VSL#3 Versus Placebo in Maintenance of Remission in Crohn's Disease
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||Randomized, Double-Blind, Placebo-Controlled Study of VSL#3 Versus Placebo in the Maintenance of Remission in Crohn's Disease|
- 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) [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- Time till flare of CD [ Time Frame: within 1 year of commencing therapy ] [ Designated as safety issue: Yes ]
- To assess whether concurrent therapy with VSL#3 leads to an improvement in the quality of life [ Time Frame: within 1 year of commencing therapy ] [ Designated as safety issue: Yes ]
- To assess whether concurrent therapy with VSL#3 reduces the severity of a flare if it occurs [ Time Frame: within 1 year of commencing therapy ] [ Designated as safety issue: Yes ]
|Study Start Date:||June 2005|
|Study Completion Date:||December 2008|
|Primary Completion Date:||December 2008 (Final data collection date for primary outcome measure)|
VSL#3 1 sachet twice a day
Other Name: VSL#3
Placebo Comparator: Placebo
Placebo 1 sachel twice a day
Other Name: Blacebo
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.
|Australia, Western Australia|
|Fremantle, Western Australia, Australia, 6160|
|Principal Investigator:||Ian C Lawrance, MD PhD||School of Medicine and Pharmacology, University of Western Australia, Fremantle Hospital|