Otagiri Shinsuke, Ohnishi Shunsuke, Miura Arisa, Hayashi Hiroshi, Kumagai Izumi, Ito Yoichi M, Katsurada Takehiko, Nakamura Shiro, Okamoto Rika, Yamahara Kenichi, Cho Kyu Yong, Isoe Toshiyuki, Sato Norihiro, Sakamoto Naoya
Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Clinical Research and Medical Innovation Center, Hokkaido University Hospital, Sapporo, Japan.
BMJ Open Gastroenterol. 2018 May 31;5(1):e000206. doi: 10.1136/bmjgast-2018-000206. eCollection 2018.
The medical treatment options for patients with Crohn's disease (CD) are limited and patients resistant to those therapies are left requiring surgical operations that usually only achieve some symptomatic relief. Mesenchymal stem cells (MSC) have been shown to be effective for the treatment of CD, and we have demonstrated in animal experiments that human amnion-derived MSCs (AMSC) are a potential new therapeutic strategy. Therefore, we designed this study to investigate the safety and efficacy of AMSCs in patients with treatment-resistant CD.
This is the protocol for an ongoing phase I/II, dual-centre, open-label, uncontrolled, dose-response study. The estimated enrolment is 6-12 patients with treatment-resistant, moderate CD. A dose of 1.0×10 cells/kg will be administered intravenously in the low-dose group at days 0 and 7. After confirming the safety of low-dose administration, a dose of 4.0×10 cells/kg will be administered intravenously in the high-dose group on days 0 and 7. The primary endpoint will measure the occurrence of adverse events related to acute infusion toxicity, and secondary endpoints will include long-term adverse events and efficacy of AMSC administration.
The Institutional Review Board of Hokkaido University Hospital approved this study protocol (approval number H29-6). A report releasing study results will be submitted to an appropriate journal.
This study is the first to investigate the safety and efficacy of AMSC use for CD treatment. Our results will advance studies on more efficient and convenient methods to overcome the limits of available CD treatments.
UMIN000029841.
克罗恩病（CD）患者的医疗选择有限，对这些疗法耐药的患者只能接受手术治疗，而手术通常只能缓解一些症状。间充质干细胞（MSC）已被证明对CD治疗有效，并且我们在动物实验中已证明人羊膜来源的间充质干细胞（AMSC）是一种潜在的新治疗策略。因此，我们设计了本研究以调查AMSC治疗耐药性CD患者的安全性和有效性。
这是一项正在进行的I/II期、双中心、开放标签、非对照、剂量反应研究的方案。预计招募6 - 12例治疗耐药的中度CD患者。低剂量组在第0天和第7天静脉注射1.0×10⁶个细胞/千克的剂量。在确认低剂量给药的安全性后，高剂量组在第0天和第7天静脉注射4.0×10⁶个细胞/千克的剂量。主要终点将测量与急性输注毒性相关的不良事件的发生情况，次要终点将包括长期不良事件和AMSC给药的疗效。
北海道大学医院机构审查委员会批准了本研究方案（批准号H29 - 6）。一份发布研究结果的报告将提交给合适的期刊。
本研究首次调查了AMSC用于CD治疗的安全性和有效性。我们的结果将推动关于克服现有CD治疗局限性的更有效和便捷方法的研究。
UMIN000029841。
