Regulatory T-cells and Crohn's Disease (CrohnReg)
The Effect of Infliximab Therapy in Crohn Patients on Regulatory T-cells
Aim: the main aim of this study is to investigate if immune cells (regulatory T-cells, Th17 cells and other immune cell types) or biomarkers can be used to predict the response or lack of response to treatment with Infliximab. If so, characteristics of the immune cells may also unveil the mechanisms behind lack of response to Infliximab.
Design: a prospective, observational study with three arms. In the treatment group, 35 patients with Crohn's disease about to start Infliximab-treatment are recruited. They have blood samples drawn at day 1 before first treatment, after 6 week, and again after 22 weeks of treatment. 12 healthy volunteers serve as a control group. Controls are only investigated once. All treatment and follow-up are according to national guidelines, and data from this study is not used by the clinicians.
Methods: the number of regulatory T-cells and pro-inflammatory T-cells (Th17 cells) is investigated using flow cytometry. From plasma and serum samples, various proteins (biomarkers), such as transforming growth factor beta (TGF-beta) and tumour necrosis factor alpha (TNF-alpha), are measured using immunoassays. Patient data (demographics and medical history) are extracted from various registries.
研究概览
详细说明
Primary analyses: patient response to Infliximab treatment is quantified using Harvey Bradshaw Index, and the response is then related to the number of regulatory T-cells, Th17 cells, and biomarker levels at baseline. The exact cut-off for response vs. non-respons will be determined and validated once all data is collected by an assessor blinded for the flow cytometry results and biomarker levels.
Plan for missing data: for patients with missing Harvey Bradshaw Index, we will first try to re-create the score using the patient records (information on well-being, abdominal pain, diarrhea, fistulae/abscesses, and extra-intestinal Crohn manifestations). If this is not possible, an experienced clinician will rate the patient's Infliximab response based on all available patient record data, but blinded for flow cytometry results and biomarker levels.
研究类型
注册 (实际的)
联系人和位置
学习地点
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Copenhagen
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Hvidovre、Copenhagen、丹麦、2650
- Hvidovre Hospital
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
取样方法
研究人群
Patients from the gastroenterology department at Hvidovre Hospital and Køge Sygehus are eligible for entry.
Healthy controls are recruited by advitising at Hvidovre Hospital.
描述
Infliximab group
Inclusion Criteria:
- Crohn's Disease
- Starting Infliximab treatment
- Patient at the gastrointestinal department at Hvidovre Hospital or Køge Sygehus
- Can understand and write Danish
- European ancestry
Exclusion Criteria:
- Not able to consent in an ethical manner (e.g. severe mental illness)
- Significant co-morbidity (e.g. cancer, HIV)
- Other immunological disease (e.g. psoriasis)
- Current treatment with biological agents
Healthy controls
Inclusion Criteria:
- No current disease
- No daily drug use
- Can understand and write Danish
- European ancestry
Exclusion Criteria:
- Not able to consent in an ethical manner (e.g. severe mental illness)
- Significant co-morbidity (e.g. cancer, HIV)
- Other immunological disease (e.g. psoriasis)
- Current treatment with biological agents
学习计划
研究是如何设计的？
设计细节
队列和干预
团体/队列 |
干预/治疗 |
|---|---|
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Infliximab
35 Crohn patients about to start Infliximab treatment, gives as i.v.
injection of 5 mg/kg at baseline, after 2 weeks, 6 weeks, and then every 8th week.
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The patients are included in the study when the decision to treat with Infliximab is already made.
This study is observational, and all treatment and clinical follow-up are according to national guidelines.
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Healthy controls
12 healthy controls without Crohn's Disease.
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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 |
|---|---|---|
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Change from baseline in number of regulatory T-cells at 6 weeks
大体时间：Baseline, 6 weeks (plus/minus 1 week)
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The number of regulatory T-cells is measured in fresh blood by flow cytometry.
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Baseline, 6 weeks (plus/minus 1 week)
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Change from baseline in number of regulatory T-cells at 22 weeks
大体时间：Baseline, 22 weeks (plus/minus 1 week)
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The number of regulatory T-cells is measured in fresh blood by flow cytometry.
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Baseline, 22 weeks (plus/minus 1 week)
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Change from baseline in Harvey Bradshaw Index at 6 weeks
大体时间：Baseline, 6 weeks (plus/minus 1 week)
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Harvey Bradshaw Index is a measure of Crohn's Disease severity.
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Baseline, 6 weeks (plus/minus 1 week)
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Change from baseline in CD161 expression at 6 weeks
大体时间：Baseline, 6 weeks (plus/minus 1 week)
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Cluster of differentiation 161 (CD161) is a T helper 17 cell (Th17)-marker, measured by flow cytometry of fresh blood samples.
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Baseline, 6 weeks (plus/minus 1 week)
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Change from baseline in CD161 expression at 22 weeks
大体时间：Baseline, 22 weeks (plus/minus 1 week)
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CD161 is a Th17-marker, measured by flow cytometry of fresh blood samples.
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Baseline, 22 weeks (plus/minus 1 week)
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Change from baseline in cytokine levels at 6 weeks
大体时间：Baseline, 6 weeks (plus/minus 1 week)
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We will measure IFN-gamma, IL-4, IL-6, IL-7, IL-10, IL-15, IL-17, and TNF-alpha by Luminex.
TGF-beta, suPAR, and IL-15 will be measured by ELISA.
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Baseline, 6 weeks (plus/minus 1 week)
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Change from baseline in cytokine levels at 22 weeks
大体时间：Baseline, 22 weeks (plus/minus 1 week)
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We will measure IFN-gamma, IL-4, IL-6, IL-7, IL-10, IL-15, IL-17, and TNF-alpha by Luminex.
TGF-beta, suPAR, and IL-15 will be measured by ELISA.
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Baseline, 22 weeks (plus/minus 1 week)
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Change from baseline in Harvey Bradshaw Index at 22 weeks
大体时间：Baseline, 22 weeks (plus/minus 1 week)
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Harvey Bradshaw Index is a measure of Crohn's Disease severity.
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Baseline, 22 weeks (plus/minus 1 week)
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合作者和调查者
调查人员
- 首席研究员：Ove Andersen, MD, PhD、Hvidovre Hospital & University of Copenhagen
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他研究编号
- H-1-2013-072
- HVH-2013-028 (注册表标识符：Datatilsynet)
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计划共享个人参与者数据 (IPD)？
IPD 计划说明
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