Dataset Information

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

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 .

SUBMITTER: Kita T

PROVIDER: S-EPMC7862507 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

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

Kita Toshihiro T Ashizuka Sinya S Ohmiya Naoki N Yamamoto Takayuki T Kanai Takanori T Motoya Satoshi S Hirai Fumihito F Nakase Hiroshi H Moriyama Tomohiko T Nakamura Masanao M Suzuki Yasuo Y Kanmura Shuji S Kobayashi Taku T Ohi Hidehisa H Nozaki Ryoichi R Mitsuyama Keiichi K Yamamoto Shojiro S Inatsu Haruhiko H Watanabe Koji K Hibi Toshifumi T Kitamura Kazuo K

Journal of gastroenterology 20201102 2

<h4>Background</h4>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.<h4>Methods</h4>This was a multi-center, double-blind, placebo-controlled phase-2a trial evaluating 28 patients in Japan with steroid-resistant U ...[more]

PMID: 33140199

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Dataset Information

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

Background

Methods

Results

Conclusions

Clinical trial registry

Publications

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

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