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IL-23 反应性免疫细胞亚群在克罗恩病患者术后复发中的作用。 (DIVE-23)

2026年11月3日 更新者：Geert D'Haens、Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

一项探讨 IL-23 反应性免疫细胞亚群在克罗恩病患者术后复发中作用的探索性研究。

Inflammatory Bowel Diseases (IBDs), including ulcerative colitis and Crohn's disease (CD), constitute a group of debilitating chronic diseases that profoundly impact patient quality of life and incurs large costs in terms of treatment and lost productivity. Incidence of IBD is rising worldwide, and there is a pressing clinical need for development of new therapies. Discovery and development of effective therapies to treat IBDs depend first on a better understanding of the underlying mechanisms, including how proinflammatory cells proliferate unchecked.

It has been established that the cytokine interleukin (IL)-23 plays a pivotal role in IBD pathophysiology and antibodies targeting IL-23 are currently in late stage development for the treatment of both CD and ulcerative colitis (UC). IL-23 is part of the IL-12 family of cytokines (which includes IL-12, IL-27 and IL-35). The p40 subunit is shared among IL-23 and IL-12; the p19 subunit is unique to IL-23. Thus far, the efficacy of selective anti-IL-23 blockade (via anti-p19 antibodies) appears 5-10% better with respect to clinical and endoscopic outcomes than targeting both IL-23 and IL-12 using anti-p40 antibodies. Understanding the effects of IL-23 (and IL-12) in IBDs requires identification of the most relevant immune cells that respond to these cytokines. One likely cell type controlled by the IL-23 pathway are innate lymphoid cells (ILCs). ILC3s (a subset of ILCs) are dominant in healthy intestinal tissue and capable of producing IL-22 which maintain intestinal epithelial homeostasis. Disturbances in the amounts of IL-22 caused by changes in the stimulatory cytokine IL-23 in tissues, may therefore cause inflammatory responses. IL-23 may facilitate the IL-12-induced shift of ILC3s to ILC1s which are contributing to the disease-causing chronic inflammation.

The DIVE 23 project is designed to understand the role of IL-23 in human IBD, in particular CD. It is hypothesized that IL-23R+ cells in the gut, are drivers of chronic inflammation in CD and determine the impact of IL-23 inhibition. To this end the investigators plan to extensively characterize the IL-23-responsive cell populations in inflamed and non-inflamed intestinal tissues of CD patients with postoperative recurrence in order to identify IL-23-responsive immune cell populations that are associated with disease activity. Patients will be treated in routine medical practice with biological agents and will undergo a second ileocolonoscopy 12-16 weeks later to investigate the impact of the different interventions on the mucosal immunology driving CD.

研究概览

地位

招聘中

条件

研究类型

观察性的

注册 (估计的)

40

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习联系方式

学习地点

  • 加拿大
    • Ontario
      • Toronto、Ontario、加拿大、1X5
  • 荷兰
    • North Holland
      • Amsterdam、North Holland、荷兰、1105
        • 招聘中
        • Amsterdam UMC
        • 接触：
        • 副研究员：
          • Lotte Oldenburg, drs
        • 首席研究员：
          • Geert D'Haens, prof dr

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

不适用

有资格学习的性别

全部

取样方法

概率样本

研究人群

The study will be performed in CD patients with postoperative recurrence. Patients will be counselled prior to their routine endoscopy (typically 6-9 months after surgery). In practice, this will be approximately be between one and two weeks before the routine endoscopy. The investigators intend to evaluate 20-30 patients for this study and recruit 40 patients. The reason for this, is that there is a possibility that patients do not have enough inflammation (Rutgeerts ≤i2a) and therefore cannot be included.

描述

Inclusion Criteria:

  • Age >/= 18 years;
  • Male or non-pregnant, non-lactating females;
  • Patients with postoperative recurrence at routine endoscopy 6-24 months following resection, defined by presence of ulcerations (endoscopic Rutgeerts' score >i2a) in the neoterminal ileum;
  • In the opinion of the investigator, the subject is capable of understanding and complying with protocol requirements;
  • The subject signs and dates a written informed consent form and any required privacy authorization prior to the initiation of any study procedures.

Exclusion Criteria:

  • Any conditions (eg, history of alcohol or substance abuse, or lack of compliance) which, in the opinion of the investigator, may interfere with the patient's ability to comply with study procedures;
  • Any condition in which one of the potential treatments are contraindicated in the opinion of the investigator (eg, cardiac failure class 3-4 according to the New York Heart Association [NYHA], multiple sclerosis, active infections).
  • Received any investigational drug in the past 30 days or 5 half-lives, whichever is longer.
  • Currently participating or planning to participate in a study involving an investigational product.
  • Active or planned pregnancy during the study.
  • Prior diagnosis of dysplasia in the colon (excluding in resected adenomas).
  • History of malignancy in the 3 years prior to randomization except for non-melanoma skin cancer.
  • Received a biologic treatment between surgery and first endoscopy.
  • Positive Clostridium difficile toxin B in faeces. Patients who test positive can be treated per local practice and still enter the study if no longer than 4 weeks after the screening visit, they test negative for Clostridium difficile toxin B.
  • Presence of a stoma without ileocolonic anastomosis or pouch.
  • Active perianal abscess or draining fistula
  • ALT or AST > 3x the upper limit of normal measured at screening
  • Increased risk of bleeding: coagulation disorder, use of anticoagulants and DOACs

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 观测模型：COHORT
  • 时间观点：PROSPECTIVE

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Changes in concentration and amounts of IL-23 responsive cells in postoperative CD at baseline endoscopy and after 12-16 weeks of routine care treatment with a biological agent.
大体时间：Week 16

Single cell analysis
Week 16

次要结果测量

结果测量
措施说明
大体时间
Changes in concentration and amounts in IL-23 pathway cytokines and mediators, at baseline and after 12-16 weeks of biological treatment.
大体时间：Week 16

Single cell analysis
Week 16
Change in modified Rutgeerts' score at baseline endoscopy and follow-up endoscopy (12-16 weeks after biological treatment)
大体时间：Week 16

Endoscopic outcome measurement
Week 16
Change in SES-CD score at baseline endoscopy and follow-up endoscopy (week 12-16, after biological treatment)
大体时间：Week 16

Endoscopic outcome measurement
Week 16
Change in the Harvey-Bradshaw Index (HBI) score at baseline visit and follow-up visits at week 8 and week 12-16.
大体时间：Week 16

Clinical outcome measurement
Week 16
Change in Robarts histopathology index (RHI) score at baseline endoscopy and follow-up endoscopy (week 12-16, after biological treatment).
大体时间：Week 16

Histology outcome measurement
Week 16

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2023年6月5日

初级完成 (估计的)

2029年1月1日

研究完成 (估计的)

2029年11月1日

研究注册日期

首次提交

2023年7月12日

首先提交符合 QC 标准的

2023年8月16日

首次发布 (实际的)

2023年8月23日

研究记录更新

最后更新发布 (实际的)

2026年11月4日

上次提交的符合 QC 标准的更新

2026年11月3日

最后验证

2026年11月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • NL82888.018.22

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

未定

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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