Adrenomedullin for steroid-resistant ulcerative colitis: a randomized, double-blind, placebo-controlled phase-2a clinical trial.
Adrenomedullin for steroid-resistant ulcerative colitis: a randomized, double-blind, placebo-controlled phase-2a clinical trial.
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肾上腺髓质素治疗类固醇抵抗性溃疡性结肠炎：一项随机、双盲、安慰剂对照的2a期临床试验
DOI：
10.1007/s00535-020-01741-4
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发表时间：
2021-03
影响因子：
6.3
通讯作者：
Kitamura K
中科院分区：
文献类型：
--
作者：
Kita T;Ashizuka S;Ohmiya N;Yamamoto T;Kanai T;Motoya S;Hirai F;Nakase H;Moriyama T;Nakamura M;Suzuki Y;Kanmura S;Kobayashi T;Ohi H;Nozaki R;Mitsuyama K;Yamamoto S;Inatsu H;Watanabe K;Hibi T;Kitamura K
肾上腺髓质素（AM）是一种生物活性肽，具有多种作用，包括粘膜愈合和免疫调节。在啮齿动物模型和初步研究中，AM对溃疡性结肠炎（UC）患者显示出有益的作用。我们进行了一项临床试验，以研究AM对UC患者的疗效和安全性。这是一项多中心、双盲、安慰剂对照的2a期临床试验，评估日本28例类固醇耐药UC患者。患者被随机分为四组，分别输注5、10、15 ng/kg/min的AM或安慰剂，每天8小时，持续14天。主要终点是2周时Mayo评分的变化。主要次要终点包括Mayo评分的变化和8周时的临床缓解率（定义为Mayo评分0）。在2周时，四组之间的主要或次要终点没有观察到差异。尽管追踪率不足，但与安慰剂组相比，高剂量AM组（15 ng/kg/min） 8周时的Mayo评分仅显著降低（- 9.3±1.2 vs - 3.0±2.8,P = 0.035）， 8周时临床缓解率显著高于安慰剂组（3/ 3,100% vs. 0/ 2,0%, P = 0.025）。我们注意到AM的血管舒张作用引起的轻微但没有严重的不良事件。在这项双盲随机试验中，我们观察到接受高剂量AM治疗的类固醇抵抗性UC患者在8周后完全缓解。JAPIC临床试验信息；日本CTI-205255（200410115290）。https://www.clinicaltrials.jp/cti-user/trial/Search.jsp。本文的在线版本（10.1007/s00535-020-01741-4）包含补充资料，仅供授权用户使用。
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. 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. 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. 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. JAPIC clinical trials information; Japic CTI-205255 (200410115290). https://www.clinicaltrials.jp/cti-user/trial/Search.jsp. The online version of this article (10.1007/s00535-020-01741-4) contains supplementary material, which is available to authorized users.
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影响因子：
158.5
作者：
SCHROEDER, KW;TREMAINE, WJ;ILSTRUP, DM
通讯作者：
ILSTRUP, DM
影响因子：
3.1
作者：
Ashizuka, Shinya;Inatsu, Haruhiko;Kitamura, Kazuo
通讯作者：
Kitamura, Kazuo
影响因子：
3
作者：
Talero, E.;Sanchez-Fidalgo, S.;Motilva, V.
通讯作者：
Motilva, V.
影响因子：
24.5
作者：
Gonzalez-Rey, E.;Fernandez-Martin, A.;Delgado, M.
通讯作者：
Delgado, M.
影响因子：
4.9
作者：
Ogata, Haruhiko;Kato, Jun;Hibi, Toshifumi
通讯作者：
Hibi, Toshifumi