Brooks D. Cash, Michael Epstein, Syed M. Shah
Background: Among adult patients diagnosed with IBS, a significant proportion endorse a mixed bowel habit pattern. There is no approved therapy for IBS-M, and it remains an unmet medical need. In IBS, gut mucosal barrier dysfunction is linked to mucosal inflammation. The enteric nervous system regulates bowel movements through the gastrocolic reflex, and this reflex can promote diarrhea or constipation when intestinal homeostasis is disturbed. This provides a biologically plausible basis to test the efficacy of anti-inflammatory compounds targeted to the intestines in patients with IBS. Compounds with anti-inflammatory activity, such as the l-menthol component of peppermint oil, may help restore homeostasis, resulting in IBS symptom improvement, including both constipation and diarrhea. PO-SST consists of ultra-purified, solid-state PO microspheres that are triple-coated to facilitate delivery to the small intestine. In view of the unmet need in IBS-M, we performed a post hoc analysis of the effects of PO-SST among patients with IBS-M in the IBSREST trial.
Methods: Subjects met Rome III criteria for IBS-M, had average daily IBS related abdominal pain of ≥ 4 on a 0-10 scale, and a TISS of ≥ 2 on a 0-4 scale. Subjects were randomly allocated to receive PO-SST 180 mg TID or identical placebo for 4 weeks. Primary analysis was based on the TISS score. Additional assessments included change from baseline in frequency and intensity of individual IBS symptoms. Results: After 4 weeks of treatment, the PO-SST arm demonstrated statistically significant reduction in the TISS score (P=0.03) and frequency (P=0.03) and reached near-significance (P=0.053) in intensity of IBS symptoms (Figure 1). For all 8 IBS symptoms measured (Figure 2), the PO-SST arm had a greater reduction in symptoms, compared to placebo, with significance reached in abdominal pain (P=0.04), constipation (P=0.008), urgency (P=0.036), and sense of incomplete evacuation (P=0.04). The symptom of pain at evacuation was numerically superior with PO-SST (P= 0.072).
Conclusion: PO-SST demonstrated reduction versus placebo in both constipation (P=0.0085) and diarrhea (P=0.2296) in IBS-M, as well as numerous other core IBS symptoms. Additional study of PO-SST in patients with IBS-M is warranted.