Efficacy and Safety of Anthocyanin-Rich Extract in Patients with Ulcerative Colitis: A Randomized Controlled Trial.

Background: Bilberries are effective in inducing clinical, endoscopic, and biochemical improvement in ulcerative colitis (UC) patients. The aim of this study was to investigate the efficacy of anthocyanin-rich extract (ACRE), the bioactive ingredient of bilberries, in a controlled clinical trial in moderate-to-severe UC. Methods: A multi-center, randomized, placebo-controlled, double-blind study with a parallel group was conducted. Initially, the study was planned for 100 patients; nevertheless, it prematurely ended due to COVID-19. Patients had moderate-to-severe active UC at screening (a Mayo score of 6-12, an endoscopic sub-score ≥ 2) and were randomized at baseline. The primary endpoint was a clinical response (week 8, a total Mayo score reduction ≥ 3 points). Fecal calprotectin (FC) and a centrally read endoscopic response were among the secondary endpoints. Results: Out of 48 patients (6 Swiss centers), 34 were randomized. Eighteen ACRE and eight placebo patients could be analyzed (per protocol set). Half (9/18) of ACRE patients and 3/8 of placebo patients responded clinically (p = 0.278). An improvement in the Mayo score was observed in the ACRE arm (77.8% vs. 62.5% placebo). FC dropped from 1049 ± 1139 to 557 ± 756 μg/g for ACRE but not for the placebo group (947 ± 1039 to 1040 ± 1179; p = 0.035). Serious adverse events were rare. Conclusions: ACRE treatment did not yield significant superiority to the placebo. Furthermore, the placebo response was unusually high. Moreover, there was a significant calprotectin decrease at the end of treatment, indicative of ACRE efficacy in UC.