Using Vedolizumab-800CW to Gain Insight Into Local Drug Distribution and Mucosal Target Cells in IBD Patients
- Conditions
- Crohn DiseaseColitis, Ulcerative
- Interventions
- Other: Fluorescence molecular imaging procedure without prior administration of vedolizumab-800CWDrug: Fluorescence molecular imaging procedure using vedolizumab-800CWCombination Product: Fluorescence molecular imaging procedure using vedolizumab-800CW with prior administration of unlabeled vedolizumab
- Registration Number
- NCT04112212
- Lead Sponsor
- University Medical Center Groningen
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 38
- 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.
- Prior vedolizumab treatment
- Vedolizumab contraindicated as therapy
- Pregnancy or breast feeding.
- Patients younger than 18 years old
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description No administration of vedolizumab-800CW Fluorescence molecular imaging procedure without prior administration of vedolizumab-800CW Patients did not receive vedolizumab-800CW but underwent a Fluorescence molecular imaging procedure to serve as a control group and compare results with patients receiving the tracer 4.5 mg vedolizumab-800CW group Fluorescence molecular imaging procedure using vedolizumab-800CW Patients received 4.5 mg vedolizumab-800CW and subsequently underwent a Fluorescence molecular imaging procedure 15 mg vedolizumab-800CW group Fluorescence molecular imaging procedure using vedolizumab-800CW Patients received 15 mg vedolizumab-800CW and subsequently underwent a Fluorescence molecular imaging procedure 75 mg vedolizumab + 15 mg vedolizumab-800CW group Fluorescence molecular imaging procedure using vedolizumab-800CW with prior administration of unlabeled vedolizumab Patients received 75mg vedolizumab + 15 mg vedolizumab-800CW and subsequently underwent a Fluorescence molecular imaging procedure 300mg vedolizumab + 15mg vedolizumab-800CW group Fluorescence molecular imaging procedure using vedolizumab-800CW with prior administration of unlabeled vedolizumab Patients received 300mg vedolizumab + 15 mg vedolizumab-800CW and subsequently underwent a Fluorescence molecular imaging procedure > 14 weeks of vedolizumab therapy + 15 mg vedolizumab-800CW group Fluorescence molecular imaging procedure using vedolizumab-800CW with prior administration of unlabeled vedolizumab Patients received 300mg vedolizumab + 15 mg vedolizumab-800CW after \>14 weeks vedolizumab therapy and subsequently underwent a Fluorescence molecular imaging procedure
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
Trial Locations
- Locations (1)
University Medical Center Groningen
🇳🇱Groningen, Netherlands