Original article—alimentary tract
The Probiotic Preparation, VSL#3 Induces Remission in Patients With Mild-to-Moderately Active Ulcerative Colitis

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Background & Aims

Probiotics can maintain ulcerative colitis (UC) in remission effectively, but little is known of their ability to induce remission. We conducted a multicenter, randomized, double-blind, placebo-controlled trial of a high-potency probiotic, VSL#3, for the treatment of mild-to-moderately active UC.

Methods

Adult patients with mild-to-moderate UC were assigned randomly to groups that were given 3.6 × 1012 CFU VSL#3 (n = 77) or placebo (n = 70), twice daily for 12 weeks. The primary end point was a 50% decrease in the Ulcerative Colitis Disease Activity Index (UCDAI) at 6 weeks. The secondary end points included remission by 12 weeks and reduction in total individual UCDAI parameters from baseline at 12 weeks. Intention-to-treat analysis was performed.

Results

At week 6, the percentage of patients with an improvement in UCDAI score that was greater than 50% was significantly higher in the group given VSL#3 (25; 32.5%) than the group given placebo (7; 10%) (P = .001). At week 12, there were 33 patients given VSL#3 (42.9%) who achieved remission, compared with 11 patients given placebo (15.7%) (P < .001). Furthermore, significantly more patients given VSL#3 (40; 51.9%) achieved a decrease in their UCDAI that was greater than 3 points, compared with those given placebo (13; 18.6%) (P < .001). The VSL#3 group had significantly greater decreases in UCDAI scores and individual symptoms at weeks 6 and 12, compared with the placebo group.

Conclusions

VSL#3 is safe and effective in achieving clinical responses and remissions in patients with mild-to-moderately active UC.

Section snippets

Design

This was a multicenter, double-blind, placebo-controlled, randomized trial. The study was conducted at 3 tertiary care centers in North India between June 2005 and August 2007.

Participants

Adult patients (>18 y) who had mild-to-moderately active UC (Ulcerative Colitis Disease Activity Index [UCDAI] score, 3–9; with minimum sigmoidoscopic score of 2) extending for more than 15 cm from the anal verge with at least one previously documented attack of active disease were included in this study. None of the

Sample Size

The sample size was based on a power of 80% and a statistical significance (alpha) of 95% (P = .05). This assumed that a response to treatment at 12 weeks, such as with oral mesalamine preparations, was expected to occur in 65% of patients treated with VSL#3 compared with 40% treated with placebo (ie, an expected difference of 25%). This assumed that the probiotic is as effective as oral mesalamine. Hence, 70 patients were required in each group with an additional 10% for drop-outs, therefore

Participant Flow

Of 187 patients screened for inclusion in the study, 40 could not be included (18 did not meet inclusion criteria, 12 were excluded, and 10 refused to participate). A total of 147 patients were randomized; 77 received VSL#3 and 70 received placebo (Supplementary Figure 1). Fifty-five patients in the VSL#3 group and 29 patients in the placebo group completed the entire study. Among the 22 patients who withdrew from the VSL#3 group, 17 had worsening of symptoms and 5 were lost to follow-up

Discussion

This was a multicenter, randomized, double-blind, placebo-controlled trial evaluating the role of the probiotic cocktail VSL#3 for treatment of mild-to-moderately active UC. The addition of VSL#3 to conventional treatment resulted in significantly higher clinical response and remission rates. Moreover, VSL#3 therapy significantly decreased the frequency of stools and rectal bleeding, resulting in overall improvement in participant well-being.

There are a few studies that have shown the

Acknowledgments

The authors express their gratitude to Professor Richard Fedorak of the University of Alberta (Edmonton, Alberta, Canada) for giving useful advice in finalizing the manuscript, and to CD Pharma (New Delhi) for providing the research grant as well as the VSL#3 and placebo for the study. The authors sincerely acknowledge the contribution of Mr Aditya R. Sahu for helping them in the conduct of the study, data analysis, and manuscript preparation.

The clinical trial is registered with Clinical Trial

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    Conflicts of interest The authors disclose no conflicts.

    Funding This study was supported by CD Pharma India Private, Ltd, New Delhi, India.

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