VSL#3 Versus Placebo in Maintenance of Remission in Crohn's Disease
Condition: Crohn's Disease
MeSH terms: Crohn Disease
Study type: Interventional
Phase: Phase 4

Summary: 
      The primary objective of the study is to compare the efficacy of the probiotic VSL#3 versus
      placebo, in addition to standard maintenance drugs, in maintaining remission in Crohn's
      disease (CD).

      The secondary objectives are:

        -  To determine the time till flare of CD patients on VSL#3 compared to placebo.

        -  To assess whether concurrent therapy with VSL#3 leads to an improvement in the quality
           of life (QOL).

        -  To assess whether concurrent therapy with VSL#3 reduces the severity of a flare if it
           occurs.
    

Detailed description: 
      Advancing knowledge regarding the biology of Crohn's Disease (CD) has identified that the
      host's innate immunity may impact on the development of intestinal inflammation. Pattern
      recognition receptors and the Toll-like receptors are able to detect both gram positive and
      gram negative bacteria, yeasts and flagellin and respond by activation of the innate immune
      system. By identification of the unmethylated CpG dinucleotide sequences found in bacteria,
      lymphocytes are stimulated, proinflammatory cytokines like interleukin (IL)-12 and the
      interferons are induced, and both the mucosal and host defences against the invading
      pathogens are increased.

      A body of evidence from clinical and experimental observations indicates a role for
      endogenous digestive microflora in the pathogenesis of inflammatory bowel disease (IBD). The
      distal ileum and the colon are the areas with highest luminal bacterial concentrations and
      represent the sites of inflammation in IBD. Probiotics have been shown to reduce intestinal
      inflammation in animal studies. In the human, probiotics may also reduce inflammation
      particularly in Crohn's disease (CD) and ulcerative colitis (UC). Probiotics are effective in
      the treatment of acute pouchitis and its prevention. Their use also appears to have some
      effect in the management of active intestinal inflammation in UC and preliminary results
      suggest a role in the maintenance of remission.

      NOD-2/CARD-15 is a gene that identifies colonic bacteria and can activate the NF-kb pathway
      in order to destroy the invading bacteria. The identification that mutation of the
      NOD-2/CARD-15 gene increases a person's susceptibility to developing CD suggests that a
      defect in the innate immunity may impact on the development of the chronic intestinal
      inflammation. CD patients are also more likely to have an increase in the mucosal
      permeability, thus allowing colonic bacteria to cross into the mucosal layer. A central role
      for the colonic bacteria would thus appear to be possible in the development and maintenance
      of intestinal inflammation and thus the potential effects and benefits of probiotics in the
      management of CD requires further investigation.

      It appears that treatment with high-potency probiotic preparations for oral bacteriotherapy
      may enhance the concentrations of protective bacteria of the endogenous digestive microflora
      and therefore may provide a therapeutic benefit in patients with CD.

      This is a phase IV multicentre, randomised, double-blind, placebo-controlled trial of VSL#3
      versus placebo in the maintenance of remission in patients with CD. The patients will be
      randomised to a treatment group receiving one sachet of VSL#3 twice a day, and a group
      receiving the placebo drug in one sachet twice a day. The patients are assessed at baseline
      and every 12 weeks until the completion of the study at 52 weeks. At every visit the patient
      will have routine blood tests for CD, a physical examination and questionnaire will be
      applied.
    

Intervention name(s): VSL#3; Placebo
Intervention type(s): Drug; Other
Intervention description(s): VSL#3 1 sachet twice a day; Placebo 1 sachel twice a day
Other intervention name(s): Blacebo
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Randomized; Double-Blind; Probiotic; Remission; Crohn's Disease