VSL#3 induces and maintains short-term clinical response in patients with active microscopic colitis: a two-phase randomised clinical trial

Abstract

Background: The probiotic mixture VSL#3 has proven efficacious in inflammatory bowel diseases and irritable bowel syndrome; however, its efficacy in microscopic colitis (MC) is being investigated.

Objective: To evaluate the safety and efficacy of a multistrain probiotic, VSL#3, in inducing clinical remission and achieving clinical response, as compared with mesalamine, in patients with active MC.

Methods: A randomised, open labelled study comparing the efficacy of 900 billion colony-forming units/day of VSL#3 (group (Gp) A) or 1.6 g of mesalamine/day (Gp B) for 8 weeks in 30 patients with MC was conducted. After a washout period of 2 weeks, Gp B received 8 weeks of VSL#3 and Gp A was off medication for the next 8 weeks. The primary end points were clinical remission and clinical response at 8 weeks.

Results: Of 30 patients, 15 were randomised in each arm. 11 patients in Gp A and 13 patients in Gp B completed 8 weeks of treatment. 5 (46%) of 11 patients in Gp A and 1 (8%) of 13 patients in Gp B attained clinical remission (p=0.022). Clinical response was seen in Gp A, as evidenced by a lower stool weight (377.6±104.5 g) as compared with Gp B (507±168.2 g; p=0.03). VSL#3 was effective in maintaining clinical response up to 10 weeks, even after discontinuation of therapy. Secondary end points like stool parameters, histology and well-being improved in both treatment groups.

Conclusions: The probiotic VSL#3 was found to offer the benefit of inducing as well as maintaining short-term clinical response in patients with active MC.

Trial registration number: The clinical trial is registered with CLINICAL TRIAL REGISTRY INDIA; http://ctri.nic.in, CTRI No. "CTRI/2008/091/000086" (registered on: 23/06/2008).

Keywords: 5-AMINOSALICYLIC ACID (5-ASA); MICROSCOPIC COLITIS; PROBIOTICS.

Figure 1

Consort flow chart showing participant flow in both the treatment groups.

Figure 2

Within-group comparison of stool parameters from 0 to 8 weeks (Gp, group; VAS, visual analogue scale). VSL#3 significantly decreased stool frequency, stool weight, stool mucus, diarrhoeal rate, with improvement in well-being. Mesalamine significantly decreased stool mucus and improved stool consistency and well-being.

Figure 3

Changes in secondary outcome measures from baseline to 18 weeks (Gp, group; VAS, visual analogue scale).The beneficial effect of VSL#3 seems to be maintained throughout the 18 weeks study period, observed as continued significant improvement in stool frequency, stool mucus and well-being.

Figure 4

Photomicrograph showing a biopsy of lung adenocarcinoma used as a positive control for inducible nitric oxide synthase (iNOS) immunostain. There is strong immunopositivity in the tumour cell nuclei and cytoplasm ((A) immunohistochemistry (IHC; iNOS) ×200). Photomicrograph of a biopsy showing baseline collagenous colitis; there is strong and diffuse immunopositivity for iNOS immunostain in surface and crypt mucosa. Few lymphocytes also showing positivity for iNOS ((B) IHC (iNOS) ×100). Eight weeks after VSL#3 treatment, there is a marked reduction in the area distribution and stain intensity of iNOS immunostain ((C) IHC (iNOS) ×40; Blue arrow showing nuclear positivity). Eighteen weeks post VSL#3 treatment, there is still a very minimum expression of iNOS in the colonic biopsy ((D) IHC (iNOS) ×40; Brown arrow showing occasional nuclear positivity).