P560 Curcumin-QingDai combination for patients with active ulcerative colitis: A randomized double-blinded placebo-controlled trial
Ben-Horin, S.(1);Salomon, N.(1)*;Karampekos, G.(2);Viazis, N.(2);Lahat, A.(1);Ungar, B.(1);Eliakim, R.(1);Kriger-Sharabi, O.(3);Reiss-Mintz, H.(4);Yanai, H.(5);Dotan, I.(6);Zittan, E.(7);Maharshak, N.(8);Hirsch, A.(9);Weitman, M.(10);Mantzaris, G.J.(2);Kopylov, U.(1);
(1)Sheba Medical Center- Tel-Avivi University, Gastroenterology, Ramat Gan, Israel;(2)Evangelismos-Polykliniki- GHA, Gastroenterology, Athens, Greece;(3)Assuta Medical Center, Gastroenterology, Ashdod, Israel;(4)Mayanei HaYeshua Medical Center, Gastroenterology, Bnei Brak, Israel;(5)Rabin Medical Center, Gastroenterology, - Petah Tikva, Israel;(6)Rabin Medical Center, Gastroenterology, Petah Tiqva, Israel;(7)Emek Medical Center, Gastroenterology, Afula, Israel;(8)Tel Aviv Medical Center, Gastroenterology, Tel-Aviv, Israel;(9)Tel-Aviv Medical Center, Gastroenterology, Tel-Aviv, Israel;(10)Bar-Ilan University, Chemistry, Ramat Gan, Israel;
Background
The herbal extracts Curcumin and QingDai (QD, Indigo) were previously shown to be effective in mild-moderate and in moderate-severe ulcerative colitis (UC), respectively. We evaluated the efficacy and safety of a combination of curcumin-QingDai (CurQD) in patients with active UC.
Methods
This was a two parts trial. Part 1 was an open label study of 4 weeks CurQD in patients with active UC, defined by a Simple Clinical Colitis Activity Index (SCCAI) score ≥5 and a modified Mayo endoscopic sub-score≥2. Part 2 was a placebo-controlled trial conducted in two centers in Israel and Greece, that randomized active UC patients at a 2:1 ratio to either enteric-coated CurQD 3gr/day or an identical placebo for eight weeks. The co-primary outcome at week 8 was clinical response (reduction in SCCAI of ≥3 points) and an objective evidence of response (Mayo endoscopic subscore improvement of ≥1 or 50% calprotectin reduction from baseline). Responding patients continued either curcumin or placebo alone for additional 8 weeks as maintenance treatment. Expression of Cyp1A1 in rectal mucosa was assessed as a measure of aryl-hydrocarbon receptor (AhR) pathway activation. Curcumin purity, and indigo and indirubin content in CurQD were confirmed by LC-MS/MS.
Results
There were 59 patients enrolled in the two study parts. In efficacy analysis of part 1, 7/10 responded including 3/10 who achieved clinical remission. For part 2, 95 patients were screened and 42 were included and randomized (48.8% biologics and/or immuno-modulators experienced, 36.6% biologics-experienced). The co-primary outcome was achieved in 43% and 8% of CurQD and placebo patients, respectively (p=0.033). Clinical response was observed in 85.7% versus 30.7% (p<0.001), 50% calprotectin-reduction in 46.4% versus 15.4% (p=0.08) and endoscopic improvement in 75% versus 20% (p=0.036), in the CurQD and placebo groups, respectively. The overall rate of adverse events was comparable between the groups. Among week-8 responders to CurQD, additional 8 weeks of treatment with curcumin alone resulted in 93%, 80% and 40% with maintained clinical response, clinical remission and clinical-biomarker response, respectively, at week 16. CurQD treatment uniquely resulted in activation of the AhR pathway, as gauged by a signficantly up-regulated expression of CYP1A1 in the rectal mucosa, which was not observed among patients receiving placebo, 5ASA or biologic drugs.
Conclusion
In this randomized controlled trial, combination CurQD was found to be effective for inducing remission in active UC patients. Induction of AhR may merit further study as a potential treatment target in active UC