Adrenomedullin for steroid-resistant ulcerative colitis: a randomized, double-blind, placebo-controlled phase-2a clinical trial

Toshihiro Kita, Sinya Ashizuka, Naoki Ohmiya, Takayuki Yamamoto, Takanori Kanai, Satoshi Motoya, Fumihito Hirai, Hiroshi Nakase, Tomohiko Moriyama, Masanao Nakamura, Yasuo Suzuki, Shuji Kanmura, Taku Kobayashi, Hidehisa Ohi, Ryoichi Nozaki, Keiichi Mitsuyama, Shojiro Yamamoto, Haruhiko Inatsu, Koji Watanabe, Toshifumi HibiKazuo Kitamura

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Background: Adrenomedullin (AM) is a bioactive peptide having many pleiotropic effects, including mucosal healing and immunomodulation. AM has shown beneficial effects in rodent models and in preliminary study for patients with ulcerative colitis (UC). We performed a clinical trial to investigate the efficacy and safety of AM in patients with UC. Methods: This was a multi-center, double-blind, placebo-controlled phase-2a trial evaluating 28 patients in Japan with steroid-resistant UC. Patients were randomly assigned to four groups and given an infusion of 5, 10, 15 ng/kg/min of AM or placebo for 8 h per day for 14 days. The primary endpoint was the change in Mayo scores at 2 weeks. Main secondary endpoints included the change in Mayo scores and the rate of clinical remission at 8 weeks, defined as a Mayo score 0. Results: No differences in the primary or secondary endpoints were observed among the four groups at 2 weeks. Despite the insufficient tracking rate, the Mayo score at 8 weeks was only significantly decreased in the high-dose AM group (15 ng/kg/min) compared with the placebo group (− 9.3 ± 1.2 vs. − 3.0 ± 2.8, P = 0.035), with its rate of clinical remission at 8 weeks being significantly higher (3/3, 100% vs. 0/2, 0%, P = 0.025). We noted mild but no serious adverse events caused by the vasodilatory effect of AM. Conclusions: In this double-blind randomized trial, we observed the complete remission at 8 weeks in patients with steroid-resistant UC receiving a high dose of AM. Clinical trial registry: JAPIC clinical trials information; Japic CTI-205255 (200410115290). https://www.clinicaltrials.jp/cti-user/trial/Search.jsp.

Original languageEnglish
Pages (from-to)147-157
Number of pages11
JournalJournal of Gastroenterology
Volume56
Issue number2
DOIs
Publication statusPublished - 02-2021

All Science Journal Classification (ASJC) codes

  • Gastroenterology

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