Near-infrared Fluorescence Molecular Imaging of Adalimumab-800CW to Elucidate the Drug Distribution Throughout Inflamed Tissue in Inflammatory Bowel Disease and Rheumotoid Arthritis
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Discrimination of inflamed and normal tissue based on in vivo and ex vivo fluorescence measurements from adalimumab-800CW gained during fluorescence endoscopy in patients with Crohn's disease (CD).
研究概览
简要总结
Inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) are both auto-immune diseases that are characterized by chronic relapsing inflammation of respectively the ileocolonic tissue and the synovium. Pathogenesis of both auto-immune diseases is attributed to the proinflammatory cytokine tumor necrosis factor α (TNFa). Adalimumab is a human monoclonal anti-TNF antibody used for treating patients with moderate to severely active IBD and RA. However, current rates of therapeutic nonresponsiveness to this antibody are variable and difficult to predict in advance, whereas patients are potentially exposed to a non-effective treatment and its potential side effects; while clinical deterioration progresses. A key unmet need is the development of a predictive tool for assessment of a therapeutic (non-) response to patients and finding an optimal dose strategy in individual patients before initiating anti-TNF therapy. Unfortunately, we currently lack crucial information about drug distribution of the drug of interest throughout the targeted inflamed tissue itself. Therefore, it remains unknown in both IBD and RA, if the drug reaches its target (in sufficient amounts) and how local drug concentrations are related to therapeutic response. Thus, we linked adalimumab to a fluorescent dye (adalimumab-800CW) in order to create a fluorescent signal of the labelled drug in the diseased tissue that we can visualize and quantify with dedicated optical fluorescence imaging systems. We hypothesize that this tracer will bind to TNFa in the mucosa/synovium and thus create a map of medicine distribution in vivo due to colocalization of the fluorescent labelled compound. Therefore, the aim of this study is to assess the feasibility of fluorescent molecular imaging of adalimumab-800CW in IBD and RA patients.
详细描述
See brief summary
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
1. Fluorescence imaging of inflammatory bowel disease and rheumatoid arthritis with adalimumab-800CW
Fluorescence imaging with 4.5 mg adalimumab-800CW in inflammatory bowel disease and rheumatoid arthritis.
干预措施: Adalimumab-800CW (Drug)
1. Fluorescence imaging of inflammatory bowel disease and rheumatoid arthritis with adalimumab-800CW
Fluorescence imaging with 4.5 mg adalimumab-800CW in inflammatory bowel disease and rheumatoid arthritis.
干预措施: Fluorescence Imaging (Device)
2. Fluorescence imaging of inflammatory bowel disease and rheumatoid arthritis with adalimumab-800CW
Fluorescence imaging with 15 mg adalimumab-800CW in inflammatory bowel disease and rheumatoid arthritis.
干预措施: Adalimumab-800CW (Drug)
2. Fluorescence imaging of inflammatory bowel disease and rheumatoid arthritis with adalimumab-800CW
Fluorescence imaging with 15 mg adalimumab-800CW in inflammatory bowel disease and rheumatoid arthritis.
干预措施: Fluorescence Imaging (Device)
3. Fluorescence imaging of inflammatory bowel disease and rheumatoid arthritis with adalimumab-800CW
Fluorescence imaging with 25 mg adalimumab-800CW in inflammatory bowel disease and rheumatoid arthritis.
干预措施: Adalimumab-800CW (Drug)
3. Fluorescence imaging of inflammatory bowel disease and rheumatoid arthritis with adalimumab-800CW
Fluorescence imaging with 25 mg adalimumab-800CW in inflammatory bowel disease and rheumatoid arthritis.
干预措施: Fluorescence Imaging (Device)
4. Fluorescence imaging of inflammatory bowel disease and rheumatoid arthritis
Fluorescence imaging without adalimumab-800CW in inflammatory bowel disease and rheumatoid arthritis.
干预措施: Fluorescence Imaging (Device)
结局指标
主要结局
Discrimination of inflamed and normal tissue based on in vivo and ex vivo fluorescence measurements from adalimumab-800CW gained during fluorescence endoscopy in patients with Crohn's disease (CD).
时间窗: Up to 1 year
The target-to-background/contrast-to-noise ratio will be calculated after fluorescence molecular endoscopy (FME) and MDSFR/SFF spectroscopy. These results will be related to the gold standard clinical care to evaluate the feasibility of fluorescence molecular endoscopy using the tracer adalimumab-800CW for the evaluation of drug distribution in patients with Crohn's disease.
Safety: number of participants with symptoms or changes in vital signs (blood pressure, heart rate and temperature) that are related to administration of adalimumab-800CW
时间窗: Up to 30 minutes after stop tracer injection
To determine the safety of adalimumab-800CW in inflammatory bowel disease (IBD) and rheumatoid arthritis patients by monitoring of vital signs (blood pressure, heart rate and temperature) before, during and after tracer infusion. These vital signs are measured before tracer administration, directly after and then every 15 minutes until 1 hour after tracer administration.
Discrimination of inflamed and normal tissue based on in vivo fluorescence measurements from adalimumab-800CW gained during fluorescence imaging of the hand of rheumatoid arthritis patients
时间窗: Up to 1 year
The target-to-background/contrast-to-noise ratio will be calculated after fluorescence imaging. These results will be related to the gold standard clinical care to evaluate the feasibility of molecular fluorescence imaging using the tracer adalimumab-800CW for the evaluation of drug distribution in patients with rheumatoid arthritis.
Discrimination of inflamed and normal tissue based on in vivo and ex vivo fluorescence measurements from adalimumab-800CW gained during fluorescence endoscopy in patients with ulcerative colitis (UC).
时间窗: Up to 1 year
The target-to-background/contrast-to-noise ratio will be calculated after fluorescence molecular endoscopy (FME) and MDSFR/SFF spectroscopy. These results will be related to the gold standard clinical care to evaluate the feasibility of fluorescence molecular endoscopy using the tracer adalimumab-800CW for the evaluation of drug distribution in patients with ulcerative colitis.
Safety: number of participants with (serious) adverse events that are related to the administration of adalimumab-800CW
时间窗: Up to 24 hours after tracer injection
(serious) adverse events will be monitored until 24 hours after tracer administration.
次要结局
- The correlation between the fluorescence intensity and the disease activity measured with the DAS28 in patients with RA.(Up to 1 year)
- The correlation between fluorescence intensity and the clinical disease activity score in ulcerative colitis using the SCCAI;(Up to 1 year)
- Quantification of fluorescence signals in vivo and ex vivo of inflamed and normal tissue using multi-diameter single-fiber reflectance, single-fiber fluorescence (MDSFR/SFF) spectroscopy measurements in IBD patients;(Up to 1 year)
- Calculation of optical properties with MDSFR/SFF spectroscopy in patients with RA(Up to 1 year)
- Correlation in IBD between the detected fluorescence signals in vivo and the clinical response to induction therapy at week 14.(Up to 1 year)
- The correlation between fluorescence intensity and the clinical disease activity score in Crohn's disease using the Crohn's Disease Activity Index (CDAI).(Up to 1 year)
- The correlation between fluorescence intensity and the endoscopic disease activity score in ulcerative colitis using the Mayo endoscopic subscore;(Up to 1 year)
- The correlation between fluorescence intensity and the disease activity score in Crohn's disease using the SES-CD score(Up to 1 year)
- The correlation and validation of fluorescence signals detected in vivo to the pathology of biopsies for IBD patients;(Up to 1 year)