A CCEPTED MANUSCRIPT
Serum calprotectin was measured in duplicate serum samples under GLP conditions by Nordic
Biosite, Finland, using the HK379 Human Calprotectin ELISA kit from Hycult Biotech.
Fecal calprotectin was measured in duplicates under GLP conditions by Synlab, Switzerland, using
an ELISA kit from Immundiagnostik AG, Germany.
Outcomes
The primary outcome of this trial was the effect of the Bif195 intervention on the AUC Lewis score
obtained by VCE from visit 2 (randomization) to visit 7 (end of treatment). As the first secondary
endpoint, the effect of the Bif195 intervention on the AUC number of ulcers obtained by VCE from
visit 2 to visit 7 was tested. Other secondary endpoints were, in hierarchical order: AUC of the pain
module from the GSRS questionnaire, AUC of the total score from the GSRS questionnaire, AUC
of blood I-FABP, AUC of red spots from the VCE procedure, AUC of fecal calprotectin and AUC
MANUSCRIPT
of blood calprotectin.
As exploratory endpoints, data stratified into tertiles (small intestine divided into thirds) on effects
of the Bif195 intervention on ulcerations observed by VCE was analysed and further post-hoc
analyses on intervention effects on prostaglandin E2 (PGE2) and thromboxane B2 (TBX2) in serum
samples downstream of COX were studied.
Safety was assessed by means of adverse events. A complete list of adverse events is provided in
Table 2.
Statistical analysis
For all data obtained, area-under-the-curve (AUC) was calculated in order to evaluate the
intervention effects by comparing the AUC in the Bif195 arm versus the placebo arm. For this
purpose, the kinetics of Lewis score for each subject over the 6 VCE visits, was fitted to a third-
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