Colitis, Ulcerative, Crohn Disease
Conditions
Keywords
Fluorescence, Endoscopy, Vedolizumab-800CW
Brief summary
Summary Vision Study Crohn's Disease (CD) and Ulcerative Colitis (UC) are chronic idiopathic inflammatory bowel diseases (IBD). Vedolizumab is a humanized monoclonal antibody against α4β7 integrin, capable of blocking the migration of several immune cells across endothelium expressing MAdCAM-1. Vedolizumab is expensive and primary non-response is high in both CD and UC. Currently there are no predictors of response to vedolizumab and the actual mechanism of action has not yet been elucidated. To clarify the mechanism of action and gain better understanding of the high primary non-response rates, the University Medical Center Groningen (UMCG) developed a tracer fluorescently labeling vedolizumab. This study aims to gain insight into vedolizumab distribution and concentrations in the gut. The current study aims to identify the vedolizumab target cells in the inflamed gut mucosa using quantitative fluorescence molecular imaging (FMI). By gaining insight into local vedolizumab concentrations, drug distribution and by discovering target cells, we expect to gain insight into the mechanism of action of vedolizumab.
Interventions
DRUGFluorescence molecular imaging procedure using vedolizumab-800CW
First vedolizumab-800CW was administered intravenously. 2-4 days later a fluorescence molecular imaging procedure was performed to enable the visualization and detection of fluorescence signals.
OTHERFluorescence molecular imaging procedure without prior administration of vedolizumab-800CW
Fluorescence molecular imaging was performed to enable the visualization and detection of fluorescence signals.
COMBINATION_PRODUCTFluorescence molecular imaging procedure using vedolizumab-800CW with prior administration of unlabeled vedolizumab
Patients on vedolizumab therapy received vedolizumab-800CW iv or patients first received an unlabeled dose of vedolizumab prior to the iv administration of vedolizumab-800CW. 2-4 days later a fluorescence molecular imaging procedure was performed to enable the visualization and detection of fluorescence signals.
Sponsors
University Medical Center Groningen
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
NONE
Intervention model description
38 IBD patients were included in the study. 1. Dose escalation, including 3 dose groups. 2. Adding a blocking dose. 3. Patients included after \>14 weeks of therapy
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Established diagnosis of IBD, or Ulcerative Colitis (UC) or Crohn's Disease (CD). * Vedolizumab naïve and eligible for vedolizumab treatment. * Age: 18 years or older. * Written informed consent.
Exclusion criteria
* Prior vedolizumab treatment * Vedolizumab contraindicated as therapy * Pregnancy or breast feeding. * Patients younger than 18 years old
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fluorescent signal in patients with IBD | After 18 months when study is completed. | Quantification of fluorescent signal after a microdose of vedolizumab-800CW in inflamed and non-inflamed tissue in patients with IBD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety of Vedolizumab-800CW in patients with IBD | Interim analysis after 30 weeks (at least 5 patients included). Complete data of all patients when study is completed. Individual patients were followed up for 1 week after vedolizumab-800CW injection for AE's, SAE's and SUSAR's. | Collect safety data of vedolizumab-800CW. Checking vital parameters and adverse events caused by the drug or intervention. Register and analyze all AE's, SAE's and SUSAR's caused by vedolizumab-800CW. |
| Semi-quantifying fluorescent signals in patients with IBD | Interim analysis after 30 weeks (at least 5 patients included). Complete data after 18 months when study is completed. | Semi-quantification of the ex vivo mean fluorescent intensity signal of vedolizumab-800CW in biopsies by calculating the mean fluorescence intensity (FImean) of biopsy images generated with a fluorescence flatbed scanner |
| FMI ex vivo analysis to detect target cells | After 18 months when study is completed. | To evaluate the degree of in vivo fluorescence intensity for differences in severity of inflammation and quantify the in vivo NIR fluorescent signal of vedolizumab-800CW using the spectroscopy probe and compare this to the ex vivo fluorescent signal levels in the biopsies taken (immunohistochemistry, RNA and DNA analysis). |
| Distribution of Vedolizumab in the inflamed gut | After 18 months when study is completed. | To assess the (sub-)cellular location of vedolizumab-800CW microscopically. |
Countries
Netherlands
Outcome results
None listed