4-week endpoint (p=0.018). There was no significant clinical benefit of FOS compared to placebo (Abstract 003). Patients receiving FOS, but not placebo, had a reduced proportion of IL-6+ intestinal DC, and increased DC staining of IL-10 (both p<0.05). No effect on DC IL-12 was seen. Throughout the intervention patients receiving FOS had a significantly greater severity of flatulence (FOS mean 10.8, SD 5.7 vs placebo 7.3, 3.6, p=0.004) and rumbling gut (mean 8.3, SD 5.0 vs 6.1, 4.1, p=0.029) compared with placebo.
Conclusion An adequately powered trial of a diet supplemented with FOS in a well defined population of patients with active Crohn's disease showed no clinical benefit despite impacting on DC immunology. Patient withdrawal was greater in patients receiving FOS.