TY - JOUR
T1 - Efficacy of Indigo Naturalis in a Multicenter Randomized Controlled Trial of Patients With Ulcerative Colitis
AU - INDIGO Study Group
AU - Naganuma, Makoto
AU - Sugimoto, Shinya
AU - Mitsuyama, Keiichi
AU - Kobayashi, Taku
AU - Yoshimura, Naoki
AU - Ohi, Hidehisa
AU - Tanaka, Shinji
AU - Andoh, Akira
AU - Ohmiya, Naoki
AU - Saigusa, Keiichiro
AU - Yamamoto, Takayuki
AU - Morohoshi, Yuichi
AU - Ichikawa, Hitoshi
AU - Matsuoka, Katsuyoshi
AU - Hisamatsu, Tadakazu
AU - Watanabe, Kenji
AU - Mizuno, Shinta
AU - Suda, Wataru
AU - Hattori, Masahira
AU - Fukuda, Shinji
AU - Hirayama, Akiyoshi
AU - Abe, Takayuki
AU - Watanabe, Mamoru
AU - Hibi, Toshifumi
AU - Suzuki, Yasuo
AU - Kanai, Takanori
AU - Nakazato, Yoshihiro
AU - Fukuda, Tomohiro
AU - Teratani, Toshiaki
AU - Ogata, Haruhiko
AU - Iwao, Yasushi
AU - Yamasaki, Hiroshi
AU - Toyonaga, Takahiko
AU - Nakano, Masaru
AU - Sameshima, Yoichi
AU - Hayashi, Ryohei
AU - Ueno, Yoshitaka
AU - Bamba, Shigeki
AU - Nakazawa, Atsushi
AU - Koike, Yuji
AU - Imai, Jin
AU - Shimoyama, Takahiro
AU - Takeuchi, Ken
AU - Nagasaka, Mitsuo
AU - Kitano, Atsuo
AU - Ashizuka, Shinya
AU - Inatsu, Haruhiko
AU - Onodera, Kei
AU - Nakase, Hiroshi
AU - Kitamura, Kazuya
N1 - Publisher Copyright:
© 2018 AGA Institute
PY - 2018/3/1
Y1 - 2018/3/1
N2 - Background & Aims: Indigo naturalis (IN) is a traditional Chinese medicine that contains ligands for the aryl hydrocarbon receptor and promotes regeneration of the mucosa by inducing production of interleukin 22. IN might induce mucosal healing in patients with ulcerative colitis (UC). We performed a randomized controlled trial to investigate the safety and efficacy of IN in patients with UC. Methods: We performed a multicenter, double-blind trial evaluating the safety of 86 patients in Japan with active UC (Mayo scores of 6 or more), enrolled from March 30 through December 27, 2016. Patients were randomly assigned to groups and given a daily dose of 0.5, 1.0, or 2.0 g IN or placebo (1:1:1:1 ratio) for 8 weeks. The primary endpoint was the rate of clinical response at week 8, defined as a 3-point decrease in the Mayo score and a decrease of at least 30% from baseline, with a decrease of at least 1 point for the rectal bleeding subscore or absolute rectal bleeding score of 0–1. The main secondary endpoint was the rate of clinical remission at week 8, defined as a Mayo score or ≤2 and no subscores with a value >1. Mucosal healing was also assessed at week 8. Results: The trial was terminated because of an external reason: a report of pulmonary arterial hypertension in a patient who used self-purchased IN for 6 months. In the intent-to-treat analysis, we observed a significant, dose-dependent linear trend in proportions of patients with clinical responses (13.6% with a clinical response to placebo; 69.6% to 0.5 g IN; 75.0% to 1.0 g IN; and 81.0% to 2.0 g IN) (Cochran-Armitage trend test P <.0001 compared with placebo). Proportions of patients in clinical remission at week 8 were significantly higher in the 1.0 g IN group (55.0%, P =.0004) and the 2.0 g IN group (38.1%, (P =.0093) than in the placebo group (4.5%). Proportions of patients with mucosal healing were 13.6% in the placebo group, 56.5% in the 0.5 g IN group, 60.0% in the 1.0 g IN group, and 47.6% in the 2.0 g IN group (P =.0278 compared with placebo). Although mild liver dysfunction was observed in 10 patients who received IN, no serious adverse events were observed. Conclusions: In a randomized, placebo-controlled trial, we found 8 weeks of IN (0.5–2.0 g per day) to be effective in inducing a clinical response in patients with UC. However, IN should not yet be used because of the potential for adverse effects, including pulmonary arterial hypertension. Clinical Trials Registry no: UMIN000021439 (http://www.umin.ac.jp/ctr/).
AB - Background & Aims: Indigo naturalis (IN) is a traditional Chinese medicine that contains ligands for the aryl hydrocarbon receptor and promotes regeneration of the mucosa by inducing production of interleukin 22. IN might induce mucosal healing in patients with ulcerative colitis (UC). We performed a randomized controlled trial to investigate the safety and efficacy of IN in patients with UC. Methods: We performed a multicenter, double-blind trial evaluating the safety of 86 patients in Japan with active UC (Mayo scores of 6 or more), enrolled from March 30 through December 27, 2016. Patients were randomly assigned to groups and given a daily dose of 0.5, 1.0, or 2.0 g IN or placebo (1:1:1:1 ratio) for 8 weeks. The primary endpoint was the rate of clinical response at week 8, defined as a 3-point decrease in the Mayo score and a decrease of at least 30% from baseline, with a decrease of at least 1 point for the rectal bleeding subscore or absolute rectal bleeding score of 0–1. The main secondary endpoint was the rate of clinical remission at week 8, defined as a Mayo score or ≤2 and no subscores with a value >1. Mucosal healing was also assessed at week 8. Results: The trial was terminated because of an external reason: a report of pulmonary arterial hypertension in a patient who used self-purchased IN for 6 months. In the intent-to-treat analysis, we observed a significant, dose-dependent linear trend in proportions of patients with clinical responses (13.6% with a clinical response to placebo; 69.6% to 0.5 g IN; 75.0% to 1.0 g IN; and 81.0% to 2.0 g IN) (Cochran-Armitage trend test P <.0001 compared with placebo). Proportions of patients in clinical remission at week 8 were significantly higher in the 1.0 g IN group (55.0%, P =.0004) and the 2.0 g IN group (38.1%, (P =.0093) than in the placebo group (4.5%). Proportions of patients with mucosal healing were 13.6% in the placebo group, 56.5% in the 0.5 g IN group, 60.0% in the 1.0 g IN group, and 47.6% in the 2.0 g IN group (P =.0278 compared with placebo). Although mild liver dysfunction was observed in 10 patients who received IN, no serious adverse events were observed. Conclusions: In a randomized, placebo-controlled trial, we found 8 weeks of IN (0.5–2.0 g per day) to be effective in inducing a clinical response in patients with UC. However, IN should not yet be used because of the potential for adverse effects, including pulmonary arterial hypertension. Clinical Trials Registry no: UMIN000021439 (http://www.umin.ac.jp/ctr/).
KW - Aryl Hydrocarbon Receptor
KW - IBD
KW - Mucosal Healing
KW - Qing-Dai
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U2 - 10.1053/j.gastro.2017.11.024
DO - 10.1053/j.gastro.2017.11.024
M3 - Article
C2 - 29174928
AN - SCOPUS:85043260143
SN - 0016-5085
VL - 154
SP - 935
EP - 947
JO - Gastroenterology
JF - Gastroenterology
IS - 4
ER -